Journal articles on the topic '324.218 3'

Aim: to identify the risk factors for conversion of endoscopic submucosal dissection to abdominal surgery.Patients and methods: the prospective cohort study included 405 patients: 166 (40.9%) males and 239 (59.1%) females. The median age was 66 (59; 72) years old; the patients underwent endoscopic submucosal dissection of colorectal epithelial neoplasms.Results: the median size of the removed neoplasms was 3.0 (2.4; 4) cm, tumor was removed en bloc in 324/363 (89.2%) cases; and R0 resection margins were detected in 218/324 (67.3%) cases. Significant risk factors for conversion were: the tumor size ≥ 3.2 cm (OR 2.9, 95% CI 1.2–7.1, p = 0.017), lifting ≤ 3 mm (OR 41, 95% CI 15–105, p = 0.000002) and the tumor vascular pattern IIIa according Sano’s capillary pattern classification (OR 4.0, 95% CI 1.3–11.9, p = 0.013).Conclusion: endoscopic submucosal dissection is a safe way to remove colorectal neoplasms. However, the presence of conversion risk factors can influence the outcome of endoscopic treatment.

BackgroundClinically evident kidney disease eventually occurs in up to one-half of SLE patients.ObjectivesTo describe sociodemographic, clinical, serological and treatment characteristics of a multicenter and multiethnic Latin American SLE cohort of patients with or without lupus nephritis (LN)MethodsGLADEL2.0 is an ongoing observational cohort. Patients were categorized according to renal involvement: Group I (LN never); II (prevalent renal involvement currently inactive); III (prevalent renal involvement, currently active) and IV (incident renal involvement). Demographic, clinical manifestations, treatments, disease activity were examined at baseline. A descriptive cross-sectional analysis was performed.ResultsA total of 991 SLE patients were included, 884 (89.2%) female and 656 (68.3%) Mestizos (Amerindian and European ancestry). Median (IQR) age at cohort entry was 35 (28-45) years and disease duration were 67 months (18-139). Patients with incident LN had a higher proportion of males, were younger, had shorter disease duration and were more frequently Mestizos. Pericarditis and anti-dsDNA were less frequent in group I and MMF in groups I and IV (Table 1). A predominance of class IV (49%) was evidenced in 510 patients in which a kidney biopsy was performed.ConclusionBaseline characteristics of GLADEL2.0 well characterized lupus patients’ cohort with or without LN are described with distinct demographic, clinical and laboratory patterns that will allow both centralized laboratory evaluation of urinary biomarkers and exploratory biomarker analyses including transcriptome and their impact on the outcome of these patients.Table 1.Sociodemographic and clinical characteristics and treatment at cohort entryVariableGroup I (n=393)Group II (n=213)Group III (n=224)Group IV (n=161)p-valueVariableGroup I (n=393)Group II (n=213)Group III (n=224)Group IV (n=161)p-valueFemale n%361/39391.9193/21390.6200/22489.3130/16180.70.002aEthnic group n%<0.001bAge (years)d39(30-48)38(30-48)30(25-37)33(25-40)<0.001cCaucasian106/37228.554/20826.037/22216.728/15917.6Disease duration (months)d77.1(32-146)106(52-187)64.4(25-130)3.0(0.7-26)<0.001Mestizo236/37263.4138/20866.3167/22275.2115/15972.3Education (years)d12.5(11-16)14(11-16)13(11-16)12(11-16)<0.001cIndigenous4/3721.12/2081.00/22202/1591.3Fevern%132/375(35.2)105/210(50.0)82/224(36.6)75/153(49.0)<0.001Afro-LAtin