Journal articles on the topic 'Art. 52 c. 2 c.p'
To see the other types of publications on this topic, follow the link: Art. 52 c. 2 c.p.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Art. 52 c. 2 c.p.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Buckner, Jan C., Karla V. Ballman, John C. Michalak, Gary V. Burton, Terrence L. Cascino, Paula J. Schomberg, Roland B. Hawkins, et al. "Phase III Trial of Carmustine and Cisplatin Compared With Carmustine Alone and Standard Radiation Therapy or Accelerated Radiation Therapy in Patients With Glioblastoma Multiforme: North Central Cancer Treatment Group 93-72-52 and Southwest Oncology Group 9503 Trials." Journal of Clinical Oncology 24, no. 24 (August 20, 2006): 3871–79. http://dx.doi.org/10.1200/jco.2005.04.6979.
Full textAbstract:
Purpose In patients with newly diagnosed glioblastoma multiforme, to determine whether cisplatin plus carmustine (BCNU) administered before and concurrently with radiation therapy (RT) improves survival compared with BCNU and RT and whether survival using accelerated RT (ART) is equivalent to survival using standard RT (SRT). Patients and Methods After surgery, patients were stratified by age, performance score, extent of surgical resection, and histology (glioblastoma v gliosarcoma) and then randomly assigned to arm A (BCNU plus SRT), arm B (BCNU plus ART), arm C (cisplatin plus BCNU plus SRT), or arm D (cisplatin plus BCNU plus ART). Results Four hundred fifty-one patients were randomly assigned, and 401 were eligible. Frequent toxicities included myelosuppression, vomiting, sensory neuropathy, and ototoxicity and were worse with cisplatin. There was no difference in toxicity between SRT and ART. Median survival times and 2-year survival rates for patients who received BCNU plus RT (arms A and B) compared with cisplatin, BCNU, and RT (arms C and D) were 10.1 v 11.5 months, respectively, and 11.5% v 13.7%, respectively (P = .19). Median survival times and 2-year survival rates for patients who received SRT (arms A and C) compared with ART (arms B and D) were 11.2 v 10.5 months, respectively, and 13.8% v 11.4%, respectively (P = .33). Conclusion Cisplatin administered concurrently with BCNU and RT resulted in more toxicity but provided no significant improvement in survival. SRT and ART produced similar toxicity and survival.
2
Lebenthal, Brener, Hershkovitz, Shehadeh, Shalitin, Lewis, Elias, et al. "A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Alpha-1 Antitrypsin (AAT) (Glassia®) in the Treatment of Recent-Onset Type 1 Diabetes." International Journal of Molecular Sciences 20, no. 23 (November 29, 2019): 6032. http://dx.doi.org/10.3390/ijms20236032.
Full textAbstract:
Our aim was to assess the efficacy, safety, and tolerability of alpha-1 antitrypsin (AAT) as a therapeutic modality for β-cell preservation in patients with recent-onset type 1 diabetes. Seventy type 1 diabetes patients (37 males; mean age 13.1 ± 4.1years) were randomized to treatment with 22 infusions of AAT (Glassia®) (60 or 120 mg/kg) or placebo. The primary outcome was the area under the curve (AUC) of C-peptide from a 2-h mixed-meal tolerance test after 52 weeks. At week 52, C-peptide was 0.9, 0.45, and 0.48 pmol/mL in the AAT-120, AAT-60, and placebo groups (p = 0.170 and p = 0.866 vs. placebo, respectively). The declines in C-peptide glycated hemoglobin (HbA1c) and the total insulin dose (U/kg) were similar across groups. Within the predefined 12–18-years subgroup, the C-peptide AUC decreased significantly in the placebo and AAT-60 groups (−0.34 and −0.54 pmol/mL, respectively, p < 0.01), with a borderline decrease in the AAT-120 group (−0.29 pmol/mL, p = 0.047). The mean HbA1c level was significantly lower in the AAT-120 group compared to the placebo (6.7% ± 0.9% vs. 8.2 ± 1.4%, p = 0.05), and a higher percentage of patients attained HbA1c ≤ 7% (75% vs. 25%, p = 0.05). AAT was tolerated well, with a similar safety profile between groups. The AAT intervention showed promise in the subgroup of adolescents with recent-onset type 1 diabetes. Further studies are warranted to determine the impact and proposed mechanism of action of AAT in β-cell preservation.
3
Kharlamova, T. V., S. L. Voznesenskiy, T. N. Ermak, G. M. Kozhevnikova, and P. V. Klimkova. "Infectious endocarditis in HIV-infected intensive care unit patients." Journal Infectology 14, no. 2 (July 13, 2022): 73–79. http://dx.doi.org/10.22625/2072-6732-2022-14-2-73-79.
Full textAbstract:
Infective endocarditis (IE) is one of the most common cardiac complications in HIV patients who are intravenous drug addicts. The presence of IE and secondary diseases in immunocompromised individuals usually requires specific diagnostic and therapeutic approach.Aim: Optimizing the diagnosis of IE in patients with advanced HIV/AIDS.Materials and methods We reviewed 429 case records of HIV/AIDS ICU patients using the modified duke criteria for diagnosis of infective endocarditis. Statistical significance (p <0.05) of data was assessed using the χ2 test.Results. 25 patients were diagnosed with IE. The male gender dominated – 68%. Mean age was 38. 60% had stage 4B HIV infection. 68% were ART naive. The medium viral load was 294560 copies / ml, while the medium CD4 count was 218 cells / μl. Fever of >38°C was a key symptom found in all patients. Blood cultures were positive in 60% cases. 80% had a high C reactive protein (CRP), and 44% had CRP levels above 100 mg/l. Procalcitonin (PCT) levels were increased in 52%. Echocardiogram revealed IE in 92%. Pneumonia was diagnosed in 92%. Fatal outcome occurred in 76%. Anemia was a predictor of severe outcome (p<0.002), while patients with leukocytosis had good prognosis (p<0.05).Conclusion. Infective endocarditis is a common complication among HIV IDUs. The most common diagnostic criteria are fever >38°C, pneumonia, anemia, leukocytosis, thrombocytopenia and echocardiographic findings. The levels of the hemoglobin and WBCs could evaluate prognosis of the disease outcome.
4
Yastrebova, E. B., O. E. Chernova, A. M. Kalyshenko, and G. A. Vertogradova. "Chronic hepatitis C in children with HIV infection: disease phenotype and efficacy of antiviral therapy." Infekcionnye bolezni 19, no. 2 (2021): 52–58. http://dx.doi.org/10.20953/1729-9225-2021-2-52-58.
Full textAbstract:
Objective. To analyze the course of chronic hepatitis C (CHC) and efficacy of its treatment in children with HIV infection. Patients and methods. This study included 29 children aged 12 to 17 years (mean age 15.1 ± 0.2 years) with perinatal HIV infection and CHC. HIV stages were distributed as follows: stage 4A in 24 individuals (82.8%), stage 4B in 4 individuals (13.8%), and stage 4B in 1 individual (3.4%). All 29 patients received antiretroviral therapy. The distribution of children by HCV genotypes was as follows: 1a in one child (3.4%), 1b in 12 children (41.4%), and 3a in 16 children (55.2%). Antiviral therapy for CHC included glecaprevir/pibrentasvir (3 tablets; 100 mg + 40 mg) once a day for 56 days. Data analysis was performed using the Statistica for Windows software (version 10.0). Results. The mean HCV RNA level was 595,666 ± 34,734 IU/mL (range: 1,100–3,863,025 IU/mL). After 4, 8, or 12 weeks of antiviral therapy for HCV, HCV RNA clearance was achieved in all study participants (p = 0.01). Before treatment initiation, mean CD4+ count was 738 ± 34 cells/μL (above 500 cells/μL), which indicated the absence of immunodeficiency in the group analyzed. Successful antiviral therapy for HCV (sustained virologic response at week 12; SVR 12) also resulted in increase of the CD4+ lymphocytes level, which was considered as a positive effect of glecaprevir/pibrentasvir (p = 0.15). We observed significant differences in the level of liver enzymes (ALT and AST) (p = 0.01) between samples collected before antiviral therapy initiation and those collected during treatment, as well as 12 weeks after its completion (SVR12). All children demonstrated good tolerance of glecaprevir/pibrentasvir; none of them had adverse events, complaints, or clinical/laboratory changes. Conclusion. Thus, all children with HIV infection and CHC achieved SVR12 after the 8-week course of antiviral therapy with glecaprevir/pibrentasvir regardless of HCV genotype. Clinical manifestations (hepatosplenomegaly in 62.1%; asthenovegetative syndrome in 31.0%) were eliminated after 8 weeks of therapy. Laboratory manifestations (hepatic cytolysis (AST/ALT)) were normalized after 4 weeks of therapy. Antiviral treatment for HCV resulted in some increase in the level of CD4+ lymphocytes. We observed no adverse events caused by glecaprevir/pibrentasvir (neither clinical symptoms nor changes in complete blood count or liver function tests), which confirms the safety of this treatment regimen. Key words: antiretroviral therapy, HIV infection, children, direct-acting antivirals, chronic hepatitis C
5
Lazova, Snezhina, Tea Alexandrova, Nadzhie Gorelyova-Stefanova, Kalin Atanasov, Iren Tzotcheva, and Tsvetelina Velikova. "Liver Involvement in Children with COVID-19 and Multisystem Inflammatory Syndrome: A Single-Center Bulgarian Observational Study." Microorganisms 9, no. 9 (September 15, 2021): 1958. http://dx.doi.org/10.3390/microorganisms9091958.
Full textAbstract:
SARS-CoV-2 infection may precede and cause various autoimmune and inflammatory diseases, including multisystem inflammatory syndrome in children (MIS-C). Therefore, we aimed to observe the clinical presentation and laboratory, instrumental and other constellations in children with MIS-C, including liver involvement. We present the outcomes from a single-center prospective observational study in which 89 children was included (60 with proven COVID-19, 10 symptomatic with confirmed COVID-19 contact and 19 diagnosed with MIS-C). Laboratory, instrumental, immunological, and clinical investigations were performed. Only 12% (n = 4) from the COVID-19 group (except the ICU cases), we found elevated AST and/or ALT (up to 100). All of the children with elevated transaminase were overweight or obese, presenting along with moderate COVID-19 pneumonia. The majority of children with MIS-C showed typical laboratory constellations with higher levels of IL-6 (120.36 ± 35.56 ng/mL). About half of the children in the MIS-C group (52%, n = 11) showed elevated transaminases. Eleven children (57.9%) presented with abdominal pain, eight (42.1%) with ascites, two (10.5%) with hepatosplenomegaly, and four (21.1%) with symptoms such as diarrhea. Mesenteric lymphadenitis was observed more often in patients with elevated LDH (327.83 ± 159.39, p = 0.077). Ascites was associated with lymphopenia (0.86 ± 0.80, p = 0.029) and elevated LDH. Hepato-splenomegaly was also more frequent in children with lymphopenia (0.5 ± 0.14, p = 0.039), higher troponin (402.00 ± 101.23, p = 0.004) and low ESR. Diarrhea was more frequent in patients with lower CRP (9.00 ± 3.44 vs. 22.25 ± 2.58, p = 0.04), and higher AST and ALT (469.00 ± 349.59 vs. and 286.67 ± 174.91, respectively, p = 0.010), and D-dimer (4516.66 ± 715.83, p = 0.001). Our data suggest that the liver can also be involved in MIS-C, presenting with typical laboratory and instrumental outcomes.
6
Karzai, Fatima H., Bamidele Adesunloye, Yangmin M. Ning, Ravi Amrit Madan, James L. Gulley, Andrea Borghese Apolo, Melony A. Beatson, et al. "Use of supportive measures to improve outcome and decrease toxicity in docetaxel-based antiangiogenesis combinations." Journal of Clinical Oncology 31, no. 6_suppl (February 20, 2013): 128. http://dx.doi.org/10.1200/jco.2013.31.6_suppl.128.
Full textAbstract:
128 Background: We have recently completed accrual of 63 patients (pts) to our study combining lenalidomide (L), with bevacizumab (B), docetaxel (D), and prednisone (P) (ART-P). Due to the lack of improved survival and the increased toxicity of anti-angiogenic docetaxel combinations in the MAINSAIL and CALGB 90410 trials we attempted to contrast and compare our studies with the failed phase III trials. Methods: Among the first 52 pts on the ART-P, 3 received L 15 mg daily, 3 had 20 mg daily, and the rest had 25 mg daily for 14 days of every 21−day cycle (C). We later enrolled 11 more pts at L 15 mg. All pts received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and enoxaparin daily throughout each C. Pegfilgrastim was given on day 2. Patients on CALGB 90410 received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and on MAINSAIL received D 75 mg/m2, L 25 mg daily for 14 days of every 21−day cycle with daily P. Patients on CALGB 90410 and MAINSAIL did not receive enoxaparin or pegfilgrastim prophylactically. Results: Median number of Cs in ART-P was 16 (3−38). PFS was 22 months and median OS has not been reached. Pts with measurable disease had 1 CR and 25 PR (86.7% RR). Two patients (3%) had deep vein thromboses. Of 1,219 cycles given, 14 cycles were complicated by febrile neutropenia (FN) (1.1%). There were no treatment related deaths. In comparison, median number of Cs in MAINSAIL L+DP arm was 6, with a PFS of 45 weeks and an OS of 77 weeks. Thirty-four pts (6.5%) developed pulmonary emboli and there were 2 deaths due to toxicity in the experimental arm. Nearly 12% of Cs were complicated by FN. In the experimental arm of CALGB 90410 trial, median OS was 22.6 months with median PFS of 9.9 months. Median number of Cs was 8, and 19 pts developed thromboses/emboli (3.6%). In addition, 7% of patients developed FN and treatment related deaths were reported at 4%. Conclusions: The use of supportive care allows the ART-P combination to be given for more cycles than were given in MAINSAIL and CALGB 90401 potentiating a longer PFS, RR and possibly OS with an improved toxicity profile. This data demonstrates the potential importance of supportive measures and is hypothesis generating for future combination studies. Clinical trial information: NCT00942578.
7
Karzai, Fatima H., Ravi Amrit Madan, Andrea Borghese Apolo, Yangmin M. Ning, Howard L. Parnes, Philip M. Arlen, Melony A. Beatson, et al. "Use of supportive measures to improve outcome and decrease toxicity in docetaxel-based antiangiogenesis combinations in metastatic castrate resistant prostate cancer (mCRPC)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e16017-e16017. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e16017.
Full textAbstract:
e16017 Background: We have completed accrual of 63 patients (pts) to our study combining lenalidomide (L), with bevacizumab (B), docetaxel (D), and prednisone (P) (ART-P) in mCRPC. Due to the lack of improved survival and the increased toxicity of anti-angiogenic docetaxel combinations in the MAINSAIL and CALGB 90401 trials, we attempted to compare and contrast our studies with these failed phase III trials. Methods: Among the first 52 pts on ART-P, 3 received L 15 mg daily, 3 received 20 mg daily, and the others received 25 mg daily for 14 days of every 21−day cycle (C). We then enrolled 11 pts at L 15 mg. All pts received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and enoxaparin daily. Pegfilgrastim was given on day 2. Patients on CALGB 90401 received D 75 mg/m2 and B 15 mg/kg on day 1, with P 10 mg. On MAINSAIL, pts received D 75 mg/m2, L 25 mg daily for 14 days of every 21−day cycle with daily P. Patients on CALGB 90401 and MAINSAIL did not receive enoxaparin or pegfilgrastim prophylactically. Results: The median number of Cs on ART-P is 18 (1-52). Median PFS is 19.1 months. Twenty-seven pts had a PR, and one pt with measurable disease had a CR. Two patients (3%) had deep vein thromboses. Of 1,334 Cs given, 14 cycles were complicated by febrile neutropenia (FN) (1%). There were no treatment related deaths. In comparison, median number of Cs in MAINSAIL L+DP arm was 6, with a PFS of 45 weeks and an OS of 77 weeks. Thirty-four pts (6.5%) developed pulmonary emboli and there were 2 deaths due to toxicity in the experimental arm. Nearly 12% of Cs were complicated by FN. In the experimental arm of CALGB 90401 trial, median OS was 22.6 months with median PFS of 9.9 months. The median number of Cs were 8 and 19 pts developed thrombosis/emboli (3.6%). In addition, 37 patients developed FN and treatment related deaths were reported at 4%. Conclusions: The use of supportive care allowed longer treatment duration with the ART-P combination as compared to D+L (MAINSAIL) and D+B (CALGB 90401), potentiating a longer PFS, RR and possibly OS with an improved safety profile. This data demonstrates the potential importance of supportive measures and is hypothesis generating for future combination studies. Clinical trial information: NCT00942578.
8
Kahl, Lesley, Grace A. McComsey, Monica Coronado Poggio, Sergio Lupo, Joss de Wet, David A. Parks, Brian Wynne, et al. "319. SWORD 1 and 2: Switch from TDF Containing Regimen to DTG+RPV Maintains Bone Mineral Density and Decreases Bone Turnover Markers Over 148 Weeks." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S169—S170. http://dx.doi.org/10.1093/ofid/ofz360.392.
Full textAbstract:
Abstract Background HIV infection and antiretroviral therapy (ART), particularly tenofovir (TDF), is associated with loss of bone mineral density (BMD). The SWORD studies demonstrated noninferiority of the 2-drug regimen (2DR) dolutegravir (DTG) + rilpivirine (RPV) to continuing current triple-therapy ART (CAR) at 48 weeks and continued viral suppression on DTG+RPV through Week 148. A substudy of SWORD 1 and 2 evaluated a change in BMD by DEXA for those participants who switched from triple ART containing TDF to DTG+RPV. The primary analysis reported at 48 weeks showed a significant increase in total hip and lumbar spine BMD and a significant decrease in bone turnover markers in patients receiving DTG+RPV compared with CAR. Here we present data through Week 148. Methods HIV-infected adult patients with HIV-1 RNA < 50 c/mL received ART containing TDF for ≥6 months prior to randomization to DTG+RPV (Early Switch group, ES) or CAR on Day 1 (Baseline, BL) through Week 48 in SWORD-1/2. CAR patients suppressed at Week 48 switched to DTG+RPV at Week 52 (Late Switch group, LS). Hip and lumbar spine BMD were measured by DEXA scans read centrally. Secondary endpoints include a change in BMD and bone turnover markers through Week 148. Results Following switch to DTG+RPV significant increases were observed for total hip in the ES and LS groups through 100 weeks with a non-significant increase at Week 148 in ES (Figure 1a). Lumbar spine BMD significantly increased from BL at 48 weeks post switch, remained increased, though not significantly from BL through Week 148 (Figure 1b). The BMD of the LS group was similar to that of the ES group through 100 weeks exposure. The majority of patients remained in their pre-switch T-score category or improved a category for both hip and spine through Wk148 (Table 1). Through Wk148, BMI increased minimally and bone turnover markers significantly decreased (P < 0.001 to 0.042 across markers) from BL/LS BL except Type I Collagen C-Telopeptide at Wk148 in the LS group (P = 0.279). Conclusion Switch to the DTG+RPV 2DR was associated with sustained improvements in BMD through Week 148, along with a reduction in bone markers. The favorable effects on skeletal health were observed despite the ageing of study patients and other factors decreasing BMD. A switch to DTG+RPV in suppressed patients provides a robust option for preserving bone health while continuing suppressive HIV treatment. Disclosures All authors: No reported disclosures.
9
Ragni, MV, OK Ndimbie, EO Rice, FA Bontempo, and S. Nedjar. "The presence of hepatitis C virus (HCV) antibody in human immunodeficiency virus-positive hemophilic men undergoing HCV "seroreversion"." Blood 82, no. 3 (August 1, 1993): 1010–15. http://dx.doi.org/10.1182/blood.v82.3.1010.1010.
Full textAbstract:
Abstract Hepatitis C virus (HCV) is a major cause of transfusion-induced chronic liver disease in hemophiliacs, with 70% to 90% being anti-HCV positive. Seroreversion or loss of antibody response to HCV has been observed in a small proportion of human immunodeficiency virus-positive [HIV(+)] anti-HCV(+) hemophilic men. Despite the seroreversion to an anti-HCV- negative state, such patients continue to show serum alanine aminotransferase (ALT) elevations and biopsy evidence of cirrhosis and/or chronic active hepatitis. To determine the cause for the loss of anti-HCV antibody, we compared first- and second-generation anti-HCV enzyme immunosorbent assay (EIA 1.0 and 2.0), second-generation recombinant immunoblot (RIBA 2.0), and HCV-RNA amplification using polymerase chain reaction (PCR) in 19 “seroreverters” before and after seroreversion. There was no difference between 19 seroreverters and 59 persistently anti-HCV-positive hemophiliacs in mean ALT (1.1 +/- 0.1 XUL v 2.0 +/- 0.2 XUL; chi 2 = 1.80, P > .05), in mean CD4 (188 +/- 36/microL v 232 +/- 28/microL; t = 0.965, P > .05), or in the rate of progression to acquired immunodeficiency syndrome (13 of 19 [68.4%] v 30 of 59 [50.9%]; chi 2 = .987, P > .05, respectively). Before seroreversion, all 19 seroreverters (100%) were positive for EIA 1.0 and 2.0 and PCR, and all but 2 of 19 (89.5%) were RIBA 2.0 positive, whereas, after seroreversion, none were positive for EIA 1.0, 15 of 19 (78.9%) were positive for EIA 2.0, 8 of 18 (44.4%) were positive for RIBA 2.0, and 18 of 19 (94.7%) were positive for PCR. There was a lower CD4 lymphocyte number after seroreversion in those who were RIBA 2.0 negative as compared with those who were RIBA 2.0 positive (32 +/- 10/microL v 171 +/- 52/microL; t = 2.638, P > .05). These results indicate that HIV(+) anti-HCV(+) hemophilic men who undergo “HCV seroreversion” are truly infectious and anti-HCV positive by second- generation tests. Anti-HCV detection in immunosuppressed hosts is significantly improved by second-generation EIA and RIBA assays.
10
Ragni, MV, OK Ndimbie, EO Rice, FA Bontempo, and S. Nedjar. "The presence of hepatitis C virus (HCV) antibody in human immunodeficiency virus-positive hemophilic men undergoing HCV "seroreversion"." Blood 82, no. 3 (August 1, 1993): 1010–15. http://dx.doi.org/10.1182/blood.v82.3.1010.bloodjournal8231010.
Full textAbstract:
Hepatitis C virus (HCV) is a major cause of transfusion-induced chronic liver disease in hemophiliacs, with 70% to 90% being anti-HCV positive. Seroreversion or loss of antibody response to HCV has been observed in a small proportion of human immunodeficiency virus-positive [HIV(+)] anti-HCV(+) hemophilic men. Despite the seroreversion to an anti-HCV- negative state, such patients continue to show serum alanine aminotransferase (ALT) elevations and biopsy evidence of cirrhosis and/or chronic active hepatitis. To determine the cause for the loss of anti-HCV antibody, we compared first- and second-generation anti-HCV enzyme immunosorbent assay (EIA 1.0 and 2.0), second-generation recombinant immunoblot (RIBA 2.0), and HCV-RNA amplification using polymerase chain reaction (PCR) in 19 “seroreverters” before and after seroreversion. There was no difference between 19 seroreverters and 59 persistently anti-HCV-positive hemophiliacs in mean ALT (1.1 +/- 0.1 XUL v 2.0 +/- 0.2 XUL; chi 2 = 1.80, P > .05), in mean CD4 (188 +/- 36/microL v 232 +/- 28/microL; t = 0.965, P > .05), or in the rate of progression to acquired immunodeficiency syndrome (13 of 19 [68.4%] v 30 of 59 [50.9%]; chi 2 = .987, P > .05, respectively). Before seroreversion, all 19 seroreverters (100%) were positive for EIA 1.0 and 2.0 and PCR, and all but 2 of 19 (89.5%) were RIBA 2.0 positive, whereas, after seroreversion, none were positive for EIA 1.0, 15 of 19 (78.9%) were positive for EIA 2.0, 8 of 18 (44.4%) were positive for RIBA 2.0, and 18 of 19 (94.7%) were positive for PCR. There was a lower CD4 lymphocyte number after seroreversion in those who were RIBA 2.0 negative as compared with those who were RIBA 2.0 positive (32 +/- 10/microL v 171 +/- 52/microL; t = 2.638, P > .05). These results indicate that HIV(+) anti-HCV(+) hemophilic men who undergo “HCV seroreversion” are truly infectious and anti-HCV positive by second- generation tests. Anti-HCV detection in immunosuppressed hosts is significantly improved by second-generation EIA and RIBA assays.
11
Muvarak, Nidal E., Shannon M. Kelley, Mario Tarasco, Maria R. Baer, Kara A. Scheibner, and Feyruz Rassool. "C-MYC and C-MYC-Regulated Micrornas Increase The Activity Of The Error-Prone ALT NHEJ Pathway Through Upregulation Of LIG3 and PARP1 In Tyrosine Kinase-Activated Leukemias." Blood 122, no. 21 (November 15, 2013): 809. http://dx.doi.org/10.1182/blood.v122.21.809.809.
