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Iannuzzo, Gabriella, Marco Gentile, Alessandro Bresciani, Vania Mallardo, Anna Di Lorenzo, Pasquale Merone, Gianluigi Cuomo, et al. "Inhibitors of Protein Convertase Subtilisin/Kexin 9 (PCSK9) and Acute Coronary Syndrome (ACS): The State-of-the-Art." Journal of Clinical Medicine 10, no. 7 (April 5, 2021): 1510. http://dx.doi.org/10.3390/jcm10071510.
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Acute Coronary Syndrome (ACS) remains one of the most frequent causes of morbidity and mortality in the world. Although the age- and gender-adjusted incidence of ACS is decreasing, the mortality associated with this condition remains high, especially 1-year after the acute event. Several studies demonstrated that PCSK9 inhibitors therapy determine a significant reduction of major adverse cardiovascular events (MACE) in post-ACS patients, through a process of plaque modification, by intervening in lipid metabolism and platelet aggregation and finally determining an improvement in endothelial function. In the EVACS (Evolocumab in Acute Coronary Syndrome) study, evolocumab allows >90% of patients to achieve LDL-C < 55 mg/dL according to ESC/EAS guidelines compared to 11% of patients who only receive statins. In the EVOPACS (EVOlocumab for Early Reduction of low-density lipoprotein (LDL)-cholesterol Levels in Patients With Acute Coronary Syndromes) study, evolocumab determined LDL levels reduction of 40.7% (95% CI: 45.2 to 36.2; p < 0.001) and allowed 95.7% of patients to achieve LDL levels <55 mg/dL. In ODYSSEY Outcome trial, alirocumab reduced the overall risk of MACE by 15% (HR = 0.85; CI: 0.78–0.93; p = 0.0003), with a reduced risk of all-cause mortality (HR = 0.85; CI: 0.73–0.98: nominal p = 0026), and fewer deaths for coronary heart disease (CHD) compared to the control group (HR = 0.92; CI: 0.76–1.11; p = 0.38). The present review aimed at describing the beneficial effect of PCSK9 inhibitors therapy early after ACS in reducing LDL circulating levels (LDL-C) and the risk of major adverse cardiovascular events, which was very high in the first year and persists higher later after the acute event.
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Iddi, Shabani, Caroline A. Minja, Vitus Silago, Asteria Benjamin, Jastine Mpesha, Shimba Henerico, Benson R. Kidenya, Stephen E. Mshana, and Mariam M. Mirambo. "High Human Immunodeficiency Virus (HIV) Viral Load and Coinfection with Viral Hepatitis Are Associated with Liver Enzyme Abnormalities among HIV Seropositive Patients on Antiretroviral Therapy in the Lake Victoria Zone, Tanzania." AIDS Research and Treatment 2019 (June 2, 2019): 1–6. http://dx.doi.org/10.1155/2019/6375714.
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Background. Liver enzymes abnormalities have been found to be common among patients on antiretroviral treatment (ART). Apart from the effects of ART on these changes, other factors that can potentially contribute to the abnormal levels of these enzymes have been found to vary in different geographical locations. This study investigated factors associated with liver enzymes abnormalities among human immunodeficiency virus (HIV) infected individuals on ART from the Lake Victoria zone, Tanzania. Methods. A cross-sectional study involving a total of 230 sera from HIV seropositive patients from different regions of the Lake Victoria zone was carried out in July 2017. All samples with required variables/parameters such as age, sex, ART regimen, and residence were serially included in the study. Hepatitis B virus (HBV) and Hepatitis C virus (HCV) detection and liver enzymes assays (alanine transaminase (ALAT) and aspartate transaminase (ASAT)) were assessed following the standard procedures. Data were analyzed by using STATA version 13. Results. The median age of the study participants was 38 (interquartile range [IQR]:30-48) years. The overall prevalence of abnormal liver enzymes was 43.04% (99/230, 95% CI: 36.6-49.3). A total of 26.09% (60/230) had elevated ASAT while 23.9% (55/230) patients had elevated ALAT levels. ASAT levels were significantly high among patients with high HIV viral load (P= 0.002) while ALAT levels were significantly high among those coinfected with hepatitis C virus (P=0.017) and hepatitis B virus (P<0.001). Conclusion. A significant proportion of HIV seropositive individuals on ART have abnormal levels of liver enzymes, which is significantly associated with high HIV viral load and viral hepatitis. This calls for the need to emphasize screening of viral hepatitis and provision of appropriate management among HIV seropositive individuals in this setting.
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Ayșe, Atay, Najafova Lamia, Kurtulmus Huseyin Mehmet, and Üşümez Aslihan. "The micro-shear bond strength of two different repair systems to indirect restorative materials." STOMATOLOGY EDU JOURNAL 7, no. 4 (2020): 233–41. http://dx.doi.org/10.25241/stomaeduj.2020.7(4).art.1.
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Introduction The aim of this study was to evaluate the micro-shear bond strength (μSBS) of different repair systems (Clearfil Repair, iGOS Repair) to restorative materials for CAD/CAM (Cerasmart, Lava Ultimate, InCoris TZI , VITA Suprinity, VITA Mark II, IPS e.max CAD, IPS Empress CAD). Methodology The 140 1.2 mm-thick specimens were prepared from CAD/CAM blocks (n=20) and thermocycled (10,000 cycles, 5–55°C, dwell time 20s). The specimens were randomly divided into two groups according to the repair system: Clearfil Repair (40% phosphoric acid+mixture of Clearfil Porcelain Bond Activator and Clearfil SE Bond Primer+Clearfil SE Bond+CLEARFIL MAJESTY ES-2) and iGOS Repair (40% phosphoric acid+ Multi Primer LIQUID+ iGOS Bond+ iGOS Universal). The composite resins were polymerized. All specimens were stored in distilled water at 37°C for 24 hours. The μSBS test was performed with a micro-shear testing machine (at 1 mm/min). The data were analyzed using two-way ANOVA, Tukey’s multiple comparison tests at a significance level of p<0.05. Each failure modes were examined under a stereomicroscope at×16 magnification. Results The type of CAD/CAM restorative material and repair system showed a significant effect on the μSBS (p<0.05). Specimens repaired with the iGOS Repair system showed the highest μSBS values than the Clearfil Repair system among all tested materials except for the InCoris TZI group (p<0.05). Conclusion All groups, except for the InCoris TZI group, repaired with iGOS Repair system showed higher μSBS than Clearfil Repair. The type of restoration and repair material is important in the success of the fracture repair.
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Orrell, Catherine, Rochelle P. Walensky, Elena Losina, Jennifer Pitt, Kenneth A. Freedberg, and Robin Wood. "HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme." Antiviral Therapy 14, no. 4 (May 2009): 523–31. http://dx.doi.org/10.1177/135965350901400414.
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Background This study aimed to evaluate HIV type-1 (HIV-1) drug resistance pretreatment and in those failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in South Africa. Methods This was an observational cohort. Genotypic resistance testing was performed on treatment-naive individuals and those failing first-line ART (confirmed HIV-1 RNA>1,000 copies/ml) from public sector clinics in Cape Town (2002–2007). Resistance profiles and mutations relative to timing of known virological failure were examined. Results In total, 230 patients (120 treatment-naive and 110 with virological failure) were included: 98% had clade C virus. Among treatment-naive patients, prevalence of primary resistance was 2.5% (95% confidence interval 0.0–5.3). Three patients had one significant reverse transcriptase mutation: K65R, Y181C and G190A. Among treatment-experienced patients, 95 (86%) individuals had therapy-limiting NNRTI mutations, including K103N (55%), V106M (31%) and Y181C (9%). The M184V mutation was the most common mutation, found in 86 (78%) patients. In total, 10 (9%) patients had the K65R mutation. More individuals tended to develop thymidine analogue mutations when sampling occurred after 6 months of detected therapy failure (10/31 [32%] individuals) compared with those who had genotyping before 6 months (15/79 [19%] patients; P=0.246). Conclusions Prevalence of primary resistance in a sample of ART-naive clade C HIV-1-infected individuals in South Africa was low during the study period. Patients failing first-line ART most often developed resistance to NNRTIs and nucleoside reverse transcriptase inhibitors, the two drug classes used in first-line therapy. Viral load monitoring in this setting is crucial and individual genotypes in those failing first-line therapy should be considered.
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Yaakoby-Rotem, Sarit, and Ronny Geva. "Asymmetric Attention Networks: The Case of Children." Journal of the International Neuropsychological Society 20, no. 4 (March 11, 2014): 434–43. http://dx.doi.org/10.1017/s1355617714000150.
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AbstractVisuospatial attention-networks are represented in both hemispheres, with right-hemisphere dominance in adults. Little is known about the lateralization of the attentional-networks in children. To assess the lateralization of attentional-networks in children aged 5 years, performance on a Lateralized-Attention-Network-Test specifically designed for children (LANT-C) was compared with performance on the Attention-Network-Test for children (ANT-C). Participants were 82 children, aged 5–6 years (55% boys, middle–class, mainstream schooling). They were examined with both the ANT-C and the LANT-C along with evaluation of intelligence and attention questionnaires. Multiple analysis of variance showed a main effect for network, with high efficiency for orienting and lower executive efficiency (accuracy; p < .001; η2 = .282). An effect for procedure, elucidated higher efficiency in the ANT-C relatively to the LANT-C (accuracy; p < .01; η2 = .097). A procedure × network interaction effect was also found, showing that this procedure difference is present in the alerting and executive networks (accuracy; p < .05; η2 = .096). LANT-C analysis showed a left visual-field advantage in alerting, (accuracy; p < .05; η2 = .066), while executing with the right hand benefitted executive performance (response-time; p < .05; η2 = .06). Results extend previous findings manifesting a right-hemisphere advantage in children's alerting-attention, pointing to the importance of lateralization of brain function to the understanding of the integrity of attention-networks in children. (JINS, 2014, 20, 1–10)
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Gardner, Viv. "Philip C. Kolin Shakespeare and Feminist Criticism: an Annotated Bibliography and CommentaryNew York: Garland, 1991. 420 p. £55. ISBN 0-82240-87386-X." New Theatre Quarterly 8, no. 31 (August 1992): 291. http://dx.doi.org/10.1017/s0266464x00006928.
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Lapshina, Z. S. "ARCHEOLOGY OF THE LOWER AMUR RIVER: TO THE STUDY OF THE SUKPAI ARTISTIC STYLE AMONG THE PETROGLYPHS OF THE AMUR AND USSURI." History: facts and symbols, no. 2 (June 9, 2022): 46–55. http://dx.doi.org/10.24888/2410-4205-2022-31-2-47-55.
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Among the hundreds of archaeological sites in the lower reaches of the Amur basin, a special place belongs to the stones and rocks with ancient drawings. The rock art of the Lower Amur region has been studied since the sixties of the nineteenth century. Among the discoverers and researchers are the names of local historians and scientists. Systematic academic scientific research of petroglyphs monuments was carried out only 100 years later, in the sixties of the twentieth century, by Soviet archaeologists. The research source base (topography, description, tracing, scientific interpretation and publication of materials) was prepared by a team of employees of the Far Eastern Archaeological Expedition of the Institute of Archeology and Ethnography of the Siberian Branch of the USSR Academy of Sciences under the leadership of A. P. Okladnikov. Pisanitsa on the Sukpai River in the Ussuri River basin is one of the new sites of rock art in the region, it was discovered in the 1980s by archaeologist V. I. Dyakov, an employee of the Institute of History, Archeology and Ethnography of the Peoples of the Far East of the Far Eastern Branch of the Russian Academy of Sciences. The article offers the experience of studying the stylistic diversity of the Lower Amur rock art monuments, namely, the drawings of the Sukpai petroglyph, which predetermines its relevance. The novelty of the study is due to the fact that the article highlights the signs of the Sukpai artistic style, the extent of its distribution among the petroglyphs of the region and adjacent territories. To write the work, a wide range of research methods was used, including the method of analyzing scientific literature, the sources were scientific papers on the topic of the study. The result of the research: a) the distinctive features of the style of plots on the rock of the Sukpai River are highlighted; b) similar images were traced on the stones and rocks of the Sikachi-Alyan-Malyshevo site; c) substantiation of the identification of the Sukpai artistic style among the petroglyphs of the Lower Amur; d) the similarity of the drawings of the sukpai style with the plots of the shamanic thematic direction of the rock art monuments of the adjacent territories of Eastern Siberia, Yakutia, the Upper and Middle Amur Region, and Transbaikalia was traced.
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Noritake, Hidenao, Yoshimasa Kobayashi, Yukimasa Ooba, Kensuke Kitsugi, Shin Shimoyama, Satoru Yamazaki, Takeshi Chida, Shinya Watanabe, Kazuhito Kawata, and Takafumi Suda. "Improved Serum Alpha-Fetoprotein Levels after Iron Reduction Therapy in HCV Patients." ISRN Hepatology 2014 (February 10, 2014): 1–7. http://dx.doi.org/10.1155/2014/875140.