American26/3727.014/2086.718/2228.114/1598.8Discoid rashn%40/376(10.6)11/210(5.2)20/224(8.9)6/151(4.0)0.025Methylprednisolone bolusn%107/349(30.7)145/199(72.9)161/205(78.5)102/142(71.8)<0.001Pleuritisn%73/373(19.6)49/208(23.6)67/224(29.9)50/153(32.7)0.003Hydroxychloroquinen%321/365(87.9)182/205(88.8)194/220(88.2)121/136(89)0.985Pericarditisn%40/375(10.7)49/209(23.4)41/224(18.3)40/152(26.3)<0.001Azathioprinen%197/291(67.7)101/205(49.3)108/216(50.0)23/89(25.8)<0.001Anti-dsDNAn%231/361(64.0)167/204(81.9)194/216(89.8)134/150(89.3)<0.001Cyclophosphamide-IVn%47/289(16.3)129/202(63.9)139/214(65.0)38/89(42.7)<0.001Anti-Smn%88/324(27.2)47/167(28.1)73/187(39.0)60/128(46.9)<0.001Mycophenolaten%75/291(25.8)151/206(73.3)183/218(83.9)35/89(39.3)<0.001Positive Anti-Cardiolipinn%79/320(24.7)41/184(22.3)38/187(20.3)12/126(9.5)0.005Tacrolimusn%1/291(0.3)6/206(2.9)28/216(13.0)3/87(3.4)<0.001Positive Anti-B2GP1n%41/254(16.1)15/148(10.1)19/149(12.8)6/106(5.7)0.037Belimumabn%23/290(7.9)8/205(3.9)7/216(3.2)3/88(3.4)0.083Low C3n%228/367(62.1)158/205(77.1)193/218(88.5)137/150(91.3)<0.001Rituximabn%25/291(8.6)21/205(10.2)37/215(17.2)6/87(6.9)0.009Low C4n%244/367(66.5)155/203(76.4)193/217(88.9)134/150(89.3)<0.001SLEDAIc2(0-6)2(0-4)10(6-16)16(11-21.2)<0.001aChi-squared test was used.bFisher exact test was used.cKruskal-Wallis test was used.dMedian and IQRREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsRomina Nieto: None declared, Rosana Quintana: None declared, Eduardo Borba: None declared, Lucia Hernández: None declared, Diana Fernández Ávila: None declared, Laura Fernanda Maurelli Torres: None declared, Paula Alba: None declared, Florencia Bordon: None declared, Fernando Arizpe: None declared, Guillermo Berbotto: None declared, Rosa Serrano Morales: None declared, María Constanza Bertolaccini: None declared, Eduardo Kerzberg: None declared, Maria Gargiulo: None declared, Anabella Rodriguez: None declared, Vitalina Barbosa: None declared, Andrese Aline Gasparin: None declared, Fernando Cavalcanti: None declared, Laissa Alvino: None declared, Luciana parente costa seguro: None declared, Lucas de Oliveira Martins: None declared, Oscar Neira: None declared, loreto massardo: None declared, Gustavo Aroca Martínez: None declared, Ivana Nieto Aristizabal: None declared, PAUL ALEJANDRO MENDEZ PATARROYO: None declared, Antonio Iglesias Gamarra: None declared, Andrés Zúñiga: None declared, Olga Lidia Vera Lastra: None declared, Mario Pérez Cristóbal: None declared, Eduardo Martin-Nares: None declared, Luis Amezcua-Guerra: None declared, YELITZA CONCEPCION GONZALEZ BELLO: None declared, Jose Octavio Gonzalez Enriquez: None declared, Dionicio Ángel Galarza-Delgado: None declared, Carolina Vázquez: None declared, Marcelo Barrios: None declared, Magaly Alva: None declared, Cristina Reategui Sokolova: None declared, Ana Quiróz Alva: None declared, Teresandris Polanco Mora: None declared, Carina Pizzarossa: None declared, Martin Rebella: None declared, Maria Elena Crespo Espindola: None declared, ALVARO DANZA: None declared, Eloisa Bonfa: None declared, Graciela S Alarcon: None declared, Federico Zazzetti Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, PA, USA, Ashley Orillion Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Spring House, PA, USA, Urbano Sbarigia Employee of: Janssen Pharmaceutica NV, Beerse, BE, Guillermo Pons-Estel: None declared.