Full textAbstract:
Abstract Constitutively activated tyrosine kinases (TK) BCR-ABL1 and FLT3/ITD not only increase cell survival and proliferation, but also increase levels of endogenous DNA damage and activity of an error-prone DNA double-strand break (DSB) repair pathway. This genomic instability leads to acquisition of genomic alterations that can result in disease progression and/or resistance to therapy. We have previously demonstrated that, in TK-activated leukemias, activity of the classic non homologous end-joining (C-NHEJ) pathway that repairs DSBs is decreased, and, as a consequence, an alternative, highly error-prone form of NHEJ (ALT NHEJ) predominates, evidenced by increased expression of DNA ligase IIIα (LIG3) and PARP1 (components of ALT NHEJ), increased frequency of large DNA deletions, and repair using DNA microhomologies. In this study, we sought to elucidate the role of a key downstream target of TKs, c-MYC, in upregulating LIG3 and PARP1 expression and consequently increasing ALT NHEJ and genomic instability. We demonstrated that MYC increases the expression of LIG3 and PARP1 through two mechanisms: 1) Increased binding to the promoters of LIG3 and PARP1, leading to increased transcription, and 2) Repression of microRNAs (miRs) that putatively regulate LIG3 and PARP1. Chemical and siRNA-mediated knockdown of MYC in MO7e-BCR/ABL and FLT3/ITD(+) MOLM14 cells results in significant reduction (p<0.05) in LIG3 and PARP1 mRNA and protein compared to controls. Chromatin immunoprecipitation assays revealed MYC binding to the promoters of LIG3 and PARP1 in AML (MOLM14) and CML (K562 and MO7e-BCR/ABL) cell lines. Additionally, transfection of PARP1 and LIG3 promoter-luciferase constructs into TK-activated (32D-FLT3/ITD, MO7e-BCR/ABL) cells showed significantly (p<0.01) increased LIG3 and PARP1 promoter activity compared to parental controls (32D, MO7e). Moreover, knockdown of MYC in 32D-FLT3/ITD and MO7e-BCR/ABL cells resulted in a significant reduction of promoter activity in luciferase assays (p<0.05). Conversely, overexpression of c-MYC in 293T cells caused an increase (p<0.05) in LIG3 and PARP1 promoter activity. We next determined whether MYC-repressed miRs that have predicted binding sites in the 3’-UTR and coding regions of LIG3 and PARP1 are involved in regulating expression of LIG3 and PARP1. We found that there was a significant inverse correlation between LIG3 expression and miR-22, miR-23a, and miR-150 (Pearson’s r ≤ -0.3, p<0.05). Similarly, there was a significant inverse correlation between PARP1 expression and miR-22, miR-23a, miR-27a, and miR-150 (Pearson r ≤ -0.3, p<0.05). Over-expression of miR-22 in the CML cell line K562 decreased both LIG3 and PARP1 protein levels by 52% and 63% respectively. Similar results were seen upon over-expression of miR-34a (59% and 45%) and miR-150 (46% and 62%) for LIG3 and PARP1. This indicates that MYC-regulated miRs may function coordinately to regulate NHEJ repair. Importantly, our functional NHEJ assays demonstrate an overall significant (p<0.05) reduction in the average size of deletions at the sites of DSB repair when MYC is knocked down, indicating a reduction in ALT NHEJ activity. To determine whether increased expression of LIG3 and PARP1 correlated with MYC expression in primary leukemia samples, we examined mRNA levels from bone marrow of 21 CML patients (12 chronic phase, 1 accelerated, 7 blast crisis, and 1 unknown). Twelve patients were resistant to Imatinib, 7 were responsive, and 2 undetermined. There was a strong positive correlation between levels of MYC and PARP1 (Pearson’s r= 0.75, p=0.001), as well as MYC and LIG3 (Pearson’s r =0.45, p=0.03). While there was no correlation between levels of gene expression and disease phase, we found that the majority of samples with elevated levels of MYC, LIG3 and PARP1 were from Imatinib-resistant patients (64%), compared to samples from Imatinib-sensitive patients (36%) (p=0.03). Additionally, 2 patient samples with TKI-resistant T315I mutation in BCR-ABL1 exhibited elevated levels of MYC, LIG3 and PARP1. Thus, increased MYC expression, and repression of miRs 22, 150 and 34a augment expression of LIG3 and PARP1, generating DSB repair errors that may lead to resistance to TKI therapy. Altered expression of MYC, LIG3, PARP1 and miRs 22, 150 and 34a may be biomarkers for those patients likely to become resistant to TKI therapy. Disclosures: No relevant conflicts of interest to declare.
12
Schmitz, Sandra, Marc Hamoir, Herve Reychler, Michele Magremanne, Birgit Weynand, Renaud Lhommel, Francois-Xavier Hanin, et al. "Safety, molecular, and imaging responses to cetuximab administered in a window pre-operative study in squamous cell carcinoma of the head and neck (SCCHN)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 5519. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.5519.
Full textAbstract:
5519 Background: Only a minority of SCCHN pts benefits from anti-EGFR mAbs. Trials with pre- and post-therapy tumor biopsies are crucial to better characterize the molecular pathways involved in treatment response or resistance. Targeted agents (TA) are often investigated in unselected end-stage cancer pts, making difficult optimal translational research. One way to resolve this issue is to perform “window” studies where a TA is given during the incompressible period between the diagnosis and surgery. Methods: We conducted a phase I/II study: cetuximab (C) was given pre-operatively to treatment-naïve SCCHN pts selected for primary curative surgery. C (400mg/m2 first wk followed by 250mg/m2/wk) was given during 2 wks (day -15 until day -1, 3 infusions) before surgery (day 0). Tumour biopsies, FDG/PET, and CT were performed at diagnosis and surgery. In the phase I, we investigated the safety of preoperative C by progressively reducing the delay between the last dose of C and surgery (minimum delay : 24 hrs ; 3+3 phase 1 design). The aims of the phase II were (i) safety, (ii) C activity by FDG-PET (Po=0.10, P1=0.35, a=0.05 and b= 0.10). As controls, 5 additional pts were included without C treatment but with the same requirements regarding biopsies and imaging. Results: The phase 1 study (n=18) demonstrated that C infusion given 24 hrs before surgery was safe. Safety was confirmed in the phase II (n=20). 90 % had a FDG-PET partial response (PR) (EORTC guideline) in the C group and 0% in the controls. 52% had a ΔSUVmax decrease of >50%. 2 pts evaluable by CT/MRI had a PR (RECIST). Then, we compared the pre-and post treatment biopsies by immunochemistry. For the whole group, C did not reduce Ki67 (p=0.1) and did not seem to induce apoptosis (caspase). However, for pts with ΔSUVmax decrease > 25% or > 50%, Ki67 was decreased (p=0.04 and 0.006). C induced downregulation of pEGFR (p=0.0004) and pERK (p=0.007) but not pAKT/AKT (Histoscore). Conclusions: Pre-operative study with C is safe. Our findings suggest that the main downstream molecular pathway blocked by C in SCCHN is the RAS/RAF/ERK. Further analyses are ongoing to better characterize molecular response and escape mechanisms.
13
Kim, Huikyung, Sangwoo Moon, Jinmi Kim, and Jiwoong Lee. "The Effect of Amniotic Membrane Transplantation on Trabeculectomy in Patients with Pseudoexfoliation Glaucoma." Journal of Ophthalmology 2022 (July 30, 2022): 1–10. http://dx.doi.org/10.1155/2022/9355206.
Full textAbstract:
Purpose. The aim is to evaluate the effect of amniotic membrane transplantation (AMT) on trabeculectomy with mitomycin C in patients with pseudoexfoliation glaucoma (PXG). Methods. This retrospective cohort study included 85 eyes of PXG who underwent trabeculectomy with or without AMT (52/33 eyes in the AMT/control group). Surgical success was defined by these criteria: (1) intraocular pressure (IOP) ≤18 mmHg and IOP reduction ≥ 20% and (2) IOP ≤15 mmHg and IOP reduction ≥ 25%. Criteria A and B defined complete success rates as patients who met these criteria without medication, respectively. Criteria C and D defined qualified success rates as patients who met these criteria with medication, respectively. Cumulative probabilities of success were compared using the Kaplan–Meier survival analysis. Cox proportional hazard models were used to evaluate the influence of AMT on surgical success accounting for confounding variables. Results. For the AMT group, compared with the control group, the complete success rates at 12 months for criterion A were 86.5% and 63.6%, respectively ( P = 0.017 ) and for criterion B, 86.4% and 63.6% ( P = 0.005 ). The qualified success rates at 12 months for criterion C were 92.1% and 75.1%, respectively ( P = 0.047 ) and for criterion D, 92.1% and 72.1% ( P = 0.021 ). On multivariable Cox regression analyses, AMT was associated with a lower failure rate on criteria A, B, and D (all P ≤ 0.047 ). Incidence of avascular bleb was higher in the control group than in the AMT group (7 vs 0 eyes; P = 0.004 ). Conclusions. In patients with PXG, trabeculectomy with AMT was associated with higher success rates and a lower incidence of avascular bleb compared with conventional trabeculectomy. Research Registration. This retrospective cohort study was registered at the Clinical Trial Registry of Korea (https://cris.nih.go.kr/cris/index/index.do, KCT0007228).
14
Karnes, Jeffrey, Hussam Al-Deen Ashab, Bruce J. Trock, Ashley Ross, Harrison Tsai, Jeffrey J. Tosoian, Nicholas Erho, et al. "Development and validation of an ADT resistance signature to predict adjuvant hormone treatment failure." Journal of Clinical Oncology 34, no. 2_suppl (January 10, 2016): 106. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.106.
Full textAbstract:
106 Background: Androgen deprivation therapy (ADT) is one of the main treatment options for locally advanced and metastatic prostate cancer. Neuroendocrine prostate cancer (NEPC) is inherently less sensitive or even resistant to ADT. NEPC can be observed de novo (e.g., small cell prostate cancer) but more commonly arises after exposure to ADT. We hypothesized that a gene expression signature of NEPC when measured in primary tumor specimens (RP) of prostatic adenocarcinoma may be useful for predicting patients with innate resistance to ADT. Methods: Expression profiles of 1023 PCa patients treated with RP were obtained from the Decipher GRID database. These were split into training (n=529) and validation (n=494) sets and stratified by the receipt of adjuvant ADT (n=243) or no adjuvant ADT (n=780). A literature review of ADT resistance and neuroendocrine genes identified 1,557 genes as candidates. This set was further filtered, using logistic regression to select a 52-gene ADT resistance signature (ARS). ARS was trained using a generalized linear model with lasso regularization. Survival c-index and Kaplan Meier was used to compare survival differences between treated and untreated patients with high and low ARS scores (defined by median split). Results: In validation cohorts, the ARS was predictive of metastasis in cohorts receiving adjuvant ADT (10-year metastasis free survival c-index of 0.69 (95% CI 0.59-0.78) as compared to 0.45 (95% CI 0.29-0.61) in patients not treated with ADT). Similarly in a separate cohort of untreated patients that received no ADT until after metastatic onset, ARS was not prognostic (c-index 0.53). Among ADT treated patients, those with low ARS scores had a 10 year MFS of 87%, versus 70% in those with high ARS scores (p<0.001). In the subset of men who received ADT after metastatic onset and who developed castrate-resistant prostate cancer (CRPC, n = 41), median time to treatment failure was 1 year in patients with high ARS compared to 2 years for those with low ARS scores (p=0.07). Conclusions: A 52-gene ADT resistance signature was developed which showed significant differences in metastasis-free survival among adjuvant hormone treated but not untreated patients.
15
Simoen, Eddy, K. Takakura, Brent Hsu, and Cor Claeys. "(Electronics and Photonics Division Award) The Impact of Defects on the Performance of Semiconductor Devices and Materials." ECS Meeting Abstracts MA2022-01, no. 31 (July 7, 2022): 1299. http://dx.doi.org/10.1149/ma2022-01311299mtgabs.
Full textAbstract:
Since the early days of the semiconductor industry, defect control has been key to the successful development of devices and circuits. It requires a thorough understanding of their formation and the impact on the electrical material parameters. This has only been possible by the invention of powerful structural, chemical and electrical characterization tools, with the device itself perhaps as the most sensitive probe. This evolution was paralleled by the development of ab initio calculation methods, based on Density Functional Theory and more recently, also TCAD tools allowing more and more refined modelling of the impact of defects on the electrical characteristics of devices. The implementation of other materials than Si and SiO2 in CMOS through the hetero-epitaxial growth on a silicon substrate for example, has renewed the interest in defect engineering during the last two decades, leading to single-defect analysis methods like Random Telegraph Noise (RTN) [1] or novel growth schemes like Aspect Ratio Trapping (ART) [2] for the removal of extended defects from the device active regions. In this presentation, some state-of-the-art analysis techniques will be highlighted, including Deep Level Transient Spectroscopy (DLTS) [3], Generation-Recombination (GR) noise and RTN spectroscopy [1,4] and p-n diode lifetime analysis [5]. These methods will be applied to several case studies. As shown in Fig. 1, threading extended defects impact the recombination lifetime of lowly-doped n-type In0.47Ga0.53As starting from a density of a few 107 cm-2. Likewise, it will be demonstrated that the GR noise observed in GaN-on-Si MOSHEMTs (Fig. 2) most likely originates from threading dislocations [6]. It is concluded that when hetero-epitaxial layers can be grown with a sufficiently low defect density, their impact will be more on the variability of the electrical parameters rather than on the effective values. In addition, the position of the defect with respect to strategic nodes like a p-n junction or depletion region largely determines its electrical impact, as has been validated by TCAD simulations. References [1] E. Simoen and C. Claeys, “Random Telegraph Signals in Semiconductor Devices”, The Institute of Physics, Bristol, UK (2016). [2] J. Z. Li et al., Appl. Phys. Lett., 91, p. 021114 (2007). [3] E. Simoen, J. Lauwaert and H. Vrielinck, Semiconductors and Semimetals, Eds. L. Romano, V. Privitera and C. Jagadish, 91, pp. 205-250, Elsevier 2015. [4] D. Boudier et al., Solid-St. Electron., 128, pp. 102-108 (2017). [5] Po-Chun (Brent) Hsu et al., J. Phys. D: Appl. Phys., 52, p. 485102 (2019). [6] K. Takakura et al., IEEE Trans. Electron Devices, 67, pp. 3062-3068 (2020). Figure 1
16
Delaloge, S., K. L. Tedesco, J. Blum, A. Gonçalves, J. Lubinski, N. Efrat, C. Osborne, C. Lebedinsky, J. C. Tercero, and F. A. Holmes. "Preliminary safety and activity results of trabectedin in a phase II trial dedicated to triple-negative (ER-, PR-, HER2-), HER2+++, or BRCA1/2 germ-line-mutated metastatic breast cancer (MBC) patients (pts)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 1010. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.1010.
Full textAbstract:
1010 Background: Trabectedin ([T]; Yondelis) binds to the minor groove of DNA; its cytotoxicity is determined by the synergistic action of two DNA repair mechanisms, the efficient nucleotide excision repair (NER) and deficient homologous recombination repair (HRR) machinery. T has EMEA authorization in soft tissue sarcoma after failure of standard treatment. Preliminary data have shown activity of T as single agent in MBC. Clinical and preclinical data suggested T may display specific activity among certain NER-intact or HRR-deficient MBC, and prompted this phase II trial dedicated to 3 subgroups: triple-negative (TN), HER-2-overexpressed, and BRCA1/2 germline-mutated MBC. Methods: T was given at 1.3 mg/m2 as a 3- hour iv infusion every 3 weeks to pts with pretreated progressive MBC: Group A: TN; Group B: HER-2+++; Group C: BRCA1/2 mutation carriers. Endpoints were objective response (OR) rate by RECIST, duration of response, progression free survival (PFS), tumor volume changes, safety and exploratory pharmacogenomics (PGx). Results: A total of 95 women (median [med] age 52, ECOG 0/1 48/52%) have been enrolled (A:50, B:24, C:21) with data available for 72 pts. Med number of prior chemotherapy regimens: 4 (1–10). Med number of T cycles administered: 2 (1–12) for all groups. The most commonly reported grade 3/4 AEs are neutropenia (29/21%), ALT (28/2%) and AST (13/0). Alopecia/stomatitis, only G1, was reported in <2% each. Long-lasting disease stabilizations were described in all groups. While OR were rare among TN MBC pts (2PR/43 evaluable), preliminary analysis by investigator shows efficacy in group C (4PR/11 evaluable). Tissue samples from 36 pts were collected for RNA expression analysis (XPG + ERCC1 + BRCA1). Preliminary results show high XPG is associated with longer PFS: 4.1 months (95% CI 2.6-not reached) versus 1.3 months (95% CI 1.2–3.7), p = 0.01. Analyses are ongoing. Conclusions: Trabectedin shows a manageable safety profile in the 3 groups of MBC with promising efficacy in certain DNA-repair machinery sub-categories defined molecularly. TN group was closed due to low response. More mature PGx results will be discussed to help selecting the patients who are at highest chance for response. [Table: see text]
17
Vergote, Ignace, Florian Heitz, Paul Buderath, Matthew A. Powell, Jalid Sehouli, Christine M. Lee, Anne L. Hamilton, et al. "A randomized, double-blind, placebo-controlled phase Ib/II study of ralimetinib, a p38 MAPK inhibitor, plus gemcitabine (G) and carboplatin (C) versus GC for women with recurrent platinum-sensitive ovarian cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 5537. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.5537.
Full textAbstract:
5537 Background: p38 mitogen-activated protein kinase (MAPK) regulates cytokine production in the tumor microenvironment and enables therapeutic resistance of cancer cells. Ralimetinib (R) is a selective small-molecule inhibitor of p38α and p38β MAPKs. Methods: Main inclusion criteria: ≥18 y; recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal, cancer after first-line treatment. Phase (Ph)1b was to determine the recommended Ph2 dose (RP2D) of R administered 12-hourly (Q12H) on Days 1-10 (21-day cycle [Q21D]) in combination with gemcitabine (G: 1000 mg/m2 on Days 3 and 10) and carboplatin (C: AUC 4 on Day 3) for 6 cycles. In Ph2, patients (pts) were randomized double-blind, 1:1 to RP2D R+GC or placebo (P)+GC, for 6 cycles, followed by R 300 mg Q12H or P on Days 1-14, Q28D until disease progression. The stratified log-rank test compared progression-free survival (PFS; primary endpoint) between treatment groups in Ph2, at a 1-sided α level of 0.2. ClinicalTrials.gov, NCT01663857. Results: 118 pts received ≥1 dose of R or P (safety population); 8 in Ph1b and 110 in Ph2 (R+GC N = 58; P+GC N = 52). The RP2D for R in combination with GC was 200 mg Q12H. The study met its primary objective (median PFS: R+GC 10.3 mo vs P+GC 7.9 mo; HR = 0.773, 2-sided p = 0.246). The secondary objectives of median overall survival (R+GC 29.2 mo vs P+GC 25.1 mo; HR = 0.827, p = 0.469) or overall response rate (R+GC 46.6% vs P+GC 46.2%; p = 0.967) were not statistically significant, and 32.4% vs 25.0% of pts had normalized CA125 at the end of cycle 6. Most pts (safety population) experienced ≥1 Grade 3/4 treatment-emergent adverse event (TEAE: R+GC 63/66 [95.5%]; P+GC 48/52 [92.3%]). Decreased neutrophil count (60.6% vs 76.9%), platelet count (43.9% vs 38.5%), and white blood cell count, (30.3% vs 26.9%), anemia (22.7% vs 25.0%), and increased alanine aminotransferase (ALT) (19.7% vs 3.8%) were the Grade 3/4 TEAEs in ≥10% of pts in the R+GC and P+GC arms, respectively. Conclusions: Addition of ralimetinib to GC resulted in modest improvements in PFS. Grade 3/4 elevated ALT was more common in the ralimetinib arm. Clinical trial information: NCT01663857.
18
Gerber, Suzannah, Jillian Price, Lynn Gerber, Ali Weinstein, and Zobair Younossi. "Diet Satisfaction and Adequate Food Intake in Patients with Chronic Liver Diseases." Current Developments in Nutrition 6, Supplement_1 (June 2022): 21. http://dx.doi.org/10.1093/cdn/nzac047.021.
Full textAbstract:
Abstract Objectives To describe relationships between diet satisfaction, ability to eat, and CLD. Methods Data collected from 354 patients with CLD was used for this analysis, including 2 items from the validated Chronic Liver Disease Questionnaire (CLDQ): item 7 “ability to eat as much as you like” (EA), and item 14 “bothered by a limitation of your diet” (SWD). Results were stratified by existing diagnosis (Cirrhosis and all-type Hepatitis) and severity of disease [Childs-Pugh score (CP-A, mild; CP-B, moderate; CP-C, severe)]; AST (abnormal > 40 U/L) and ALT (abnormal > 55 U/L). Ordinal Logistic Regression, with odds and likelihood ratios, modeled disease severity CP A-C; general linear models examined EA and SWD. All models adjusted for age and sex. Results 354 CLD patients were included [mean age 50.4y (±11.2); 51% male; 222 cirrhosis; 145 hepatitis; 135 with abnormal AST; 131 abnormal ALT; 100 had CP score A; 83 CP-B; 38 CP-C] Of those included, 31% (n = 110) reported low EA (EA-L), and 25% (n = 88) reported low SWD (SWD-L). In patients with cirrhosis, 36% (n = 80) reported EA-L, and 33% (n = 73) SWD-L. 30% (n = 43) of patients with hepatitis reported EA-L, and 22% SWD-L. 33% (n = 45) of patients with abnormal AST reported EA-L, 30% (n = 41) SWD-L; 40% (n = 52) of those with abnormal ALT reported EA-L, 35% (n = 46) SWD-L. 50% (n = 19) with CP-C had EA-L, 63% (n = 24) SWD-L. 43% (n = 36) with CP-B had EA-L, 39% (n = 32) SWD-L. 25% (n = 25) with CP-A had EA-L, 17% (n = 17) SWD-L. Worsening CP scores were 22.68x (p = .0004) more likely associated with EA-L; the odds of patients with CP-C reporting EA-L was 3.3x greater compared normal CP. Similarly, worse CP scores were 56.99x (p < .0001) more likely associated with SWD-L; odds of patients with CP-C reporting SWD-L were 16.2x greater compared to normal. EA described 23% of variance in SWD (p < .0001), and SWD explained 25% of the variance in EA (p < .0001). Sex was significantly associated with SWD (0.55 ± 0.2, p < .0001), age was not. Neither were significant for EA. Conclusions EA-L and SWD-L strongly relate to worsening disease severity as documented by CP scores. Diet satisfaction and ability to eat as much as you like should be monitored closely for patients with CLD, especially those with cirrhosis because these symptoms signal loss of lean mass– a health risk, and one that may preclude eligibility for life-saving liver transplantation. Funding Sources NIFA National Needs Fellowship
19
Miluski, Piotr, Marcin Kochanowicz, Jacek Zmojda, and Dominik Dorosz. "Multicolor emission of Tb3+/Eu3+ co-doped poly(methyl methacrylate) for optical fibre technology." Photonics Letters of Poland 9, no. 4 (December 31, 2017): 110. http://dx.doi.org/10.4302/plp.v9i4.788.
Full textAbstract:
The article presents multicolor emission observed in poly(methyl methacrylate) specimens co-doped by trivalent terbium and europium ions. The bright luminescence was obtained using organometallic complexes of lanthanides and energy transfer antenna effect. Spectroscopic characterization exhibit wide excitation spectrum according to chelating structure of used complexes and characteristic Tb3+ and Eu3+ emission peaks in luminescence spectra. The calculated CIE 1931 chromaticity coordinates confirm that colorful emission from green to red can be obtained using proposed materials. Full Text: PDF ReferencesJ.-H. Jou, M.-C. Sun, H.-H. Chou, C.-H. Li, "White organic light-emitting devices with a solution-processed and molecular host-employed emission layer", Appl. Phys. Lett. 87, 043508 (2005). CrossRef R. Mac Ciarnain, D. Michaelis, T. Wehlus, A. F. Rausch, N. Danz, A. Brauer, A. Tünnermann, "Emission from outside of the emission layer in state-of-the-art phosphorescent organic light-emitting diodes", Organic Electronics 44, 115 (2017). CrossRef G. Williams, C. Backhouse, H. Aziz, "Integration of Organic Light Emitting Diodes and Organic Photodetectors for Lab-on-a-Chip Bio-Detection Systems", Electronics 3, 43 (2014). CrossRef P. Miluski, D. Dorosz, M. Kochanowicz and J. Żmojda, "Fluorescent polymeric optical fibre illuminator", Electronics Letters, 52, 18 (2016). CrossRef L. Bilro, N. Alberto, J. L.Pinto, R. Nogueira, "Optical Sensors Based on Plastic Fibers", Sensors 12, 12184 (2012). CrossRef P. Miluski, D. Dorosz, J. Żmojda, M. Kochanowicz, J. Dorosz, "Luminescent Polymer Optical Fibre Sensor for Temperature Measurement", Acta Phys. Pol. A 127, 730 (2015) CrossRef C. Lethien, C. Loyez, J. P. Vilcot, N. Rolland, P. A. Rolland, "Exploit the Bandwidth Capacities of the Perfluorinated Graded Index Polymer Optical Fiber for Multi-Services Distribution", Polymers 3, 1006 (2011). CrossRef J. Zubia, J. Arrue, "Plastic Optical Fibers: An Introduction to Their Technological Processes and Applications", Opt. Fiber Technol. 7, 101 (2001). CrossRef N. Sultanovaa, S. Kasarovaa, I. Nikolov, "Dispersion Properties of Optical Polymers", Acta Physica Polonica A 116, 585 (2009). CrossRef J. Arrue, F. Jiménez, I. Ayesta, M. Asunción Illarramendi, J. Zubia, "Polymer-Optical-Fiber Lasers and Amplifiers Doped with Organic Dyes", Polymers 3,1162 (2011). CrossRef P. Miluski, M. Kochanowicz, J. Żmojda, "Spectroscopic investigation of organic co-doped PMMA for optical fiber technology", Journal Of Optoelectronics And Advanced Materials, 19, 379 (2017). DirectLink P. Miluski, M. Kochanowicz, J. Żmojda, and D. Dorosz, "Emission properties and energy transfer in Perylene-Rhodamine 6 G co-doped polymeric fiber", Chinese Optics Letters 14, 12, 121602 (2016). CrossRef H. Liang, Z. Yang, L. Xiao, F. Xie, " Radiative transition probability of a europium (III) chelating polymer", Optoelectronics And Advanced Materials ? Rapid Communications 4, 9, 1396 (2010). CrossRef H. Jiu, J. Ding, Y. Sun, J. Bao, C. Gao, Q. Zhang, "Fluorescence enhancement of europium complex co-doped with terbium complex in a poly(methyl methacrylate) matrix", Journal of Non-Crystalline Solids 352, 197 (2006). CrossRef K. Kuriki, S. Nishihara, Y. Nishizawa, A. Tagaya, Y. Koike, Y. Okamoto, "Spectroscopic properties of lanthanide chelates in perfluorinated plastics for optical applications", Journal of the Optical Society of America B 19, 8, 1844 (2002). CrossRef P. Miluski, M. Kochanowicz, J. Żmojda, D. Dorosz, "Luminescent properties of Tb3+-dopedpoly(methyl methacrylate) fiber" Chinese Optics Letters, 15, 7, 070602 (2017). DirectLink P. Miluski, M. Kochanowicz, J. Żmojda, D. Dorosz, "Properties of Eu3+ doped poly(methyl methacrylate) optical fiber", Optical Engineering, 56, 2, 027106 (2017). CrossRef D. Oh, N. Song and J.-J. Kim, "Plastic optical amplifier using europium complex", Proc. SPIE, 4282, (2001). CrossRef X. Xu, H. Ming, Q. Zhang, "Optical-transition probabilities of Nd3+ ions in polymer optical fibers", Optics Communications 199, 369 (2001). CrossRef Z.-Q. Zheng, H. Liang, H. Ming, Q.-J. Zhang, X.-H. Han, G.-Z. Wang, J.-P. Xie, "Optical Transition Probability of Sm 3+ Ions in a Polymer Optical Fibre", Chin. Phys. Lett. 21, 2, 291 (2004). CrossRef
20
Arcasoy, Murat O., Paul Hanlon, Ping Fu, Charles Steenbergen, and Elizabeth Murphy. "Mechanisms of Erythropoietin-Mediated Cardioprotection during Ischemia-Reperfusion Injury: Role of Protein Kinase C Signaling." Blood 104, no. 11 (November 16, 2004): 2907. http://dx.doi.org/10.1182/blood.v104.11.2907.2907.