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Background and Aims. To examine the changes in serum alpha-fetoprotein (AFP) levels after iron reduction by therapeutic phlebotomy in chronic hepatitis C patients. Methods. This retrospective study included 26 chronic hepatitis C patients. The patients were developed iron depletion by repeated therapeutic phlebotomies. Results. Iron reduction therapy significantly reduced the median level of serum AFP from 13 to 7 ng/mL, ALT from 96 to 50 IU/L, gamma-glutamyl transpeptidase (GGT) from 55 to 28 IU/L, and ferritin from 191 to 10 ng/mL (P<0.001 for each). The rate of decline in the AFP level correlated positively only with that in GGT (r=0.695, P=0.001), although a spurious correlation was observed between the rates of decline for AFP and ALT. The AFP level normalized (<10 ng/mL) posttreatment in eight (50%) of 16 patients who had elevated pretreatment AFP levels. Normalized post-treatment ALT and GGT levels were seen in 12% (3 of 26) and 39% (7 of 18) of the patients, respectively. Multivariate analysis identified a post-treatment GGT level of <30 IU/L as an independent factor associated with post-treatment AFP normalization (odds ratio, 21; 95% confidence interval, 1.5–293; P=0.024). Conclusions. Iron reduction by therapeutic phlebotomy can reduce serum AFP and GGT levels in chronic hepatitis C patients.
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Martins, Vitor F., Jessica R. Dent, Kristoffer Svensson, Shahriar Tahvilian, Maedha Begur, Shivani Lakkaraju, Elisa H. Buckner, et al. "Germline or inducible knockout of p300 or CBP in skeletal muscle does not alter insulin sensitivity." American Journal of Physiology-Endocrinology and Metabolism 316, no. 6 (June 1, 2019): E1024—E1035. http://dx.doi.org/10.1152/ajpendo.00497.2018.
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Akt is a critical mediator of insulin-stimulated glucose uptake in skeletal muscle. The acetyltransferases, E1A binding protein p300 (p300) and cAMP response element-binding protein binding protein (CBP) are phosphorylated and activated by Akt, and p300/CBP can acetylate and inactivate Akt, thus giving rise to a possible Akt-p300/CBP axis. Our objective was to determine the importance of p300 and CBP to skeletal muscle insulin sensitivity. We used Cre-LoxP methodology to generate mice with germline [muscle creatine kinase promoter (P-MCK and C-MCK)] or inducible [tamoxifen-activated, human skeletal actin promoter (P-iHSA and C-iHSA)] knockout of p300 or CBP. A subset of P-MCK and C-MCK mice were switched to a calorie-restriction diet (60% of ad libitum intake) or high-fat diet at 10 wk of age. For P-iHSA and C-iHSA mice, knockout was induced at 10 wk of age. At 13–15 wk of age, we measured whole-body energy expenditure, oral glucose tolerance, and/or ex vivo skeletal muscle insulin sensitivity. Although p300 and CBP protein abundance and mRNA expression were reduced 55%–90% in p300 and CBP knockout mice, there were no genotype differences in energy expenditure or fasting glucose and insulin concentrations. Moreover, neither loss of p300 or CBP impacted oral glucose tolerance or skeletal muscle insulin sensitivity, nor did their loss impact alterations in these parameters in response to a calorie restriction or high-fat diet. Muscle-specific loss of either p300 or CBP, be it germline or in adulthood, does not impact energy expenditure, glucose tolerance, or skeletal muscle insulin action.
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Glotov, Andrey S., Oleg S. Glotov, Mikhail V. Moskalenko, Viktor A. Rogozkin, Tatyana E. Ivashchenko, and Vladislav S. Baranov. "Analysis of genes polymorphisms of renin-angiotensine systems in population, athletes and elderly people." Ecological genetics 2, no. 4 (December 15, 2004): 40–43. http://dx.doi.org/10.17816/ecogen2440-43.
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We analyzed AGT (M235T), ACE (I/D), AGTR1 (A1166C) genes polymorphisms of renin-angiotensine systems in population, athletes and elderly people by PCR/RFLP methods. It was shown increasing of M/T genotype of AGT gene in rowers compared with population group (46 and 34%, accordantly), I/D of ACE (55 and 48%, accordantly) and decreasing of A/C genotype of AGTR1 gene (38 and 51%). It was detected significantly increasing of M/T genotype of AGT gene elderly people compared with population group (56 and 34%, accordantly, x2=l 1,828, p=0,0006). The received data allow to make the assumption of a possible role renin-angiotensine systems in process of ageing and active physical working capacitу
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Mackens, Shari, Stéphanie Pareyn, Panagiotis Drakopoulos, Tine Deckers, Linde Mostinckx, Christophe Blockeel, Ingrid Segers, et al. "Outcome of in-vitro oocyte maturation in patients with PCOS: does phenotype have an impact?" Human Reproduction 35, no. 10 (September 20, 2020): 2272–79. http://dx.doi.org/10.1093/humrep/deaa190.
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Abstract STUDY QUESTION Does the phenotype of patients with polycystic ovary syndrome (PCOS) affect clinical outcomes of ART following in-vitro oocyte maturation? SUMMARY ANSWER Cumulative live birth rates (CLBRs) after IVM were significantly different between distinct PCOS phenotypes, with the highest CLBR observed in patients with phenotype A/HOP (= hyperandrogenism + ovulatory disorder + polycystic ovaries), while IVM in patients with phenotype C/HP (hyperandrogenism + polycystic ovaries) or D/OP (ovulatory disorder + polycystic ovaries) resulted in lower CLBRs (OR 0.26 (CI 0.06–1.05) and OR 0.47 (CI 0.25–0.88), respectively, P = 0.03). WHAT IS KNOWN ALREADY CLBRs in women with hyperandrogenic PCOS phenotypes (A/HOP and C/HP) have been reported to be lower after ovarian stimulation (OS) and ART when compared to CLBR in women with a normo-androgenic PCOS phenotype (D/OP) and non-PCOS patients with a PCO-like ovarian morphology (PCOM). Whether there is an influence of the different PCOS phenotypes on success rates of IVM has been unknown. STUDY DESIGN, SIZE, DURATION This was a single-centre, retrospective cohort study including 320 unique PCOS patients performing their first IVM cycle between April 2014 and January 2018 in a tertiary referral hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS Baseline patient characteristics and IVM treatment cycle data were collected. The clinical outcomes following the first IVM embryo transfer were retrieved, including the CLBR defined as the number of deliveries with at least one live birth resulting from one IVM cycle and all appended cycles in which fresh or frozen embryos were transferred until a live birth occurred or until all embryos were used. The latter was considered as the primary outcome. A multivariate regression model was developed to identify prognostic factors for CLBR and test the impact of the patient’s PCOS phenotype. MAIN RESULTS AND THE ROLE OF CHANCE Half of the patients presented with a hyperandrogenic PCOS phenotype (n = 140 A/HOP and n = 20 C/HP vs. n = 160 D/OP). BMI was significantly different between phenotype groups (27.4 ± 5.4 kg/m2 for A/HOP, 27.1 ± 5.4 kg/m2 for C/HP and 23.3 ± 4.4 kg/m2 for D/OP, P < 0.001). Metformin was used in 33.6% of patients with PCOS phenotype A/HOP, in 15.0% of C/HP patients and in 11.2% of D/OP patients (P < 0.001). Anti-müllerian hormone levels differed significantly between groups: 12.4 ± 8.3 µg/l in A/HOP, 7.7 ± 3.1 µg/l in C/HP and 10.4 ± 5.9 µg/l in D/OP patients (P = 0.01). The number of cumulus-oocyte complexes (COC) was significantly different between phenotype groups: 25.9 ± 19.1 COC in patients with phenotype A/HOP, 18.3 ± 9.0 COC in C/HP and 19.8 ± 13.5 COC in D/OP (P = 0.004). After IVM, patients with different phenotypes also had a significantly different number of mature oocytes (12.4 ± 9.3 for A/HOP vs. 6.5 ± 4.2 for C/HP vs. 9.1 ± 6.9 for D/OP, P < 0.001). The fertilisation rate, the number of usable embryos and the number of cycles with no embryo available for transfer were comparable between the three groups. Following the first embryo transfer, the positive hCG rate and LBR were comparable between the patient groups (44.7% (55/123) for A/HOP, 40.0% (6/15) for C/HP, 36.7% (47/128) for D/OP, P = 0.56 and 25.2% (31/123) for A/HOP, 6.2% (1/15) for C/HP, 26.6% (34/128) for D/OP, respectively, P = 0.22). However, the incidence of early pregnancy loss was significantly different across phenotype groups (19.5% (24/123) for A/HOP, 26.7% (4/15) for C/HP and 10.2% (13/128) for D/OP, P = 0.04). The CLBR was not significantly different following univariate analysis (40.0% (56/140) for A/HOP, 15% (3/20) for C/HP and 33.1% (53/160) for D/OP (P = 0.07)). When a multivariable logistic regression model was developed to account for confounding factors, the PCOS phenotype appeared to be significantly correlated with CLBR, with a more favourable CLBR in the A/HOP subgroup (OR 0.26 for phenotype C/HP (CI 0.06–1.05) and OR 0.47 for phenotype D/OP (CI 0.25–0.88), P = 0.03)). LIMITATIONS, REASONS FOR CAUTION These data should be interpreted with caution as the retrospective nature of the study holds the possibility of unmeasured confounding factors and misassignment of the PCOS phenotype. Moreover, the sample size for phenotype C/HP was too small to draw conclusions for this subgroup of patients. WIDER IMPLICATIONS OF THE FINDINGS Caucasian infertile patients with a PCOS phenotype A/HOP who undergo IVM achieved a higher CLBR than their counterparts with C/HP and D/OP. This is in strong contrast with previously reported outcomes following OS where women with PCOS and hyperandrogenism (A/HOP and C/HP) performed significantly worse. For PCOS patients who require ART, the strategy of OS followed by an elective freeze-all strategy remains to be compared with IVM in a prospective fashion; however, the current data provide support for IVM as a valid treatment option, especially in the most severe PCOS phenotypes (A/HOP). Our data suggest that proper patient selection is of utmost importance in an IVM programme. STUDY FUNDING/COMPETING INTEREST(S) The clinical IVM research has been supported by research grants from Cook Medical and Besins Healthcare. All authors declared no conflict of interest. TRIAL REGISTRATION NUMBER N/A.
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Nikseresht, Mahmoud, Mohammad Reza Hafezi Ahmadi, and Mehdi Hedayati. "Detraining-induced alterations in adipokines and cardiometabolic risk factors after nonlinear periodized resistance and aerobic interval training in obese men." Applied Physiology, Nutrition, and Metabolism 41, no. 10 (October 2016): 1018–25. http://dx.doi.org/10.1139/apnm-2015-0693.
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This study compared the effects of nonlinear resistance training (NRT), aerobic interval training (AIT), and detraining on adipokines and cardiometabolic risk factors in middle-aged obese men. Thirty-three obese men were randomly allocated to NRT (n = 12), AIT (n = 10), and control (CON, n = 11) groups. Subjects in experimental groups performed exercise protocols 3 days per week for 12 weeks followed by a 4-week detraining period. The NRT involved 55 min of weight training with flexible periodization. The AIT consisted of running on a treadmill (4 × 4-min intervals at 90% of maximal heart rate, with each interval separated by 3 min at 65%). Peak oxygen consumption increased significantly after training compared with CON (P < 0.01), but it increased more in the AIT group than in the NRT group (P = 0.004). After detraining, peak oxygen consumption decreased significantly in both training groups (P < 0.001); however, the value in the AIT group was still higher than that in the CON group (P = 0.003). No significant changes were observed in serum levels of omentin-1 and interleukin (IL)-18 after training (P > 0.05), but omentin-1 decreased significantly in both training groups and IL-18 increased significantly in the NRT group after detraining (P < 0.05). High-density lipoprotein cholesterol (HDL-C) increased significantly after training in the AIT group compared with the CON group (P < 0.05) and returned to the pre-training level after detraining. Conversely, apelin-13 increased significantly in response to training, compared with baseline (P < 0.05), and remained unchanged after detraining. Both training regimens had similar effects on most markers; however, AIT seems to have stronger anti-coronary disease effects (as indicated by HDL-C and peak oxygen consumption) than NRT.
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Mahmood, Sabina, Kazumi Togawa, Miwa Kawanaka, Gouichi Niiyama, and Gotaro Yamada. "An Analysis of Risk Factors for Developing Hepatocellular Carcinoma in a Group of Hepatitis C Patients with Stage 3 Fibrosis following Interferon Therapy." Cancer Informatics 6 (January 2008): CIN.S644. http://dx.doi.org/10.4137/cin.s644.
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The risk of Hepatocellular carcinoma (HCC) is high in HCV-infected patients who have biochemically and histologically active chronic hepatitis. To observe the long prognosis of Chronic Hepatitis C (CHC) patients with stage 3 fibrosis (F3), 55 CHC patients after initial Interferon (IFN) therapy were followed up for up to 12 years (average 9.8 ± 2.3 years). According to the annual average alanine aminotransferase (ALT) levels, patients were grouped into, low (ALT ≤g 30 IU/l); moderate (ALT >30 <80 IU/l) and high (ALT ≥ 80 IU/l) ALT groups. Eleven patients were re-treated with IFN. During the follow-up period of 12 years, HCC developed in 26 patients with an average annual incidence of 3.9%. Biochemical responders to initial IFN therapy (n = 8) and those re-treated with IFN (n = 10), except 1, did not develop HCC. Cox regression analysis to evaluate risk factors for HCC occurrence, found development of Liver Cirrhosis within 3 years of initial IFN therapy( P = 0.05) and the 3 year annual average ALT post initial IFN therapy ( P = 0.033) to be significant. The 12 year annual average ALT was also found to be significantly related to HCC occurrence ( P = 0.016), on univariate analysis. Patients belonging to the continuously low ALT group (ALT ≤ 30 IU/l for ≥3 years), did not develop HCC or receive IFN re-treatment. In CHC patients with F3, after initial IFN therapy, keeping ALT continuously low, below 30 IU/l for 3 years or more seems important. Continuing treatment with anti-inflammatory drugs along with subsequent IFN re-treatment may prevent or delay HCC even in elderly patients.