218 Background: Molecular assays are used to improve risk stratification in prostate cancer. This study determined how the 17-gene Genomic Prostate Score (GPS) assay guides treatment decisions in patients with NCCN favorable intermediate-risk prostate cancer. Methods: This retrospective study included 324 patients from 7 urology practices in the United States. All patients had NCCN favorable intermediate-risk prostate cancer, defined as <50% positive biopsy cores and only one of the following risk factors: grade group 2 (Gleason Score 3+4), clinical stage T2b-T2c, or PSA 10-20 ng/mL. All patients also had a GPS assay report dated May 2017 to April 2019. The GPS assay allows risk stratification into post-GPS very low-, low-, favorable intermediate-, unfavorable intermediate-, and high-risk groups, with higher GPS scores representing increased risk. Data were collected from patients' charts/electronic health records. The proportion of patients who selected active surveillance (AS) over immediate definitive treatment and AS, monotherapy, or multimodal therapy was calculated with 95% confidence intervals (CI) using the Clopper-Pearson method. Results: Patients comprised 79% with Gleason Score 3+4, 19% with PSA 10-20 ng/mL, and 2% with clinical stage T2b; median GPS result was 26. Post-GPS risk groups were 0%, 16%, 11%, 57%, and 16% very low-, low-, favorable intermediate-, unfavorable intermediate-, and high-risk groups respectively. Overall, 31% (95% CI 26%, 36%) of patients selected active surveillance (AS), with rate declining as post-GPS risk increased: 57% (95% CI 42%, 71%) selected AS in the post-GPS low-risk, 51% (95% CI 34%, 69%) in the post-GPS favorable intermediate-risk, 26% (95% CI 20%, 33%) in the post-GPS unfavorable intermediate-risk, and 6% (95% CI 1%, 16%) in the post-GPS high-risk group. Post-GPS unfavorable intermediate/high risk-patients were more likely to receive monotherapy than low/favorable intermediate-risk patients (high, 72%; unfavorable intermediate, 64%; favorable intermediate, 37%; and low, 37%); high-risk patients were more likely to receive multimodal therapy (high, 23%; unfavorable intermediate, 10%; favorable intermediate, 11%; and low, 6%). Median follow-up time was 18 months, and one prostate cancer-related metastasis and 2 deaths (neither prostate cancer-related) were reported. Complications (erectile dysfunction, urinary/bowel incontinence) were more common in treated than AS patients. AS persistence was 91% (95% CI 82%, 95%) at 12 months; patients discontinued AS due to disease progression (61%) or patient preference/unknown reasons (39%). Conclusions: The GPS result is associated with selection of AS and treatment intensity in this first examination of genomic classifiers in a cohort of prostate cancer patients with NCCN favorable intermediate-risk.

AbstractApproval and prescription of psychotropic drugs should be informed by the strength of evidence for efficacy. Using a Bayesian framework, we examined (1) whether psychotropic drugs are supported by substantial evidence (at the time of approval by the Food and Drug Administration), and (2) whether there are systematic differences across drug groups. Data from short-term, placebo-controlled phase II/III clinical trials for 15 antipsychotics, 16 antidepressants for depression, nine antidepressants for anxiety, and 20 drugs for attention deficit hyperactivity disorder (ADHD) were extracted from FDA reviews. Bayesian model-averaged meta-analysis was performed and strength of evidence was quantified (i.e. BFBMA). Strength of evidence and trialling varied between drugs. Median evidential strength was extreme for ADHD medication (BFBMA = 1820.4), moderate for antipsychotics (BFBMA = 365.4), and considerably lower and more frequently classified as weak or moderate for antidepressants for depression (BFBMA = 94.2) and anxiety (BFBMA = 49.8). Varying median effect sizes (ESschizophrenia = 0.45, ESdepression = 0.30, ESanxiety = 0.37, ESADHD = 0.72), sample sizes (Nschizophrenia = 324, Ndepression = 218, Nanxiety = 254, NADHD = 189.5), and numbers of trials (kschizophrenia = 3, kdepression = 5.5, kanxiety = 3, kADHD = 2) might account for differences. Although most drugs were supported by strong evidence at the time of approval, some only had moderate or ambiguous evidence. These results show the need for more systematic quantification and classification of statistical evidence for psychotropic drugs. Evidential strength should be communicated transparently and clearly towards clinical decision makers.