Full textAbstract:
Abstract The biologic effects of erythropoietin (EPO) are mediated by its cellular receptor EPOR, a member of the cytokine receptor superfamily. EPOR expression in non-hematopoietic cells is associated with novel biologic effects for EPO in diverse organ systems. We recently demonstrated functional EPOR expression in adult rat cardiac myocytes and found that recombinant EPO exerts a rapid cardioprotective effect during ischemia-reperfusion injury of the isolated, perfused heart. Here we investigated the mechanisms of the cardioprotective effect of EPO using Langendorff-perfused rat hearts while left-ventricular-developed pressure (LVDP) was measured continuously to assess contractile function. Hearts were treated directly with EPO in the presence or absence of inhibitors of specific signal transduction pathways prior to normothermic global ischemia followed by reperfusion. Post-ischemic recovery of contractile function was determined by measuring LVDP at the end of reperfusion and expressed as a percentage of the baseline pre-treatment measurement. We investigated EPO-mediated activation of signal transduction pathways in the isolated, perfused heart and observed phosphorylation of p44/p42 MAP kinases ERK 1/2 (Thr202/Tyr204) and protein kinase B/Akt (Ser473), a downstream target of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Furthermore, EPO treatment of the isolated, perfused heart was associated with translocation of protein kinase C (PKC) ε and δ isoforms to the membrane fraction. We investigated the role of specific signaling pathways in EPO-mediated cardioprotection by employing inhibitors targeting PI3K, PKC and MAP kinase kinase (MEK1). PI3K inhibitors LY294002 and wortmannin attenuated EPO-induced phosphorylation of Akt but had no effect on EPO-mediated cardioprotection. MEK1 inhibitor U0126 had no effect on EPO-mediated cardioprotection. The PKC catalytic inhibitor chelerythrine (chel) significantly inhibited EPO-mediated improvement in post-ischemic recovery of LVDP (figure 1). Hearts pre-treated with EPO exhibited significantly improved post-ischemic recovery of LVDP compared to control hearts (mean±SE: 72±3 in EPO-treated versus 35±3% in control hearts, P<0.05 by ANOVA and Bonferroni post-hoc test, n=10 experiments each group) and the protective effect of EPO was significantly inhibited in chel-treated hearts (52±4% in EPO+chel versus 72±3% in EPO-treated hearts, P<0.05, n=10). As a control, treatment of the hearts with chelerythrine alone had no significant effect on LVDP (49±4%) compared to control hearts. These data demonstrate that EPO-mediated activation of the PKC signaling pathway is required for the cardioprotective effect of EPO during ischemia-reperfusion injury. Figure Figure
21
Osbrough, S. L., J. S. Frederiksen, and C. S. Frederiksen. "The effects of model climate bias on ENSO variability and ensemble prediction." ANZIAM Journal 60 (October 18, 2019): C215—C230. http://dx.doi.org/10.21914/anziamj.v60i0.14092.
Full textAbstract:
New methods are presented for determining the role of coupled ocean-atmosphere model climate bias on the strength and variability of the El Nino-Southern Oscillation (ENSO) and on the seasonal ensemble prediction of El Nino and La Nina events. An intermediate complexity model with a global atmosphere coupled to a Pacific basin ocean is executed with parallelised algorithms to produce computationally efficient year-long forecasts of large ensembles of coupled flow fields, beginning every month between 1980 and 1999. Firstly, the model is provided with forcing functions that reproduce the average annual cycle of climatology of the atmosphere and ocean based on reanalysed observations. We also configure the model to generate realistic ENSO fluctuations. Next, an ensemble prediction scheme is employed which produces perturbations that amplify rapidly over a month. These perturbations are added to the analyses and give the initial conditions for the ensemble forecasts. The skill of the forecasts is presented and the dependency on the annual and ENSO cycles determined. Secondly, we replace the forcing functions in our model with functions that reproduce the averaged annual cycles of climatology of two state of the art, comprehensive Coupled General Circulation Models. The changes in skill of subsequent ensemble forecasts elucidate the roles of model bias in error growth and potential predictability.
References C. S. Frederiksen, J. S. Frederiksen, and R. C. Balgovind. ENSO variability and prediction in a coupled ocean-atmosphere model. Aust. Met. Ocean. J., 59:35–52, 2010a. URL http://www.bom.gov.au/jshess/papers.php?year=2010. C. S. Frederiksen, J. S. Frederiksen, and R. C. Balgovind. Dynamic variability and seasonal predictability in an intermediate complexity coupled ocean-atmosphere model. In Proceedings of the 16th Biennial Computational Techniques and Applications Conference, CTAC-2012, volume 54 of ANZIAM J., pages C34–C55, 2013a. doi:10.21914/anziamj.v54i0.6296. C. S. Frederiksen, J. S. Frederiksen, J. M. Sisson, and S. L. Osbrough. Trends and projections of Southern Hemisphere baroclinicity: the role of external forcing and impact on Australian rainfall. Clim. Dyn., 48:3261–3282, 2017. doi:10.1007/s00382-016-3263-8. J. S. Frederiksen, C. S. Frederiksen, and S. L. Osbrough. Seasonal ensemble prediction with a coupled ocean-atmosphere model. Aust. Met. Ocean. J., 59:53–66, 2010b. URL http://www.bom.gov.au/jshess/papers.php?year=2010. J. S. Frederiksen, C. S. Frederiksen, and S. L. Osbrough. Methods of ensemble prediction for seasonal forecasts with a coupled ocean-atmosphere model. In Proceedings of the 16th Biennial Computational Techniques and Applications Conference, CTAC-2012, volume 54 of ANZIAM J., pages C361–C376, 2013b. doi:10.21914/anziamj.v54i0.6509. P. R. Gent, G. Danabasoglu, L. J. Donner, M. M. Holland, E. C. Hunke, S. R. Jayne, D. M. Lawrence, R. B. Neale, P. J. Rasch, M. Vertenstein, P. H. Worley, Z.-L. Yang, and M. Zhang. The community Climate System Model version 4. J. Clim., 24:4973–4991, 2011. doi:10.1175/2011JCLI4083.1. S. Grainger, C. S. Frederiksen, and X. Zheng. Assessment of modes of interannual variability of Southern Hemisphere atmospheric circulation in CMIP5 models. J. Clim., 27:8107–8125, 2014. doi:10.1175/JCLI-D-14-00251.1. E. Kalnay, M. Kanamitsu, R. Kistler, W. Collins, D. Deaven, L. Gandin, M. Iredell, S. Saha, G. White, J. Woollen, Y. Zhu, M. Chelliah, W. Ebisuzaki, W. Higgins, J. Janowiak, K. C. Mo, C. Ropelewski, J. Wang, A. Leetmaa, R. Reynolds, R. Jenne, and D. Joseph. The NCEP/NCAR 40-year reanalysis project. B. Am. Meteorol. Soc., 77:437–472, 1996. doi:10.1175/1520-0477(1996)077<0437:TNYRP>2.0.CO;2. H. A. Rashid, A. Sullivan, A. C. Hirst, D. Bi, X. Zhou, and S. J. Marsland. Evaluation of El Nino-Southern Oscillation in the ACCESS coupled model simulations for CMIP5. Aust. Met. Ocean. J., 63:161–180, 2013. doi:10.22499/2.6301.010. K. E. Taylor, R. J. Stouffer, and G. A. Meehl. An overview of CMIP5 and the experiment design. Bull. Am. Meteorol. Soc., 93:485–498, 2012. doi:10.1175/BAMS-D-11-00094.1.
22
Wu, R., L. Wang, X. Zheng, Y. Wang, G. Wang, X. Li, and X. Li. "THU0242 REGULATORY ROLE OF TRANSCRIPTION FACTOR BLIMP-1 IN SJÖGREN’S SYNDROME." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 348. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2618.
Full textAbstract:
Background:The pathogenesis of primary sjögren’s syndrome (pSS) is multifactorial. Self-antigen-driven responses perform a vital function in the development of autoimmune diseases [1]. B cells, only 20-25% of total infiltrating cells in labial glands, are the cellular basis for spontaneous antibody production [2].Genome-wide association studies (GWAS) have identified Blimp-1 as a susceptibility gene for autoimmune diseases and played an important role in the pathogenesis of autoimmune diseases [3].Objectives:To investigate the expression and effect of B lymphocyte induced maturation protein 1 (Blimp-1) in pSS and the correlation of Blimp-1 with B cell subsets and clinical features.Methods:The PRDM1 mRNA expression in B lymphocyte and labial gland were examined by RT-PCR. The levels of B cell subsets were examined by flow cytometry. Hematoxylin-eosin (HE) staining and immunohistochemistry (IHC) were used to examine the invasion degree of lymph cell and Blimp-1 distribution, respectively. The correlation of PRDM1 mRNA with B cell subsets and clinical indicators were also analyzed.Results:The levels of PRDM1 mRNA expression of B cells were significantly higher in SS than in healthy controls (HC) and which were also significantly higher in the high immunoglobulin (Ig) group than that in normal Ig group (P<0.02, Fig. 1a-b). The number of CD19+B cells and CD138+ plasma cells(PC) have increased while the CD27+ cells decreased in SS(P<0.05). The percentage of PC and PC/B is positively correlated with PRDM1 mRNA(r=0.380,P=0.002;r=0.317,P=0.009, Fig. 1c-d). Blimp-1 expression level showed a positive correlation with invasion degree of lymph cell in histology (Fig. 2a-c), Ig levels and ESSDAI score and an inverse correlation with the glucocorticoids usage (Fig. 3c).Fig. 1(a-b) RT-PCR showed that PRDM1 mRNA expression in SS patients and HC. (c-d) Correlation between PRDM1 mRNA expression and PC and PC/B.Fig. 2(a) Expression of Blimp-1 in labial glands of sjögren’s syndrome. (b) PRDM1 mRNA levels in different invasion degree of lymph cell group. (c) Correlation between PRDM1 mRNA expression and invasion degree of lymph cell. *p<0.05, ***p<0.001.Fig. 3(a-b) RT-PCR showed that PRDM1 mRNA expression in different usage of glucocorticoids. (c) Correlation between PRDM1 mRNA expression and different glucocorticoid usage. **p<0.01, ***p<0.001.Conclusion:Blimp-1 displayed high expression in SS, which could affect pSS disease activity. SS activity is suppressed by glucocorticoid which might be through inhibition of Blimp-1.References:[1]Kapsogeorgou EK, Abu-Helu RF, Moutsopoulos HM, Manoussakis MN (2005) Salivary gland epithelial cell exosomes: A source of autoantigenic ribonucleoproteins. Arthritis Rheum 52(5):1517-21.https://doi.org/10.1002/art.21005[2]Arneth BM (2019) Impact of B cells to the pathophysiology of multiple sclerosis. J Neuroinflammation 16(1):128.https://doi.org/10.1186/s12974-019-1517-1[3]Bönelt P, Wöhner M, Minnich M et al (2019) Precocious expression of Blimp-1 in B cells causes autoimmune disease with increased self-reactive plasma cells. EMBO J 38(2). pii:e100010.https://doi.org/10.15252/embj.2018100010Table 1.Clinical characteristics of pSS and HC.HC(n=17)pSS(n=50)Sex (Male/Female)0/170/50Age(x±s)45.24±18.5546.8±11.05Xerostomia(positive/negative)0/1743/7Keratoconjunctivitis sicca0/1735/15Arthralgia0/1732/18Fatigue0/1718/32ESSDAI(x±s)-2.78±1.61 (0~7)ESSPRI(x±s)-3.3±1.39 (1~6)ANA(positive/negative)-49/1SSA-49/1SSB-18/32pSS: primary sjögren ‘s syndrome; HC: Healthy controls; ESSDAI: The European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index; ESSPRI: EULAR Sjögren’s Syndrome Patient Reported Index.** P<0.01,*** P<0.001.Acknowledgments :This study was supported by the grants from the National Natural Science Foundation of China (81871271).Disclosure of Interests: :None declared
23
Merli, Michele, Michele Spina, Stefano Luminari, Claudia Basilico, Clara Targhetta, Carlo Visco, Alessandro Levis, et al. "Prognostic Models to Predict Survival In Indolent and Aggressive Non-Hodgkin's Lymphomas Associated with Hepatitis C Virus Infection: a Multicenter Italian Study on 1,043 Patients." Blood 116, no. 21 (November 19, 2010): 2821. http://dx.doi.org/10.1182/blood.v116.21.2821.2821.
Full textAbstract:
Abstract Abstract 2821 Epidemiological studies demonstrated that HCV is associated with B-cell NHL. A precise prognostication of HCV+ NHL is not available; in particular, the impact of liver toxicity on the outcome of pts treated with (immuno)-chemotherapy is not fully clarified. Aim of the present study was to analyse clinical and virological characteristics, toxicity and prognosis of a large series of indolent and aggressive HCV+ NHL. We studied 1,043 pts with HCV+ NHL diagnosed and treated from January 1993 to December 2009 in 15 italian hematologic institutions; 539 cases were aggressive NHL (522 DLBCL) and 504 indolent NHL (265 MZL). All pts were HIV negative, 3% carried HBsAg and 91% were HCV-RNA+. Thirteen out of 56 HCV-RNA negative pts cleared HCV by means of antiviral therapy before NHL diagnosis. An (immuno)-chemotherapy regimen was administered as first-line treatment in 859 pts: 537 received CHOP-like regimen (+ Rituximab 243), 66 III generation regimen, 174 alkylators, 30 purine analogues, 31 other regimens, 21 R alone. Doses of chemotherapy since first cycle were reduced in 31% of pts. A watch-and-wait policy was adopted in 82 pts, other treatments in 68 pts and anti-HCV antiviral therapy in 34 pts with indolent NHL (12 of whom obtained both a complete virologic and hematologic response). Hepatic toxicity was evaluable in 597 patients: among 347 pts with normal ALT at NHL diagnosis, 52 (15%) developed WHO hepatic toxicity ≥ grade 2; among 250 pts (42%) with abnormal ALT, 26 (11%) experienced ALT increase >3.5 times baseline value. Overall, a significant liver toxicity developed in 78 pts (13%) (15% of aggressive NHL and 10% of indolent NHL). Use of Rituximab was not associated with significant liver toxicity (p=0.4); particularly, in DLBCL, R-CHOP and CHOP showed the same rate of significant hepatic toxicity (15%, p=ns), although maximum grade of liver toxicity was registered earlier in patients treated with R-CHOP than in those treated with CHOP (before 3rd cycle respectively in 57% vs 41%, p=0.006). Planned treatment was not completed in 134 pts (29 for liver toxicity). After a median F-UP of 2.6 years, 321 pts died (24 for liver failure). 5-yrs OS was 76% for indolent NHL and 62% for DLBCL. In indolent NHL, the parameters associated with a shorter OS in univariate analysis were: elevated LDH (p<0.001), ECOG ≥2 (p<0.001), AA stage III-IV (p=0.04), age > 60 yrs (p<0.001), B symptoms (p<0.001), serum albumin <3.5 g/dl (p<0.001), Child score (p=0.003), HCV-RNA >106 UI/ml (p<0.02), no antiviral therapy at any time (p<0.001). According to a forward stepwise multivariate Cox regression analysis on OS the following parameters retained statistical significance: ECOG ≥2 (HR 2.82, p=0.005), age > 60 yrs (HR 2.11, p=0.02), AA stage III-IV (HR 2.0, p=0.04), no antiviral therapy at any time (HR 2.56, p=0.01). In DLBCL, the parameters associated with a shorter OS in univariate analysis were: elevated LDH (p<0.001), ECOG ≥2 (p<0.001), AA stage III-IV (p<0.001), age > 60 yrs (p=0.003), liver involvement by lymphoma (p=0.02), B symptoms (p<0.001), serum albumin <3.5 g/dl (p<0.001), INR >1.7 (p=0.01), Child score (p<0.001), HCV-RNA >106 UI/ml (p<0.001), HBsAg+ (p=0.01), HAI grade >9 and/or fibrosis stage >2 at liver biopsy (p=0.03). Moreover IPI, aaIPI and R-IPI were predictive for OS (p<0.001). According to a forward stepwise multivariate Cox regression analysis on OS the following parameters retained statistical significance: ECOG ≥2 (HR 3.12, p=0.001), HCV-RNA >106 UI/ml (HR 3.59, p=0.001), serum albumin <3.5 g/dl (HR 2.53, p=0.01), while other IPI factors (age, AA stage, LDH, extranodal sites) were excluded from the final model. We combined the 3 factors significantly associated to a worse OS (ECOG, albumin, HCV-RNA load) in a new HCV Prognostic Score (HPS) able to discriminate 3 categories of risk (low=0; intermediate=1; high risk ≥2 factors) (p<0.001) (Fig. 1). After adjusting by IPI in multivariate Cox regression analysis, the HPS retained prognostic effect (p<0.001), while IPI itself did not. In conclusion, a significant proportion of pts with HCV+ NHL, when treated with conventional (immuno)-chemotherapy, develops severe liver toxicity. In indolent NHL, employment of antiviral therapy at any time during lymphoma history ameliorates OS. In HCV+ DLBCL, addition of rituximab to CHOP scheme does not increase hepatic toxicity; moreover, the new score HPS performs better than IPI in discriminating different risk categories. Disclosures: No relevant conflicts of interest to declare.
24
Hapidin, Winda Gunarti, Yuli Pujianti, and Erie Siti Syarah. "STEAM to R-SLAMET Modification: An Integrative Thematic Play Based Learning with R-SLAMETS Content in Early Child-hood Education." JPUD - Jurnal Pendidikan Usia Dini 14, no. 2 (November 30, 2020): 262–74. http://dx.doi.org/10.21009/jpud.142.05.
Full textAbstract:
STEAM-based learning is a global issue in early-childhood education practice. STEAM content becomes an integrative thematic approach as the main pillar of learning in kindergarten. This study aims to develop a conceptual and practical approach in the implementation of children's education by applying a modification from STEAM Learning to R-SLAMET. The research used a qualitative case study method with data collection through focus group discussions (FGD), involving early-childhood educator's research participants (n = 35), interviews, observation, document analysis such as videos, photos and portfolios. The study found several ideal categories through the use of narrative data analysis techniques. The findings show that educators gain an understanding of the change in learning orientation from competency indicators to play-based learning. Developing thematic play activities into continuum playing scenarios. STEAM learning content modification (Science, Technology, Engineering, Art and Math) to R-SLAMETS content (Religion, Science, Literacy, Art, Math, Engineering, Technology and Social study) in daily class activity. Children activities with R-SLAMETS content can be developed based on an integrative learning flow that empowers loose part media with local materials learning resources.
Keyword: STEAM to R-SLAMETS, Early Childhood Education, Integrative Thematic Learning
References
Ali, E., Kaitlyn M, C., Hussain, A., & Akhtar, Z. (2018). the Effects of Play-Based Learning on Early Childhood Education and Development. Journal of Evolution of Medical and Dental Sciences, 7(43), 4682–4685. https://doi.org/10.14260/jemds/2018/1044
Ata Aktürk, A., & Demircan, O. (2017). A Review of Studies on STEM and STEAM Education in Early Childhood. Journal of Kırşehir Education Faculty, 18(2), 757–776.
Azizah, W. A., Sarwi, S., & Ellianawati, E. (2020). Implementation of Project -Based Learning Model (PjBL) Using STREAM-Based Approach in Elementary Schools. Journal of Primary Education, 9(3), 238–247. https://doi.org/10.15294/jpe.v9i3.39950
Badmus, O. (2018). Evolution of STEM, STEAM and STREAM Education in Africa: The Implication of the Knowledge Gap. In Contemporary Issues in Science, Technology, Engineering, Arts and Mathematics Teacher Education in Nigeria.
Björklund, C., & Ahlskog-Björkman, E. (2017). Approaches to teaching in thematic work: early childhood teachers’ integration of mathematics and art. International Journal of Early Years Education, 25(2), 98–111. https://doi.org/10.1080/09669760.2017.1287061
Broadhead, P. (2003). Early Years Play and Learning. In Early Years Play and Learning. https://doi.org/10.4324/9780203465257
Canning, N. (2010). The influence of the outdoor environment: Den-making in three different contexts. European Early Childhood Education Research Journal, 18(4), 555–566. https://doi.org/10.1080/1350293X.2010.525961
Clapp, E. P., Solis, S. L., Ho, C. K. N., & Sachdeva, A. R. (2019). Complicating STEAM: A Critical Look at the Arts in the STEAM Agenda. Encyclopedia of Educational Innovation, 1–4. https://doi.org/10.1007/978-981-13-2262-4_54-1
Colucci, L., Burnard, P., Cooke, C., Davies, R., Gray, D., & Trowsdale, J. (2017). Reviewing the potential and challenges of developing STEAM education through creative pedagogies for 21st learning: how can school curricula be broadened towards a more responsive, dynamic, and inclusive form of education? BERA Research Commission, August, 1–105. https://doi.org/10.13140/RG.2.2.22452.76161
Conradty, C., & Bogner, F. X. (2018). From STEM to STEAM: How to Monitor Creativity. Creativity Research Journal, 30(3), 233–240. https://doi.org/10.1080/10400419.2018.1488195
Conradty, C., & Bogner, F. X. (2019). From STEM to STEAM: Cracking the Code? How Creativity & Motivation Interacts with Inquiry-based Learning. Creativity Research Journal, 31(3), 284–295. https://doi.org/10.1080/10400419.2019.1641678
Cook, K. L., & Bush, S. B. (2018). Design thinking in integrated STEAM learning: Surveying the landscape and exploring exemplars in elementary grades. School Science and Mathematics, 118(3–4), 93–103. https://doi.org/10.1111/ssm.12268
Costantino, T. (2018). STEAM by another name: Transdisciplinary practice in art and design education. Arts Education Policy Review, 119(2), 100–106. https://doi.org/10.1080/10632913.2017.1292973
Danniels, E., & Pyle, A. (2018). Defining Play-based Learning. In Encyclopedia on Early Childhood Development (Play-Based, Issue February, pp. 1–5). OISE University of Toronto.
DeJarnette, N. K. (2018). Implementing STEAM in the Early Childhood Classroom. European Journal of STEM Education, 3(3), 1–9. https://doi.org/10.20897/ejsteme/3878
Dell’Erba, M. (2019). Policy Considerations for STEAM Education. Policy Brief, 1–10.
Doyle, K. (2019). The languages and literacies of the STEAM content areas. Literacy Learning: The Middle Years, 27(1), 38–50. http://proxy.libraries.smu.edu/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=eue&AN=133954204&site=ehost-live&scope=site
Edwards, S. (2017). Play-based learning and intentional teaching: Forever different? Australasian Journal of Early Childhood, 42(2), 4–11. https://doi.org/10.23965/ajec.42.2.01
Faas, S., Wu, S.-C., & Geiger, S. (2017). The Importance of Play in Early Childhood Education: A Critical Perspective on Current Policies and Practices in Germany and Hong Kong. Global Education Review, 4(2), 75–91.
Fesseha, E., & Pyle, A. (2016). Conceptualising play-based learning from kindergarten teachers’ perspectives. International Journal of Early Years Education, 24(3), 361–377. https://doi.org/10.1080/09669760.2016.1174105
Finch, C. R., Frantz, N. R., Mooney, M., & Aneke, N. O. (1997). Designing the Thematic Curriculum: An All Aspects Approach MDS-956. 97.
Gess, A. H. (2019). STEAM Education. STEAM Education, November, 2011–2014. https://doi.org/10.1007/978-3-030-04003-1
Gronlund, G. (n.d.). “ Addressing Standards through Play-Based Learning in Preschool and Kindergarten .”
Gronlund, G. (2015). Planning for Play-Based Curriculum Based on Individualized Goals to Help Each Child Thrive in Preschool and Kindergarten Gaye Gronlund.
Gull, C., Bogunovich, J., Goldstein, S. L., & Rosengarten, T. (2019). Definitions of Loose Parts in Early Childhood Outdoor Classrooms: A Scoping Review. The International Journal of Early Childhood Education, 6(3), 37–52.
Hapidin, Pujianti, Y., Hartati, S., Nurani, Y., & Dhieni, N. (2020). The continuous professional development for early childhood teachers through lesson study in implementing play based curriculum (case study in Jakarta, Indonesia). International Journal of Innovation, Creativity and Change, 12(10), 17–25.
Hennessey, P. (2016). Full – Day Kindergarten Play-Based Learning : Promoting a Common Understanding. Education and Early Childhood Development, April, 1–76. gov.nl.ca/edu
Henriksen, D. (2017). Creating STEAM with Design Thinking: Beyond STEM and Arts Integration. Steam, 3(1), 1–11. https://doi.org/10.5642/steam.20170301.11
Inglese, P., Barbera, G., La Mantia, T., On, P., Presentation, T., Reid, R., Vasa, S. F., Maag, J. W., Wright, G., Irsyadi, F. Y. Al, Nugroho, Y. S., Cutter-Mackenzie, A., Edwards, S., Moore, D., Boyd, W., Miller, E., Almon, J., Cramer, S. C., Wilkes-Gillan, S., … Halperin, J. M. (2014). Young Children’s Play and Environmental Education in Early Childhood Education. PLoS ONE, 2(3), 9–25. https://doi.org/10.1586/ern.12.106
Jacman, H. (2012). Early Education Curriculum. Pedagogical Development Unit, FEBRUARY 2011, 163. https://www.eursc.eu/Syllabuses/2011-01-D-15-en-4.pdf
Jay, J. A., & Knaus, M. (2018). Embedding play-based learning into junior primary (Year 1 and 2) Curriculum in WA. Australian Journal of Teacher Education, 43(1), 112–126. https://doi.org/10.14221/ajte.2018v43n1.7
Kennedy, A., & Barblett, L. (2010). Supporting the Early Years Learning Framework. Research in Practise Series, 17(3), 1–12.