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Barreda Coaquira, Ana, Delia Yerba Centeno, Maritza Ochoa Pezo, and Rosa Maria Zegarra Pierola. "Art and its relevance in the emotional well-being of people." Universidad Ciencia y Tecnología 25, no. 111 (December 5, 2021): 33–39. http://dx.doi.org/10.47460/uct.v25i111.513.
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Art, considered in its manifestations, whether through music, singing, painting, dancing, and all the possible expressions it can have, is undoubtedly a beautiful way to enrich the soul, the spirit, and human emotions. In this work, the different forms of understanding art, and the benefits that it can have on people, are exposed. It that art in its multiple manifestations can help control stress, anxiety, and depression. For this purpose, the investigators use bibliographic support to compare academic scenarios, artistic expressions that allow people to improve their emotional, physical, and psychological health. For this purpose, is implemented a bibliographic search to comparing academic scenarios, artistic manifestations that allow people to improve their emotional, physical, and psychological health. On the other hand, it was possible to verify that music performed as a half-hour therapy helps children with catastrophic illnesses, relieving pain.
Keywords: art, human emotions, artistic expressions.
References
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Dirajlal-Fargo, Sahera, Vanessa El-Kamari, Lukasz Weiner, Lingpeng Shan, Abdus Sattar, Manjusha Kulkarni, Nicholas Funderburg, et al. "Altered Intestinal Permeability and Fungal Translocation in Ugandan Children With Human Immunodeficiency Virus." Clinical Infectious Diseases 70, no. 11 (July 1, 2019): 2413–22. http://dx.doi.org/10.1093/cid/ciz561.
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Abstract Background Children with perinatally acquired human immunodeficiency virus (HIV; PHIVs) face a lifelong cumulative exposure to HIV and antiretroviral therapy (ART). The relationship between gut integrity, microbial translocation, and inflammation in PHIV is poorly understood. Methods This is a cross-sectional study in 57 PHIVs, 59 HIV-exposed but uninfected children, and 56 HIV-unexposed and -uninfected children aged 2–10 years old in Uganda. PHIVs were on stable ART with HIV-1 RNA <400 copies/mL. We measured markers of systemic inflammation, monocyte activation, and gut integrity. Kruskal-Wallis tests were used to compare markers by group and the Spearman correlation was used to assess correlations between biomarkers. Results The mean age of all participants was 7 years and 55% were girls. Among PHIVs, the mean CD4 % was 34%, 93% had a viral load ≤20 copies/mL, and 79% were on a nonnucleoside reverse transcriptase inhibitor regimen. Soluble cluster of differentiation 14 (sCD14), beta-D-glucan (BDG), and zonulin were higher in the PHIV group (P ≤ .01). Intestinal fatty acid binding protein (I-FABP) and lipopolysaccharide binding protein (LBP) did not differ between groups (P > .05). Among PHIVs who were breastfed, levels of sCD163 and interleukin 6 (IL6) were higher than levels in PHIV who were not breastfed (P < .05). Additionally, in PHIVs with a history of breastfeeding, sCD14, BDG, LBP, zonulin, and I-FABP correlated with several markers of systemic inflammation, including high-sensitivity C-reactive protein, IL6, d-dimer, and systemic tumor necrosis factor receptors I and II (P ≤ .05). Conclusions Despite viral suppression, PHIVs have evidence of altered gut permeability and fungal translocation. Intestinal damage and the resultant bacterial and fungal translocations in PHIVs may play a role in the persistent inflammation that leads to many end-organ diseases in adults. Despite viral suppression, children with perinatally acquired human immunodeficiency virus (HIV) in Uganda have evidence of alterations in intestinal permeability and fungal translocation, compared to HIV-exposed but uninfected and HIV-unexposed children, which may play a role in HIV-associated chronic inflammation.
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Porojan, Liliana, Roxana-Diana Vasiliu, Sorin-Daniel Porojan, and Mihaela-Ionela Bîrdeanu. "Surface Quality Evaluation of Removable Thermoplastic Dental Appliances Related to Staining Beverages and Cleaning Agents." Polymers 12, no. 8 (August 3, 2020): 1736. http://dx.doi.org/10.3390/polym12081736.
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(1) Background: Thermoplastic materials are not inert and subject to changes in the oral environment, which affect their surface quality. Color stability and topographic characteristics of clear thermoplastic appliances are critical considerations. The study aimed to evaluate the optical changes and surface topography of different thermoplastic materials related to staining beverages and cleaning agents. (2) Methods: Thermoplastic polyethylene terephthalate glycol (PET-G) material specimens were selected for the study: S (Duran, Scheu-Dental GmbH, Iserlohn, Germany), D (Biolon, Dreve Dentamid GmbH, Unna, Germany), and B (Crystal, Bio Art Dental Equipment, Sao Carlos, Brazil). Four different media were involved for immersion: coffee (C) and black tea (T) at 55 °C, Coca-Cola (K) at 5 °C, and distilled water (W) at 22 °C. As for cleaning, chemical options and mechanical brushing were selected (P-powder, T-tablets, and X-brushing). Color changes, and mean surface roughness were measured at 24 h, 48 h, and after 7 days. Statistical analysis was performed. After the testing period, atomic force microscopy (AFM) analyses and SEM images were registered in order to characterize the surface topography. (3) Results: Quantitative color change evaluations revealed a slight change in color after 24 h and an extremely marked change after 48 h, respective 7 days. Mean roughness values are kept below the clinically acceptable limit of 0.20 µm for all samples. Related to mean nanoroughness values Sa, and 3D evaluations of the surface quality, Biolon samples have demonstrated the most constant behavior, while Crystal samples are visibly influenced by water immersion. Related to the cleaning method, the topography of Duran samples was influenced by mechanical brushing. (4) Conclusions: Nanoscale investigations provided high accuracy and more realistic surface quality examinations of the examined samples compared to profilometry. Both SEM and AFM should be used for a more detailed description of the surface topography.
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Faderl, Stefan, Meir Wetzler, David Rizzieri, Gary Schiller, Madan Jagasia, Robert Stuart, Siddhartha Ganguly, et al. "Clofarabine Plus Cytarabine Compared With Cytarabine Alone in Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia: Results From the CLASSIC I Trial." Journal of Clinical Oncology 30, no. 20 (July 10, 2012): 2492–99. http://dx.doi.org/10.1200/jco.2011.37.9743.
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Purpose To compare the receipt of clofarabine plus cytarabine (Clo+Ara-C arm) with cytarabine (Ara-C arm) in patients ≥ 55 years old with refractory or relapsed acute myelogenous leukemia (AML). Patients and Methods Patients were randomly assigned to receive either clofarabine (Clo) 40 mg/m2 or a placebo followed by Ara-C 1 g/m2 for five consecutive days. The primary end point was overall survival (OS). Secondary end points included event-free survival (EFS), 4-month EFS, overall remission rate (ORR; complete remission [CR] plus CR with incomplete peripheral blood count recovery), disease-free survival (DFS), duration of remission (DOR), and safety. Results Among 320 patients with confirmed AML (median age, 67 years), the median OS was 6.6 months in the Clo+Ara-C arm and 6.3 months in the Ara-C arm (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00). The ORR was 46.9% in the Clo+Ara-C arm (35.2% CR) versus 22.9% in the Ara-C arm (17.8% CR; P < .01). EFS (HR: 0.63; 95% CI, 0.49 to 0.80; P < .01) and 4-month EFS (37.7% v 16.6%; P < .01) favored the Clo+Ara-C arm compared with Ara-C arm, respectively. DFS and DOR were similar in both arms. Overall 30-day mortality was 16% and 5% for CLO+Ara-C and Ara-C arms, respectively. In the Clo+Ara-C and Ara-C arms, the most common grade 3 to 4 toxicities were febrile neutropenia (47% v 35%, respectively), hypokalemia (18% v 11%, respectively), thrombocytopenia (16% v 17%, respectively), pneumonia (14% v 10%, respectively), anemia (13% v 0%, respectively), neutropenia (11% v 9%, respectively), increased AST (11% v 2%, respectively), and increased ALT (10% v 3%, respectively). Conclusion Although the primary end point of OS did not differ between arms, Clo+Ara-C significantly improved response rates and EFS. Study follow-up continues, and the role of clofarabine in the treatment of adult patients with AML continues to be investigated.
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Dillon, John. "C. LUNA and A.-P. SEGONDS (eds) Proclus, Commentaire sur le Parménide de Platon, Livre VI. Paris: Les Belles Lettres, 2017. Pp. cxv + 472. €55. 9782251006130." Journal of Hellenic Studies 139 (October 14, 2019): 274–76. http://dx.doi.org/10.1017/s0075426919000429.
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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.
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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.
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Pinilla, Juan Carlos, and Natalia Da Silva Borges. "Prevalencia de Cystoisospora suis en granjas porcinas intensivas de la región central de Venezuela." Revista de la Facultad de Medicina Veterinaria y de Zootecnia 64, no. 1 (January 1, 2017): 11–23. http://dx.doi.org/10.15446/rfmvz.v64n1.65811.
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It was carried out an investigation at the central region of Venezuela from January to June 2014 with the aim to determine the prevalence of coccidian Cystoisospora suis in intensive swine herds. For parasitic determination 572 litters were selected with signsof diarrhea. Likewise, 1.712 fecal samples were also collected in mature pigs. Stoolsamples were cultured in a 2.5% potassium dichromate solution and later processedby coprological technique. The results of this investigation indicated that C. suis was observed in 55 herds (82.1%) and 210 litters (36.7%) with the highest prevalence values in first two weeks of age (P < 0.05). Regarding to mature pigs, there was a significant correlation (rho = 0.35; P < 0.05) among oocysts excretion in piglets and sows, suggesting that sows may act as infection sources. Sows parity was statistically correlated with the prevalence values in litters as in lactating sows (P < 0.05). This might indicate that as parity increase, prevalence decreases in these groups. Probably these findings are associated with unknown immunologic mechanisms. It is concluding that C. suis is broadly distributed in Venezuela and it could be controlled by improving conditions sanitary herd, however, non elucidated immunologic mechanisms might be involved in the protozoa transmission cycle.
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Choi, Jungmin, Aranzazu Manzano, Weilai Dong, Stefania Bellone, Elena Bonazzoli, Luca Zammataro, Xiaotong Yao, et al. "Integrated mutational landscape analysis of uterine leiomyosarcomas." Proceedings of the National Academy of Sciences 118, no. 15 (April 5, 2021): e2025182118. http://dx.doi.org/10.1073/pnas.2025182118.
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Uterine leiomyosarcomas (uLMS) are aggressive tumors arising from the smooth muscle layer of the uterus. We analyzed 83 uLMS sample genetics, including 56 from Yale and 27 from The Cancer Genome Atlas (TCGA). Among them, a total of 55 Yale samples including two patient-derived xenografts (PDXs) and 27 TCGA samples have whole-exome sequencing (WES) data; 10 Yale and 27 TCGA samples have RNA-sequencing (RNA-Seq) data; and 11 Yale and 10 TCGA samples have whole-genome sequencing (WGS) data. We found recurrent somatic mutations in TP53, MED12, and PTEN genes. Top somatic mutated genes included TP53, ATRX, PTEN, and MEN1 genes. Somatic copy number variation (CNV) analysis identified 8 copy-number gains, including 5p15.33 (TERT), 8q24.21 (C-MYC), and 17p11.2 (MYOCD, MAP2K4) amplifications and 29 copy-number losses. Fusions involving tumor suppressors or oncogenes were deetected, with most fusions disrupting RB1, TP53, and ATRX/DAXX, and one fusion (ACTG2-ALK) being potentially targetable. WGS results demonstrated that 76% (16 of 21) of the samples harbored chromoplexy and/or chromothripsis. Clinically actionable mutational signatures of homologous-recombination DNA-repair deficiency (HRD) and microsatellite instability (MSI) were identified in 25% (12 of 48) and 2% (1 of 48) of fresh frozen uLMS, respectively. Finally, we found olaparib (PARPi; P = 0.002), GS-626510 (C-MYC/BETi; P < 0.000001 and P = 0.0005), and copanlisib (PIK3CAi; P = 0.0001) monotherapy to significantly inhibit uLMS-PDXs harboring derangements in C-MYC and PTEN/PIK3CA/AKT genes (LEY11) and/or HRD signatures (LEY16) compared to vehicle-treated mice. These findings define the genetic landscape of uLMS and suggest that a subset of uLMS may benefit from existing PARP-, PIK3CA-, and C-MYC/BET-targeted drugs.
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Medrano, Mayte, María Victoria Barbado-Gonzalez, Nuria Campillo, Francisco Hidalgo, Teresa Caballero-Velazquez, Olga Perez-Lopez, Maria Sole-Rodriguez, Jose Ignacio Piruat-Palomo, and Jose A. Perez-Simon. "Cannabinoids Derivatives Exert a Potent Antileukemic Effect By Modifying the Pattern of Membrane Sphingolipids." Blood 128, no. 22 (December 2, 2016): 4718. http://dx.doi.org/10.1182/blood.v128.22.4718.4718.