There is limited knowledge about the possible effect of unabsorbed dietary antioxidants that reach the large intestine on bowel habits. The aim of the present study was to investigate whether a dietary recommendation directed to increase diet total antioxidant capacity (TAC) is able to affect gut function in human subjects. In this cross-over intervention, nineteen subjects followed a high-TAC (HT) and a low-TAC (LT) diet for 2 weeks, which were comparable for energy, macronutrient, total dietary fibre and alcohol contents. At the end of each intervention period, the 48 h stool output was recorded. In the faecal samples obtained from a subset of nine subjects, moisture, pH, ammonia content,LactobacillusandBifidobacteriumcounts, faecal water antioxidants and genotoxicity were measured. A 3 d weighed food record was used to assess the diet composition during HT and LT diet intake. Significant increases in the intake of TAC, vitamins E and C and phenolic compounds were observed during the HT diet intake. The higher intake of antioxidants led to increased 48 h stool output (324 (sd38) g in HTv. 218 (sd22) g in LT), and to higher TAC and total phenolic concentrations in faecal water. No significant variation in the other measured parameters was observed between the diets. In conclusion, a diet selected to raise the intake of dietary antioxidants is able to increase stool bulk and antioxidant content of faeces.

Abstract Abstract 3896 Chronic lymphocytic leukemia (CLL) is associated with an increased incidence of other cancers (OC). Potential risk factors for OC in CLL include immune disturbances, shared risk factors, genetic predisposition and chemotherapy. While reports on OC in patients with CLL have been typically descriptive in nature, detailed information regarding the clinical features of OC, relationship with the time of diagnosis of CLL, patient characteristics, prognostic factors and survival have been missing. We report an analysis of OC in pts with CLL requiring therapy, with a post therapy observation time of 5 years or longer. We reviewed our database and selected pts with CLL seen at our center who underwent treatment and who have a follow-up of at least 5 years after therapy. We studied pts with an OC either before or after the diagnosis and/or treatment of CLL and compared them with patients without OC. Richter's transformation of CLL was not considered an OC in this analysis. A total of 1,364 pts with CLL referred between 1963 and 2007 with a median follow up time of 8.2 years (range 5–28) were studied. Among these, we identified 324 pts (24%) with OC. Sixty-eight pts were diagnosed with >1 OC [2 OC (62 pts), 3 OC (4 pts) or 4 OC (2 pts)], for a total of 400 individual OC. Of the 324 pts with OC, OC preceded the diagnosis of CLL in 117 pts (36%), with a median time from OC to CLL of 80 (0–455) months, OC occurred after the diagnosis of CLL but before treatment in 49 pts (15%), with median time from CLL to OC of 22 (0–131) months. OC occurred after treatment of CLL in 158 pts (49%), with a median time from treatment to OC of 94 (0–304) months. The type, frequency and timing of OC are summarized in table 1. Clinical characteristics and traditional prognostic factors were not significantly different between pts with and without OC, with the exception of age, as pts with OC are older than pts without OC at the time of referral (median age: 60 vs 55 years, p<.0001). We next analyzed the distribution of the newer prognostic parameters in these two groups. Fifty-three % of pts with OC had unmutated IGHV genes, 65% were ZAP70+, 22% CD38+, 8% had del17p, 27% del11q, 22% +12, 20% negative FISH, and 23% del13q. Sixty-one % of pts without OC had unmutated IGHV genes, 58% were ZAP70+, 26% CD38+, 6% had del17p, 17% del11q, 22% +12, 26% negative FISH, and 29% del13q. A trend toward significance (p.07) for a higher incidence of del11q was observed in pts with OC. At the time of this analysis 536 (39%) pts have died and 828 (61%) are alive. One hundred seventy six/324 (54%) pts with OC are alive, vs 652/1040 (63%) pts without OC (p<.007). Median overall survival (OS) has not been reached in either pt group at a median follow up of 95 (61–284) months for pts with OC and 98 (61–340) months for pts without OC. Causes of death were: progression of CLL (99), CLL-related complications (121), OC (43), complications of stem cell transplant (16), events unrelated to CLL (39) and unknown causes (218). In pts with OC, the OC itself was the cause of death in 37%. Other causes of death were CLL/CLL-related complications in 44%, complications of stem cell transplant in 8%, and events unrelated to CLL in 11%. In contrast, in pts without OC CLL/CLL-related complications accounted for 83% of deaths, complications of stem cell transplant for 4%, and events unrelated to CLL for 13%. In conclusion, in pts with CLL requiring therapy and with post therapy follow up of >5 years, the incidence of OC is 24%. Among pts with OC, there is a trend for higher number of pts with del11q. In pts with OC, OC itself is a major cause of death, while the vast majority of deaths among pts without OC are caused by CLL or CLL-related complications. Table 1. Distribution of OC (1364 pts). Site of OC 1st case Total cases OC prior/at CLL OC after CLL After diagnosis After treatment NMSC1 124 144 41 26 77 PROSTATE 43 54 18 7 29 MELANOMA 26 34 16 2 16 BREAST 23 26 14 2 10 MDS/AML2 16 18 0 0 18 LUNG 14 21 0 1 20 NEUROENDOCRINE 3 6 1 0 5 HEAD AND NECK 12 16 3 2 11 UROTHELIAL CELL CANCERS 11 12 7 2 3 GI3 (including pancreas and liver) 10 18 4 3 11 KIDNEY 10 11 4 3 4 NHL4 and MM5 8 12 0 0 12 TESTIS/OVARY 6 6 4 0 2 THYROID 6 7 5 1 1 SARCOMAS 4 5 4 0 1 UTERUS 2 3 3 0 0 OTHERS6 6 7 3 0 4 TOTALS 324 400 127 49 224 1 non-melanoma skin cancers; 2 myelodysplastic syndrome/acute myeloid leukemia; 3 gastrointestinal; 4 non-Hodgkin's lymphoma; 5 multiple myeloma; 6 includes: brain, nasopharyngeal, penis carcinoma, mesothelioma, unknown primary. Disclosures: No relevant conflicts of interest to declare.