Keung, C. P. C., & Cheung, A. C. K. (2019). Towards Holistic Supporting of Play-Based Learning Implementation in Kindergartens: A Mixed Method Study. Early Childhood Education Journal, 47(5), 627–640. https://doi.org/10.1007/s10643-019-00956-2
Keung, C. P. C., & Fung, C. K. H. (2020). Exploring kindergarten teachers’ pedagogical content knowledge in the development of play-based learning. Journal of Education for Teaching, 46(2), 244–247. https://doi.org/10.1080/02607476.2020.1724656
Krogh, S., & Morehouse, P. (2014). The Early Childhood Curriculum : Inquiry Learning Through Integration.
Liao, C. (2016). From Interdisciplinary to Transdisciplinary: An Arts-Integrated Approach to STEAM Education. Art Education, 69(6), 44–49. https://doi.org/10.1080/00043125.2016.1224873
Lillard, A. S., Lerner, M. D., Hopkins, E. J., Dore, R. A., Smith, E. D., & Palmquist, C. M. (2013). The impact of pretend play on children’s development: A review of the evidence. Psychological Bulletin, 139(1), 1–34. https://doi.org/10.1037/a0029321
Maxwell, L. E., Mitchell, M. R., & Evans, G. W. (2008). Effects of Play Equipment and Loose Parts on Preschool Children’s Outdoor Play Behavior: An Observational Study and Design Intervention. Children, Youth and Environments, 18(2), 37–63.
McLaughlin, T., & Cherrington, S. (2018). Creating a rich curriculum through intentional teaching. Early Childhood Folio, 22(1), 33. https://doi.org/10.18296/ecf.0050
Mengmeng, Z., Xiantong, Y., & Xinghua, W. (2019). Construction of STEAM Curriculum Model and Case Design in Kindergarten. American Journal of Educational Research, 7(7), 485–490. https://doi.org/10.12691/education-7-7-8
Milara, I. S., Pitkänen, K., Laru, J., Iwata, M., Orduña, M. C., & Riekki, J. (2020). STEAM in Oulu: Scaffolding the development of a Community of Practice for local educators around STEAM and digital fabrication. International Journal of Child-Computer Interaction, 26, 100197. https://doi.org/10.1016/j.ijcci.2020.100197
Moomaw, S. (2012). STEM Begins in the Early Years. School Science and Mathematics, 112(2), 57–58. https://doi.org/10.1111/j.1949-8594.2011.00119.x
Peng, Q. (2017). Study on Three Positions Framing Kindergarten Play-Based Curriculum in China: Through Analyses of the Attitudes of Teachers to Early Linguistic Education. Studies in English Language Teaching, 5(3), 543. https://doi.org/10.22158/selt.v5n3p543
Pyle, A., & Bigelow, A. (2015). Play in Kindergarten: An Interview and Observational Study in Three Canadian Classrooms. Early Childhood Education Journal, 43(5), 385–393. https://doi.org/10.1007/s10643-014-0666-1
Pyle, A., & Danniels, E. (2017). A Continuum of Play-Based Learning: The Role of the Teacher in Play-Based Pedagogy and the Fear of Hijacking Play. Early Education and Development, 28(3), 274–289. https://doi.org/10.1080/10409289.2016.1220771
Quigley, C. F., Herro, D., & Jamil, F. M. (2017). Developing a Conceptual Model of STEAM Teaching Practices. School Science and Mathematics, 117(1–2), 1–12. https://doi.org/10.1111/ssm.12201
Ridgers, N. D., Knowles, Z. R., & Sayers, J. (2012). Encouraging play in the natural environment: A child-focused case study of Forest School. Children’s Geographies, 10(1), 49–65. https://doi.org/10.1080/14733285.2011.638176
Ridwan, A., Rahmawati, Y., & Hadinugrahaningsih, T. (2017). Steam Integration in Chemistry Learning for Developing 21st Century Skills. MIER Journail of Educational Studies, Trends & Practices, 7(2), 184–194.
Rolling, J. H. (2016). Reinventing the STEAM Engine for Art + Design Education. Art Education, 69(4), 4–7. https://doi.org/10.1080/00043125.2016.1176848
Sancar-Tokmak, H. (2015). The effect of curriculum-generated play instruction on the mathematics teaching efficacies of early childhood education pre-service teachers. European Early Childhood Education Research Journal, 23(1), 5–20. https://doi.org/10.1080/1350293X.2013.788315
Sawangmek, S. (2019). Trends and Issues on STEM and STEAM Education in Early Childhood. Képzés És Gyakorlat, 17(2019/3-4), 97–106. https://doi.org/10.17165/tp.2019.3-4.8
Science, A. I. (n.d.). STEM Project-Based Learning.
Spencer, R., Joshi, N., Branje, K., Lee McIsaac, J., Cawley, J., Rehman, L., FL Kirk, S., & Stone, M. (2019). Educator perceptions on the benefits and challenges of loose parts play in the outdoor environments of childcare centres. AIMS Public Health, 6(4), 461–476. https://doi.org/10.3934/publichealth.2019.4.461
Taylor, J., Bond, E., & Woods, M. (2018). A Multidisciplinary and Holistic Introduction.
Varun A. (2014). Thematic Approach for Effective Communication in Early Childhood Education Thematic Approach for effective communication in ECCE. International Journal of Education and Psychological Research (IJEPR), 3(3), 49–51. https://www.researchgate.net/publication/289868193
Wang, X., Xu, W., & Guo, L. (2018). The status quo and ways of STEAM education promoting China’s future social sustainable development. Sustainability (Switzerland), 10(12). https://doi.org/10.3390/su10124417
Whitebread, D. D. (2012). The Importance of Play. Toy Industries of Europe, April, 1–55. https://doi.org/10.5455/msm.2015.27.438-441
Wong, S. M., Wang, Z., & Cheng, D. (2011). A play-based curriculum: Hong Kong children’s perception of play and non-play. International Journal of Learning, 17(10), 165–180. https://doi.org/10.18848/1447-9494/cgp/v17i10/47298
Zosh, J. M., Hopkins, E. J., Jensen, H., Liu, C., Neale, D., Hirsh-Pasek, K., Whitebread, Solis, S. L., & David. (2017). Learning through play : a review of the evidence (Issue November). The LEGO Foundation.
25
Čelakovská, Jarmila, Josef Bukač, Eva Cermákova, Radka Vaňková, Hana Skalská, Jan Krejsek, and Ctirad Andrýs. "Analysis of Results of Specific IgE in 100 Atopic Dermatitis Patients with the Use of Multiplex Examination ALEX2—Allergy Explorer." International Journal of Molecular Sciences 22, no. 10 (May 17, 2021): 5286. http://dx.doi.org/10.3390/ijms22105286.
Full textAbstract:
Background and aim: Progress in laboratory diagnostics of IgE-mediated allergy is the use of component-resolved diagnosis. Our study analyses the results of specific IgE to 295 allergen reagents (117 allergenic extracts and 178 molecular components) in patients suffering from atopic dermatitis (AD) with the use of ALEX2 Allergy Explorer. Method: The complete dermatological and allergological examination, including the examination of the sensitization to molecular components with ALEX2 Allergy Explorer testing, was performed. The statistical analysis of results was performed with these methods: TURF (total unduplicated reach and frequency), best reach and frequency by group size, two-sided tests, Fisher’s exact test, and chi-square test (at an expected minimum frequency of at least 5). Results: Altogether, 100 atopic dermatitis patients were examined: 48 men, 52 women, the average age 40.9 years, min. age 14 years, max. age 67 years. The high and very high level of specific IgE was reached in 75.0% of patients to 18 molecular components: from PR-10 proteins (Aln g 1, Bet v 1, Cor a1.0103, Cor a1.0401, Fag s 1), lipocalin (Can f 1), NPC2 family (Der f 2, Der p 2), uteroglobin (Fel d 1), from Alternaria alternata (Alt a 1), Beta expansin (Lol p 1, Phl p 1), molecular components from Timothy, cultivated rye (Secc pollen) and peritrophin-like protein domain Der p 23. The high and very high level of specific IgE to other lipocalins (Fel d 7, Can f 4), to arginine kinase (Bla g 9, German cockroach), and to allergen extracts Art v (mugwort), and Cyn d (Bermuda grass) reached 52.0% of patients. The severity of AD is in significant relation to the sensitization to molecular components of storage mites (Gly d 2, Lep d 2—NPC2 family), lipocalins (Can f 1, Can f 2, Can f 4, and Can f 6), arginine kinase (Asp f 6, Bla g 9, Der p 20, Pen m 2), uteroglobin (Fel d 1, Ory c 3), Mn superoxide dismutase (Mala s 11), PR-10 proteins (Fag s 1, Mal d 1, Cor a 1.0401, Cor a 1.0103), molecular components of the peritrophin-like domain (Der p 21, Der p 23), and to Secc pollen. In the subgroup of patients suffering from bronchial asthma, the significant role play molecular components from house dust mites and storage mites (Lep d 2, Der p 2, Der f 2—NPC2 family), cysteine protease (Der p 1), peritrophin-like protein domain (Der p 21, Der p 23), enolase from Alternaria alternata (Alt a 6), and Beta expansin Phl p 1. Conclusion: The results of our study demonstrate the detailed profile of sensitization to allergens reagents (allergen extract and molecular components) in patients with atopic dermatitis. We show the significance of disturbed epidermal barrier, resulting in increased penetration of allergens. We confirmed the significant relationship between the severity of AD, the occurrence of bronchial asthma and allergic rhinitis, and high levels of specific IgE to allergen reagents. Our results may be important for regime measures and immunotherapy; Der p 23 shall be considered as an essential component for the diagnosis and specific immunotherapy of house dust mite allergy.
26
Petri, M. A., G. Bertsias, M. Daniels, N. L. Fox, B. H. Hahn, A. Hammer, J. Harris, H. Quasny, C. Tani, and A. Askanase. "POS0183 THE EFFECT OF BELIMUMAB ON SRI-4 RESPONSE IN MULTIPLE SUBGROUPS OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS OF A LARGE INTEGRATED ANALYSIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 323.1–323. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1807.
Full textAbstract:
BackgroundBelimumab (BEL) is approved for the treatment of active autoantibody-positive systemic lupus erythematosus (SLE).1 Four Phase 3 studies have consistently demonstrated greater SLE Responder Index (SRI) response rates with BEL vs placebo (PBO).2-5 This robust dataset allows for additional exploration of the onset of efficacy of BEL and response rates by patient (pt) characteristics.ObjectivesTo perform a post hoc analysis evaluating the effect of BEL on SRI-4 response across a large, pooled population and pt subgroups.MethodsThe Belimumab Summary of Lupus Efficacy (Be-SLE) integrated analysis evaluated data from adults with SLE from 5 double-blind, PBO-controlled BEL trials: BLISS-76, BLISS-52, BLISS-NEA, BLISS-SC, and EMBRACE.2-6 Pts were randomised to BEL (monthly intravenous 10 mg/kg or weekly subcutaneous 200 mg) or PBO, plus standard therapy. Data were collected every 4 weeks (wks) from baseline (BL) to Wk 52. The SRI-4 response rate (a composite measure that includes ≥4-point reduction in Safety of Estrogens in Lupus Erythematosus National Assessment - SLE Disease Activity Index [SELENA-SLEDAI] score, stable Physician Global Assessment [PGA] increase of <0.3, and no new British Isles Lupus Assessment Group [BILAG] 1A/2B organ domain scores) by visit and time to first SRI-4 response maintained through Wk 52 were determined for both treatment groups. SRI-4 response rates at Wk 52 were evaluated by BL characteristic subgroups: SELENA-SLEDAI score; SLE International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score; disease duration; biomarker levels (anti-dsDNA, complement [C]3/C4); glucocorticoid (GC), immunosuppressant (IS), and antimalarial (AM) use.ResultsOverall, 3086 pts were included (BEL, n=1869; PBO, n=1217). Most were female (94.4%); mean (standard deviation [SD]) age was 37.0 (11.6) years. Mean (SD) SLE duration was 6.4 (6.4) years.At Wk 52, in the overall population, significantly more BEL vs PBO pts were SRI-4 responders (Figure 1). A significantly greater proportion of SRI-4 responders was observed with BEL vs PBO as early as Wk 8 (38.4% vs 33.3%; odds ratio, OR [95% confidence interval, CI] 1.25 [1.07, 1.46]; p=0.0060), which continued to increase to Wk 52 (54.8% vs 41.6%; OR [95% CI] 1.70 [1.46, 1.98]; p<0.0001). At Wk 52, more BEL vs PBO pts had a 4-point reduction in SELENA-SLEDAI (56.3% vs 43.1%; OR [95% CI] 1.71 [1.47, 2.00]; p<0.0001), no worsening in PGA (76.6% vs 67.9%; OR [95% CI] 1.52 [1.28, 1.79]; p<0.0001), and no new BILAG 1A/2B organ domain scores (77.1% vs 69.4%; OR [95% CI] 1.47 [1.25, 1.74]; p<0.0001). Pts on BEL were 52% more likely to experience an SRI-4 response that was maintained through Wk 52 (hazard ratio, HR [95% CI] 1.52 [1.36, 1.69]; p<0.0001).Figure 1.SRI-4 response at Wk 52 in the overall population and by BL characteristic subgroups.*OR (95% CI) and p-value are from a logistic regression model for BEL vs PBO comparison with covariates of treatment group, study and BL SELENA-SLEDAI score (≤9 vs ≥10)SRI-4 response rates were significantly higher with BEL vs PBO in most subgroups, with the highest response rates observed in pts with SELENA-SLEDAI score of ≥10, low C3 and/or C4 + anti-dsDNA ≥30 IU/ml, and low C3 and/or C4 at BL (Figure 1).ConclusionSignificantly more pts receiving BEL had SRI-4 response rates that occurred from Wk 8 and were maintained through Wk 52 compared with pts receiving PBO. The efficacy of BEL was consistent across multiple pt subgroups, with higher response rates in pts with SELENA-SLEDAI scores of ≥10, low C3 and/or C4 + anti-dsDNA ≥30 IU/ml and low C3 and/or C4 at BL. These results further substantiate the benefits of BEL in the treatment of adults with SLE.References[1]GlaxoSmithKline. Benlysta US prescribing information. 2021[2]Furie R, et al. Arthritis Rheumatol 2011;63(12):3918–30[3]Navarra SV, et al. Lancet 2011;377(9767):721–31[4]Stohl W, et al. Arthritis Rheum 2017;69(5):1016–27[5]Zhang F, et al. Ann Rheum Dis 2018;77(3):355–63[6] Ginzler E, et al. Arthritis Rheum 2021; doi: 10.1002/art.41900AcknowledgementsThis analysis was funded by GlaxoSmithKline (GSK). Medical writing support was provided by Lulu Hill, MPharmacol, Fishawack Indicia Ltd. UK, part of Fishawack Health, and was funded by GSK.Disclosure of InterestsMichelle A Petri Consultant of: GSK, Grant/research support from: GSK, George Bertsias Speakers bureau: Pfizer, Aenorasis, UCB, Novartis, Lilly, SOBI, Consultant of: Novartis, GSK, AstraZeneca, Grant/research support from: GSK, Pfizer, Mark Daniels Shareholder of: GSK, Employee of: GSK, Norma Lynn Fox Shareholder of: GSK, Employee of: GSK, Bevra H. Hahn Consultant of: UCB, GSK, Anne Hammer Shareholder of: GSK, Employee of: GSK, Julia Harris Shareholder of: GSK, Employee of: GSK, Holly Quasny Shareholder of: GSK, Employee of: GSK, Chiara Tani Speakers bureau: GSK, AstraZeneca, Anca Askanase Consultant of: AstraZeneca, Aurinia Pharmaceuticals Inc., Amgen, AbbVie Inc., BMS, GSK, Grant/research support from: AstraZeneca, Eli Lilly and Company, GSK, Idorsia Pharmaceuticals Ltd, Janssen Pharmaceuticals, Pfizer
27
Zheng, Wen-bin, Yi Dai, Jing Hu, Di-chen Zhao, Ou Wang, Yan Jiang, Wei-bo Xia, Xiao-ping Xing, and Mei Li. "EFFECTS OF BISPHOSPHONATES ON OSTEOPOROSIS INDUCED BY DUCHENNE MUSCULAR DYSTROPHY: A PROSPECTIVE STUDY." Endocrine Practice 26, no. 12 (December 2020): 1477–85. http://dx.doi.org/10.4158/ep-2020-0073.
Full textAbstract:
Objective: Duchenne muscular dystrophy (DMD) is a severe X-linked progressive neuromuscular disease that brings a significantly increased risk of osteoporosis and bone fractures. We prospectively evaluated the effects of oral and intravenous bisphosphonates on the bones of children with DMD. Methods: This study included a total of 52 children with DMD. They were divided into zoledronic acid (ZOL), alendronate (ALN), and control groups according to bone mineral density (BMD) and history of fragility fractures. For 2 years, all patients took calcium, vitamin D, and calcitriol. Meanwhile, 17 patients received infusions of ZOL, and 18 patients received ALN. BMD, serum levels of alkaline phosphatase (ALP) and the cross-linked C-telopeptide of type I collagen (β-CTX) were evaluated. Results: After 24 months of treatment, the percentage changes in lumbar spine BMD were 23.2 ± 9.7% and 23.6 ± 8.8% in the ZOL and ALN groups (all P<.01 vs. baseline). The increases did not differ between the ZOL and ALN groups, but were significantly larger than those of the control group ( P<.01). Serum β-CTX and ALP levels, respectively, were decreased by 44.4 ± 18.0% and 31.9 ± 26.7% in the ZOL group and by 36.0 ± 20.3% and 25.8 ± 14.4% in the ALN group (all P<.01 vs. baseline). Conclusion: Zoledronic acid and alendronate had similar protective effects to increase bone mineral density and reduce bone resorption in children with DMD, which were superior to treatment of calcium, vitamin D, and calcitriol. Abbreviations: 25OHD = 25 hydroxyvitamin D; ALN = alendro-nate; ALP = alkaline phosphatase; ALT = alanine aminotransferase; BMD = bone mineral density; BP = bisphosphonate; Ca = calcium; β-CTX = cross-linked C-telopeptide of type I collagen; DMD = Duchenne muscular dystrophy; FN = femoral neck; GC = glucocorticoid; LS = lumbar spine; ZOL = zoledronic acid
28
Saidov, Marat Z., Suleiman N. Mammaev, Halina M. Magadova, Rita Maratovna Balamirzoeva, Zulfia Sh Magomedova, Zarema S. Magomedova, and Aishat U. Gamzaeva. "Genetic polymorphism of renin-angiotensin-aldosterone system in type 2 diabetes and in combination with arterial hypertension among Dagestan inhabitants." Diabetes mellitus 22, no. 6 (February 28, 2020): 568–76. http://dx.doi.org/10.14341/dm10207.
Full textAbstract:
BACKGROUND: Type 2 diabetes and arterial hypertension are frequent comorbidities under which activation the renin-angiotensin-aldosterone system is important pathogenetic link. The functional state of the RAAS is genetically determined. Genetic polymorphisms of the RAAS system associated with the development of both type 2 diabetes and arterial hypertension have been identified and mapped. Associations of polymorphic variants of the RAAS genes with type 2 diabetes and arterial hypertension among the inhabitants of Dagestan have not been studied.
AIM: Studying the association of the most relevant polymorphic variants of the C521T and T704C AGT gene, as well as the A1166C AGTR1 gene with type 2 diabetes and when combining type 2 diabetes with arterial hypertension among Dagestan inhabitants.
METHODS: We examined 16 patients with type 2 diabetes, 59 patients with type 2 diabetes combined with arterial hypertension and 51 patients with arterial hypertension, all residents of Dagestan. The control group included 47 healthy persons of the same age group. SNP polymorphisms were investigated by the method of allele-specific Real-Time PCR. The C521T and T704C polymorphisms of the AGT gene and the A1166C polymorphism of the AGTR1 gene were studied.
RESULTS: In the group of patients with a combination type 2 diabetes with arterial hypertension, the genotype CT of the C521T polymorphism of the AGT gene is less common compared to the control (23% vs. 43%, 2 = 3,868, p = 0,049), OR score 0,4 (0,2-0,9 ). The situation is similar with the TC genotype of the T704C polymorphism of the AGT gene (39% versus 61%, 2 = 4,282, p = 0,039). OR was 0,4 (0,20,8).On the contrary, in the same patients, but the carriers of the homozygous CC genotype of the T704C polymorphism of the AGT gene, OR exceeded one and made 2.5 (1.02-5.9), the frequency of occurrence was 42% vs. 23%, 2 = 3,363, p = 0,05. The frequency of the mutant allele C of the A1166C polymorphism of the AGTR1 gene in patients with arterial hypertension alone was 31% vs. 14%, 2 = 5.496, p = 0,019, OR 2,5 (1,2-5,0). The frequency of the wild allele A in these same patients was 69% versus 84%, 2 = 5,496, p = 0,019, OR 0,4 (0,2-0,8). A similar situation is determined with the AA genotype (52% versus 73%, 2 = 3,609, p = 0,05), OR = 0,4 (0,1-0,9).
CONCLUSIONS: The association of the C521T and T704C polymorphisms, as well as the A1166C candidate genes AGT and AGTR1 with type 2 diabetes and arterial hypertension, is an important component in assessing the susceptibility to the development of these diseases in Dagestan residents.
29
Merli, Michele, Alessandro Re, Michele Bibas, Davide Dalu, Emanuele Ravano, Guido Gini, Carlo Visco, et al. "Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases." Blood 138, Supplement 1 (November 5, 2021): 1434. http://dx.doi.org/10.1182/blood-2021-151174.
Full textAbstract:
Abstract Background: Hepatitis C virus (HCV) chronic infection has been associated with increased risk of non-Hodgkin lymphoma (NHL) in people living with human immunodeficiency virus (HIV) as well as with a trend of inferior overall survival (OS) in HIV-associated NHL in the modern antiretroviral therapy (ART) era (Besson 2020). The recent introduction of interferon (IFN)-free direct-acting antivirals (DAAs) led to the achievement of sustained virologic response (SVR) in nearly all treated patients (pts) with negligible toxicity in all settings, including HIV/HCV coinfected pts, in which, however, careful attention to interactions with ART is required. We recently showed that DAAs' administration after immuno-chemotherapy (I-CT) may improve long-term outcome in HIV-negative HCV-associated diffuse large B-cell lymphomas (DLBCL) pts (Merli 2019), however, only scant data have been reported so far about the use of DAAs in HIV/HCV coinfected NHL pts. METHODS: We retrospectively collected clinical and virological features, treatments and outcome data of all consecutive pts with NHL and HIV/HCV co-infection, diagnosed and treated at 13 Italian centers between 2005 and 2021, with a special focus on pts affected by DLBCL and treated with DAAs. Only pts who received ART were included. The primary endpoints were SVR rate after DAAs and 2-year OS in HIV/HCV-positive NHL pts. RESULTS: Overall, we collected data of 74 HIV/HCV coinfected pts with NHL (69 males, 93%), including 52 DLBCL, 13 Burkitt lymphoma (BL), 5 plasmablastic lymphoma (PL), 1 anaplastic large-cell ALK negative, 1 T lymphoblastic, 1 gastric MALT and 1 lymphoplasmacytic lymphoma (Table 1). Median age was 51 years (22-57). Previous AIDS defining event was recorded in 16 cases (22%). The main HIV transmission group was represented by intravenous drug users (69%). Stage was III-IV in 63 pts (85%) and aaIPI was ≥2 in 57 pts (77%). At NHL diagnosis 38% of pts had CD4+ <200/mmc and 31% ≥400 HIV-RNA copies/ml. ARL-IPI score was intermediate or high in 49 pts (64%). HCV genotype was 1 in 26 pts (58%), 3 in 12 (27%) and 4 in 7 (15%). Cirrhosis was present in 39% of pts (Child-Pugh B or C in 25%). Overall, 70 pts underwent curative first line therapy alongside ART, including (R-)CHOP-like in 50 (71%), (R-)EPOCH in 9 (13%), (R-)CODOX-M/IVAC in 8 (11%). Rituximab was used in 53% of cases (60% in DLBCL). 46 pts (66%) achieved a complete response (CR), 7 (10%) a partial response (PR), while 17 (24%) did not respond or progressed. At a median follow-up of 1.8 years (95%CI 0.1-12.3), 33 pts (45%) progressed, with a 2-year PFS of 53.5% (95%CI 40.7-64.8), and 38 (51%) died (30 due to NHL, 7 to infections and 1 to hepatocellular carcinoma), with a 2-year OS of 58.2% (95%CI 45.7-78.9). Two-year OS for DLBCL was 61.4% (95%CI 46.3-73.4), significantly higher than BL (39%, 95%CI 14.1-62.8; p=.0.47, Fig. 1). Considering anti-HCV therapy, 13 pts received IFN-based regimens, 5 of whom achieved SVR (38%). After 2016, 21 pts (14 DLBCL, 3 BL, 2 indolent and 2 T-cell lymphoma), including 4 who previously failed IFN, received various DAAs regimens after I-CT (sofosbuvir-based in 20). Toxicity of DAAs was minimal, with only 2 grade (G) ≥2 adverse events (1 G2 peripheral neuropathy and 1 G2 insomnia). SVR was achieved in 20/21 pts (95%): notably, the only non-responder had discontinued DAAs autonomously. DAAs use was associated with improved OS in all pts (p=0.01) and in DLBCL (p=0.04) and with better PFS (p=0.01) in all pts. Similarly, the achievement of SVR after either DAAs or IFN predicted a better OS (Fig.2) and PFS in all pts (p=0.005 and p=0.008, respectively) and in DLBCL (p=0.018 and p=0.047, respectively). The impact of DAAs and SVR on OS remained significant also if considering only pts who achieved CR or PR after I-CT (p<0.05). At univariate analysis, age >60 years (p=0.02), ARL-IPI (p=0.013), PS ECOG ≥2 (p=0.018) were associated with inferior OS. By applying multivariate Cox regression analysis, age >60 years (HR 67.9, 95% CI 7.2- 643.3, p<0.001), ARL-IPI (HR 2.87, 95%CI 1.03-8.06, p=0.044) and SVR after IFN or DAAs (HR 0.30, 95%CI 0.12-0.75, p=0.01) retained independent prognostic influence on OS. CONCLUSIONS: In this very high risk series of HIV/HCV coinfected pts with NHL, mainly represented by DLBCL, the administration of DAAs after I-CT resulted feasible and effective (SVR 95%), and displayed an independent favourable influence on OS. These results strongly support DAAs' use in this hard to treat population. Figure 1 Figure 1. Disclosures Tisi: Incyte: Membership on an entity's Board of Directors or advisory committees; BWS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zilioli: Roche, Italfarmaco: Consultancy, Honoraria; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations; Takeda: Other: travel expenses, accommodation; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau. Passamonti: AbbVie: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Arcaini: Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy; Gilead Sciences: Research Funding; Celgene: Speakers Bureau.