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Abstract Endocannabinoid system is a set of ligands, receptors and endogenous enzymes which modulate a variety of physiological effects. There are two well-characterized cannabinoid receptors, CB1 (mainly expressed in Central Nervous System) and CB2 (mainly in hematopoietic cells). Here, we tested the effect of the cannabinoid WIN-55 212-2 in acute myeloid leukemia (AML) in vitro, ex vivo and in vivo and studied the molecular signaling pathways involved in this effect. Moreover, we synthesized a new family of twelve cannabinoids that are specific to CB2 receptor. For their design and synthesis, computational techniques of docking, analytical and spectroscopic techniques such as mass spectrometry (MS) were used. To assess the anti-leukemia effect of the different cannabinoids, we analyzed cell viability by MTT and flow cytometry using six human AML cell lines, primary cells from healthy donors (hematopoietic progenitor cells (HPC) and lymphocytes) and blasts from AML patients. Cannabinoids induced a potent proapoptotic effect on AML cell lines and on primary leukemic cells, which was not observed in normal HPC and lymphocytes from healthy donors. Fragmentation of PARP and activation of caspases 2, 3, 8 and 9 were confirmed by western-blot. Other proteins involved in the effect of cannabinoids were p-AKT, p-ERK 1/2, p-38 and p- JNK. Also studies on p-PERK, p-IRE1 and CHOP confirmed an increased endoplasmic reticulum stress upon exposure to cannabinoids. Mitochondrial damage was analyzed by flow cytometry using TMRE and by MitoSOXTMRed. These assays confirmed a very early mitochondrial damage in leukemic cells which was not observed in normal hematopoietic progenitor cells. Moreover, we analyzed the ceramide levels, a membrane lipid associated with death/survival cell processes by HPLC and immunohistochemistry. Remarkably, we observed significant differences in the amounts of certain subtypes of ceramides in untreated versus treated leukemic cells. The proapoptotic effect of cannabinoids on AML cells was abolished upon co-culture with either CB2 receptor antagonists or with pancaspase inhibitors. Finally, NOD/scid/IL-2R gammae null (NSG) mice were xenotransplanted with HL60 cell line. We confirmed disease infiltration in bone marrow (BM) by BM aspirates and flow cytometry assays. Once the presence of leukemic cells was confirmed, treatment with vehicle, WIN-55 cannabinoid at a dose of 5 mg/kg/day or citarabine (ARA-C) at 50 mg/kg during 5 days was administered. We observed a significantly increased survival among mice treated with WIN-55 cannabinoid as compared to both the control group and the group treated with ARA-C. In addition, we tested in vivo the effect of these compounds on normal hematopoiesis by treating healthy BALB-C mice. We confirmed that cannabinoids did not affect the viability of the different populations of hematopoietic progenitors (LK, GMP, CMP) and, moreover, an increased platelet count was observed in treated mice. Our findings indicate that cannabinoids display a highly selective proapoptotic effect against leukemic cells. Several pathways are involved in this effect, the modification in the ceramide pattern playing a main role. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.
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Greene, Kevin. "Rushden: the Early Fine Wares. By P. J. Woods and B. C. Hastings, edited and revised by K. Brown. 29.5 × 21 cm. Pp. 118, 55 figs. Northampton: Northamptonshire County Council, 1984. ISBN 0-947590-00-5. £6.50 (p/b)." Antiquaries Journal 65, no. 2 (September 1985): 507–8. http://dx.doi.org/10.1017/s0003581500027487.
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Mancuso, Maria E., Elena Santagostino, Maria G. Rumi, Silvia Linari, Antonio Coppola, Angiola Rocino, Alfonso Iorio, et al. "High Efficacy of Combination Therapy with Pegylated Interferon and Ribavirin in Hemophiliacs with Chronic Hepatitis C." Blood 106, no. 11 (November 16, 2005): 3219. http://dx.doi.org/10.1182/blood.v106.11.3219.3219.
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Abstract Pegylated interferon (Peg-IFN) plus ribavirin is the standard treatment for patients with chronic hepatitis C. In a multicenter open trial, we assessed the efficacy and tolerability of this treatment in 78 HIV negative hemophiliacs (age: 20–64 years) with persistently high transaminase values. Sixty-four were naïve and 14 were relapsers to IFN monotherapy. Cirrhosis was clinically detected in 12 patients (15%). HCV genotype was 1 in 69%, 2a/c in 14%, 3a in 14% and 4 in 3%. Peg-IFN alpha-2b was given subcutaneously at doses of 1.5 mcg/Kg/week for 48 weeks in genotypes 1 and 4 and for 24 weeks in genotypes 2 and 3; oral ribavirin at 800–1200 mg/day based on body weight. Treatment was stopped in patients with polymerase chain reaction positive HCV-RNA at month 6. Results: 11 patients (14%) withdrew for side effects (4) or non-compliance (7). Neutropenia (<500 cells/mmc), decompensated diabetes, ALT flares, and vomiting not responding to antiemetic drugs were reasons for treatment discontinuation. The median fall in hemoglobin levels was 3.1 g/dL. Weight loss (38%), fatigue (33%) and cephalalgia (15%) were frequent side effects. Thirty-two patients (41%) required dose reduction of ribavirin (23, 29%) or Peg-IFN (20, 26%). At the end of the 6-month follow-up, sustained virological response (SVR) was achieved in 43 patients (55%): 40/64 naïve (63%) and 3/14 relapsers (21%, p = 0.007). Five patients (6%), all relapsers to IFN monotherapy, had a virological breakthrough during treatment and 4 (5%) relapsed during the post-treatment follow-up period. SVR was obtained in 86% genotypes 2/3 and 43% genotypes 1/4 (p = 0.001). Predictors of SVR were evaluated by univariate analysis in the 64 naïve patients. SVR was significantly associated with HCV infection type 2 and 3 (86% vs 50% in HCV type 1 and 4; p = 0.008), absence of cirrhosis (97.5% vs 75% in non-responders; p = 0.02) and higher pre-treatment serum ALT levels (111 vs 75 IU/L in non-responders; p = 0.02). SVR rates did not differ in relation to patient’s age, pretreatment HCV viremia, median disease duration and compliance to full-dose treatment. Conclusions: combination therapy with Peg-IFN plus ribavirin is the recommended therapeutic option for hemophiliacs with hepatitis C chronic infection. Relapsers to IFN monotherapy may benefit of re-treatment with Peg-IFN plus ribavirin achieving at least 20% SVR. Genotype 2 and 3 infection is the most significant predictor of SVR.
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Nishiyama, Tomoki. "Sedation during Artificial Ventilation by Continuous Intravenous Infusion of Midazolam: Effects of Hepatocellular or Renal Damage." Journal of Intensive Care Medicine 12, no. 1 (January 1997): 40–44. http://dx.doi.org/10.1177/088506669701200105.
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To evaluate the effects of hepatocellular or renal damage on therapeutic doses of midazolam and emergence time after withdrawal of the drug, 87 patients under continuous sedation with midazolam on artificial ventilation were prospectively studied. They needed continuous sedation for 12 hours or more. They included 55 patients with normal hepatocellular and renal functions (C group), 21 patients with hepatocellular damage (II group), and 11 patients with hepatocellular and renal damage (HR group). Midazolam was initiated with an intravenous dose of 0.1 mg/kg followed by 0.05 mg/kg/hr. Dosage was regulated to maintain a state in which patients responded to verbal command and had bucking responses to endotracheal suctioning. The three groups were compared with respect to midazolam dosage, emergence time, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels and urine volume. The mean doses of midazolam in the C, H, and HR groups were 0.083 ± 0.038 mg/kg/hr, (mean ± standard deviation) 0.073 ± 0.037 mg/kg/hr, and 0.088 ± 0.048 mg/kg/hr, respectively, showing no differences among these groups. Emergence time was significantly longer in the H group (333 ± 263 min; p < 0.005) and the HR group (305 ± 225 min; p < 0.025) than in the C group (171 ± 106 min). No effect of midazolam administration was seen on AST, ALT, BUN, Cr, and urine volume in all groups. In conclusion, presence of hepatocellular or renal damage did not alter required dosage of midazolam. Hepatocellular damage prolonged emergence time, but renal damage had no more additive effect. There was no evidence of hepatocellular and renal damages during treatment.
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Titiana, Asih, Ktut Murniati, and Eka Kasymir. "ANALISIS EFISIENSI PEMASARAN PRODUKSI JAGUNG DI KECAMATAN BANDAR SRIBHAWONO KABUPATEN LAMPUNG TIMUR." Jurnal Ilmu-Ilmu Agribisnis 8, no. 2 (June 23, 2021): 235. http://dx.doi.org/10.23960/jiia.v9i2.5081.
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This study aims to analyze the efficiency of corn marketing. The research method used is a survey method. Data collection was carried out in Bandar Sribhawono District of East Lampung Regency in January - March 2019. Farmer respondents were chosen randomly and marketing agency respondents were taken by following the marketing flow. Data used are primary and secondary data. The analysis method used is the S-C-P (Structure, Conduct, Performance) model. The results showed that the corn marketing system in Bandar Sribhawono Sub-district has not been efficient, because the market structure faced by farmers was the oligopsonistic market structure, market behavior shows that farmers are still disadvantaged and act as price takers, there was one marketing channel with producer share (PS) below 55%, high marketing margin and profit margin ratio (RPM) does not spread evenly. Key words: corn, efficiency, marketing
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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.
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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
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Nedogoda, S. V., E. V. Chumachek, A. A. Ledyaeva, V. V. Tsoma, A. S. Salasyuk, V. O. Smirnova, V. Yu Hripaeva, R. V. Palashkin, and E. A. Popova. "OPTIMAL ORGANOPROTECTION, CONTROL OF bLOOD PRESSURE AND METAbOLIC DISORDER WITH THE FIxED COMbINATION OF LISINOPRIL, AMLODIPINE AND ROSUVASTATIN IN SYSTEMIC HYPERTENSION." Russian Journal of Cardiology, no. 4 (May 9, 2018): 49–55. http://dx.doi.org/10.15829/1560-4071-2018-4-49-55.
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Aim. Evaluation of the ability of the fixed combination of lisinopril, amlodipine and rosuvastatin (Equamer) in achievement of additional angioprotection in patients with systemic arterial hypertension (AH) and high pulse wave velocity (PWV), regardless of previous antihypertensive therapy (AHT).Material and methods. To the open multicenter observational study 24 weeks duration, 60 patients included, taking double AHT during 6 months. All participants underwent ambulatory 24 hour blood pressure (BP) monitoring, applanation tonometry (augmentation index and central BP), pulse wave velocity assessment, laboratory tests (lipids, fasting glucose, insulin resistance index (HOMA), leptin, high sensitive C-reactive protein (hsCRP) before and after transition to the fixed combination of lisinopril, amlodipine and rosuvastatin (Equamer).Results. By the data from office BP measurement, after transition of patients from the double combinations to fixed combination of lisinopril, amlodipine and rosuvastatin, there was additional decrease of systolic BP (SBP) by 14,3% and diastolic BP (DBP) by 18,5%. By the data from ABPM, decrease of SBP was 16,1%, and DBP — 21,8%. Combination of lisinopril, amlodipine and rosuvastatin decreased PWV by 14,4%, augmentation index by 14,5%, central SBP by 8,1% (p<0,01 for all comparisons with baseline). Fixed combination of lisinopril, amlodipine and rosuvastatin made it to decrease low density lipoproteides by 44%, triglycerides by 36,1% and increase of high density lipoproteides by 10,3% (p<0,01 for all with baseline). Usage of combination of lisinopril, amlodipine and rosuvastatin showed significant decrease of insulin resistance, hsCRP and leptin levels.Conclusion. Fixed combination of lisinopril, amlodipine and rosuvastatin makes it to better control BP, improve vascular elasticity parameters (augmentation index, PWV, central BP) and facilitates the improvement of lipid and glucose metabolism, decrease of inflammation, leptin resistance in patients taking at baseline double antihypertensive therapy.
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Lemoine, Sandrine, Gallic Beauchef, Lan Zhu, Emmanuelle Renard, Olivier Lepage, Massimo Massetti, André Khayat, Philippe Galera, Jean-Louis Gérard, and Jean-Luc Hanouz. "Signaling Pathways Involved in Desflurane-induced Postconditioning in Human Atrial Myocardium In Vitro." Anesthesiology 109, no. 6 (December 1, 2008): 1036–44. http://dx.doi.org/10.1097/aln.0b013e31818d6b09.
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Background Isoflurane and sevoflurane have been shown to elicit myocardial postconditioning, but the effect of desflurane remain unknown. The authors studied the mechanisms involved in desflurane-induced myocardial postconditioning. Methods Contracting isolated human right atrial trabeculae (34 degrees C, stimulation frequency 1 Hz) were exposed to 30-min hypoxia followed by 60-min reoxygenation. Desflurane at 3%, 6%, and 9% was administered during the first 5-min of reoxygenation. Postconditioning with 6% desflurane was studied in the presence of 1 microM calphostin C, a protein kinase C inhibitor; 800 mm 5-hydroxydecanoate, a mitochondrial adenosine triphosphate-sensitive potassium channels antagonist; 1 microM Akt inhibitor; 20 microM PD89058, an extracellular-regulated kinase 1/2 inhibitor; and 1 microM SB 202190, a p38 mitogen-activated protein kinase inhibitor. The force of contraction at the end of the 60-min reoxygenation period was compared (mean +/- SD). The p38 mitogen-activated protein kinase phosphorylation was studied using Western blotting. Results Desflurane at 3% (77 +/- 10% of baseline), 6% (90 +/- 14% of baseline), and 9% (86 +/- 11% of baseline) enhanced the recovery of force after 60 min of reoxygenation as compared with the control group (51 +/- 9% of baseline; P < 0.001). Calphostin C (55 +/- 3% of baseline), 5-hydroxydecanoate (53 +/- 3% of baseline), Akt inhibitor (57 +/- 8% of baseline), PD89058 (64 +/- 6% of baseline), and SB 202190 (61 +/- 3% of baseline) abolished desflurane-induced postconditioning. Western blot analysis showed that 6% desflurane increased p38 mitogen-activated protein kinase phosphorylation. Conclusions In vitro, desflurane postconditioned human atrial myocardium through protein kinase C activation, opening of mitochondrial adenosine triphosphate-sensitive potassium channels, Akt and extracellular-regulated kinase 1/2 activation, and p38 mitogen-activated protein kinase phosphorylation.