Context: Fatty liver is associated with an increased risk of type 2 diabetes, but whether an increased risk remains in people in whom fatty liver resolves over time is not known. Objective: The objective of the study was to assess the risk of incident diabetes at a 5-year follow-up in people in whom: 1) new fatty liver developed; 2) existing fatty liver resolved, and 3) fatty liver severity worsened over 5 years. Design and Methods: A total of 13 218 people without diabetes at baseline from a Korean occupational cohort were examined at baseline and after 5 years, using a retrospective study design. Fatty liver status was assessed at baseline and follow-up as absent, mild, or moderate/severe using standard ultrasound criteria. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for incident diabetes at follow-up were estimated after controlling for multiple potential confounders. Results: Two hundred thirty-four people developed incident diabetes. Over 5 years, fatty liver resolved in 828, developed in 1640, and progressed from mild to moderate/severe in 324 people. Resolution of fatty liver was not associated with a risk of incident diabetes [aOR 0.95 (95% CIs 0.46, 1.96), P = .89]. Development of new fatty liver was associated with incident diabetes [aOR 2.49 (95% CI 1.49, 4.14), P &lt; .001]. In individuals in whom severity of fatty liver worsened over 5 years (from mild to moderate/severe), there was a marked increase in the risk of incident diabetes [aOR 6.13 (2.56, 95% CI 14.68) P &lt; .001 (compared with the risk in people with resolution of fatty liver)]. Conclusion: Change in fatty liver status over time is associated with markedly variable risks of incident diabetes.