30
Hering, B. J., C. C. Browatzki, A. Schultz, R. G. Bretzel, and K. F. Federlin. "Clinical Islet Transplantation — Registry Report, Accomplishments in the past and Future Research Needs." Cell Transplantation 2, no. 4 (July 1993): 269–82. http://dx.doi.org/10.1177/096368979300200403.
Full textAbstract:
This review provides the results of a recent analysis of the Islet Transplant Registry on clinical adult islet transplants performed worldwide through June 30, 1992. Between December 12, 1893 and June 30, 1992, 167 adult islet transplants were performed at 25 institutions worldwide, including 104 at 9 institutions in North America, 62 at 15 institutions in Europe, and 1 elsewhere. The total number of diabetic patients reported to be insulin independent after adult islet allotransplantation through June 30,1992, was 19. In an analysis by era, the percentage of patients that showed positive basal C-peptide levels (i.e. ≥ 1 ng/mL at ≥ 1 mo) posttransplant, and that became insulin independent (>1 wk) in the 1985-1989 era (n = 35 cases) were 20% and 6%, and in the 1990-1992 era (n = 69 cases) were 64% and 20%, respectively, and thus have improved significantly (p < 0.001 and p < 0.05). For the 1990-1992 period, the percentage of patients who showed positive basal C-peptide levels post-transplant, and who became insulin independent in the single donor pancreas group (n = 31 cases) were 52% and 13%, and in the multiple donor pancreata group (n = 36 cases) were 75% and 28%, respectively. Islet graft function rates were nearly identical for grafts prepared from pancreata stored ≤6 h (n = 27) and >6 ≤ 12 h (n = 29), so that 67% and 72% showed positive basal C-peptide levels, and 30% and 21% of the recipients became insulin independent, respectively. No single patient showed islet graft function sufficient to allow withdrawal from insulin, if the pancreata have been stored for more than 12 h. In regard to recipient category for the six groups, namely IAK (islet after kidney), SIK (simultaneous islet kidney transplantation), SIL (simultaneous islet liver transplantation), SIL(C) (simultaneous islet liver transplantation after cluster operation), SIKL (simultaneous islet kidney liver transplantation), and SIH-L (simultaneous islet heart-lung transplantation), the number of patients who showed positive basal C-peptide levels post-transplant was 11 (58%), 17 (57%), 5 (83%), 8 (80%), 1 (50%), and 0 (0%), and the number of insulin independent patients was 4 (21%), 4 (13%), 0 (0%), 6 (60%), 0 (0%), and 0 (0%), respectively. Comparing the two largest recipient categories, namely IAK and SIK, no difference in the outcome of these transplants was apparent. The only sites of transplantation in the period between 1990-1992 were the liver, epiploic flap, and spleen, with the total number of recipients being 60 (90%), 4 (6%), and 3 (4%), respectively. For these three groups, the number of patients who showed positive basal C-peptide levels was 38 (63%), 2 (50%), and 1 (33%), and the number of insulin independent patients was 13 (22%), 0 (0%) and 0 (0%), respectively. In the overwhelming majority of cases, recipient selection was not based on prospective HLA donor/recipient matching. In different categories of HLA mismatching (i.e., AB-, DR-, BDR-, and ABDR-mismatch) no obvious tendency or difference in outcome could be demonstrated. In the 1990-1992 period, 16 patients (24%) received OKT3, 26 patients (39%) received ALS, ALG, or ATG, and 25 patients (37%) received neither monoclonal nor polyclonal T-cell antibodies for induction immunosuppression. For the three groups mentioned, the number of patients who showed positive basal C-peptide levels was 12 (86%), 16 (62%), and 15 (60%), and the number of insulin independent patients was 2 (14%), 6 (23%), and 6 (24%), respectively. A synopsis of all pretransplant C-peptide-negative Type I diabetic patients who succeeded in insulin independence revealed certain common characteristics, such as transplantations of ≥8000 islet equivalents per kilogram body weight, a purity of transplanted islets ≥ 50% (in all but one case), the liver as implantation site, and OKT3 or ALG/ ALS/ATG for induction immunosuppression (“state of the art” cases). Because it has been unequivocally proven that islet transplantation can be performed successfully in association with other organ transplants, more attention should be drawn to the nonuremic, nonkidney Type I diabetic patients, who have not been reported in a single case since 1990. This is the real target group, that could benefit most from islet replacement. However, islet transplantation in this recipient category will only have an undisputable indication, if low-risk, but effective methods other than life-long immunosuppression to protect the islet graft from rejection can be developed.
31
Yesilipek, M. Akif, Gulsun Karasu, Zuhre Kaya, Baris B. Kuskonmaz, Vedat Uygun, Ilkiz Dag, Asli Birkent, and Mehmet Ertem. "Interim Results from a Phase 2, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with Beta-Thalassemia Major." Blood 126, no. 23 (December 3, 2015): 959. http://dx.doi.org/10.1182/blood.v126.23.959.959.
Full textAbstract:
Abstract Introduction: Hematopoietic stem cell transplantation (HSCT) is being increasingly used as curative therapy for severe disorders of the hematopoietic system and transfusional iron overload (TIO) contributes considerably to treatment-related morbidity and mortality after HSCT. Management of iron overload in the post-HSCT setting may be complicated since the use of therapeutic phlebotomies is often not feasible due to ongoing anemia and compliance to deferoxamine is low. Studies that evaluate the safety dose of deferasirox (DFX), which is the most commonly used chelation therapy, in this setting are limited. Purpose & Methods: This is a prospective, phase 2, multicenter, single-arm study to evaluate the efficacy and safety of iron chelation with oral DFX in beta-thalassemia major (TM) patients who have undergone HSCT. The study was conducted in 7 centers from Turkey. The primary objective was to evaluate if DFX could provide clinically safe chelation in a target pool of 26 pediatric patients with TIO within a minimum of 6 months and maximum of 2 years after related/unrelated HSCT. Patients had to be transfusion-independent and have iron overload at screening defined by serum ferritin (SF) of >1000 μg/L or cardiac MRI T2* <20 ms or liver iron concentration (LIC, by MRI R2) of ≥5 mg/g. The study included male and female TM patients ≥2 to <18 years old who had undergone HSCT with a washout period from immunosuppressive therapy of at least 3 months. Patients received DFX at an initial dose of 10 mg/kg/day with up titration every 3 months by 5 mg/kg/day per investigator judgment to a maximum of 20 mg/kg/day. Therapy continued for 52 weeks or until SF reached below 500 μg/L. Aside from AE monitoring, assessments were undertaken at baseline and every 28 days (unless closer assessments were need for dose initiation and adjustment) and included complete blood counts, biochemistry and urinalysis, and SF. MRI assessment of liver (R2) and cardiac (T2*) iron were also conducted at baseline and 52 weeks. Results: Interim data from the first 18 of 26 patients (mean age 8.3 years, 66.7% males) who completed 12 months follow up are presented in this analysis. A total of 97 AEs were recorded in the 18 patients. The majority of AEs were of Grade I (n=57) or II (n=34) severity. Five (5.2%) were suspected to be related to study drug and 6 AEs (6.2%) were considered serious. Five (5.2%) AEs resulted in study drug temporary interruption or dose adjustment, 2 (2.1%) required hospitalization, 54 (55.7%) required concomitant medication, while 36 (37.1%) had no action taken. Three patients had dose decrease due to AEs. The dose was re-escalated up to 20 mg/kg/day after the AEs resolved. In total, 11 (61.1%) patients achieved 20 mg/kg/day. Only one patient dropped out due to progressive ALT increase. Median ALT level decreased from 26 IU/L (range: 10-117) at baseline to 18 IU/L (range: 9-101) at week 52. The median SCr was similar at baseline 0.4 mg/dL (range: 0.2-0.6) and week 52 0.4 mg/dL (range: 0.2-0.8). Median cystatin C was similar at baseline 0.7 mg/mL (range: 0.6-0.9) and week 52 0.7 mg/mL (range: 0.5-1.1) (Figure 1A-B). Five patients had proteinuria at baseline and increased proteinuria compared to previous visit by dipstick analysis was described in 7 (38.9%) patients, irrespective of DFX dose by 52 weeks. No patient with proteinuria required any dose adjustments by 52 weeks. SF significantly and consistently decreased throughout the 52 weeks from a median of 1752.3 μg/L (range: 873.7-2716) to 915.2 μg/L (range: 250.1-2740), p<0.001 (Figure 2). At week 52, 6 (33.3%) patients had reached SF <500 μg/L. LIC also significantly decreased from a median of 9.9 mg/g (range: 4.8-43) to 4.1 mg/g (range 0.9-8.5), p<0.001. Cardiac T2* increased from a median of 26.1 ms (range: 18.7-41) to 28.8 ms (18.5-44), p=0.605. Conclusions: Our preliminary results showed that DFX up to 20 mg/kg/day is safe and effective in reducing iron burden for TM patients following HSCT. This was evident through significant reductions of systemic, hepatic and cardiac iron overload. Final data from the completed study should confirm these findings and establish the role for DFX in this patient population. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Dag: Novartis: Employment. Birkent:Novartis: Employment.
32
Abdul Razzack, A., S. Abdul Razzack, P. Shenasan, N. Shenasan, S. Mishra, R. Zarrar, J. Pablo Sosa, et al. "POS0701 ANIFROLUMAB, AN ANTI-INTERFERON-Α RECEPTOR MONOCLONAL ANTIBODY IN SYSTEMIC LUPUS ERYTHEMATOSUS- A META ANALYSIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 600.1–600. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2782.
Full textAbstract:
Background:Type I interferons such as Anifrolumab have been implicated in Systemic lupus erythematosus (SLE) pathogenesis on the basis of increased interferon-stimulated gene expression and genetic susceptibility. Little is known regarding its efficacy and safety profile.Objectives:To assess the efficacy and safety of Anifrolumab in patients with SLE.Methods:Electronic databases (PubMed, Embase, Scopus, Cochrane) were searched from inception until December 15th, 2020. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p<0.05. The primary outcome of interest was British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). Secondary outcomes included the proportion of patients who achieved an SLE responder index of 4 (SRI-4) reduction of 50% or more in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), reductions in the glucocorticoid dose and adverse effects.Results:A total of three studies1,2,3 with 839 participants (Anifrolumab=372, Placebo=467) were included in our analysis. Follow-up duration was at week 52. A statistically significant different was observed in the Anifrolumab arm in terms of BICLA response (OR 0.44 95%CI 0.34-0.59;p < 0.00001, I2=4), ≥50% reduction in CLASI activity score (OR 0.36 95%CI 0.21-0.60;p=0.0001, I2=0), glucocorticoid reduction (OR 0.41 95%CI 0.28-0.59;p<0.00001; I2=0) and SRI-4 response (OR 0.52 95% CI 0.30-0.90; p=0.02, I2=75). However, Adverse events were less likely in the placebo arm as compared to Anifrolumab (OR 1.54 95%CI 1.05-2.25; p=0.03; I2=0).Conclusion:Anifrolumab was found to be more effective than placebo for the management of SLE, but may also cause more severe adverse effects.References:[1]Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, Bae SC, Brohawn PZ, Pineda L, Berglind A, Tummala R; TULIP-2 Trial Investigators. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020 Jan 16;382(3):211-221. doi: 10.1056/NEJMoa1912196. Epub 2019 Dec 18. PMID: 31851795.[2]Furie R, Khamashta M, Merrill JT, Werth VP, Kalunian K, Brohawn P, Illei GG, Drappa J, Wang L, Yoo S; CD1013 Study Investigators. Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017 Feb;69(2):376-386. doi: 10.1002/art.39962. PMID: 28130918; PMCID: PMC5299497.[3]Furie RA, Morand EF, Bruce IN, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol 2019; 1(4):e208-e219.Disclosure of Interests:None declared
33
Wadhva, Rajesh Kumar, Muhammad Manzoorul Haque, Nasir Hassan Luck, Abbas Ali Tasneem, Zaigham Abbas, and Muhammad Mubarak. "Diagnostic accuracy of aspartate aminotransferase to platelet ratio index and fibrosis 4 scores in predicting advanced liver fibrosis in patients with end-stage renal disease and chronic viral hepatitis: Experience from Pakistan." Journal of Translational Internal Medicine 6, no. 1 (March 28, 2018): 38–42. http://dx.doi.org/10.2478/jtim-2018-0008.
Full textAbstract:
Abstract Objectives The aim was to assess the diagnostic accuracy of APRI and FIB-4 in assessing the stage of liver fibrosis in end stage renal disease (ESRD) patients with chronic viral hepatitis and to compare the two tests with standard tru-cut liver biopsy. Material and Methods The study was conducted at Sindh Institute of Urology and Transplantation Karachi (SIUT) from May 2010 to May 2014. All ESRD patients, being considered as candidates for renal transplantation and in whom liver biopsy was performed were included. Fibrosis stage was assessed on liver biopsy using Ishak scoring system. The serum transaminases and platelet counts were used to calculate APRI and FIB-4 scores. Results Out of 109 patients, hepatitis C and B virus infections were present in 104 (95.4%) and 3(2.8%), respectively, while 2 (1.8%) patients had both infections. The mean Ishak fibrosis score was 1.95 ± 2. Advanced fibrosis was noted in 37 (34%) patients. Univariate analysis showed that advanced liver fibrosis was associated with lower platelets counts (P=0.001) and higher aspartate aminotransferase (AST) (P=0.001), alanine aminotransferase (ALT) (P=0.022), APRI score (P=0.001) and FIB-4 score (P=0.001). On logistic regression analysis, only APRI score (P < 0.001) was found to be the independent variable associated with advanced liver fibrosis. APRI score cutoff ≥1 indicating advanced fibrosis showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 91.9%, 90.3%, 82.9%, 95.6%, respectively with area under the curve (AUC) of 0.97. Similarly, a FIB-4 score cutoff ≥1.1 had sensitivity, specificity, PPV and NPV of 70.27%, 66.67%, 52% and 81.36%, respectively with AUC of 0.74. Conclusion APRI is more accurate noninvasive test for assessing advanced liver fibrosis in ESRD patients as compared to FIB-4. It can be used to obviate the need for liver biopsy in this high risk population.
34
Burnett, Alan K., William J. Kell, Anthony H. Goldstone, Donald Milligan, Ann Hunter, Archie G. Prentice, Nigel H. Russell, Brenda Gibson, Keith Wheatley, and Robert K. Hills. "The Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy for AML Improves Disease Free Survival without Extra Toxicity: Preliminary Analysis of 1115 Patients in the MRC AML15 Trial." Blood 108, no. 11 (November 16, 2006): 13. http://dx.doi.org/10.1182/blood.v108.11.13.13.
Full textAbstract:
Abstract The MRC AML15 Trial is primarily for patients with any form of AML who are under 60 years. One of the questions addressed was whether the addition of the immunoconjugate, Gemtuzumab Ozogamicin (GO) to induction (course 1) and/or consolidation (course 3) is beneficial. In induction patients are randomised to receive either DA (Daunorubicin/Ara-C) or ADE (Ara-C/Daunorubicin/Etoposide) or FLAG-Ida (Fludarabine/Ara-C/Idarubicin/G-CSF) and in consolidation either MACE (Amsacrine/Etoposide) or HD Ara-C (3.0g/m2 or 1.5g/m2 per dose). Our prior pilot trial had shown that GO 3mgs/m2 could be safely added to day 1 of each of these treatments (Kell et al Blood102, 4277–4283). Here we report the preliminary results of the effect of combining GO with induction chemotherapy. This randomisation achieved its recruitment target and was closed on 30 June 2006. All other comparisons in the trial, including GO in consolidation, remain open. Patients: A total of 1115 patients were randomised between July 2002 and June 2006. The median age was 49 (range 0–71) years: 53% of patients were male: 92% (n=1027) had de novo disease: 95% had WHO performance score of <2: 43% received DA, 43% FLAG-Ida, and 14% ADE. (Recruitment to ADE+GO opened in June 2005). Patients with WBC > 30 x 109/l and LFT’s > normal were initially excluded but admitted from March 2004. APL patients were not eligible for entry. 15% of patients with data had favourable 71% intermediate, and 14% adverse cytogenetics. Over 83% were CD33 positive. Results: The overall remission rate was 85% with no differences between the arms for GO vs no GO in CR (85% vs 85%) induction death (8% vs 7%) or resistant disease (7% vs 8%). There was a modest increase in mucositis on the GO arm in course 1 only (p=0.04) and increased AST and Alt toxicity in C1 (p=.002; p=.03) but no difference in bilirubin grades. GO patients used more platelets (19 vs 14; p<0.0001), but not red cells, and had more days on IV antibiotics (20.6 vs 18.6 p=0.001). The haemopoietic recovery and days in hospital were similar. With a median follow-up of 15 months (range 0–45), there is no significant difference in deaths in CR (GO vs no GO): 36 vs 45 (HR 0.75; CI.49–1.16 p=0.2), but relapse was reduced: 37% vs 52% at 3 years (HR 0.70 (0.52–0.92) p=0.01) resulting in an improved DFS: 51% vs 40% at 3 years (HR 0.72 (0.56–0.91) p=0.008). There is so far no significant difference in OS (53% vs 46% at 3 years; HR 0.91(0.73–1.14) p=0.4). Conclusion: This preliminary analysis of 1115 randomised patients indicates that the addition of GO to induction chemotherapy can reduce the relapse risk without adding significant extra toxicity and this has significantly improved the DFS in the GO arm. Longer follow up is required to determine the impact on survival.
35
Carradice, Duncan, Peter Shuttleworth, Jeffrey Szer, Andrew Roberts, and Andrew Grigg. "Tissue Iron Overload Is Common Post Transplantation (Allo BMT) and Is Associated with Red Cell Transfusion Load and HFE Genotype." Blood 104, no. 11 (November 16, 2004): 2262. http://dx.doi.org/10.1182/blood.v104.11.2262.2262.
Full textAbstract:
Abstract In order to analyse the incidence of iron overload after allo BMT and assess the role of venesection in preventing complications, we retrospectively analysed 168 consecutive patients undergoing allo BMT at our institution from 1998–2003 surviving at least one year. Iron studies were performed routinely pre-BMT, at D100, one & two years post BMT. Iron overload was defined by at least one of the following criteria i)liver biopsy (n=24), one of : a) dry weight iron concentration >80μmol/g; b) iron index >1.9; c) Perl’s stain grade 3 or 4, ii) CT liver iron >1.0mg/ml (n=13) iii) raised ferritin >1000 μg/L and transferrin saturation >55% on 2 occasions, persisting >6/12 post BMT (n=11), iv) venesection >5g iron (n=1). Using these criteria, iron overload occurred in 49/168 (29%) pts. 12/119 in the non-overloaded group had further investigation but did not meet the criteria; liver biopsy (n=10) or CT (n=2). Elevated ferritin, particularly early post-transplant, did not reliably predict for iron overload, with 55/91 evaluable patients having values >1000μg/L at D100 not fulfilling the criteria for iron overload. There was no difference between overloaded and non-overloaded patients with respect to age or sex. Acute (15/49 vs. 26/113) or chronic liver GVHD (25/46 vs. 47/105) was not different between the two groups (both p>0.05). Only 3 patients were hepatitis B sAg+ or hepatitis C Ab+. The iron overloaded group was more likely to i) have been transplanted for acute leukaemia (29/49 vs. 33/119; p 0.0002) ii) be C282Y heterozygotes (11/46 vs. 10/110, p 0.02) (iii) been transfused more units of red cells (mean 42 vs. 19; p<0.0001) and iv) have persistently abnormal liver function post-transplant, ALT (IU/ml; normal <55) at 1 year 77 vs. 52 and at 2 years 67 vs. 37 (all p<0.05). There was no effect of hetero- or homozygosity for H63D. 63 patients were analysed for the S65C, V59M and Q283P mutations. One patient was heterozygous for the S65C mutation (non-overloaded group). A mean of 12.3 units were venesected in 22 patients (range 2–46), all of whom had received >25 units of red cells. ALT fell significantly (mean pre venesection 189 IU/ml, post 36, p<0.05), as did transferrin saturation (mean pre venesection 68%, post 29%, p<0.05). We conclude that tissue iron overload is common after BMT, that biochemical measures of iron stores (ferritin and transferrin saturation) may be unreliable in this context, particularly in the early post BMT period and that radiological or histological assessment to distinguish hyperferritinaemia due to inflammation from true tissue iron overload may be required. Patients at risk of iron overload (transfusions >25 units, C282Y heterozygotes) should be closely monitored and early venesection therapy instituted to minimise organ damage.
36
Vierkant, Robert Alan, Jodi M. Carter, Stacey J. Winham, Chen Wang, Jennifer M. Kachergus, Ji Shi, Raymond M. Moore, et al. "Abstract 2203: Towards prediction of breast cancer risk in benign biopsies with high-plex GeoMx spatial protein profiling." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2203. http://dx.doi.org/10.1158/1538-7445.am2022-2203.
Full textAbstract:
Abstract Background: Biopsy diagnoses of benign breast disease (BBD) confer a 1.5- to 4-fold increased risk of developing breast cancer (BC) compared with women without BBD. Previously, we reported that decreased numbers of specific immune cell types in lobules of BBD biopsies predicted increased BC risk, suggesting the promise of future tissue biomarker studies to define BC risk markers among BBD patients. Thus, we applied protein-based GeoMx® Digital Spatial Profiling (DSP) to BBD biopsies preceding BC (cases) and to BBD biopsies from cancer-free patients (controls) to identify possible BC risk markers, which we then evaluated in subsequent BC tissues and in surrounding normal lobules of cases. Methods: Archived pathology slides of BBD biopsies were reviewed and used to guide preparation of TMAs containing 1.0-mm diameter FFPE cores of lobules from an age- and cohort-period-matched set of 91 cases and 88 controls from the Mayo Clinic BBD Cohort. For patients who later developed BC, we prepared TMAs of BC tissue and surrounding mapped normal lobules. We applied GeoMx® DSP (immune and canonical signaling proteins) to both sets of TMAs. Following QC and data normalization, associations of case status with log-transformed biomarker expression in lobules of BBD biopsies were carried out using linear mixed modeling approaches, accounting for multiple ROIs per individual. Biomarkers significantly associated with case status (p<0.05) were further examined in BCs and adjacent normal lobules, using similar approaches. Results: The mean age at BBD biopsy was 52 years, and at BC diagnosis of cases, 61.4 years (mean time from BBD to BC was 10.2 years). A family history of BC was more frequent among cases (70% versus 43%; chi-square p=0.002). Of 72 biomarkers tested, 46 (64.4%) were evaluable after QC and normalization and 5 were associated with BC risk after adjustment for family history of BC: BCL2 (p=0.005), STING (p=0.006), CD44 (p=0.02), S100 protein (p=0.03) and pan-AKT (p=0.05); each showed higher levels in lobules of BBD biopsies of controls than cases. Three unique patterns appeared when examining these biomarkers across tissue type within cases: for BCL2 (p=5 x 10-9) and STING (p=2 x 10-19), levels were high in both BC and lobules surrounding BC but low in preceding BBD; for GAPDH (p=4 x 10-53) and pan-AKT (p=2 x 10-33), levels were high in BC, low in preceding BBD, and moderate in lobules surrounding BC; and for CD44 (p=2 x 10-6) and S100B (p=2 x 10-49), levels were low in BC, high in lobules surrounding BC and moderate in preceding BBD. Conclusions: Using a novel TMA of lobules in combination with DSP, we preliminarily identified immune-based and PI3 kinase-related protein biomarkers in BBD biopsies associated with BC risk. In case-only analyses, these markers demonstrated complex differences between lobules in BBD biopsies, subsequent BCs and adjacent normal lobules. Citation Format: Robert Alan Vierkant, Jodi M. Carter, Stacey J. Winham, Chen Wang, Jennifer M. Kachergus, Ji Shi, Raymond M. Moore, Bryan M. McCauley, Laura M. Pacheco-Spann, E A. Thompson, Derek C. Radisky, Amy C. Degnim, Mark E. Sherman. Towards prediction of breast cancer risk in benign biopsies with high-plex GeoMx spatial protein profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2203.
37
Sydorova, A., and O. Iaremenko. "POS1248 URIC ACID AND COVID-19: PATTERN OF CHANGES AND ASSOCIATION WITH PROGNOSIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 958–59. http://dx.doi.org/10.1136/annrheumdis-2022-eular.3479.
Full textAbstract:
BackgroundCoronavirus disease causes a proximal tubule dysfunction of kidneys, inducing uric acid loss [1]. It has been established that several changes in laboratory markers (C-reactive protein (CRP), ferritin, interleukin-6 (IL-6)) can predict the severity of Covid-19 [2]. The purpose of this retrospective study was to analyze whether uric acid could act as another predictor of severe Covid-19.ObjectivesTo evaluate the relationship between the severity of Covid-19 and uric acid levels on admission to the hospital.MethodsThis retrospective study included 150 hospitalized patients with confirmed Covid-19 (mean age 60.3±14.6 years; 52% were men), the severity of which was determined by the presence and type of oxygen support: (1) without O2, (2) O2 by mask or nasal cannula, (3) continuous positive airway pressure, (4) positive bi-pressure in the airways or high-flow oxygen, (5) invasive ventilation. Among them, 90 subjects required oxygen support, and 60 people didn’t. The mortality rate in our study was 9.3%. The average uric acid level was compared with patients without Covid-19 (40 subjects). The study included patients who didn’t receive urate-lowering therapy. Levels of CRP, ferritin, IL-6, D-dimer were also determined on admission. The Spearman’s rank coefficient was used for measuring correlation.ResultsThe mean uric acid level in patients with coronavirus disease was 251.5±104.1 µmol/L; without Covid-19 it was significantly higher — 328.6±96.9 µmol/L (p<0.001). Approximately one in four (24.6%) Covid-19 patients had uric acid levels below the lower limit of normal (208 µmol/L for men, 155 µmol/L for women). A decrease in serum uric acid levels was also observed in patients suffering from asymptomatic hyperuricemia or gout. However, there was no correlation between uric acid levels and disease severity (r=0.01, p=0.88). Also, uric acid levels did not correlate with other laboratory markers of severe Covid-19 (CRP: r=0.07, p=0.73; ferritin: r=0.15, p=0,07; IL-6: r=0.11, p=0,22; D-dimer: r=0.02, p=0,79).ConclusionLow uric acid levels are common in patients with Covid-19, but are not predictive of a more severe course of this disease. A correlation between uric acid and the level of other laboratory markers of severe Covid-19 was not found.References[1]Dufour, I., Werion, A., Belkhir, L. et al. (2021). Serum uric acid, disease severity and outcomes in COVID-19. Crit Care 25, 212 https://doi.org/10.1186/s13054-021-03616-3[2]Huang, I., Pranata, R., Lim, M. A., et al. (2020). C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis. Therapeutic advances in respiratory disease, 14, 1753466620937175. https://doi.org/10.1177/1753466620937175Disclosure of InterestsNone declared
38
Gozalbes-Cravioto, Enrique, and Helena Gozalbes García. "Hallazgos de monedas greco-massaliotas en la provincia de Cuenca (España)." Vínculos de Historia Revista del Departamento de Historia de la Universidad de Castilla-La Mancha, no. 11 (June 22, 2022): 280–95. http://dx.doi.org/10.18239/vdh_2022.11.12.