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Lakshmi, Seetha, Kimberly Atrubin, Andrew Myers, Jonathan Teter, Ripal Jariwala, Kristen Zeitler, Laura Haubner, Terri Ashmeade, and Maya Balakrishnan. "2348. Incorporating Electronic Medical Record Hard Stops to Reduce Inappropriate Clostridioides difficile Testing at an Academic Medical Center: A Quality Improvement Study." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S807—S808. http://dx.doi.org/10.1093/ofid/ofz360.2026.
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Abstract Background Clostridioides difficile is the most common pathogen causing healthcare-associated infections. This study highlights the multi-disciplinary efforts to reduce C. difficile infections (CDI) at a large, tertiary care teaching facility. Methods A quality improvement study was performed between March 2017 and April 2018, using six Plan-Do-Study-Act cycles that included transmission prevention, diagnostic stewardship, education, and antimicrobial stewardship. Process measures included hand hygiene, isolation precautions, low-level disinfection compliance, number of tests ordered, lab cancelation of tests, and compliance with the Electronic Medical Record (EMR) hard stop for patients with laxative use, and negative C.difficile test in the past 7 days. Results A total of 2,046 C. difficile tests were ordered during the initiative. Of the 124 patients with a positive C. difficile LabID event, 50% were male with a median age of 65 years (range: 11–92 years). A 53% reduction in C. difficile LabID events (7.5 to 4 events per 10,000 patient-days, P < 0.001), with a pronounced decrease between cycle 4 and 5 (5.4 to 2.9 events per 10,000 patient-days, P < 0.001) was achieved. The largest decrease in C. difficile lab tests ordered was seen after implementation of the EMR hard-stop (cycle 5), with fewer than 0.5 LabID events per 1,000 patient-days for each subsequent month after EMR hard-stop implementation. Frequent reasons for physician phone calls to Infection prevention department was related to chronic use of lactulose in patients with cirrhosis (30%) and unexplained diarrhea (70%). Based on provider feedback, EMR changes were made to remove lactulose from the hard-stop and offer infectious disease consultation upfront. There was 99% compliance with electronic medical record hard stop. There was a nonsignificant increase in lab cancelations due to inappropriate stool specimens over time (1.9% to 3.1% from cycle 1 to 6, P = 0.28) A 55% reduction in hospital-onset CDI surveillance events (from 6.9 to 3.2 per 10,000 patient-days, P < 0.001) was noted. Conclusion A multi-disciplinary Quality Improvement initiative is a successful strategy in reducing CDI events, with the largest decrease seen with introduction of EMR hard stops. Disclosures All authors: No reported disclosures.
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Ozen, S., N. Aktay, E. Lainka, A. Duzova, A. Bakkaloglu, and T. Kallinich. "Disease severity in children and adolescents with familial Mediterranean fever: a comparative study to explore environmental effects on a monogenic disease." Annals of the Rheumatic Diseases 68, no. 2 (September 18, 2008): 246–48. http://dx.doi.org/10.1136/ard.2008.092031.
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Background:Worldwide, familial Mediterranean fever (FMF) is the most common autoinflammatory disease. It has been suggested that environmental factors affect the phenotype as some patients do not develop the complication of secondary amyloidosis.Objective:To analyse whether disease severity in Turkish children with FMF, living in Turkey and Germany is different.Patients and methods:A total of 55 Turkish children living in Turkey were compared with 45 Turkish children born and raised in Germany. Mean age among the group from Turkey and Germany was 42.2 and 44.29 months, respectively. M694V was the leading mutation in both groups. The severity scores were compared with two scoring systems, modified according to published paediatric data for dosage.Results:There was no significant difference between the mean C-reactive protein and erythrocyte sedimentation rate levels of the two groups. According to the modified Sheba Center score, 78.2% of patients from the group living in Turkey had a severe course compared with 34.1% from the group living in Germany. The modified score of Pras et al also showed more severe disease in the patients from Turkey. The difference between the two groups for both scoring systems were significant (both p<0.05).Conclusions:We believe the modified scores that we introduce can be widely used for children. Our results suggest that the environment affects the phenotype of a monogenic disease of the innate inflammatory pathway.
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Okihara, K., I. Takeuchi, O. Ukimura, N. Takaha, A. Kawauchi, and T. Miki. "Prognostic outcome in Japanese men with prostate cancer treated with androgen-deprivation therapy (ADT) alone: Data from multi-institutional cooperative study in Kyoto Prostate Cancer Registry (KPCR)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e16106-e16106. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e16106.
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e16106 Background: There is scarce data of ADT alone concerning prognostic outcome in terms of clinical stage, and in comparison with radical treatments specifically in men without metastatic diseases. The aim of this study was to analyze prognostic outcome for ADT alone, and to assess the significant prognostic parameters in Japanese men. Methods: Database in the KPCR, which is a multi-institutional urologic cancer registry, was screened to identify prostate cancer patients who received ADT alone between 1988 and 2008. Clinical data including age, clinical stage, biopsy differentiation, initial prostate-specific antigen (PSA) level and type of ADT: luteinizing hormone-releasing hormone (LH-RH) monotherapy or combined androgen blockade (CAB), were analyzed. Time to prostate cancer relapse as well as cause specific survivals were also analyzed. Results: Of 1167 men with prostate cancer registered in KPCR, 373 patients (32%) received primary ADT and continued ADT alone during the observation period. Of those men, age and PSA level ranged from 52 to 95 y.o (median: 75) and from 2.17 to 8,650 ng/ml (median: 23.5), respectively. The numbers of clinical stage in A to B, C and D were 148 (40%), 127 (34%), and 98 (26%), respectively. The observation period ranged from 1 to 125 months (median: 55). Of the 373 men, 113 men (30%) recurred after the primary ADT. Of the 131men, 36 men (10%) changed from LH-RH monotherapy to CAB, and 46 (12%) and 52 men (14%) underwent anti-androgen alternative therapy and secondary hormonal therapy using estramustine phosphate and/or oral dexamethasone, respectively. There was a significant difference in 5-year cause specific survival between stage A-C (98%) and D (63%, p < 0.0001). Cox proportional hazards multivariate regression analyses revealed that localized cancer (stage A and B) was the most significant prognostic factor in the time to relapse (p < 0.0001) as well as the cause specific survival (p < 0.0001). Conclusions: There was substantial number of men with localized disease who were treated ADT alone. The use of ADT therapy alone appeared to have favor prognosis in the majority of patients without metastatic diseases, at least for an intermediate period. No significant financial relationships to disclose.
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Hosseini, Elahe S., Hamed H. Kashani, Hossein Nikzad, Alireza Soleimani, Hamed Mirzaei, Mohammd R. Tamadon, and Zatollah Asemi. "Diabetic Hemodialysis: Vitamin D Supplementation and its Related Signaling Pathways Involved in Insulin and Lipid Metabolism." Current Molecular Medicine 19, no. 8 (September 5, 2019): 570–78. http://dx.doi.org/10.2174/1566524019666190618144712.
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Background: This study was conducted to determine the effects of vitamin D supplementation on some of the gene expressions related to insulin and lipid metabolism in diabetic hemodialysis (HD) patients. Methods: A double-blind, randomized, placebo-controlled clinical trial was carried out in 55 patients with diabetic HD. The current project used two groups in which each subject received vitamin D supplements (50,000 IU, n=28) or placebo (50,000 IU, n=27) every 2 weeks for 12 weeks. Gene expression analyses (RT-PCR) were included to obtain the rate of gene expression of the related insulin and lipid metabolism genes in peripheral blood mononuclear cells (PBMCs) of patients with diabetic HD. Results: Our data revealed that consumption of vitamin D supplementation enables to overexpress the peroxisome proliferation-activated receptor gamma (PPAR-γ) (P=0.001), AKT (P=0.04), PI3K (P=0.02), insulin receptor substrate-1 (IRS1) (P0.008) and glucose transporter type 4 (GLUT-4) (P=0.01) and downregulate the expression of protein kinase C (PKC) (P=0.001) in patients with diabetic HD than control group following the 12-week intervention. In addition, vitamin D supplementation downregulated low-density lipoprotein receptor (LDLR) (P=0.03) expression in the subjects with diabetic HD than the control group. Vitamin D supplementation did not show any effects on the expression of pyruvate dehydrogenase kinase 1 (PDK1) (P=0.37), IRS2 (P=0.90) and lipoprotein (a) [Lp(a)] (P=0.05). Conclusions: Our findings confirmed that diabetic HD subjects who received the vitamin D supplementation (for 12 weeks), showed a significant overexpression in the PPAR-γ, AKT, PI3K, IRS1 and GLUT4 genes, and also showed a significant downregulation in the PKC and LDLR genes. Moreover, no effects on PDK1, IRS2 and Lp(a) expression were observed.
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Batalla, Alberto, Ruth Alvarez, Julián R. Reguero, Sergio Hevia, Gustavo Iglesias-Cubero, Victoria Alvarez, Arturo Cortina, et al. "Synergistic Effect between Apolipoprotein E and Angiotensinogen Gene Polymorphisms in the Risk for Early Myocardial Infarction." Clinical Chemistry 46, no. 12 (December 1, 2000): 1910–15. http://dx.doi.org/10.1093/clinchem/46.12.1910.
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Abstract Background: Several studies based on different populations worldwide have described an association between cardiovascular diseases and genetic variations in the apolipoprotein E (APOE), angiotensinogen (AGT), angiotensin receptor type 1 (AT1R), and angiotensin-converting enzyme (ACE) genes. In addition, there is growing evidence of an interaction between hypercholesterolemia and the renin-angiotensin system in the risk for hypertension and atherosclerosis. Methods: To determine whether the DNA polymorphisms in APOE (ε2, ε3, and ε4 alleles), AGT (M235T), AT1R (1166 A/C), and ACE (I/D) are associated with early onset of myocardial infarction (MI), we genotyped 220 patients and 200 controls <55 years of age. Patients and controls were males from the same homogeneous Caucasian population. Data concerning hypertension, diabetes, and tobacco consumption were recorded. The lipid profiles of patients and controls were also determined. Results: APOE, ACE, AGT, and AT1R allele and genotype frequencies did not differ between patients and controls. None of these polymorphisms was related to the biochemical values in patients or controls. The frequency of individuals who were both APOEε4 allele carriers and AGT-TT homozygotes was significantly higher in patients than in controls (11% vs 3.5%; P = 0.0037). In patients, the frequency of ε4 carriers was significantly higher (P <0.00001) in those who were AGT-TT (46%) than those who were AGT-MT/MM (14%). Mean cholesterol was significantly higher in AGT-TT + APOE ε34/44 patients than in the TM/MM + ε34/44 or TT + ε23/33 genotypes (P = 0.029). Conclusions: Our data suggest a synergistic effect between the APOE and AGT polymorphisms and early MI. The increased risk could be mediated in part through higher cholesterol concentrations among individuals who are AGT-TT + APOEε4 allele carriers.
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Eng, C., Y. Xing, Y. N. You, G. J. Chang, P. Das, J. Phillips, R. A. Wolff, M. A. Rodriguez-Bigas, A. Ohinata, and C. H. Crane. "Cisplatin (C) based chemoradiation (CXRT) for locally advanced squamous cell carcinoma (SCCA) of the anal canal (AC): A 20-year perspective." Journal of Clinical Oncology 29, no. 4_suppl (February 1, 2011): 482. http://dx.doi.org/10.1200/jco.2011.29.4_suppl.482.
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482 Background: The standard of care for locally advanced SCCA of the AC is 5-fluorouracil (5-FU)/mitomycin C (MMC) with concurrent XRT. C was evaluated with 5-FU in 2 large phase III studies (RTOG 98-11 and ACT II) to establish superiority over 5-FU/MMC. Neither study showed significant differences for disease-free survival (DFS) or overall survival (OS). RTOG 98-11 reported reduced colostomy-free survival (CFS) in the C-induction arm; no differences were noted in the ACT II study. We present our 20-year experience with C for locally advanced SCCA of the AC which has been adopted as the standard unless contraindicated. Methods: A retrospective, single institution analysis for locally advanced SCCA of the AC was completed in patients (pts) that received concurrent 5-FU/C/XRT from 1989-2009. Medical records were reviewed for history of STDs, chronic immunosuppression, stage, dose of XRT, toxicity, clinical response (CR), recurrence, and OS. Multidisciplinary management included surgical, radiation, and medical oncologists. OS, DFS, and CFS were calculated using the K-M method. The log-rank test was used to compare OS among these subgroups. Results: 185 pts were identified (51 M:134 F). The median age was 56 (35-83 y.o.). AJCC stage was I (n = 25); II (n = 76); IIIA (n = 36); and IIIB (n = 48). The median XRT dose was 55 Gy in 30 fractions. 181 pts were evaluable for response; 4 were lost to follow up. Complete CR (cCR) was noted in 169 pts (93%); partial response (n = 12); 6 pts received an APR. After a median follow up of 8.6 years, 14 pts (8%) developed local recurrence; 11 received salvage surgery. 16 pts (9%) developed distant metastases (DM). The 5-yr DFS = 81%, 5-yr OS = 85% and 5-yr CFS was 88%. By univariate analysis, N-stage was a poor prognostic indicator for 5-yr DFS (p = 0.02) and DM (p = 0.046) but not OS or CFS. Increased T-stage correlated with salvage surgery (p = 0.005). Conclusions: Cisplatin-based chemoradiation for locally advanced SCCA of the anal canal resulted in favorable DFS, OS, and CFS compared to historical data and phase III studies. Platinum-based therapy for anal cancer appears to be an acceptable alternative to MMC and should be considered as a standard option for locally advanced disease. No significant financial relationships to disclose.