(1) Background: Benzene, toluene, and xylene isomers (BTX) are present in gasoline. Exposure to benzene may lead to the appearance of a series of signs, symptoms, and complications, which are characterized by benzene poisoning, which is an occupational disease. This study evaluated the presence of signs and symptoms related to occupational exposure and whether occupational exposure to BTX is associated with the development of hematological changes. (2) Material and Methods: This cross-sectional epidemiological study included 542 participants, in which 324 were gas station workers (GSWs) and 218 were office workers (OWs) with no occupational exposure to benzene. To characterize the type of exposure (exposed and not exposed), trans,trans-Muconic acid (tt-MA), Hippuric acid (HA), and Methylhippuric acid (MHA) were used as exposure biomarkers. The tt-MA analysis revealed that the GSWs had 0.29 mg/g of urinary creatinine and the OWs had 0.13 mg/g of urinary creatinine. For HA, the GSWs presented 0.49 g/g of creatinine while the OWs presented 0.07. MHA analysis revealed that the GSWs had 1.57 g/g creatinine and the OWs had 0.01 g/g creatinine. Occupation habits and clinical symptoms were collected by questionnaire and blood samples were analyzed for hematological parameters. The persistence of hematological changes was evaluated with three serial blood collections every 15 days followed by laboratory hematological analysis. A descriptive analysis by the Chi-square test method was performed to evaluate the association between occupational exposure to fuels and the occurrence of changes in hematological parameters. (3) Results: In the GSWs, the most described signs and symptoms were somnolence (45.1%), headache (38.3%), dizziness (27.5%), tingling (25.4%), and involuntary movement (25%). Twenty GSWs that presented hematological alterations performed serial collections fifteen days apart. In addition, these workers presented total leukocyte counts above the upper limit and lymphocyte counts close to the lower limit. Leukocytosis and lymphopenia are hematological alterations present in chronic benzene poisoning. (4) Conclusions: The results found an initial change in different hematological parameters routinely used in clinics to evaluate health conditions. These findings reveal the importance of valuing clinical changes, even in the absence of disease, during the health monitoring of gas station workers and other groups that share the same space.

Abstract Background: Many factors influence the choice of salvage therapy in relapsed/refractory multiple myeloma (RRMM), including various disease characteristics such as light chain and heavy chain subtypes. Patients with light chain only myeloma are a biologically and phenotypically distinct subset of patients from those with IgG, IgA, IgM, or IgD disease. Evidence exists that the presence of different paraprotein heavy and light chain subtypes may affect treatment outcomes. We investigated the effect of the presence of paraprotein heavy and light chain types on the efficacy and safety of pegylated liposomal doxorubicin (PLD) + bortezomib (B) versus B alone based on the phase III randomized trial of PLD+B vs. B alone in RRMM, which demonstrated improved time to progression (TTP) with PLD+B (Orlowski, JCO 2007). Methods: Eligible patients were randomized to bolus IV B 1.3 mg/m2 on days 1, 4, 8, and 11 of each 3-week cycle (n=322) or to the same B regimen plus IV PLD 30 mg/m2 on day 4 (n=324) of each cycle. The subsets of patients with light chain and heavy chain multiple myeloma subtypes were analyzed retrospectively. Results: The presence of light chain myeloma was observed in 77 patients. Few patients had IgM/IgD subtype myeloma (4 and 6 patients, respectively), while the majority of patients had IgG (n=379) or IgA (n=265) subtypes. Time to disease progression (TTP) and complete response (CR) + partial response (PR) rates for PLD+B vs B alone in patients with light chain, IgG, and IgA myeloma subtypes are listed in the table. PLD+B B P valueb Hazard Ratioc a. Based on Kaplan-Meier product-limit estimates. b. Based on stratified Log-rank test. c. A hazard ratio &gt;1 indicates an advantage for PLD+B. d. Cochran-Mantel-Haenszel test controlling for Beta2 microglobulin and response to initial treatment. Light chain, N 40 37 TTP, Median days (95% CI)a 276 (171, n/a) 117 (85, 173) .003 3.09 (1.42, 6.73) Total CR+PR, n/evaluable (%) 22/39 (56) 10/33 (30) .030d IgG subtype, N 182 197 TTP 282 (221, 331) 199 (170, 222) .002 1.67 (1.20, 2.31) Total CR+PR 70/173 (41) 81/194 (42) .915d IgA subtype, N 88 77 TTP 250 (218, n/a) 205 (177, 236) .506 1.22 (0.68, 2.18) Total CR+PR 46/79 (58) 39/72 (54) .723d Results showed that the combination of PLD+B had significant benefit over B alone in TTP (PLD+B led to longer TTP than B alone) for IgG paraprotein and light chain subtypes. Safety profiles for the 2 regimens in these subsets of patients with heavy or light chain myeloma were consistent with the known toxicities of the 2 agents used. Conclusions: These data demonstrate that the combination of PLD+B is an important treatment option in patients with RRMM. Patients with light chain only disease had the largest incremental benefit from the addition of PLD with an absolute increase in TTP of 159 days as well as an increase in the overall response rate from 30% to 56%.