Full textAbstract:
Publicamos una pequeña serie de monedas, relacionadas con las piezas conocidas inicialmente como de ejemplares “tipo Auriol”. Se trata de varias imitaciones greco-massaliotas, relacionadas con el ciclo numismático griego del Occidente mediterráneo. La importante novedad de las mismas se fundamenta en el lugar de hallazgo, pues este se ha producido en una zona interior de la Península Ibérica, donde hasta el momento no se había documentado el descubrimiento de numismas de este tipo. Palabras clave: moneda, imitaciones, edetanosTopónimos: Massalia, Emporion, AuriolPeriodo: Edetanos ABSTRACTThe text presents a small series of coins, similar to those initially known as "Auriol type". These are various Greek-Massalian imitations, related to the Greek numismatic cycle of the Western Mediterranean. What makes these coins particularly interesting is their place of discovery, since they were found in an inland area of the Iberian Peninsula, where the appearance of specimens of this type had not previously been documented. Keywords: coin, imitations, AuriolPlace names: Massalia, Emporion,Period: edetans REFERENCIASAmorós, J. V. (1934), Les monedes emporitanes anteriors a les dracmes, Barcelona, Gabinet Numismàtic de Catalunya.Arévalo González, A. (2002), “La moneda griega foránea en la Península Ibérica”, en Actas del X Congreso Nacional de Numismática, Madrid, Museo Casa de la Moneda, pp. 1-15.Babelon, E. C. F. (1901), Traité des monnaies grecques et romaine, vol. 1, Paris, Ernest Leroux Editeur.Benezet, J., Delhoeste, J. Lentillon, J.-P. (2003), “Une monnaie du “type d´Auriol” dans la plaine roussillonnaise”, Cahiers Numismatiques, 158, pp. 5-8.Blancard, M. (1870-1871), “Iconographie des monnaies du trésor d´Auriol acquises par le cabinet des médailles de Marseille”, en Mémoires del´Académie des Sciences, Belles-Lettre et Arts de Maseille, Marseille, Barlatier-Feissat Pére et fils, pp. 17-33.Blanchet, A. (1905), Traité des monnaies gauloises, vol. 1, Paris, Ernest Leroux Editeur.Campo Díaz, M. (1987), “Circulación de monedas massaliotas en la Península Ibérica (s. V-IV a. C.)”, en Mélanges offerts au docteur J. B. Colbert de Beaulieu, Paris, Leópard d`or, pp. 175-187.— (1997), “La moneda griega y su influencia en el contexto indígena”, en Historia monetaria de Hispania antigua, Madrid, Jesús Vico, pp. 19-49.— (2002), “Las emisiones de Emporion y su difusión en el entorno ibérico”, La monetazione dei Focei in Occidente, Atti dell´XI Convegno del Centro Internazionale di studi Numismatici, Roma, Istituto italiano di Numismatica, pp. 139-165.— (2003), “Les primeres imatges gregues: l´inici de les fraccionàries d´Emporion”, en VII Curs d´Història Monetaria d´Hispània. Les imatges monètaries: llenguatge i significat, Barcelona, Museu Nacional d´Art de Catalunya, pp. 25-45. Campo Díaz, M. y Sanmartí, E. (1994), “Nuevos datos para ña cronología de las monedas fraccionarias de Emporion: revisión del tesoro Neapolis-1926”, Huelva Arqueológica, 13, pp. 153-172.Chevillon, J. A. (2002), “Les monnaies archaïques d´Emporion dans le trésor d´Auriol”, Bulletin de la Société Française de Numismatique, 57, pp. 30-33.Chevillon, J. A., Bertaud, O. y Guernier, R. (2008), “Nouvelles données relatives au monnayage archaïque massaliète”, Revue Numismatique, 164, pp. 209-244.Chevillon, J. A. Ripollès, P. P. (2014), “The Greeck Far West: un exceptional adaptation of a design from Asia Menor with bull und lion foreparts”, Journal of the Numismatic Association of Australia, 25, pp. 44-46.Chevillon, J. A., Ripollès, P. P. y López, C. (2013), “Les têtes de taureau dans le mnnayage postarchaïque empuritain du V siècle av. J. C.”, OMNI. Revue Numismatique, 6, pp. 10-14. De Saucy, F., De Berthélemy, A. y Hucher, E. (1875), “Examen détaillée du trésor d´Auriol (Bouches-du-Rhone)”, en Mélanges de Numismatique 1, Paris, Le Mans, pp. 12-44.Furtwängler, A. E. (1971), “Remarques sur les plus anciennes monnaies frapées en Espagne”, Schweizer Münzblätter, 81, pp. 13-21.— (1978), Monnaies grecques en Gaule. Le trésor d´Auriol et le monnayage de Massalia 525/520-460 av. J. C., Fribourg.— (2002), “Monnaies grecques en Gaule: nouvelles trouvalles (6ème-5 ème s. av. J.-C.)”, en La monetazione dei Focei in Occidente. Atti dell`XI Convegno del Centro Internazionale di Studi Numismatici, Rome, Istituto italiano di Numismatica, pp. 93-11.García-Bellido, M. P. (1993), Las cecas libio-fenicias, Ibiza, Museu Arqueologic d´Eivissa e Formentera.— (1998), “La moneda griega de Iberia”, en Los griegos en España, Madrid, Ministerio de Cultura, pp. 158-178. — (2017), “Las copias de la moneda Tipo Auriol en el Golfo de León: foceos y nativos”, Gaceta Numismática, 194, pp. 3-14.Gozalbes Cravioto, E. (2014), “La economía monetaria en la provincia de Cuenca en la antigüedad”, E. Gozalbes Cravioto, J. A. Hernández Rubio y J. A. Almonacid Clavería (coords.), Cuenca: historia en sus monedas, Cuenca, Universidad de Castilla-La Mancha, pp. 55-84.— (2017a), “La ceca de Ikalesken y el problema de su localización”, Gaceta Numismática, 193, pp. 3-19.— (2017b), “Una pieza de Urkesken y la localización de la ceca”, Gaceta Numismática, 193, pp. 21-30.Gozalbes Fernández de Palencia, M. y Ripollès, P. P. (2002), “Nuevos hallazgos de monedas foráneas en el territorio de Arse-Saguntum”, en P. P. Ripollès y M. M. Llorens, Arse-Saguntum. Historia monetaria de la ciudad y su territorio, Sagunto, Fundación Bancaja, pp. 528-533.Gozalbes García, H. y Gozalbes Cravioto, E. (2017), “Une obole massaliote datant du Ve siècle av. J. C. sur le territoire de Cuenca (Espagne)”, Bulletin de la Société Française de Numismatique, 72.2, pp. 52-56.Guadán, A. M. (1968), Las monedas de plata de Emporion y Rhode vol. I, Barcelona, Ayuntamiento de Barcelona.— (1970), Las monedas de plata de Emporion y Rhode, vol. II, Barcelona, Ayuntamiento de Barcelona.Lambert, E. (1864), Essai sur la numismatique gauloise du Nord-Ouest de la France, Paris, Derache.Maurel, G. (2013), Corpus des monnaies de Marseille et Provence, Languedoc oriental et vallée du Rhone (520-20 av. notre ère), Montpellier, Omni, 2013.Omos, R. (1995), “Usos de la moneda en la Hispania prerromana y problemas de lectura iconográfica”, en M. P. García-Bellido y R. M. Centeno (eds.), La moneda hispánica. Ciudad y territorio, Madrid, Consejo Superior de Investigaciones Científicas, pp. 41-52.Planas Palau, A. y Martí Mañanes, A. (1991), Las monedas de otras cecas encontradas en Ibiza, Ibiza, Puig Castellar. Ripollès, P. P. (1982), La circulación monetaria en la Tarraconense mediterránea, Valencia, Federico Domenech. — (1985), “Las monedas del tesoro de Morella, conservadas en la B. N de París”, Acta Numismàtica, 19, (1985), pp. 47-64.— (1989), “Fracciones ampuritanas. Estado de la investigación”, Archivo de Prehistoria Levantina, 19,pp. 303-317.— (2005), “Las acuñaciones antiguas de la península Ibérica: dependencias e innovaciones”, en C. Alfaro, C. Marcos y P. Otero (coords.), Actas del XIII Congreso Internacional de Numismática, vol. 1, Madrid, Ministerio de Cultura, pp. 187-208.— (2011), “Cuando la plata se convierte en moneda: Iberia oriental”, en Barter, Money and Coinage in the Ancienr Mediterranean (10th-1st Centuries B.C.). Actas del IV Encuentro Peninsular de Numismátic Antigua, Madrid, Consejo Superior de Investigaciones Científicas, pp. 213-226.— (2013), “Ancient Iberian Coinage”, Documentos Digitales de Arqueología, 2, pp. 1-55.— (2015), “Los divisores ampuritanos con cabeza de carnero y puntos en el campo”, OMNI. Revue Numismatique, 9, pp. 13-16.Ripollès, P. P. Chevillon, J. A. (2013), “The Archaic coinage of Emporion”, The Numismatic Chronicle, 173, pp. 1-21.Ripollès, P. P. y Llorens, M. M. (2002), Arse-Saguntum. Historia monetaria de la ciudad y su territorio, Sagunto, Fundación Bancaja.Rodríguez Casanova, I. (2014), “El tesoro de Valeria: nuevas aportaciones sesenta años después”, en E. Gozalbes, J. A. Hernández Rubio y J. A. Almonacid (coords.), Cuenca: la Historia en sus monedas, Cuenca, Universidad de Castilla-La Mancha, pp. 85-106.Savès, G. (1976), Les monnaies gauloises à la croix, Toulouse, Privat, 1976.Villaronga, L. (1987), “Les oboles massaliotes à la roue et leurs imitations dans la Péninsule Ibérique”, en Mélanges offerts au docteur J. B. Colbert de Beaulieu, Paris, Leópard d`or, 1987, pp. 769-777.— (1995), “L´emissió emporitana amb cap de be i revers de creu puntejada de la segona meitat del segle V a.C.”, Acta Numismática, 25, (1995), pp. 17-33.— (1997), Monedes de plata emporitanes dels secles V-VI a. C., Barcelona, Leandre, 1997.— (2003), “La troballa de l´Emporà”, Acta Numismàtica, 33, pp. 15-46.Villaronga, L. Benages, J. (2011), Ancient Coinage of the Iberian Peninsula. Greek, Punic, Iberian, Roman, Barcelona, Societat Catalana d´Estudis Numismàtics, 2011 (citado como ACIP).
39
Yin, Changhong, Tae-Hoon Chung, Janet Ayello, Tae-Hyun Park, Carmella van de Ven, Mitchell S. Cairo, and Sanghoon Lee. "Overexpression Of Deleted In Lymphocytic Leukemia 1 (DLEU1) Significantly Induces Programmed Cell Death and Inhibits Cell Proliferation In Primary Mediastinal B-Cell Lymphoma (PMBL): DLEU1 May Be a Tumor Suppressor Gene In a Subset Of Patients With PMBL." Blood 122, no. 21 (November 15, 2013): 3852. http://dx.doi.org/10.1182/blood.v122.21.3852.3852.
Full textAbstract:
Abstract Background Primary Mediastinal large B-cell lymphoma (PMBL) is a rare form of Non Hodgkin Lymphoma (NHL) representing 2% of mature B-cell non-Hodgkin lymphoma in patients less than 18 years of age (Lones/Cairo et al., JCO, 2000; Burkhardt et al., BJH, 2005). PMBL has similar histo-pathological features along the biologic spectrum between Diffuse Large B-Cell Lymphoma (DLBCL) and classical HL (cHL) (Abramson et al., Blood, 2005). We have recently reported that a significantly decrease in EFS among children and adolescent PMBL patients compared with other stage III non-PMBL pediatric DLBCL patients following FAB/LMB96 therapy, suggesting that children and adolescent PMBL may be an inherently different B-NHL (Gerrard/Cairo et al., Blood, 2013). Nevertheless, the genetic mechanisms underlying the pathogenesis of PMBL remain unknown. Using high-resolution, microarray-based genomic techniques chromosomal losses at 13q14 was identified in 5 of the 37 (13%) PMBL tumor samples indicating localization of potential tumor suppressor genes at 13q that may be involved in the etiology of PMBL (Wessondorf, et al, Leuk., 2007). DLEU1 (Deleted in lymphocytic Leukemia 1) is a Burkitt lymphoma (BL) classifier gene (Dave et al., NEJM, 2006) and is located in the chromosome 13q14.3 region. DLEU1 interacts with 19 proteins including of c-Myc, RASSF1, TUBB2C and UBR1. DLEU1 has been implicated as a tumor suppressor in BL (Lee/Yin/Cairo et al., ASH, 2012) and in chronic lymphocytic leukemia (Garding et al., Plos Genet., 2013). Objectives We hypothesize that DLEU1 may act as a tumor suppressor gene through induction of caspase-3/7 activity thereby inhibiting cell proliferation and down-regulation of constitutively activated signaling pathways in PMBL. Methods The full length of cDNA encoding DLEU1 was fused into pEGFP-N3 vector and pEGFP-DLEU1fusion construct (Lee/Yin/Cairo et al., ASH, 2012) was transfected into Karpas-1106P cells using Amaxa Nucleofector kit, followed by the manufacturer’s instruction. Forty-eight hours post transient transfection, total RNA was extracted and 1ug of total RNA was used for cDNA synthesized as above. For comparison of mRNA expression of network genes, quantitative RT-PCR was performed by CFX96 Real-time (Bio-rad). The expression of DLEU1 protein in DLEU1 transient transfected Karpas-1106P cells was confirmed both by western blotting analysis and under fluorescent microscope. In brief, the total lysates was prepared from DELU1 transfected cells at 48hours post-transfection, and membrane was hybridized with Rabbit polyclonal DLEU1 antibody (ProteinTech) on immune blotting. MTS (Promega) and Caspase 3/7 assay (Promega) were employed to examine the effects on cell proliferation and apoptosis. Statistical significance was determined by one tailed paired Student t-test. Results The expression of DLEU1 mRNA in DLEU1 transiently transfected Karpas-1106P (DLEU1-Karpas) cells was significantly higher than empty vector alone transfected cell as mock control (78-fold increase, p<0.01). Comparing mRNA expression of DLEU1 network genes in DLEU1-Karpas cells to mock control cells, we observed a significant decrease in mRNA expression of the anti-apoptotic gene, Bcl-xL (73% reduction, p<0.01) and suppressors of cell signaling genes, SOCS1 and SOCS3 (52% reduction, p<0.05 and 44% reduction, p<0.01, respectively). There was a significant reduction in the mRNA expression of oncogenes, Pim-1 and c-Myc (72% reduction, p<0.04 and 54% reduction, p<0.03) respectively, in DLEU1-Karpas cells compared to mock control cells. Cell proliferation was significantly inhibited 18% (p<0.03) whereas Caspase 3/7 activity was significantly increased 1.5-fold (p<0.03) in DLEU1-Karpas cells at 48hours post transfection. Lastly, we found significant decreases of protein expression in phoshpho-Akt (67% reduction, p<0.01), phoshpho-ikBa (48% reduction, p<0.02), phoshpho-STAT3 (15% reduction, p<0.02) and c-Myc (25% reduction, p<0.01), respectively in DLEU1-Karpas cells. Conclusions We demonstrated that transient overexpression of DLEU1 1) significantly inhibits cell proliferation and induces programmed cell death, and 2) downregulates constitutively activated signaling pathways in PMBL, and therefore, DLEU1 may in part act as a tumor suppressor gene in a subset of patients with PMBL. Disclosures: No relevant conflicts of interest to declare.
40
Hapidin, Erie Siti Syarah, Yuli Pujianti, and Winda Gunarti. "Instilling Children's Ocean Literacy Through Comic Media: STEAM to R-SLAMET Learning Design for ECE educators." JPUD - Jurnal Pendidikan Usia Dini 16, no. 1 (April 30, 2022): 01–16. http://dx.doi.org/10.21009/jpud.161.01.
Full textAbstract:
Ocean literacy is currently at the forefront of the development of the notion of marine environmental sustainability. It is critical to compare ocean literacy ideas in curriculum standards. Comics Convey various messages of maritime insight content on integrated, contextual, and meaningful learning. This study aims to design STEAM (to R-SLAMET; Religion, Science, Literacy, Art, Math, Engineer, and Technology) learning that contains ocean literacy messages in a comic media. Through the qualitative research method with study case type, researchers seek to aid early childhood education (ECE) educators in designing R-SLAMET learning through the media to overcome maritime cultural literacy problems. The participants of this study consisted of three educators and 43 children. The findings show that the natural play experience of early childhood can be a source of inspiration to find ocean literacy through R-SLAMET learning activities. Contextual play by children becomes a reference for designing comic-based R-SLAMET learning. Comic media can integrate R-SLAMET learning in improving children's ocean literacy.
Keywords: children ocean literacy, comic media, STEAM to R-SLAMET learning design
References:
Arthur, J. (1990). Cultural Literacy. College English, 52(3), 281–281. JSTOR. https://doi.org/10.2307/377758
Campbell, D. T., & Stanley, J. C. (2015). Experimental and Quasi-Experimental Designs for Research. Ravenio Books. https://books.google.co.id/books?id=KCTrCgAAQBAJ
Castek, E. J., Hagerman, M. S., Woodard, R., Bonine, K., Coiro, J., Graville, C., Jordan, M., Mencher, R., Olivares, M., Smith, B. E., Stornaiuolo, A., Sult, L., Tan, E., Tucker-raymond, E., & Wen, W. (2019). Principles for Equity-centered Design of STEAM Learning-through-Making. 34–35.
Chang, C.-C., Hirenkumar, T. C., & Wu, C.-K. (2021). The Concept of Ocean Sustainability in Formal Education—Comparative Ocean Literacy Coverage Analysis of the Educational Standards of India and the USA. Sustainability, 13(8), 4314. https://doi.org/10.3390/su13084314
Chujan, W., Kilenthong, W. T., Patricia, A., Robert, J., Richard, C., Charles, D., John, D., Jere, E., Leslie, A., Jerome, S., Robert, C., Bancroft, K., Lee, J., Carol, S., Lees, N., Mills, R., Haley, S., Eleanor, E., Robert, P., … Erden, F. T. (2019). An early evaluation of a HighScope-based curriculum intervention in rural Thailand. International Journal of Innovation, Creativity and Change, 12(103), 17–25. https://doi.org/10.7822/omuefd.604939
Creswell, J. W. (2015). Educational research: Planning, conducting, and evaluating quantitative and qualitative research (Fifth edition). Pearson.
Fortner, R. W., & Mayer, V. J. (1989). Marine and aquatic education – a challenge for science educators. Science Education, 73(2), 135–154. https://doi.org/10.1002/sce.3730730203
Hapidin, Gunarti, W., Pujianti, Y., & Siti Syarah, E. (2020). STEAM to R-SLAMET Modification: An Integrative Thematic Play Based Learning with R-SLAMETS Content in Early Child-hood Education. JPUD - Jurnal Pendidikan Usia Dini, 14(2), 262–274. https://doi.org/10.21009/jpud.142.05
Hapidin, Nurjannah, S. H. (Universitas N. J. (2018). Pengembangan Model Pembelajaran Tematik Seribu. Pendidikan Usia Dini, 12(Marine Education), 51–65. https://doi.org/10.21009/JPUD.121
Hartley, B. L., Thompson, R. C., & Pahl, S. (2015). Marine litter education boosts children’s understanding and self-reported actions. Marine Pollution Bulletin, 90(1), 209–217. https://doi.org/10.1016/j.marpolbul.2014.10.049
Hawthorne, M., & Alabaster, T. (1999). Citizen 2000: Development of a model of environmental citizenship. Global Environmental Change, 9(1), 25–43. https://doi.org/10.1016/S0959-3780(98)00022-3
Hermawanti, O., & Susilaningsih, S. (2020). Development of Educational Comic Media Based on PowerPoint Class III Indonesian Language Content. Elementary School Teacher, 4(2), 5. https://doi.org/10.15294/est.v4i2.29027
Hidayat, S., & Ridwan. (2017). Kebijakan poros maritim dan keamanan nasional indonesia: Tantangan dan harapan. Pertahanan & Bela Negara, 7(3), 107–121.
Koutníková, M. (2018). The Application of Comics in Science Education. Acta Educationis Generalis, 7(3), 88–98. https://doi.org/10.1515/atd-2017-0026
Melliou, K., Moutafidou, A., & Bratitsis, T. (2014). Digital Comics Use to Develop Thinking Dispositions in Early Childhood Education. 2014 IEEE 14th International Conference on Advanced Learning Technologies, 502–504. https://doi.org/10.1109/ICALT.2014.148
Mogias, A., Boubonari, T., Realdon, G., Previati, M., Mokos, M., Koulouri, P., & Cheimonopoulou, M. Th. (2019). Evaluating Ocean Literacy of Elementary School Students: Preliminary Results of a Cross-Cultural Study in the Mediterranean Region. Frontiers in Marine Science, 6, 396. https://doi.org/10.3389/fmars.2019.00396
Mokos, M., Realdon, G., & Zubak Čižmek, I. (2020). How to Increase Ocean Literacy for Future Ocean Sustainability? The Influence of Non-Formal Marine Science Education. Sustainability, 12(24). https://doi.org/10.3390/su122410647
Ntobuo, N. E., Arbie, A., & Amali, L. N. (2018). The Development of Gravity Comic Learning Media Based on Gorontalo Culture. Jurnal Pendidikan IPA Indonesia, 7(2), 246–251. https://doi.org/10.15294/jpii.v7i2.14344
Oliver, K. L. (1998). A Journey into Narrative Analysis: A Methodology for Discovering Meanings. Journal of Teaching in Physical Education, 17(2), 244–259. https://doi.org/10.1123/jtpe.17.2.244
Pramitasari, M., Yetti, E., & Hapidin, H. (2018). Pengembangan Media Sliding Book Untuk Pengenalan Sains Kehidupan (Life Science) Kelautan Untuk Anak Usia 6-7 Tahun. JPUD - Jurnal Pendidikan Usia Dini, 12(2), 281–290. https://doi.org/10.21009/jpud.122.09
Puspitorini, R., Prodjosantoso, A. K., Subali, B., & Jumadi, J. (2017). Penggunaan Media Komik Dalam Pembelajaran Ipa Untuk Meningkatkan Motivasi Dan Hasil Belajar Kognitif Dan Afektif. Jurnal Cakrawala Pendidikan, 3(3). https://doi.org/10.21831/cp.v3i3.2385
Rahmatullah, R., Inanna, I., Rakib, M., Mustari, M., & Rabania, R. (2020). Developing Tematic Economic Comic with Characters for Early Childhood. Journal of Educational Science and Technology (EST), 293–300. https://doi.org/10.26858/est.v6i3.14949
Rina, N., Suminar, J. R., Damayani, N. A., & Hafiar, H. (2020). Character education based on digital comic media. International Journal of Interactive Mobile Technologies, 14(3), 107–127. https://doi.org/10.3991/ijim.v14i03.12111
Santoro, F., Santin, S., Gail, S., Fauville, G., & Tuddenham, P. (2017). Ocean Literacy for All; A toolkit. UNESCO United Nations Educational.
Steel, B. S., Smith, C., Opsommer, L., Curiel, S., & Warner-Steel, R. (2005). Public ocean literacy in the United States. Ocean & Coastal Management, 48(2), 97–114. https://doi.org/10.1016/j.ocecoaman.2005.01.002
Syarah, E. S., Yetti, E., Fridani, L., Yufiarti, Hapidin, & Pupala, B. (2019). Electronic comics in elementary school science learning for marine conservation. Jurnal Pendidikan IPA Indonesia, 8(4), 500–511. https://doi.org/10.15294/jpii.v8i4.19377
Tatalovic, M. (2009). Science comics as tools for science education and communication: A brief, exploratory study. Journal of Science Communication, 8(4).
Tuddenham, P., Schoedinger, S., Cava, F., & Strang, C. (2005). Science Content and Standards for Ocean Literacy: A Report on Ocean Literacy. https://doi.org/10.13140/RG.2.2.12126.84804
Visbeck, M. (2018). Ocean science research is key for a sustainable future. Nature Communications, 9(1), 690. https://doi.org/10.1038/s41467-018-03158-3
Yulianti, D., Khanafiyah, S., & Sulistyorini, S. (2016). Inquiry-Based Science Comic Physics Series Integrated with Character Education. 7.
Yunandar, Y. (2018). Budaya Bahari Dam Tradisi Nelayan di Indonesia. Sabda: Jurnal Kajian Kebudayaan, 1(1), 22. https://doi.org/10.14710/sabda.v1i1.13243
41
Dimogiannis, Konstantinos, Andrzej Sankowski, Conrad Holc, Graham Newton, Darren Anthony Walsh, James O'Shea, Andrei Khlobystov, and Andrzej Sankowski. "Understanding the Mg Cycling Mechanism on a MgTFSI-Glyme Electrolyte." ECS Meeting Abstracts MA2022-01, no. 4 (July 7, 2022): 574. http://dx.doi.org/10.1149/ma2022-014574mtgabs.