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Nelson, Matthew J., M. Brennan Harris, Marvin O. Boluyt, Hyun Seok Hwang, and Joseph W. Starnes. "Effect of N-2-mercaptopropionyl glycine on exercise-induced cardiac adaptations." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 300, no. 4 (April 2011): R993—R1000. http://dx.doi.org/10.1152/ajpregu.00405.2010.
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The purpose of this study was to test the hypothesis that exercise-induced cardiac adaptations would be attenuated by the free radical scavenger N-2-mercaptopropionyl glycine (MPG). Male Sprague-Dawley rats were divided into four groups ( n = 9–13 per group) for 3–4 wk: sedentary (S), S+MPG (100 mg/kg ip daily), exercised on a treadmill (E) (60 min/day, 5 days/wk, at a speed of 20 m/min up a 6° grade in a 6°C room), or E+MPG given 10 min prior to exercise. Additional rats ( n = 55) were used to determine acute exercise effects on myocardial redox state [nonprotein nonglutathione sulfhydryls (NPNGSH)] and PI3K/Akt signaling pathway activation. Compared with S, NPNGSH levels were 48% lower in E ( P < 0.05) and unchanged in E+MPG ( P > 0.05). MPG also attenuated exercise-induced activation of the signaling proteins Akt and S6. Hearts from the 4-wk groups were weighed, and cardiac function was evaluated using an isolated perfused working heart preparation. Similar increases ( P < 0.05) in both exercised groups were observed for heart weight and heart weight-to-body weight ratio. Cardiac function improved in E vs. S, as indicated by greater ( P < 0.05) external work performed (cardiac output × systolic pressure) and efficiency of external work (work/V̇o2). MPG prevented these exercise-induced functional improvements. Skeletal muscle mitochondria content increased to similar levels in E and E+MPG. This study provides evidence that free radicals do not play an essential role in the development of exercise-induced cardiac hypertrophy; however, they appear to be involved in functional cardiac adaptations, which may be mediated through the PI3K/Akt pathway.
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Eradat, Herbert, Sebastian Grosicki, John Catalono, Walter Cosolo, Irina Dyagil, Thomas J. Kipps, Beiyao Zheng, et al. "Preliminary Results of a Phase II Open-Label, Randomized Study of the BH3 Mimetic Protein Navitoclax (ABT-263) with or without Rituximab for Treatment of Previously Untreated B-Cell Chronic Lymphocytic Leukemia." Blood 120, no. 21 (November 16, 2012): 190. http://dx.doi.org/10.1182/blood.v120.21.190.190.
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Abstract Abstract 190 Introduction: Overexpression of Bcl-2 in Chronic Lymphocytic Leukemia (CLL) is associated with enhanced CLL-cell resistance to spontaneous or chemotherapy-induced apoptosis. The BH3 mimetic protein navitoclax (ABT-263) specifically inhibits Bcl-2, and related proteins Bcl-xL and Bcl-w, and can induce apoptosis of CLL cells in vitro. Phase I evaluation in relapsed/refractory CLL patients demonstrated 35% overall response rate (Roberts, 2012). Dose-limiting thrombocytopenia due to Bcl-xL inhibition was mitigated using a lead-in dosing schedule to allow the bone marrow to achieve a compensatory increase in platelets prior to dose escalation to the MTD of 250 mg. Based on the promising single-agent data, a Phase II trial randomized trial compared the safety, pharmacokinetics, and biologic activity of treatment with navitoclax and rituximab (RTX) versus RTX alone. Methods: Patients with CLL who required initial treatment according to iwCLL criteria (Hallek et al, 2008) were stratified by Binet stage and high-risk cytogenetic features (17p deletion and/or 11q deletion), and randomized 1:1:1 to receive RTX weekly for 8 wks (375 mg/m2 wk 1, 500 mg/m2 wks 2–8) (Arm A), or RTX for 8 wks plus navitoclax daily for 12 wks (250 mg/day following a 7–14 day lead-in period of 100 mg/day) (Arm B), or RTX for 8 wks plus navitoclax daily as in Arm B, but continued treatment with navitoclax until disease progression, relapse, or unacceptable toxicity (Arm C). Arm A to Arm B crossover was permitted. Response rate was assessed by iwCLL CLL response criteria at week 12, and every 12 weeks during follow-up. The study was stopped after the last patient had completed ≥ 12 weeks of treatment and week-12 response assessment. Results: Baseline characteristics and prognostic factors for the 118 randomized patients were generally balanced among the three treatment arms. Median age was 63 years (range 38–94), and 55% were Binet stage B+C. Median baseline lymphocyte count was 53,000 mm3 (range 7,000–552,000/mm3). FISH analyses identified higher than expected rates of deletion of 11q or 17p in the CLL cells of 32% or 28% of patients, respectively. Median time on study was 32 weeks overall (24 wks for Arm A, 33 wks Arm B, and 44 wks Arm C). AEs of Grade 3–4 that were more common (> 5% greater) in a navitoclax-treated arm compared with the RTX arm included thrombocytopenia, neutropenia, leukopenia, anemia, GI symptoms (diarrhea, abdominal pain), chills, fatigue, ALT/AST/bilirubin elevations, and infusion-related reactions (to RTX). Thrombocytopenia, neutropenia, and hepatic enzyme elevations were generally reversible when navitoclax was stopped and/or dose-reduced; however, 12 patients (15%) discontinued navitoclax due to laboratory abnormalities (9 due to ALT elevations). Neutropenia responded to growth factors. One serious event of epistaxis occurred related to the thrombocytopenia. Two deaths occurred on study, one on the RTX-only arm due to a pulmonary embolus and one on Arm B due to hypotension and dyspnea related to a severe RTX infusion reaction. Investigator-assessed objective response (CR and PR) rate was 35% for Arm A, 55% for Arm B (p=0.19 vs A), and 70% for Arm C (p=0.0034 vs A). All responses were PRs except for 2 CRs in Arm C. All responses were confirmed by CT (and BM for CR) ≥ 8 wks after clinical response assessment. While the presence of 17p deletion appeared to result in a lower response rate to RTX alone (Arm A, ORR 18%, 2/11 pts), it did not appear to affect the response to ABT-263 and RTX (Arm B, ORR 73%, 8/11 pts); Arm C, ORR 50%, 5/10 pts. Limited PFS results appeared consistent with the responses by arm, with a longer PFS associated with the longer duration of ABT-263 treatment on Arm C; however, the magnitude of PFS differences could not be precisely quantified due to the limited follow-up and patient number. Preliminary pharmacokinetic analysis did not detect any drug interaction between navitoclax and RTX. Conclusions: Navitoclax in combination with RTX weekly × 8 was generally well-tolerated as initial therapy for CLL patients and demonstrated greater clinical activity than treatment with RTX alone as well as responses in patients with 17p deletion. The preliminary results of this study indicate that a BH3-mimetic inhibitor of Bcl-2 could be highly effective when used in combination with RTX for treatment of patients with CLL. Disclosures: Eradat: Genentech: Research Funding. Off Label Use: BH3 Mimetic Protein Navitoclax (ABT-263). Catalono:Genentech: Consultancy. Kipps:Genentech: Research Funding. Zheng:Genentech: Employment. Yalamanchili:Genentech: Employment. Sahasranaman:Genentech: Employment. Hurst:Genentech: Employment. Ho:Genentech: Employment.
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Strashok, L. A., and M. A. Khomenko. "Serotonin levels in adolescents with obesity and nonalcoholic fatty liver disease." Ukrainian Journal of Pediatric Endocrinology, no. 3-4 (November 30, 2022): 27–32. http://dx.doi.org/10.30978/ujpe2022-3-4-27.
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The prevalence of obesity has reached epidemic proportions not only among adults, but also in the pediatric population. Expectedly the number of obesity-associated diseases, including nonalcoholic fatty liver disease (NAFLD) etc., increases, too. The pathogenesis of these conditions has common links, some of them are well known, others are being investigated. The latter include hormones of the gastrointestinal tract. They are considered as a part of the body’s humoral regulation. These compounds regulate energy balance of a body, and insulin resistance. It is assumed they can affect obesity and NAFLD pathogenesis.
Objective — to determine serotonin levels in adolescents with obesity and NAFLD.
Materials and methods. An examination of 108 adolescents aged 12—17 years with obesity (55 boys and 53 girls) was carried out. The control group consisted of 32 healthy adolescents (18 boys and 14 girls). Depending on the hepatobiliary pathology all patients were divided into two groups: 1st group included 29 (26.9 %) adolescents with functional disorders of the biliary tract (FDBT), and 2nd group consisted of 79 patients (73.1 %) with NAFLD and FDBT.All patients underwent a comprehensive clinical and anamnestic examination, clinical and biochemical blood tests, including determination of the levels of γ-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), total bilirubin and its fractions, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), atherogenic coefficient (AC) value. Levels of fasting glucose and immunoreactive insulin (IRI), HOMA-IR index, and blood serotonin level were also determined. An ultrasound examination of the abdominal cavity was performed.
Results and discussion. According to the clinical and anamnestic data, there were no differences between the groups of adolescents with obesity, depending on the existing hepatobiliary pathology, except for a higher value of the WC/Height in patients with NAFLD and FDBT (p < 0.01). The results of laboratory investigations demonstrated that in patients with NAFLD and FDBT, compared to patients with FDBT, the following parameters were higher: fasting glucose level (p < 0.05), IRI (p < 0.01), the value of the HOMA-IR index and the frequency of its increase (p < 0.01), levels of ALT and AST activity (p < 0.05), the levels of triglycerides and VLDL-C (p < 0.05). The level of serotonin was higher in the group of patients with NAFLD and FDBT compared to the control group (p < 0.015).
Conclusions. Adolescents with obesity, accompanied by NAFLD and FDBT, had higher rates characterizing abdominal obesity, carbohydrate and lipid metabolism, liver enzyme activity compared to patients with FDBT. Serotonin levels were higher in the group of patients with NAFLD and FDBT compared to the control group.
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Mancuso, Maria Elisa, Alessio Aghemo, Paolo Bucciarelli, Elena Santagostino, Mariagrazia Rumi, Massimo Colombo, and Pier M. Mannucci. "Transient Elastography (Fibroscan®) In Adult Patients with Inherited Bleeding Disorders and Chronic Hepatitis C." Blood 116, no. 21 (November 19, 2010): 1413. http://dx.doi.org/10.1182/blood.v116.21.1413.1413.
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Abstract Abstract 1413 Hepatitis virus C (HCV) infection is common in patients with inherited bleeding disorders due to the past use of plasma-derived clotting factor concentrates not treated with virucidal methods. The prognosis of the infection and the outcome of antiviral therapy are related to the stage of liver fibrosis. Since liver biopsy, the gold standard to grade fibrosis, is rarely performed in these patients for cost-benefit reasons, it is important to consider non invasive methods to assess fibrosis such as liver stiffness measurement with transient elastography (TE, Fibroscan®), a technique already validated in non hemophilic patients. We measured TE in 170 patients with inherited bleeding disorders and HCV infection (positive serum HCV-RNA). The main characteristics of these patients are reported in the Table. Steatosis was detected by abdominal ultrasound. Cirrhosis was defined by the presence of irregular liver edge, splenomegaly, dilated portal vein and/or esophageal varices combined either with low platelet count and/or reduced albumin/cholinesterase levels. TE was successfully performed in all but 3 patients, 2 of whom for Body Mass Index (BMI) > 30 kg/m2. Overall, the median value of liver stiffness was 7.2 kPa (interquartile range, IQR: 5.3–11.1) with a median success rate of 100% (IQR: 91–100) and a median IQR value of 1.0 (IQR: 0.7–1.9). HCV genotype or the presence of steatosis did not influence the TE values, whereas higher values were observed in patients with cirrhosis than in those without (median 19.8 kPa, IQR: 14.3–28.1 vs 6.8 kPa, IQR: 5.1–9.1, respectively; p< 0.01). In particular, 18/22 (82%) cirrhotic patients had a liver stiffness value ≥ 12.0 kPa, a cut-off previously identified as associated with severe fibrosis in HCV infected patients. Overall, splenomegaly was present in 51 patients (30%), 16 with cirrhosis and 35 without. In 31/35 (89%) of the latter, TE values were < 12 kPa. Moreover, among patients without cirrhosis, 12 (8%) had TE values ≥ 12 kPa: those patients had ALT and GGT levels significantly higher than patients with TE values < 12 kPa (p<0.05 for both variables). In our cohort TE had a 83% sensitivity, a 95% specificity and a 94% negative predictive value for the detection of severe fibrosis. In the same patients we measured the aspartate aminotransferase-to-platelet ratio index (APRI), a simple non-invasive biochemical marker of liver fibrosis. Median APRI values were significantly higher in patients with cirrhosis than in those without (1.6 vs 0.5, respectively; p<0.01), and a value > 1.5 was observed in 12/22 (55%) patients with cirrhosis. An APRI >1.5 had a 96% specificity and a 93% negative predictive value for the detection of severe fibrosis. Univariate and multivariate linear regression analyses were performed to investigate the relationship between log transformed TE and demographic (age, BMI) or laboratory (ALT, GGT, APRI) variables potentially influencing the TE values. By univariate analysis a linear association was found with age, ALT, GGT, APRI and BMI values (p<0.01 for each). In multivariate analysis APRI, ALT and GGT showed the strongest association with TE, while the statistical significance for BMI and age was marginal. The entire model explained about 50% of the variance of TE (R2= 0.49). Our results confirm that TE is a good tool to assess liver fibrosis also in patients with inherited bleeding disorders and chronic hepatitis C and shows that it can be performed safely in a great proportion of patients with a high success rate. The value of biochemical markers of necroinflammation (such as ALT and GGT) at the time of TE performance may influence the result and should be taken into account in the interpretation of the test. Disclosures: No relevant conflicts of interest to declare.