INTRODUCTION: Disc degeneration with loss of disc height can be an indication to fuse patients with lumbar spondylosis. However, its relevance for spondylolisthesis is unknown. METHODS: The Quality Outcomes Database was queried for adult patients who underwent fusion for single-level degenerative grade 1 lumbar spondylolisthesis. Pfirrmann grade at the level to be fused was assessed on preoperative sagittal T2-weighted MRI. VAS-back pain (BP-VAS), VAS-leg pain (LP-VAS), and ODI were collected preoperatively and at 3, 12, 24, 36, and 60 months postoperatively. RESULTS: The query returned 395 patients. Mean age (95% CI) was 60 (58.9-61.1) years; 39.5% were male. None had a Pfirrmann grade 1 disc. One (0.3%) had a grade 2 disc, 53 (13.4%) had a grade 3 disc, 245 (62%) had a grade 4 disc, and 96 (24.3%) had a grade 5 disc. Posterior-only approach was performed in 92.6%; interbody graft was placed in 92.7%. Mean BP-VAS (95% CI) at baseline, 3 months, 12 months, 24 months, 36 months, and 60 months were 7.1 (6.8-7.3) (n = 343), 3.1 (2.8-3.3) (n = 353), 2.9 (2.6-3.2) (n = 305), 3.2 (2.8-3.5) (n = 283), 3.5 (2.9-4.1) (n = 107), and 3.7 (3.3-4.0) (n = 324). Mean LP-VAS (95% CI) were 6.7 (6.4-7.0) (n = 392), 2.3 (2.0-2.6) (n = 353), 2.2 (1.9-2.6) (n = 306), 2.6 (2.2-2.9) (n = 284), 2.8 (2.2-3.4) (n = 107), and 2.8 (2.4-3.1) (n = 322). Mean ODI (95% CI) were 49.4 (47.8-51.1) (n = 392), 27.4 (25.3-29.5) (n = 347), 22.9 (20.6-25.2) (n = 313), 22.4 (20.1-24.8) (n = 291), 22.4 (18.3-26.4) (n = 97), and 25.9 (23.7-28.2) (n = 325). Utilizing linear regression, Pfirrmann grade was not associated with improvements in VAS-BP, VAS-LP, or ODI at any time point in unadjusted and adjusted analyses (p > 0.05). CONCLUSIONS: Patients who undergo fusion for single-level grade 1 spondylolisthesis are likely to experience significant and sustained improvements in pain and function regardless of severity of disc degeneration.

This applied research was conducted by employing both quantitative and qualitative innovative research methods. This research investigates the satellite data of four spectral bands sent from the Small Multi-Mission Satellite (SMMS). Each band was analyzed to create color composition indices of the western areas of Thailand. Band 1 had a wavelength between 0.43 and 0.52 micrometers, Band 2 between 0.52 and 0.60 micrometers, Band 3 between 0.63 and 0.69 micrometers, and Band 4 between 0.76 and 0.90 micrometers. Three layers of satellite data were overlaid in non-repeating arrangements. Bands showing grayscale were substituted by three additive primary colors of blue, green, and red. The arrangements were permutated into 24 indices: 123, 124, 132, 134, 142, 143, 213, 214, 231, 234, 241, 243, 312, 314, 321, 324, 341, 342, 412, 413, 421, 423, 431, and 432. The data of color composition indices were then analyzed to create the land-use indices. The visual interpretation of the three levels of land-use classification were used in this procedure. The result was a land-use classification with 15 indices: City, Commercial, and Services; Airport; Golf Course; Paddy Field; Field Crop; Perennial; Aquacultural Land; Shrimp Farm; Evergreen Forest; Deciduous Forest; Mangrove Forest; Marine; River; Canal; Reservoir; and Road.