Full textAbstract:
The Magnesium battery is considered a potential a high energy, sustainable successor to the lithium-ion battery, due to an almost two-fold increase in the volumetric capacity of magnesium compared to lithium (Li), decreased probability of dendritic growth, cheaper raw material costs, and high natural abundance.[1]–[3] Current electrolytes have been found to be insufficiently stable towards the Mg electrode, leading to reduction of the electrolyte and formation of a solid electrolyte interphase (SEI), which is believed to be detrimental to performance.[4]–[6] Our previous study [7] indicated a cycling mechanism at Mg surface in a Mg(TFSI)2-based electrolyte occurring through Mg deposits and an evolution of interphase chemistry during conditioning that is critical for stable cycling in the Mg(TFSI)2-glyme electrolyte. However, unlike Li metal batteries,[8], [9] where the Li plating and nucleation mechanism has been studied in depth, this is not the case for Mg batteries. In this study, we have combined electrochemical analysis with state-of-the-art cryo-focus ion beam scanning electron microscopy (FIB-SEM) and energy-dispersive X-ray spectroscopy (EDX), aiming to give insight into the Mg nucleation & growth mechanism. In doing so, we are able to reveal the detailed chemical and structural composition of the Mg deposits for the first time. Our studies are performed in Mg(TFSI)2-tetraglyme electrolyte as the leading base electrolyte for the battery. By linking the structure of Mg deposits to their state of charge and cycling performance, we can conclusively demonstrate the origin of the high overpotential in the battery. In addition, we show how Mg is reversibly plated and stripped within the deposit and demonstrate how the structure and size of the Mg deposit fluctuates to accommodate this process. Image caption: Electron microscopy images of the cross -section of a Mg particle after discharge etched using cryo-FIB-SEM, showing. a) secondary electron images of the exposed cross-section and b) In lens secondary electron images highlighting the distinct regions of the particle: Mg-rich inner core, MgO-rich outer core and interphase. References: [1] G. N. Newton, L. R. Johnson, D. A. Walsh, B. J. Hwang, and H. Han, ACS Sustain. Chem. Eng., vol. 9, no. 19, pp. 6507–6509, May 2021 [2] M. Fichtner, Magnesium Batteries: Research and Applications, vol. 2020, no. 23. Royal Society of Chemistry, 2019 [3] J. W. Choi and D. Aurbach, Nat. Rev. Mater., vol. 1, no. 4, p. 16013, 2016 [4] J. Muldoon, C. B. Bucur, and T. Gregory, Chem. Rev., vol. 114, no. 23, pp. 11683–11720, Dec. 2014 [5] A. Ponrouch, J. Bitenc, R. Dominko, N. Lindahl, P. Johansson, and M. R. Palacin, Energy Storage Mater., vol. 20, no. pp. 253–262, Feb. 2019 [6] R. Attias, M. Salama, B. Hirsch, Y. Goffer, and D. Aurbach, Joule, vol. 3, no. 1, pp. 27–52, 2019 [7] C. Holc, K. Dimogiannis, E. Hopkinson, and L. R. Johnson, ACS Appl. Mater. Interfaces, vol. 13, no. 25, pp. 29708–29713, Jun. 2021 [8] Z. Yu et al. Nat Energy, vol 5, pp.526–533 Jun. 2020 [9] B. Liu, J. G. Zhang and W. Xu, Joule, vol 2, no. 16, pp. 833-845, May 2018 Figure 1
42
Antonczak, Laurent, Marion Neukam, and Sophie Bollinger. "When industry meets academia." Pacific Journal of Technology Enhanced Learning 4, no. 1 (February 1, 2022): 14–16. http://dx.doi.org/10.24135/pjtel.v4i1.134.
Full textAbstract:
This presentation focuses on a transdisciplinary approach to innovative and collaborative learning practices driven by technology. It highlights two salient elements associated with industry practices and processes in relation to learning and educational contexts: empowerment of individuals and communities of practice through technology, and a broader consideration of industrial approaches to the concept of learning and teaching enhanced within a digital environment.
More precisely, this presentation will feature some of the key theoretical frameworks used in three different settings of learning and teaching in France with regards to the life-long learning approach thanks to Social and Emotional Learning (SEL) (WEF, 2016). It will also discuss the positive effect of the Internet and its affordances (Southerton & Taylor, 2020) on reducing the differences between theoretical and applied knowledge via professional-focused communities (Danvers, 2003). Thus, it will briefly explain that spatial and cognitive learning proximities (Lave & Wenger 1991; Fruchter, 2001) can be reduced by virtue of technology (Anders, 2016; Antonczak, 2019; Glazewski & Hmelo-Silver, 2019) and that ‘computer-supported collaborative learning’ methods can facilitate social and shared problem-solving (Sawyer, 2005; Levallet & Chan, 2018; Presicce et al., 2020) without the ‘restriction of time and place’ (Cheng et al., 2019, 489). Additionally, it will point out some aspects of problem-solving through ‘emancipatory learning and social action’ (Merriam, 2001, 9) through the use of ‘actual’ content and ‘actionable feedback’ (Woods & Hennessy, 2019) enhanced by digital tools and tactics.
Next, it will focus on three case studies by concisely presenting key specifics for each of the courses, including the various digital tools used and followed by some quick interim reflections.
Then it will summarise the challenges and the barriers encountered across the different practices such as virtual delivery, the size of the students' groups and some connectivity considerations. It will be followed by the principal advantages and opportunities, like the professionalisation dimension through interactive and authentic learning enhanced by affordances. And it will conclude with some managerial recommendations as experiential and practical methods (knowledge codification) thanks to industry-based teaching supported by digital technologies.
The presentation will close with the overall conclusion in relation to digital technology and some of the key 21st-century career skills. In general, the findings will be of interest to academics, practitioners and policymakers. The added value of this transdisciplinary investigation is that it improves research on collaborative innovation and collective knowledge by creating a bridge between the fields of Education and Business.
Bibliography
Anders, A. (2016). Team communication platforms and emergent social collaboration practices. International Journal of Business Communication, 53(2), pp. 224-261.
Ananiadou, K. & M. Claro (2009). 21st Century Skills and Competences for New Millennium Learners in OECD Countries, OECD Education Working Papers, No. 41, OECD Publishing.
Antonczak, L. (2019). Scaling-up collaborative practices through mobile technology. The 25th International Conference on Engineering/International Technology Management Conference (ICE/ITMC), June 17-19, Nice.
Askay, D. A. & Spivack, A. J. (2010). The multidimensional role of trust in enabling creativity within virtual communities of practice: A theoretical model integrating swift, knowledge-based, institution-based, and organizational trust. In 43rd Hawaii International Conference on System Sciences, Hawaii, pp. 1-10.
Cairns, L. (2000). The process/outcome approach to becoming a capable organization. In Australian Capability Network Conference, Sydney, 1-14.
Cheng, E. W., Chu, S. K., & Ma, C. S. (2019). Students’ intentions to use PBWorks: a factor-based PLS-SEM approach. Information and Learning Sciences, 120(7/8), 489-504.
Cochrane, T., Antonczak, L., Guinibert, M., Mulrennan, D., Rive, V., & Withell, A. (2017). A framework for designing transformative mobile learning. In Mobile Learning in Higher Education in the Asia-Pacific Region ( 25-43). Springer, Singapore.
Danvers, J. (2003). Towards a radical pedagogy: Provisional notes on learning and teaching in art & design. International Journal of Art & Design Education, 22(1), 47-57.
Dewey, J. (1991). Logic: The theory of inquiry. In J. A. Boydston (Ed.), John Dewey: The Later Works, 1925–1953, Vol. 12 (1-5). Carbondale, IL: SIU Press. [Originally published in 1938]
Dziuban, C., Graham, C. R., Moskal, P. D., Norberg, A., & Sicilia, N. (2018). Blended learning: the new normal and emerging technologies. International Journal of Educational Technology in Higher Education, 15(1), 1-16.
Fruchter, R. (2001). Dimensions of teamwork education. International Journal of Engineering Education, 17(4/5), 426-430.
Glazewski, K. D., & Hmelo-Silver, C. E. (2019). Scaffolding and supporting the use of information for ambitious learning practices. Information and Learning Sciences, 120(1/2), 39-58.
Hase, S. & Kenyon, C. (2007). Heutagogy: A child of complexity theory. Complicity: An International Journal of Complexity and Education, 4(1), 111-119.
Lave, J. & Wenger, E. (1991). Situated Learning: Legitimate Peripheral Participation. Cambridge: Cambridge University Press.
Levallet, N., & Chan, Y. E. (2018). Role of Digital Capabilities in Unleashing the Power of Managerial Improvisation. MIS Quarterly Executive, 17(1), 1-21.
Lewin, K. (1947). Group decision and social change. Readings in Social Psychology, 3(1), 197-211.
McKenney, S., & Reeves, T. C. (2013). Systematic review of design-based research progress: Is a little knowledge a dangerous thing?. Educational Researcher, 42(2), 97-100.
Makri, S., Ravem, M., & McKay, D. (2017). After serendipity strikes: Creating value from encountered information. Proceedings of the Association for Information Science and Technology, 54(1), 279-288.
Mascheroni, G., & Vincent, J. (2016). Perpetual contact as a communicative affordance: Opportunities, constraints, and emotions. Mobile Media & Communication, 4(3), 310-326.
Merriam, S. B. (2001). Andragogy and self-directed learning: Pillars of adult learning theory. New Directions for Adult and Continuing Education, 89, 3-13.
Pont, B. (2013). Learning Standards, Teaching Standards and Standards for School Principals: A Comparative Study. Rapport no. EDU/WKP(2013)14. Centre of Study for Policies and Practices in Education (CEPPE). Retrieved from: http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=EDU/WKP(2013)14&docLanguage=En (accessed December 31, 2020).
Presicce, C., Jain, R., Rodeghiero, C., Gabaree, L. E., & Rusk, N. (2020). WeScratch: an inclusive, playful and collaborative approach to creative learning online. Information and Learning Sciences, 121(7/8), 695-704.
Reeves, T. C. (2005). Design-based research in educational technology: Progress made, challenges remain. Educational Technology, 45(1), 48-52.
Southerton, C., & Taylor, E. (2020). Habitual disclosure: Routine, affordance, and the ethics of young peoples social media data surveillance. Social Media+ Society, 6(2), https://doi.org/10.1177/2056305120915612
43
Thompson, Michael A., Brent A. Bauer, Laura L. Loehrer, Stephen S. Cha, Jayawant N. Mandrekar, Amit Sood, and Dietland L. Wahner-Roedler. "Double-Blind, Placebo-Controlled, Randomized Clinical Trial of the Effect of the Dietary Supplement S-Adenosyl-L-Methionine (AdoMet) on Plasma Homocysteine (Hcy) Levels in Healthy Human Subjects." Blood 108, no. 11 (November 16, 2006): 1481. http://dx.doi.org/10.1182/blood.v108.11.1481.1481.
Full textAbstract:
Abstract BACKGROUND: S-adenosyl-L-methionine (AdoMet or SAM-e®) is a commonly used nutritional supplement available in the United States since 1999. AdoMet is metabolized to homocysteine (Hcy), a potential cardiovascular risk factor. A few open-label, single-arm studies have reported on the effect of exogenous AdoMet on the levels of Hcy in humans; however, this has not been tested in a double-blind, randomized clinical trial. As a nutritional supplement, AdoMet is subject only to limited regulation by the FDA, despite being used to treat clinical diseases such as depression and osteoarthritis. AdoMet is the methyl donor for small molecule, DNA, RNA, and protein methylation reactions; therefore, further understanding the biology of the AdoMet/Hcy system is important. We hypothesized that exogenous AdoMet would increase plasma Hcy levels. METHODS: In a double-blind, placebo-controlled, randomized clinical trial, 93 healthy human subjects were screened and 52 were treated with placebo (26) or 800 mg per day AdoMet (26) pills for 4 weeks. Pre- and post-treatment Hcy levels were measured. The primary endpoint was change in Hcy level. Secondary endpoints included an interim Hcy level, high sensitivity C-reactive protein (hsCRP) levels, lipid profile, and transaminases. Exclusion criteria included pregnancy and concurrent use of medications associated with changes in Hcy. RESULTS: Of 52 subjects enrolled, 45 were evaluable at the end of treatment. Subject characteristics and dropout rates were similar between placebo and control groups. Adverse events were minor and were not different between placebo and AdoMet. The primary endpoint, change in Hcy, was not significantly different between the groups (mean (umol/L), baseline: 7.43 (placebo), 8.25 (AdoMet), P=0.358; 4 week: 7.66 (placebo), 8.06 (AdoMet), P = 0.683; Baseline − 4 week: 0.23 (placebo), −0.19 (AdoMet), P = 0.427). No statistically significant difference in change in Hcy or hsCRP at 2 or 4 weeks was noted. This was true for both absolute differences as well as relative percent changes. A small decrease in ALT was observed at 2 weeks in the AdoMet group compared to the placebo group (P = 0.027). AdoMet is used in the treatment of liver diseases. There was a small, but statistically significant (P = 0.028) decrease in total cholesterol in the AdoMet group as compared to the placebo group. Interestingly, a subject with the highest baseline Hcy level had a decline in Hcy on AdoMet. Study limitations include no evaluation of AdoMet serum levels or measurement of the effect of AdoMet on DNA methylation patterns. CONCLUSIONS: AdoMet seems well tolerated and in a dose of 800 mg/day for 4 weeks does not appear to significantly affect Hcy levels in the blood. Future clinical trials of AdoMet should monitor Hcy levels with extended use of AdoMet to confirm its safety with long term use. Clinicaltrials.gov ID: NCT00284011.
44
Diana Putri Amalia. M, Elindra Yetti, and Tjipto Sumadi. "Motions and Songs to Improve Basic Literacy through Animation Videos." JPUD - Jurnal Pendidikan Usia Dini 16, no. 2 (November 30, 2022): 224–39. http://dx.doi.org/10.21009/jpud.162.03.
Full textAbstract:
The government incurs huge costs because of low literacy rates, which are associated with higher crime rates, poor health, and higher welfare costs, therefore the stimulation of basic literacy from an early age is important. This study aims to examine the effectiveness of animated motion learning media and songs that are interesting, innovative, and effective for improving basic literacy aspects of early childhood. This mixed-method design with the research and development stages of the ADDIE model was tested for the effectiveness of the media through a paired sample test. The research was divided into three stages, starting from needs analysis, product development, and product evaluation, involving 11 respondents in the effectiveness test. The data collection technique was carried out using a basic literacy instrument grid questionnaire, for child development, while for the feasibility of the media or products being developed it was also through a questionnaire from experts. Data were analyzed qualitatively and quantitatively. The results of the study show that there is a significant increase in basic literacy values through learning media. The findings of the integration of quantitative and qualitative data form the basis for preparing the final product to revise and complement the deficiencies of movement and song-learning media.
Keywords: basic literacy, animation media, motion, and song, early childhood
References:
Abidin, Y. (2015). Multiliteracy Learning An Answer to the Challenges of 21st Century Education in the Indonesian Context [Pembelajaran Multiliterasi Sebuah Jawaban atas Tantangan Pendidikan Abad Ke -21 dalam Konteks Keindonesiaan (D. Sumayyah, Ed.)]. PT Refika Aditama.
Bedard, C., Bremer, E., & Cairney, J. (2020). Evaluation of the Move 2 Learn program, a community-based movement and pre-literacy intervention for young children. Physical Education and Sport Pedagogy, 25(1), 101–117. https://doi.org/10.1080/17408989.2019.1690645
Bers, M. U. (2018). Coding, playgrounds, and literacy in early childhood education: The development of KIBO robotics and ScratchJr. 2018 IEEE Global Engineering Education Conference (EDUCON), 2094–2102.
Bhadra, A., Brown, J., Ke, H., Liu, C., Shin, E., Wang, X., & Kobsa, A. (2016). ABC3D - Using an Augmented Reality Mobile Game to Enhance Literacy in Early Childhood. 0–3.
Dodge, D. T., Colker, L. J., & Heroman, C. (2002). Creative Curriculum for Presschool (Fourth Edi). Cataloging in Publication.
Edwards, L. C. (2013). Music and Movement A way of Life for the Young Child (Seventh Ed). Pearson Education, Inc.
Fadillah, M., Filasofa, L. M. K., Wantini, Akbar, E., & Fauziyah, S. (2014). Early Childhood Education Edutainment (Creating Interesting, Creative, and Fun Learning) [Edutaintment Pendidikan Anak Usia Dini (Menciptakan Pembelajaran Menarik, Kreatif, dan Menyenangkan)]. Kencana Prenadamedia Group.
Fajriyah, L. (2018). Development of Emergent Literacy in Early Childhood [Pengembangan Literasi Emergen Pada Anak Usia Dini]. Proceedings of the ICECRS, 1(3). https://doi.org/10.21070/picecrs.v1i3.1394
Fox, J. E., & Schirrmacher, R. (2015). Art & Creative Development for Young Children (Eighth Edi). Cengage Learning.
Graber, K. C., & Woods, A. M. (2013). Physical Education & Activity for Elementary Classroom Teachers. Mc Graw Hill.
Heydon, R., McKee, L., & O’Neill, S. (2018). Singing our song: The affordances of singing in an intergenerational, multimodal literacy programme. Literacy, 52(3), 128–136. https://doi.org/10.1111/lit.12135
Jamaris, M. (2017). Multiple Intelligences Measurement [Pengukuran Kecerdasan Jamak]. Ghalia Indonesia.
Juniasih, I. (2015). Increasing Movement Creativity Through Story-Based Educational Dance Activities (Tarita) PAUD PPs Jakarta State University [Peningkatan Kreativitas Gerak Melalui Kegiatan Tari Pendikan Berbasis Cerita ( Tarita ) PAUD PPs Universitas Negeri Jakarta]. Jurnal Pendidikan Usia Dini, 9(2), 319–342.
Karaca, N. H. (2017). Implementation Of Thinking Creatively in Action And Movement Test For Turkish Children Eylem Ve Harekette Yaratıcı Düşünme Testi’nin Türk Çocuklarına Uyarlanması. Mehmet Akif Ersoy Üniversitesi Eğitim Fakültesi Dergisi, 0(42), 240. https://doi.org/10.21764/efd.26968
Lastari, A. A. I. I. A., Gading, I. K., & Antara, P. A. (2016). Audiovisual to Improve Kinesthetic Intelligence in Group B Children [Audiovisual Untuk Meningkatkan Kecerdasan Kinestetik Pada Anak Kelompok B]. Journal Pendidikan Anak Usia Dini Universitas Pendidikan Ganesha, 4(2).
Mariati, P., & Asmara, B. (2017). Development of Innovative Learning Models of Motion and Thematic Songs for Integrated Early Childhood Post Teachers (Ppt) in the City of Surabaya [Pengembangan Model Pembelajaran Inovatif Gerak Dan Lagu Tematik Bagi Guru Pos Paud Terpadu ( Ppt ) Di Kota Surabaya]. Jurnal Anak Usia Dini Dan Pendidikan Anak Usia Dini, 3, 9–20.
Mayesky, M. (2002). Creative activities for Young Children (7 Th Editi). Delmar Thomson Learning.
Nash, K., Howard, J., Miller, E., Boutte, G., Johnson, G., & Reid, L. (2018). Critical racial literacy in homes, schools, and communities: Propositions for early childhood contexts. Contemporary Issues in Early Childhood, 19(3), 256–273. https://doi.org/10.1177/1463949117717293
Pogue, B. J. (2018). Using Music and Movement to Enhance Cognitive Development Using Music and Movement to Enhance Cognitive Development. Education.
Priansa, D. J. (2017). Development of Innovative, Creative, and Achievement Learning Strategies & Models in Understanding Students [Pengembangan Strategi & Model Pembelajaran Inovatif, Kreatif, dan Prestatif dalam Memahami Peserta Didik]. Pustaka Setia.
Rakhmawati, N. I. S. (2016). The Use of Playing Strategy through Movements and Songs in Dealing Hypersensitivity Problems for Early Childhood. Proceedings of International Research Clinic & Scientific Publications of Educational Technology, 2013, 6–29.
Rasi, P., Vuojärvi, H., & Ruokamo, H. (2019). Media Literacy for All Ages. Journal of Media Literacy Education, 11(2), 1–19. https://doi.org/10.23860/jmle-2019-11-2-1
Respati, R., Nur, L., & Rahman, T. (2018). Motion and Song as a Model for Stimulating the Development of Kinesthetic Intelligence in Early Children [Gerak Dan Lagu Sebagai Model Stimulasi Pengembangan Kecerdasan Kinestetik Anak Usia Dini]. Jurnal Pendidikan Usia Dini, Vol.12(No.2), 321–330. https://doi.org/10.21009/JPUD.122.13
Rowe, M. L., Kirby, A. L., Dahbi, M., & Luk, G. (2022). Promoting Language and Literacy Skills through Music in Early Childhood Classrooms. The Reading Teacher, n/a(n/a). https://doi.org/10.1002/trtr.2155
Ruhaena, L. (2015). Multisensory Models: Solutions to Stimulate Literacy in Preschool Children [Model Multisensori: Solusi Stimulasi Literasi Anak Prasekolah]. Jurnal Psikologi, 42(1), 47–60.
Safitri, N., & Agustinus. (2017). Stimulation Dance Creations Art on Gross Motor Development Children Aged. Indonesian Journal of Early Childhood Education Studies, 6(1). https://doi.org/10.15294/ijeces.v6i1.15785
Tomblin, J. B., Oleson, J., Ambrose, S. E., Walker, E. A., & Moeller, M. P. (2018). Early Literacy Predictors and Second-Grade Outcomes in Children Who Are Hard of Hearing. Child Development, 91(1), e179–e197. https://doi.org/10.1111/cdev.13158
Tomblin, J. B., Oleson, J., Ambrose, S. E., Walker, E. A., & Moeller, M. P. (2020). Early Literacy Predictors and Second-Grade Outcomes in Children Who Are Hard of Hearing. Child Development, 91(1), e179–e197. https://doi.org/10.1111/cdev.13158
Trost, W. J., Labbé, C., & Grandjean, D. (2017). Rhythmic entrainment as a musical affect induction mechanism. Neuropsychologia, 96, 96–110. https://doi.org/10.1016/j.neuropsychologia.2017.01.004
Widhianawati, N. (2011). The Effect of Movement and Song Learning in Improving Musical Intelligence and Kinesthetic Intelligence in Early Children [Pengaruh Pembelajaran Gerak dan Lagu dalam Meningkatkan Kecerdasan Musikal dan Kecerdasan Kinestetik Anak Usia Dini]. Jurnal Upi Edu, 2, 220–228.
Yetti, E., & Muanivah, H. (2017). Improved Intelligence Kinesthetic Children Ages 5-6 Years through Activities of Motion and Song. 1, 16–20.
Yetti, E., Syafnita, T., & Siti Syarah, E. (2019). The Effect of Motion and Song on Children`s Speaking Ability. 178(ICoIE 2018), 429–433. https://doi.org/10.2991/icoie-18.2019.92
45
Dreo, B., D. R. Pietsch, R. Husic, A. Lackner, J. Fessler, J. Rupp, A. S. Muralikrishnan, J. Thiel, M. Stradner, and P. Bosch. "POS1063 STAT PHOSPHORYLATION AS A MARKER FOR DISEASE ACTIVITY IN PATIENTS WITH PSORIATIC ARTHRITIS: AN EXPLORATIVE ANALYSIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 854.1–854. http://dx.doi.org/10.1136/annrheumdis-2022-eular.767.
Full textAbstract:
BackgroundNumerous cytokines that influence disease activity in psoriatic arthritis (PsA) are modulators of the Janus Kinases/Signal Transducers and Activators of Transcription (JAK/STAT) pathway. The JAK1/STAT1/STAT3/STAT5 network can drive the expansion of Th17 and regulatory T cells via proinflammatory cytokines in PsA joints,[1], [2] while hyperphosphorylation of STAT3 in immune cells has previously been shown to promote PsA pathogenesis through the Interleukin (IL)-23/IL-17/IL-22 axis.[3] Therefore, the phosphorylation status of STAT molecules in leucocytes of PsA patients may indicate active disease and could potentially guide treatment with JAK inhibitors.ObjectivesTo analyse phosphorylated STAT (pSTAT) levels of circulating leucocyte subsets in PsA patients with active and inactive diseaseMethodsWhole blood was drawn on consecutive PsA patients fulfilling the CASPAR criteria[4] to perform flow cytometry analysis using the BD FACSLyric platform. Disease activity was assessed using the Disease activity for psoriasis arthritis (DAPSA) score.[5] All steps from storage of drawn blood to cell fixation were performed at 4°C to prevent auto-activation of leucocytes. The geometric mean fluorescence intensities (gMFI) of pSTATs in granulocytes, monocytes, B cells and CD4+/- naïve/memory T cells were compared between patients with moderate to high (MoDA/HDA) and remission to low disease activity (REM/LDA). Correlation analysis between gMFIs and DAPSA scores were performed.ResultsForty-two patients (female ratio: 0.48) with established PsA (median ± standard deviation, age: 56 ± 12.54 years, disease duration: 8.50 ± 7.10 years) were included in this study. Twenty-one percent of patients were in MoDA/HDA, while the remaining 79% were in REM/LDA. Patients in MoDA/HDA showed significantly higher pSTAT3 levels in CD4+ naïve (gMFI median ± standard deviation: 284.5 ± 79.9 vs 238 ± 92.9, p = 0.011), CD4- naïve (297 ± 107.5 vs 238 ± 98.4, p = 0.04), CD4+ memory (227 ± 62.9 vs 190.5 ± 72.2, p = 0.009) and CD4- memory T cells (209 ± 66.8 vs 167.0 ± 64.9, p = 0.036). On the other hand, PsA patients in remission or low disease activity displayed higher pSTAT1 levels in granulocytes (2509 ± 1887 vs 1330.5 ± 784.1, p = 0.040) and monocytes (255 ± 230 vs 144 ± 62.5, p = 0.049). Positive correlations were found between DAPSA scores and pSTAT3 in CD4+ naïve and memory T cells (Spearman’s correlation coefficient rho (ρ) = 0.5, p = 0.0012 and ρ = 0.47, p = 0.0025 resp.) whereas pSTAT1 in granulocytes and monocytes were negatively correlated with the DAPSA scores (ρ = -0.45, p = 0.0074 and ρ = -0.34, p = 0.05).ConclusionDifferential phosphorylation of STAT3 and STAT1 molecules in circulating leucocyte subsets indicates PsA disease activity. Further studies to examine the value of STAT phosphorylation patterns guiding JAK inhibitor therapy are underway.References[1]U. Fiocco et al., “Ex vivo signaling protein mapping in T lymphocytes in the psoriatic arthritis joints,” J. Rheumatol., vol. 93, pp. 48–52, 2015, doi: 10.3899/jrheum.150636.[2]S. K. Raychaudhuri, C. Abria, and S. P. Raychaudhuri, “Regulatory role of the JAK STAT kinase signalling system on the IL-23/IL-17 cytokine axis in psoriatic arthritis,” Ann. Rheum. Dis., vol. 76, no. 10, pp. e36–e36, 2017.[3]E. Calautti, L. Avalle, and V. Poli, “Psoriasis: A STAT3-centric view,” International Journal of Molecular Sciences, vol. 19, no. 1. MDPI AG, Jan. 06, 2018, doi: 10.3390/ijms19010171.[4]W. Taylor, D. Gladman, P. Helliwell, A. Marchesoni, P. Mease, and H. Mielants, “Classification criteria for psoriatic arthritis: Development of new criteria from a large international study,” Arthritis Rheum., vol. 54, no. 8, pp. 2665–2673, 2006, doi: 10.1002/art.21972.[5]M. M. Schoels, D. Aletaha, F. Alasti, and J. S. Smolen, “Disease activity in psoriatic arthritis (PsA): Defining remission and treatment success using the DAPSA score,” Ann. Rheum. Dis., vol. 75, no. 5, pp. 811–818, 2016, doi: 10.1136/annrheumdis-2015-207507.Disclosure of InterestsBarbara Dreo: None declared, Daniel Ruben Pietsch: None declared, Rusmir Husic Speakers bureau: MSD, Lilly und Abbvie, Angelika Lackner: None declared, Johannes Fessler: None declared, Janine Rupp: None declared, Anirudh Subramanian Muralikrishnan: None declared, Jens Thiel Speakers bureau: GSK, BMS, AbbVie, Novartis, Consultant of: GSK, Novartis, Grant/research support from: BMS, Martin Stradner Speakers bureau: Eli Lilly, Pfizer, MSD, BMS, AbbVie, Janssen, Consultant of: Eli Lilly, AbbVie, Janssen, Philipp Bosch Grant/research support from: Pfizer
46
Mayuranathan, Thiyagaraj, Jonathan S. Yen, Gregory A. Newby, Yu Yao, Shaina N. Porter, Kaitly J. Woodard, Jingjing Zhang, et al. "Adenosine Base Editing of γ-Globin Promoters Induces Fetal Hemoglobin and Inhibit Erythroid Sickling." Blood 136, Supplement 1 (November 5, 2020): 21–22. http://dx.doi.org/10.1182/blood-2020-141498.