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Martins, Igor Magno Nicurgo Borges Rosa, Luanna Stefanny Vieira Oliveira Gomes, Daniel Pasquini, and Milla Alves Baffi. "Production and characterization of cellulases and hemicellulases from a consortium between Pleurotus ostreatus and Aspergillus niger cultured in agro-industrial wastes." Research, Society and Development 10, no. 10 (August 14, 2021): e396101019020. http://dx.doi.org/10.33448/rsd-v10i10.19020.
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The enzyme biosynthesis using agricultural wastes by solid state fermentation (SSF) and the study of their physicochemical properties are meaningful approaches to improve the biomass hydrolysis. Among them, β-glucosidases and β-xylosidases are key enzymes at the lignocellulose depolymerization, which act in the cleavage of oligosaccharides in monosaccharides. In this study, the production of hemicellulases and cellulases by Pleurotus ostreatus and Aspergillus niger monocultures or in consortium was investigated, using raw sugarcane bagasse (SB) and wheat bran (WB) as substrates. The highest enzymatic activities were observed in the crude extract produced by P. ostreatus PLO6 and A. niger SCBM4 consortium with 98.5, 62.9, 3.8, 12.4, 13.3 and 20.2 U/g for β-glucosidase (β-glu), β-xylosidase (Bxyl), filter paper cellulase (FPase), xylanase (Xyl), exoglucanase (Exgl) and endoglucanase (Engl), respectively. The pH and temperature effects on β-glu and β-xyl were characterized. Optimal activities were obtained at pH 4.0 and 45 °C for β-glu and 3.5 and 55 °C for β-xyl. Both enzymes were stable at acid pH and presented thermostability. The results indicated that the enzymatic cocktail demonstrated potential characteristics for future applications in saccharifications. The use of sugarcane bagasse and wheat bran for microbial growth contributed to aggregate value to these byproducts.
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Hama Rahim, Bestun Rahim, Ali Hattem Hussain, Mohammed Omer Mohammed, and Kamal Jalal Rashid. "Epidemiological and Clinical Characteristics of Hepatitis C Viral Infections in Tertiary Centres in Sulaimani City / Kurdistan Region of Iraq." Kurdistan Journal of Applied Research 2, no. 2 (July 30, 2017): 29–35. http://dx.doi.org/10.24017/science.2017.2.4.
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Hepatitis C infection is one of the most common causes of chronic liver disease. It is growing threat and main burden on public health. Globally more than 170 million people are infected with hepatitis C virus (HCV), up to 4 million new infections annually and each year more than 350000 dies of HCV related complications, including cirrhosis and hepatocellular carcinoma (HCC). Thus this descriptive case-series study was conducted in five health facilities in Sulaimani city, from 23rd December 2015 to 10th of June 2016. The data were collected from 180 HCV infected patients by face to face interview; they were interviewed privately by using a structured questionnaire. P-values of ≤0.05 were considered statistically significant. Out of 180 patients, 45% were males and 55% were females, the mean age of the cases was 33.18 years, regarding marital status 55.5% of the cases were single. The majority of the cases were diagnosed by routine screening. Most of the patients (70.7%) had no signs and symptoms at the time of diagnosis. In each patient at least two identifiable risk factors for getting HCV infection were reported. Among the patients that had genotype test, 67.2% of them infected with genotyope1. More than three-quarters of the participants had elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST). More future studied parameters and practical skills should be performed to significantly reduce the risk of HCV infection in Sulaimani.
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Almogbil, Hanaa H., Fadi P. Nasrallah, and Vesna Zderic. "Effectiveness of 3 MHz ultrasound in ex vivo scleral delivery of macromolecules of different sizes." Journal of the Acoustical Society of America 151, no. 4 (April 2022): A79. http://dx.doi.org/10.1121/10.0010718.
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Therapeutic ultrasound offers a novel approach for enhancing scleral delivery of macromolecules for treatment of various ocular diseases. Our previous in vitro diffusion cell studies showed that 3 MHz ultrasound could enhance scleral delivery of Avastin (MW: 149 kDa). We tested similar ultrasound parameters in an ex vivo whole eye rabbit model by using fluorescently labeled FITC-dextran of various sizes (40, 70, and 150 kDa) to mimic the sizes of the current macromolecules drugs for treatment of retinopathies. 3 MHz ultrasound was applied for 5 min on the sclera of the eye submersed in a macromolecule solution, and then the eyes were left in the solution for another 55 min while in the 34.6 °C water bath. Ultrasound was not turned on for the sham-treated group. Temperature modeling was performed to assess the safety of 5-min ultrasound application in the eye. The fluorescence intensity values of FITC-150 group were statistically different (p < 0.05) between the ultrasound-treated (1809.4, n = 8) and their sham-treated group (1185.8, n = 8). However, the FITC-70 and -50 groups lacked any appreciable difference between their ultrasound-treated (1313.6, n = 8) and (1646.3, n = 6), and their sham-treated groups (1431, n = 8) and (1121.8, n = 6), respectively. Thermal simulations demonstrated a temperature rise of 4.6 °C, while experimentally the maximum temperatures was 4.4 °C.
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Wong, K. R., C. A. Berry, and M. G. Cogan. "Alpha 1-adrenergic control of chloride transport in the rat S1 proximal tubule." American Journal of Physiology-Renal Physiology 270, no. 6 (June 1, 1996): F1049—F1056. http://dx.doi.org/10.1152/ajprenal.1996.270.6.f1049.
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To identify in vivo the specific alpha-adrenergic receptor mediating direct neural control of chloride transport in the rat S1 proximal convoluted tubule (PCT), the major effector site of neural regulation, microperfusion was employed in conjunction with the alpha 1- and alpha 2-adrenergic receptor antagonists, prazosin and rauwolscine. Using a glomerular ultrafiltrate-like perfusate, prazosin markedly inhibited chloride transport by -42% (302 +/- 10 to 176 +/- 5 peq.mm-1.min-1, P < 0.0001). Using a sodium chloride perfusate, which measures the active component of chloride absorption (J(Cl)act) (control, 153 peq.mm-1.min-1) plus a constant passive (479 peq.mm-1.min-1) component, both prazosin and acute renal denervation reduced J(Cl)act by -38% and -44% (-58 and -67 peq.mm-1.min-1, each P < 0.05). In contrast, rauwolscine caused no significant change in J(Cl)act using either perfusate. Prazosin regulates chloride transport via protein kinase C (PKC), since preactivation of PKC by phorbol abolished inhibitory impact of prazosin. Inhibition of J(Cl)act by prazosin (-58 peq.mm-1.min-1) was fully additive to either the stimulation or inhibition (losartan) of angiotensin II (55 or -49 peq.mm-1.min-1), which uses the adenosine 3',5'-cyclic monophosphate (cAMP) second messenger system [observed changes, not significantly different from 0 and -99 peq.mm-1.min-1; expected changes, not significantly different from 0 and -107 peq.mm-1.min-1]. In conclusion, neural control of S1 PCT chloride absorption in vivo is mediated by alpha 1-adrenergic receptors, which can selectively regulate J(Cl)act by altering PKC activity, independently of the cAMP second messenger system.
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Situmorang, Yesaya Twin, Wirta Agustin, M. Khairul Anam, Rini Yanti, Mardainis Mardainis, and Rahmaddeni Rahmaddeni. "Sistem Pengendalian Persediaan Perlengkapan Perorangan Lapangan Menggunakan Metode Economic Order Quantity dan Reorder Point." JURIKOM (Jurnal Riset Komputer) 9, no. 6 (December 30, 2022): 2092. http://dx.doi.org/10.30865/jurikom.v9i6.5133.
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[1] A. Junaidi and C. Sumirat, “Aplikasi Persediaan Barang PT. CAD Solusindo Menggunakan Metode Waterfall,” Jurnal Sisfokom (Sistem Informasi dan Komputer), vol. 7, no. 1, p. 28, 2018, doi: 10.32736/sisfokom.v7i1.280.[2] N. Apriyani and A. Muhsin, “Analisis Pengendalian Persediaan Bahan Baku Dengan Metode Economic Order Quantity Dan Kanban Pada Pt Adyawinsa Stamping Industries,” Opsi, vol. 10, no. 2, p. 128, 2017, doi: 10.31315/opsi.v10i2.2108.[3] M. Sukamto, “ANALISIS PENGENDALIAN PERSEDIAAN BAHAN BAKU DENGAN METODE FIXED ORDER INTERVAL (FOI) TERHADAP BIAYA TOTAL PERSEDIAAN DAN LABA OPERASI PADA RESTORAN BENEDICT,” Jurnal Mozaik, vol. 9, no. 1, pp. 81–93, 2017.[4] Haslindah, A. S. Iriani, M. Ardi, and Zulkifli, “PENERAPAN MANAJEMEN PERSEDIAAN DALAM MENGANTISPASI KERUGIAN BARANG DAGANGAN DI TOKO MEGA JILBAB,” Banco: Jurnal Manajemen dan Perbankan Syariah, vol. 2, no. 2, pp. 58–68, 2020, doi: 10.35905/banco.v2i2.1811.[5] P. C. P. Dewi, N. T. Herawati, and M. A. Wahyuni, “Analisis Pengendalian Persediaan Dengan Metode (EOQ) Economic Order Quantity Guna Optimalisasi Persediaan Bahan Baku Pengemas Air Mineral,” Jurnal Akuntansi Profesi, vol. 10, no. 2, pp. 54–65, 2019.[6] R. Jappi and D. F. Koan, “PENERAPAN INVENTORY MANAGEMENT DALAM MENINGKATKAN PROFITABILITAS DI TOKO X KUPANG,” Calyptra: Jurnal Ilmiah Mahasiswa Universitas Surabaya , vol. 3, no. 1, pp. 1–16, 2014.[7] T. Lukmana and D. Trivena, “Penerapan Metode EOQ dan ROP (Studi Kasus: PD. BARU),” Jurnal Teknik Informatika dan Sistem Informasi, vol. 1, no. 3, pp. 271–279, 2015.[8] N. Hartih Aeni, Satibi, and G. Pamudji Widodo, “Penerapam Metode Economic Order Quantity Dan Reorder Point Dalam Meningkatkan Efisiensi Persediaan Obat,” Jurnal Manajemen dan Pelayanan Farmasi, vol. 3, no. 4, pp. 249–254, 2013.[9] T. Rafliana and B. R. Suteja, “Penerapan Metode EOQ dan ROP untuk Pengembangan Sistem Informasi Inventory Bengkel MJM berbasis Web,” Jurnal Teknik Informatika dan Sistem Informasi, vol. 4, no. 2, pp. 345–354, 2018.[10] D. Misbachul Umami, M. Fuad Fauzul Mu, and R. Rakhmawati, “ANALISIS EFISIENSI BIAYA PERSEDIAAN MENGGUNAKAN METODE EOQ (ECONOMIC ORDER QUANTITY) PADA PT. XYZ Analysis of Cost Efficiency on Inventory System Using EOQ (Economic Order Quantity) Method in The PT. XYZ,” Jurnal Agroteknologi, vol. 12, no. 1, pp. 64–70, 2018.[11] M. K. Anam, T. Nasution, S. Erlinda, L. Efrizoni, and Susanti, “The Analysis and Optimization of Business Processes for Students in Higher Education Based on Togaf 9 . 2,” Scientific Journal of Informatics, vol. 8, no. 2, pp. 230–243, 2021, doi: 10.15294/sji.v8i1.29952.[12] I. P. C. P. Dewi, I. N. T. Herawati, and I. made A. Wahyuni, “ANALISIS PENGENDALIAN PERSEDIAAN DENGAN METODE (EOQ) ECONOMIC ORDER QUANTITYGUNA OPTIMALISASI PERSEDIAAN BAHAN BAKU PENGEMAS AIR MINERAL,” Jurnal Akuntansi Profesi, vol. 10, no. 2, pp. 55–65, 2019.[13] R. Cahya Pratiwi, C. Iswahyudi, and R. Yuliana Rachmawati, “SISTEM MANAJEMEN PERSEDIAAN BARANG DAGANG MENGGUNAKAN METODE SAFETY STOCK DAN REORDER POINT BERBASIS WEB (STUDI KASUS: ART KEA CENTRO PLAZA AMBARRUKMO YOGYAKARTA),” Jurnal SCRIPT, vol. 7, no. 2, pp. 213–222, 2019.[14] M. Jamaris, H. Saputra, M. K. Anam, K. Andesa, and Rahmaddeni, “Sistem Marketplace Pencarian Lapangan Futsal Menggunakan Metode Haversine Berbasis Android,” JURNAL ILMIAH KOMPUTER GRAFIS, vol. 15, no. 1, pp. 53–65, 2022, doi: 10.51903/pixel.v15i1.712.[15] H. Asnal et al., “Sistem Monitoring Persediaan Stok Onderdil Menggunakan Metode Reorder Point Pada Sani Computer,” 2022.[16] M. K. Anam and R. Anwar, “Penerapan Aplikasi Pendukung Touring Pada Komunitas Motor Berbasis Android,” Edumatic: Jurnal Pendidikan Informatika, vol. 4, no. 1, pp. 1–10, 2020, doi: 10.29408/edumatic.v4i1.1980.[17] M. K. Anam and H. Ulayya, “Implementasi dan Analisa SARDrive Sebagai Media Penyimpanan Cloud,” JUITA: Jurnal Informatika, vol. 8, no. 1, pp. 83–90, 2020, doi: 10.30595/juita.v8i1.5748.