Full textAbstract:
Rare variants in the γ-globin (HBG2 and HBG1) promoters cause sustained postnatal expression of fetal hemoglobin (HbF, α2γ2) in red blood cells (RBCs). This benign condition is termed hereditary persistence of fetal hemoglobin (HPFH). Individuals with HPFH variants are protected from β-hemoglobinopathies including sickle cell disease and β-thalassemia. Our group and others have used CRIPSR/Cas9-mediated non-homologous end joining to generate HPFH-like insertion-deletion (indel) mutations in the γ-globin promoter. However, simultaneous double-stranded breaks (DSBs) in the tandem duplicated γ-globin genes can result in loss or inversion of the intervening genetic material and/or chromosomal rearrangements. More generally, Cas9-associated DSBs can elicit a cytotoxic DNA repair response leading to cell death or evoke p53 loss with malignant transformation. Base editor (BE) proteins represent a promising approach to install precise nucleotide substitutions without DSBs. Adenosine base editors (ABEs), consisting of catalytically impaired Cas9 fused to a modified adenosine deaminase, create targeted A:T-to-G:C mutations. Here we describe the use of ABEs to recapitulate naturally occurring HPFH variants in hematopoietic stem cells (HSCs). We electroporated ABE7.10-single guide (sg) RNA ribonucleoprotein (RNP) complex into mobilized peripheral blood CD34+ hematopoietic stem and progenitor cells (HSPCs) to recreate 3 different HPFH variants in the HBG1/2 promoters (-198 T>C, -175 T>C and -113 A>G). Measured editing frequency was maximal on day 10 after electroporation and transferred to erythroid differentiation media. 20% editing efficiency was observed for the -198 site, 58% for -175 and 50% for -113. Indel frequencies were <2% at each of the three sites, reflecting a low rate of DSBs. Fetal hemoglobin levels in erythroid cells generated in vitro from A base-edited CD34+ HSPCs were 26±4% (-198 T>C), 60±10% (-175 T>C), and 42±7% (-113 A>G) versus14±2% in unedited control cells. Base editing at the -175 site in sickle cell disease (SCD) donor CD34+ HSPCs resulted in the induction of HbF to 55% in erythroid progeny compared to 6% in controls. After exposure to hypoxia (2% oxygen), reticulocytes generated from -175 T>C-edited CD34+ HSPCs exhibited sickling rates of 24%, compared to 52% in controls. Thus, creation of this variant, which generates a de novo binding site for the transcriptional activator TAL1, reactivates erythroid cell HbF to levels that inhibit sickle hemoglobin polymerization and cell sickling. To assess base editing in HSCs, we used ABE RNP to modify the -175 site in SCD donor CD34+ HSPCs, followed by transplantation into NBSGW mice. The editing frequency in CD34+ HSPCs before transplantation was ~30% and declined to approximately 20% in bone marrow-repopulating donor cells at 16 weeks post-transplantation. Editing frequencies were similar in CD34+ donor cell-derived myeloid, erythroid, and B cells, indicating that hematopoietic differentiation was not altered. Bone marrow erythroblasts derived from base-edited and control CD34+ HSPCs exhibited similar maturation profiles and enucleation. Erythroblasts generated in vivo from SCD patient HSPCs exhibited 32±2% HbF compared to unedited controls (4±1%) (n=4, P>0.0001). Our studies provide proof of concept that adenosine base editors can be used therapeutically for β-hemoglobinopathies. Specifically, generation of the -175 T>C HPFH mutation in patient HSCs followed by autologous transplantation represents a new therapeutic approach for SCD and β-thalassemia. Disclosures Yen: Beam Therapeutics: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Sharma:Spotlight Therapeutics: Consultancy; Magenta Therapeutics: Other: Research Collaboration; CRISPR Therapeutics, Vertex Pharmaceuticals, Novartis: Other: Clinical Trial PI. Liu:Pairwise Plants: Consultancy, Patents & Royalties; Editas Medicine: Consultancy, Patents & Royalties; Beam Therapeutics: Consultancy, Patents & Royalties; Prime Medicine: Consultancy, Patents & Royalties. Weiss:Beam Therapeuticcs: Consultancy, Current equity holder in private company; Esperion Therapeutics: Consultancy, Current equity holder in private company; Novartis: Consultancy, Current equity holder in private company; Cellarity Inc.: Consultancy, Current equity holder in private company; Rubius Inc.: Consultancy, Current equity holder in private company.
47
Gomez Garcia, Antonio Ramon, Pamela Merino Salazar, and Michael Silva Pena-Herrera. "Mortality due to road traffic injuries in older adults in the Republic of Ecuador between 1990 and 2018: a descriptive study." Universidad Ciencia y Tecnología 26, no. 112 (March 8, 2022): 17–25. http://dx.doi.org/10.47460/uct.v26i112.541.
Full textAbstract:
The present study aimed to estimate the trend in road traffic injury mortality in older adults (60 years of age or older) and comparison with those <60 years of age in Ecuador (1990-2018). Official death records and population projections were used to calculate mortality rates per 100,000 population, rate ratios, years of potential life lost (YPLL), and trends. Those under 60 years of age had mortality rates of 16.7 (per 100,000) compared to 36.2 (per 100,000) for older adults, with an increasing trend in YPLL. Older adults recorded fewer deaths than the younger population. However, it is necessary to develop road safety strategies oriented to the progressive aging of the Ecuadorian population.
Keywords: older adults, traffic accidents, mortality, trends, Ecuador.
References
[1]World Health Organization (2018, May 17). Global Status Report on Road Safety 2018 [Online]. Available: https://www.who.int/violence_injury_prevention/road_safety_status/2018/en/
[2]A. F. Algora-Buenafé, M. Russo-Puga, P. R. Suasnavas-Bermúdez, P. Merino-Salazar and A. R. Gómez-García,"Tendencias de los accidentes de tránsito en Ecuador: 2000-2015", Gerencia y Políticas de Salud, vol. 16, n.º 33, pp. 52–58, noviembre de 2017. [Online]. Available: https://doi.org/10.11144/javeriana.rgps16-33.tate. [Last Access: September 2nd, 2021 ].
[3]Pan American Health Organization (2019, June 22). Status of Road Safety in the Region of the Americas [Online]. Available: http://iris.paho.org/xmlui/handle/123456789/51088.
[4]S. J. Eun, "Trends in mortality from road traffic injuries in South Korea, 1983–2017: Joinpoint regression and age-period-cohort analyses", Accident Analysis &Prevention, vol. 134, p. 105325, January 2020. [Online]. Available: https://doi.org/10.1016/j.aap.2019.105325. [Last Access: September 2nd, 2021 ].
[5]S. Azami-Aghdash, M. H. Aghaei, and H. Sadeghi-Bazarghani, "Epidemiology of Road Traffic Injuries among Elderly People; A Systematic Review and Meta-Analysis", Bulletin of Emergency and Trauma, vol. 6, n.º 4, pp. 279–291, October 2018. [Online]. Available: https://doi.org/10.29252/beat-060403. [Last Access: September 7th, 2021 ].
[6]Y. Abolfathi Momtaz, R. Kargar, R. Hosseiny, and R. Sahaf, "Rate and pattern of road traffic accidents among older and younger drivers", Healthy Aging Research, vol. 7, n.º 2, June 2018, art. n.º e18. [Online]. Available: https://doi.org/10.1097/hxr.0000000000000018. [Last Access: October 13th, 2021 ].
[7]P. Martínez, D. Contreras and M. Moreno, "Safe mobility, socioeconomic inequalities, and aging: A 12-year multilevel interrupted time-series analysis of road traffic death rates in a Latin American country", PLOS ONE, vol. 15, n.º 1, enero de 2020, art. n.º e0224545. [Online]. Available: https://doi.org/10.1371/journal.pone.0224545. [Last Access: October 10th, 2021 ].
[8]G. Bergen et al., "How do older adult drivers self-regulate? Characteristics of self-regulation classes defined by latent class analysis", Journal of Safety Research, vol. 61, pp. 205–210, June 2017. [Online]. Available: https://doi.org/10.1016/j.jsr.2017.01.002. [Last Access: October 9th, 2021 ]
[9]Instituto Nacional de Estadística y Censos (2018, February 2). Registros Estadísticos de Nacidos Vivos, Defunciones Fetales y Defunciones Generales [Online]. Available: https://www.ecuadorencifras.gob.ec/nacimientos_y_defunciones.
[10]Instituto Nacional de Estadística y Censos (2017, August 2). Proyecciones Demográficas, 2010 – 2020. [Online]. Available: https://sni.gob.ec/proyecciones-y-estudios-demograficos.
[11]W. Y. Yee, "Road traffic injuries in the elderly", Emergency Medicine Journal, vol. 23, n.º 1, pp. 42–46, January 2006. [Online]. Available: https://doi.org/10.1136/emj.2005.023754. [Last Access: October 21st, 2021]
[12]L. McElroy, J. Juern, A. Bertleson, Q. Xiang, A. Szabo and J. Weigelt, "A single urban center experience with adult pedestrians struck by motor vehicles", WMJ:official publication of the State Medical Society of Wisconsin, vol. 112(3), pp. 117-122, 2013.
[13]K. Bhalla, M. Naghavi, S. Shahraz, D. Bartels and C. J. L. Murray, "Building national estimates of the burden of road traffic injuries in developing countries from all available data sources: Iran", Injury Prevention, vol. 15, n.º 3, pp. 150–156, June 2009. [Online]. Available: https://doi.org/10.1136/ip.2008.020826. [Last Access: October 1st, 2021].
[14]D. Bartels, K. Bhalla, S. Shahraz, J. Abraham, R. Lozano and C. J. L. Murray, "Incidence of road injuries in Mexico: country report", International Journal of Injury Control and Safety Promotion, vol. 17, n.º 3, pp. 169–176, September 2010. [Online]. Available: https://doi.org/10.1080/17457300903564553. [Last Access: November 16th, 2021].
[15]W. R. Boot, C. Stothart and N. Charness, "Improving the Safety of Aging Road Users: A Mini-Review", Gerontology, vol. 60, n.º 1, pp. 90–96, 2014. [Online]. Available: https://doi.org/10.1159/000354212. [Last Access: November 6th, 2021]
[16]Y. L. Michael, E. P. Whitlock, J. S. Lin, R. Fu, E. A. O'Connor and R. Gold, "Primary Care–Relevant Interventions to Prevent Falling in Older Adults: A Systematic Evidence Review for the U.S. Preventive Services Task Force", Annals of Internal Medicine, vol. 153, n.º 12, p. 815, December 2010. [Online]. Available: https://doi.org/10.7326/0003-4819-153-12-201012210-00008.[Last Access: November 29th, 2021]
[17]H. Etehad, S. Yousefzadeh-Chabok, A. Davoudi-Kiakalaye, D. A. Moghadam, H. Hemati and Z. Mohtasham-Amiri, "Impact of road traffic accidents on the elderly", Archives of Gerontology and Geriatrics, vol. 61, n.º 3, pp. 489–493, November de 2015. [Online]. Available: https://doi.org/10.1016/j.archger.2015.08.008. [Last Access: November 3th, 2021].
[18]B. H. Ang, W. S. Chen and S. W. H. Lee, "Global burden of road traffic accidents in older adults: A systematic review and meta-regression analysis", Archives of Gerontology and Geriatrics, vol. 72, pp. 32–38, September 2017. [Online]. Available: https://doi.org/10.1016/j.archger.2017.05.004. [Last Access: December 19th, 2021]
[19]J. P. Thompson, M. R. J. Baldock and J. K. Dutschke, "Trends in the crash involvement of older drivers in Australia", Accident Analysis & Prevention, vol. 117, pp. 262–269, August 2018. [Online]. Available: https://doi.org/10.1016/j.aap.2018.04.027. [Last Access: December 16th, 2021].
48
Lim, Kathleen, Sarah Gibson, Tao Jin, Eric Hsi, Matt Kalaycio, Edward A. Copelan, Mikkael A. Sekeres, Ronald Sobecks, and Anjali Advani. "OCT-2 Expression and OCT-2/BOB.1 Co-Expression Predict Prognosis in Patients with Newly Diagnosed Acute Myelogenous Leukemia." Blood 112, no. 11 (November 16, 2008): 1486. http://dx.doi.org/10.1182/blood.v112.11.1486.1486.
Full textAbstract:
Abstract OCT-2 and its co-activator, BOB.1, are B-cell associated transcription factors, and are expressed in a subset of pts with acute myelogenous leukemia (AML). Pathways downstream of OCT-2 may serve as therapeutic targets. However, the prognostic significance of OCT-2 and BOB.1 expression in pts with AML is unclear. We evaluated OCT-2 and BOB.1 expression in pts with newly diagnosed AML, and the prognostic impact of expression on achievement of complete remission (CR), risk of relapse, and overall survival (OS). Methods: Between 1998–2005, adult pts with newly diagnosed AML and an available diagnostic BM biopsy performed at the Cleveland Clinic were evaluated. B5-fixed core biopsies were reviewed for areas with the highest concentration of blasts. A tissue microarray was constructed, and the cores were arrayed in duplicate. Immunohistochemistry was performed for OCT-2 (1:200 dilution; polyclonal; Santa Cruz Biotechnology) and BOB.1 (1:500 dilution, polyclonal; Santa Cruz Biotechnology) using automated stainers and heat induced epitope retrieval. Staining was scored as the percent of blasts with nuclear staining. For the purposes of dichotomous classification, nuclear staining in ≥ 10% of the blasts was considered positive. OCT-2 and BOB.1 expression were analyzed both per 10% increase, and as dichotomous variables. Cox proportional hazards analysis was used to identify univariate and multivariate risk factors. Variables included: age at diagnosis, cytogenetic (CG) risk group, gender, OCT-2 expression, BOB.1 expression, history of antecedent hematologic disorder (AHD), CD117 (c-kit) expression, and white blood count (WBC) at diagnosis. Results: One-hundred and seventy-nine pts with newly diagnosed AML were treated with induction chemotherapy, and 99 pts had evaluable BM core biopsies. The median age at diagnosis was 57 yrs (range 17–79), and 52% were male. Fourteen percent of pts had favorable CG, 54% intermediate risk, 25% unfavorable, and 7% unknown CG as defined by CALGB criteria. The median WBC at diagnosis was 10.6 k/uL (range 0.4–259.0), and 28% of pts had an AHD. Nineteen percent of pts co-expressed OCT-2 and BOB.1, 35% expressed neither OCT-2 or BOB.1, and 12% expressed BOB.1 alone. Seventy-seven percent of pts achieved a CR with induction therapy. In first CR, 16% received an allogeneic BMT, 9% received autologous BMT, and 56% received consolidation chemotherapy. The median OS for all pts was 15.5 months after diagnosis, and the median time from diagnosis to relapse was 9.4 months. On univariate analysis, pts with co-expression of OCT-2 and BOB.1 (HR 0.45, 95% CI 0.24–0.84, p=0.013) or poor risk CG had a lower CR rate. OCT-2 expression (per 10% increase) (HR 1.11, 95% CI 1.02–1.21, p=0.013), age at diagnosis (per 10 year increase), and poor risk CG were associated with a decreased PFS. Pts with co-expression of OCT-2 and BOB.1 (HR 2.25, 95% CI 1.00–5.05, p=0.049), poor risk CG, or history of an AHD had an increased risk of relapse. OCT-2 expression (per 10% increase) (HR 1.10, CI 1.01–1.20, p=0.024), age at diagnosis, or poor risk CG, were associated with a decreased OS. On multivariate analysis, age at diagnosis and CG risk group remained statistically significant prognostic factors. The co-expression of OCT-2/BOB.1 also remained prognostic for achievement of CR (HR 0.44, 0.23–0.82, p=0.010) and increased risk of relapse (HR 2.30, 1.01–5.24, p=0.047) (Table 1). In the subgroup of pts without an AHD, the risk of relapse was more striking in pts with co-expression of OCT-2 and BOB.1 (HR 3.24, 1.38–7.64, p=0.007). When OCT-2 and BOB.1 were evaluated separately, and co-expression was not included in the multivariate analysis, OCT-2 (per 10% increase), was associated with a decreased PFS (HR 1.10, 1.01–1.20, p=0.036) and a trend towards a worse OS (HR=1.10, 0.99–1.21, p=0.063) (Table 1). Conclusions: OCT-2 expression and OCT-2/BOB.1 co-expression are associated with a poor prognosis in pts with newly diagnosed AML. OCT-2 may act as a cell survival factor by mediating expression of other factors, such as BCL-2. Therefore, targeting pathways activated downstream of OCT-2, such as the anti-apoptotic gene, BCL-2; the cell surface antigen CD36; and interleukin-2 may potentially improve the prognosis of these particular pts. Table 1 Multivariate Analysis CR Risk of Relapse PFS OS OCT-2/BOB.1 Co-Expression HR.44, p=.01 HR 2.30, p=.047 OCT-2 (per 10% increase) HR 1.10, p=.036 HR=1.10, p=.06
49
Melgarejo, Osvaldo. "Estilo de vida nocturno: ¿Epidemia de la fata de sueño?" Medicina Clínica y Social 1, no. 3 (January 5, 2018): 224–26. http://dx.doi.org/10.52379/mcs.v1i3.39.
Full textAbstract:
Touitou Y, Reinberg A, Touitou D. Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: Health impacts and mechanisms of circadian disruption. Life Sci. 2017;173:94-106. https://doi.org/10.1016/j.lfs.2017.02.008
Sinclair KL, Ponsford JL, Taffe J, Lockley SW, Rajaratnam SM. Randomized controlled trial of light therapy for fatigue following traumatic brain injury. Neurorehabil Neural Repair. 2014;28(4):303-313. http://doi.org/10.1177/1545968313508472
Duffy JF. Czeisler CA. Effect of Light on Human Circadian Physiology. Sleep Med Clin. 2009;4(2):165-177. https://doi.org/10.1016/j.jsmc.2009.01.004
Lamond N, Jay SM, Dorrian J, Ferguson SA, Jones C, Dawson D. The dynamics of neurobehavioural recovery following sleep loss. J Sleep Res. 2007;16(1):33-41. https://doi.org/10.1111/j.1365-2869.2007.00574.x
Carskadon, MA. Acebo, C. Seifer, R. Extended nights, sleep loss, and recovery sleep in adolescents. Arch Ital Biol. 2001;139(3):301-312. URL.
Schmid S, Hallschmid M, Schultes B. The metabolic burden of sleep loss. The Lancet Diabetes & Endocrinology 2015;3(1):52-62. https://doi.org/10.1016/S2213-8587(14)70012-9
Dube N, Khan K, Loehr S, Chu Y, Veugelers P. The use of entertainment and communication technologies before sleep could affect sleep and weight status: a population-based study among children. Int J Behav Nutr Phys Act. 2017;14(1):97. https://doi.org/10.1186/s12966-017-0547-2
Krahe A [Internet]. Academy of Clinical Sleep Disorders Disciplines; c2016 [cited 14 Dec 2017]. CDC Declares Insufficient Sleep a "Public Healthcare Problem" [approx. 2 screens]. Available from: http://acsdd.org/2016/12/07/rand-corp-insufficient-sleep/
Sleep Foundation [Internet].org; c2011 [cited 14 Dec 2017]. Annual Sleep in America Poll Exploring Connections with Communications Technology Use and Sleep [approx. 5 screens]. Available from: https://sleepfoundation.org/media-center/press-release/annual-sleep-america-poll-exploring-connections-communications-technology-use-
Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, et al. Rotating night shifts and risk of breast cancer in women participating in the Nurses Health Study. J Natl Cancer Inst. 2011;93(20):1563-1568. URL.
Schernhammer ES, Kroenke CH, Laden F, Hankinson SE. Night work and risk of breast cancer. 2006;17(1):108-111. URL.
Miró E, Cano-Lozano C, Buela-Casal G. Sueño y calidad de vida. colomb. psicol. 2005;14:11-27. URL.
Marshall N. The sleep loss epidemic: hunting ninjas in the dark. Journal of Sleep Research. 2015;24(1):1-2. https://doi.org/10.1111/jsr.12277
Morin CM, Hauri PJ, Espie CA, Spielman AJ, Buysse DJ, Bootzin RR. Nonpharmacologic treatment of chronic insomnia: an American Academy of Sleep Medicine review. Sleep 1999;22(8):1134-1156. URL.
Foley L, Maddison R, Jiang Y, Marsh S, Olds T, Ridley K. Presleep Activities and Time of Sleep Onset in Children. Pediatrics. 2013;131(2):276-282. URL.
Irish LA, Kline CE, Gunn HE, Buysse DJ, Hall MH. The role of sleep hygiene in promoting public health: A review of empirical evidence. Sleep Med Rev. 2015;22:23-36. https://doi.org/10.1016/j.smrv.2014.10.001
50
Cai, Qichun, Hui-qiang Huang, Bing Bai, Suxia Lin, Yan Gao, Yi Xia, XiaoXiao Wang, and Jiabin Lu. "IL-6 Promotes Cell Proliferation and Antiapoptosis Through Activation Of The JAK/STAT3 Pathway In Patients With NK/T - Cell Lymphoma and Correlates With Poor Treatmemt Outcome." Blood 122, no. 21 (November 15, 2013): 1758. http://dx.doi.org/10.1182/blood.v122.21.1758.1758.
Full textAbstract:
Abstract Backgroud It has been demonstrated that Natural/killer T-cell lymphoma (NK/TCL) derives from chronic EBV infection of nasopharynx. In recent years, IL-6 has been proved to be associated with a variety of inflammation-related malignancies in terms of carcinogenesis, tumor proliferation and metastasis. However, there hasn’t been any report about IL-6 on the pathogenesis and development of NK/TCL. Patients and Methods From January 2005 to December 2012, the paraffin sections of 91 patients with NK/TCL in Sun Yat-sen University Cancer Center were collected. The activation/expression of NF-ΚB(P50, P52, P65), IL-6,P-STAT3(Tyr705),BCL-2 in tumor microenviroment were investigated by immunohistochemistry. The NK/TCL cell lines were treated by IL-6(80ng/ml) and neutralizing IL-6 antibody, then the viability and apoptosis of lymphoma cell lines (NK-YS, SNK-6 and SNT-8) were assessed by CCK-8 and flow cytometry; and the expression of p-STAT3, BCL-2, BCL-XL, MCL-1, Survivin、p-ERK and p-AKT were examined by Western blot . Results Overall, ninety-one patients with NK/TCL were analyzed. There were 68 male patients. The median age was 43 years (range 10-68 years). There were 52, 14 and 25 patients diagnosed as stage I, II and IV disease, respectively. Sixty-one patients had B symptoms. The P52 activation was observed in the microenviroment of most patients, while P65 and P50 activation were observed in minority of patients. In patients with P52 activation, P52 activation was observed both in macrophages and lymphoma cells, and vice versa. IL-6 was primarily secreted by macrophages and tumor cells, and 69.2% (63/91) patients were positive (IL-6 secreting cells ≥ 10 / HP). The STAT3 activation was observed in 67.0% (61/91) of patients, most of which were combined with expression of BCL-2. The expression of P52、IL-6、P-STAT3、bcl-2 in the microenvironment of NK/TCL were in uniform (all positive or all negative). Patients with positive expression of IL-6 were associated with fever, advanced stage, high serum level of C-reactive protein (CRP), chemotherapy resistance and poor survival (P < 0.05). Comparing with blank control group and the neutralizing IL-6 antibody group, the cell viability and antiapoptosis ratio of NK-YS、 SNK-6、SNT-8 cells were higher in the IL-6 group (P<0.05). Constitutive activation of p-STAT3, BCL-2, BCL-XL, MCL-1, and survivin were observed in the NK/TCL cell lines. IL-6 could up-regulate the expression of these proteins. The expression of p-ERK and p-AKT were irrelevant with IL-6 or IL-6 antibody treatment. Conclusions The NK-κB(P52)/IL-6/STAT3 pathway is activated in tumor microenvironment, and is associated with fever, advanced stage, high serum level of CRP in patients with NK/TCL. IL-6 could activate the JAK/STAT3 pathway in NK/T lymphoma cell lines, and promote lymphoma proliferation and anti-apoptosis. The activation of NK-κB(P52)/IL-6/STAT3 pathway may lead to chemotherapy resistance and poor survival in patients with NK/TCL. Disclosures: No relevant conflicts of interest to declare.