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Pinilla-León, Juan Carlos, and Natalia Da Silva Borges. "Factores de riesgo asociados a la infección por Cystoisospora suis en granjas porcinas de la región central de Venezuela." Revista de la Facultad de Medicina Veterinaria y de Zootecnia 64, no. 2 (May 1, 2017): 25–43. http://dx.doi.org/10.15446/rfmvz.v64n2.67210.
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It was carried out an investigation in Venezuela with the aim of studying the epidemiological aspects of Cystoisospora suis in intensive swine herds. Sixty-seven intensive swine herds were included. For parasite determination 572 litters with signs of diarrhea, as well as 1,712 faecal samples from mature pigs were selected. Stool samples were cultured in a 2.5% potassium dichromate solution and later processed by copro-parasitological technique. Epidemiological surveys were applied on each farm. The results indicated that C. suis was observed in 55 herds (82.1%) and 210 litters (36.7%). Regarding to litters, oocysts were observed in piglets less than three days of life, which could indicate the existence of alternative infection way. Regarding to mature pigs, there was a significant correlation (rho = 0.35; P < 0.05) among oocysts excretion in piglets and sows, suggesting that sows may act as infection sources. Sows parity was statistically correlated with the prevalence values in litters as in lactating sows (P < 0.05). This might indicate that as parity increase, prevalence decreases in these groups. Probably, these findings are associated with unknown immunologic mechanisms. The herd size did not affect the presence of the parasite, however, farms with plastic floors showed greater control of the infection. It is concluded that non elucidated immunologic mechanisms might be involved in the protozoa transmission cycle and play an important role in the development of Cystoisosporosis Porcina.
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Heist, Rebecca Suk, Monica Motwani, Fabrice Barlesi, Jonathan Wade Goldman, Karen Kelly, Yan Sun, Jun Wu, Bruce Allen Bach, and D. Ross Camidge. "c-Met expression and response to telisotuzumab vedotin (teliso-v) in patients with non-small cell lung cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 9023. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.9023.
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9023 Background: c-Met overexpression (OE) and MET amplification (amp) are prognostic of poor outcome for non-small cell lung cancer (NSCLC). Telisotuzumab vedotin (ABBV-399; teliso-v [T]), an anti–c-Met Ab and monomethyl auristatin E drug conjugate, showed efficacy as monotherapy (mono) and combined with erlotinib (T+Er) in a phase 1/1b trial (NCT02099058) in NSCLC patients (pts) with c-Met OE. Here, c-Met OE (by immunohistochemistry [IHC]) and its association with T efficacy were explored. IHC, mRNA, and amp platforms for MET were also compared. Methods: Archival tissue from pts with NSCLC in the phase 1/1b trial was examined. c-Met was assessed centrally by IHC with SP44 Ab (Ventana Medical Systems) and pts with c-Met OE (membrane H-score [H-S] of ≥150) were enrolled. MET mRNA expression was analyzed from total RNA and sequenced on HiSeq 3000 (Illumina). MET amp was analyzed by FISH ( MET/ CEP7 ratio of ≥2) or whole-exome sequencing (copy number ≥2). Efficacy in the T mono every 2 (TQ2W) or 3 (TQ3W) weeks and the T+Er EGFR mutant cohorts was assessed for IHC H-S ≥150 and ≥225. Results: As of Dec 2018, 238 pts with NSCLC were screened centrally for c-Met OE. Of these, 118 pts were enrolled. For screened pts, 76%/37% of nonsquamous (NSQ, n = 201) and 58%/16% of squamous (SQ, n = 32) pts had H-S ≥150/≥225; 75%/41% of NSQ and 55%/16% of SQ NSCLC pts had ≥50% cells with 2+/3+ staining intensity. MET amp was reported for 5 pts, all with high H-S (≥270); there was an association between MET amp and MET RNA levels (n = 4) (t-test p value: 0.0002). See Table for ORR and median PFS by H-S and T treatment. Conclusions: c-Met expression prevalence in NSCLC showed a similar trend as in previous reports. In T+Er-treated pts, ORR was higher for those with c-Met H-S ≥225 than ≥150– < 225, suggesting that biomarker expression may act as an effect size multiplier. Optimization of the c-Met IHC cutoff warrants further investigation. Clinical trial information: NCT02099058. [Table: see text]
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Časl, Martin T., Branka Šurina, Ines Glojnarić-Spasić, Ervin Pape, Nada Jagarinec, and Stjepan Kranjčević. "Serum Amyloid a Protein in Patients with Acute Myocardial Infarction." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 32, no. 2 (March 1995): 196–200. http://dx.doi.org/10.1177/000456329503200212.
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The concentrations of four acute phase proteins were measured in sera of 40 patients with acute myocardial infarction (AMI) to evaluate their behaviour from day-to-day and to find out if they can serve for early prediction of postinfarction complications and mortality rate. Peak levels of serum amyloid A protein (SAA) were increased up to 5000-fold above the normal value and those of C-reactive protein (CRP) about 100-fold, 3 days after AMI. α 1-antichymotrypsin (ACT) and α 1-acid glycoprotein (AGP) peak levels were increased up to eightfold above their normal values. Patients who developed postinfarction complications had significantly higher SAA values on admission than those without complications (mean values of 379 and 45 mg/L, respectively; P < 0·0001). Using a level of 100 mg/L on admission as a reference value gave a reasonable sensitivity and predictive value for complications (73%) and a very good sensitivity (80%) for early prediction of fatal outcome. Patients with SAA values above this limit had double the risk of complications and four times the risk of a fatal outcome. The correlation with CRP values was lower than it was with SAA values ( P = 0·028) using a level of 15 mg/L on admission as reference value gave low sensitivity (55%) and predictive value (60%) for complications as well as low sensitivity for early prediction of fatal outcome (60%). The present study did not allow prediction of complications or mortality based on ACT or AGP values.
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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.
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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
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Hearn, Jason W. D., Ghada AbuAli, Cristina Magi-Galluzzi, Chandana A. Reddy, Kai-Hsiung Chang, Eric A. Klein, and Nima Sharifi. "HSD3B1 and resistance to androgen deprivation therapy in prostate cancer." Journal of Clinical Oncology 33, no. 7_suppl (March 1, 2015): 156. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.156.
Full textAbstract:
156 Background: The somatic mutation HSD3B1(1245A>C) has been mechanistically linked to castration-resistant prostate cancer by encoding a mutant enzyme that augments intratumoral dihydrotestosterone synthesis. Given the HSD3B1(1245C) allele is also frequently found in the germline, we hypothesized men inheriting this variant allele would exhibit resistance to androgen deprivation therapy (ADT), as manifested by worse clinical outcomes. Methods: We used a prospectively maintained prostate cancer registry to identify men treated with ADT for biochemical failure in the post-prostatectomy setting who were without evidence of metastatic disease at the time of ADT initiation. We analyzed progression-free survival, distant metastasis-free survival, and overall survival according to HSD3B1 genotype using Kaplan-Meier methods. Cox proportional hazards regression was performed to evaluate potential gene-dosage effects, with homozygous wild-type men serving as the reference group. Demographic and treatment characteristics were compared across genotypes to assess for possible confounders using Fisher’s exact test and Kruskal-Wallis analysis of variance. Results: Of 118 men genotyped, 37% were homozygous wild-type, 53% were heterozygous, and 10% were homozygous variant. Demographic and treatment characteristics did not differ across groups. Median progression-free survival diminished as a function of the number of variant alleles inherited (6.6 years in homozygous wild-type men, 4.1 years in heterozygotes, and 2.5 years in homozygous variant men; P=0.01). Median distant metastasis-free survival likewise decreased according to the number of variant alleles inherited (9.1 years in homozygous wild-type men, 6.8 years in heterozygotes, and 3.6 years in homozygous variant men; P=0.01). Finally, overall survival also diminished with the number of variant alleles inherited (5-year and 10-year overall survival: 82% and 55% in homozygous wild-type men, 74% and 35% in heterozygotes, and 58% and 0% in homozygous variant men; P=0.006). Conclusions: Inheritance of the variant HSD3B1(1245C) allele that enhances dihydrotestosterone synthesis may predict resistance to ADT for prostate cancer. These findings require validation.
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Tazzari, PierLuigi, Veronica Papa, Francesca Ricci, Francesca Chiarini, Camilla Evangelisti, Giovanni Martinelli, Andrea Bontadini, James McCubrey, and Alberto M. Martelli. "Synergistic Proapoptotic Activity of Recombinant TRAIL Plus the Akt Inhibitor Perifosine in Acute Myelogenous Leukemia Cells-a Novel Therapeutic Approach for Leukemia Displaying Elevated Akt Signaling." Blood 112, no. 11 (November 16, 2008): 957. http://dx.doi.org/10.1182/blood.v112.11.957.957.
Full textAbstract:
Abstract The Tumor Necrosis Factor (TNF) family member TNF-Related Apoptosis Inducing Ligand (TRAIL) was originally reported to induce apoptosis in many tumor cells but not in normal cells in vivo and thus represents a promising anticancer cytokine. The in vitro cytotoxic response of acute myelogenous leukemia (AML) cell lines to recombinant TRAIL varies from good to moderate, however, a number of in vitro studies have convincingly demonstrated that AML primary cells are resistant to the proapoptotic activity of TRAIL used as a single agent. To potentiate the response of AML cells to TRAIL cytotoxicity, we have adopted a strategy of combining perifosine, a novel Akt inhibitor, with recombinant TRAIL. The rationale for using such a combination is that perifosine was recently described to increase TRAIL-R2 receptor expression and decrease cellular FLICEinhibitory (c-FLIP, an inhibitor of caspase-8 activation) protein in human lung cancer cells. Both perifosine and TRAIL, when used alone, induced cell death by apoptosis in THP- 1 AML cells, which normally express constitutively active Akt and nonfunctional p53. Perifosine treatment, at concentrations well below the IC50 (0.5 μM), dephosphorylated Akt on Ser473 and increased TRAIL-R2 levels, as demonstrated by flow cytometry, western blot, and RT-PCR. Perifosine also downmodulated cFLIP-L and XIAP levels. However, perifosine did not affect expression of TRAIL-R1 and TRAIL-R4 receptors, or of other proteins which are critical for TRAIL-mediated proapoptotic signaling, including FADD and Mcl-1. Perifosine and TRAIL strongly synergized to induce cytotoxicity as suggested by calculation of the combination index (CI range: 0.15–0.37). The combined treatment resulted in upregulation of caspase-8 activity and apoptosis which was markedly reduced by a selective caspase-8 inhibitor (Z-IETD-FMK). While cFLIP-L and XIAP downregulation was dependent on inhibition of NF-κB activity caused by perifosine, upregulation of TRAIL-R2 expression was dependent on generation of reactive oxygen species (ROS) by perifosine which in turn sequentially activated protein kinase C (PKC)α, JNK2, and c-Jun. A ROS scavenger (N-acetylcysteine), siRNA downregulation of either PKCα or c-Jun, or a JNK1/2 selective pharmacological inhibitor (SP600125), all markedly impaired perifosine-dependent TRAIL-R2 upregulation. Perifosine synergized with TRAIL by inducing apoptosis exclusively in primary AML cells displaying constitutive activation of the Akt pathway. Also in primary AML blasts, perifosine upregulated TRAIL-R2 levels, downmodulated the expression of both c-FLIP and XIAP, and increased Ser 63 p-c-Jun levels, without affecting the expression of FADD. Remarkably, perifosine increased p-JNK2 levels and TRAIL-R2 expression in primary AML patient blasts (CD34+, CD38Low/Neg, CD123+) enriched in putative leukemic stem cells. Perifosine and TRAIL combined treatment was effective in inducing apoptosis (55–60%) in this immature blast population, as documented by a quadruple staining flow cytometric technique for CD34+, CD38Low/Neg, CD123+, Annexin V+ blast cells. The combined treatment negatively affected the clonogenic activity of CD34+ cells from AML patients with Akt activation. In contrast, CD34+ cells from healthy donors and AML patients without Akt activation were resistant to perifosine plus recombinant TRAIL treatment. Our findings suggest that a combination consisting of perifosine plus recombinant TRAIL might offer a novel therapeutic strategy for AML displaying enhanced Akt signaling by overcoming critical mechanisms of apoptosis resistance. Moreover, this kind of combination therapy could be effective also in AML cases exhibiting nonfunctional p53 or low levels of p53.