A specific guanine nucleotide-binding protein, Gk, is the link by which muscarinic receptors activate atrial potassium channels (Science Wash. DC 235: 207-211, 1987). In adult guinea pigs, the alpha-subunit at picomolar concentrations mediates the holo-G protein effect (Science Wash. DC 236: 442-445, 1987), but in chick embryo it has been reported that the beta gamma-dimer at nanomolar concentrations rather than the alpha-subunit is the effective mediator (Nature Lond. 325: 321-326, 1987). This difference might have a phylogenetic or ontogenetic basis, and the present experiments tested these possibilities. Preactivated alpha k derived from human red blood cell Gk, when applied to the intracellular surface of inside-out membrane patches from the atria of embryonic chick, neonatal rat, and adult guinea pig activated single K+ channel currents. In each case, the alpha k-activated channels had the same single-channel conductance and mean open time as the muscarinic agonist-activated channels. Half-maximal activation was achieved at alpha k-concentrations of 2.4-13.8 pM. Hence, alpha k-activation of these K+ channels is independent of differences in age or species. The detergent 3-[3-cholamidopropyl)-dimethyammoniol]-1-propanesulfonate (CHAPS), which was used by Logothetis et al. (Nature Lond. 325: 321-326, 1987) at 184 microM to suspend the hydrophobic beta gamma-dimers, activated the same currents. We conclude that the effects of the beta gamma-dimer on these K+ channels is unknown and that as we had proposed earlier (Science Wash. DC 236: 442-445, 1987) it is the alpha-subunit that mediates the Gk effect.

We previously reported that the type II secreted phospholipase A2 (sPLA2) promoter from positions (-326 to +20) ([-326;+20] promoter) is negatively regulated by two adjacent regulatory elements, C (-210 to -176) and D (-247 to -210). This study examines in greater detail the way in which this negative regulation operates. Successive 5' deletions of the [-326;+20] type II sPLA2 promoter indicated that the region upstream of position -195 inhibits the transcription activity sixfold in HepG2 cells but not in HeLa cells. Although the whole [-326;-176] region decreased the activity of a heterologous thymidine kinase promoter, this effect was orientation and position sensitive. C/EBP beta, C/EBP alpha, and C/EBP delta, which bind to element C, prevented the inhibition of promoter activity. Electrophoretic mobility shift experiments identified the binding of NF1-like proteins to the [-225;-218] site, which overlaps an insulin response-like sequence, 5'-TGTTTTG-3'. This sequence bound a factor which also recognized the promoters of the apolipoproteins C-III and A-II. Substitutions preventing the binding of this factor or the NF1-like proteins did not increase the transcription activity, but substitution in the [-217;-204] sequence blocked the transcription inhibition. This sequence did not bind any double-strand binding factor, but its antisense strand is critical for the binding of single-strand binding proteins to the [-232;-191] region. We therefore suggest that these single-strand binding proteins are involved in the inhibitory mechanism.

Abstract. Weekly vertical profiles of ammonia (NH3) were measured at 16 heights on the Beijing 325 m meteorological tower for 1 year from March 2016 to March 2017. The average NH3 concentrations exceeded 4 µg m−3 at all heights with an overall average (±1σ) value of 13.3 (±4.8) µg m−3. The highest NH3 concentrations along the vertical profiles mostly occurred from 32 to 63 m, decreasing both towards the surface and at higher altitudes. Significant decreases in NH3 concentrations were only found at the top two heights (280 and 320 m). These results suggest an NH3 rich atmosphere during all seasons in urban Beijing, from the ground to at least 320 m. The highest seasonal NH3 concentrations across the profile were observed in summer (18.2 µg m−3) with high temperature, followed by spring (13.4 µg m−3), autumn (12.1 µg m−3) and winter (8.3 µg m−3). A significant vertical variation in the NH3 concentration was only found in summer. Source region analyses suggest that air masses from intensive agricultural regions to the south contribute most to the high NH3 concentrations in Beijing. Local sources such as traffic emissions also appear to be important contributors to atmospheric NH3 in this urban environment.

Abstract Imatinib mesylate (Gleevec®), has been found both effective and cost-effective for treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST).This study examines the relationship between compliance and health care utilization and costs. This retrospective study used claims from a large national US health plan. Patients (pts) had ≥2 imatinib claims from 6/1/01–3/31/05; ≥1 yr follow-up (F/U) after the 1st imatinib claim; diagnosis of CML (ICD9 205.1 ×) or GIST (ICD9 159.0, 159.8, 159.9 or evaluation of claims by independent hematologist-oncologist). Compliance was measured each in F/U Yrs 1 and 2 with medication possession ratio (MPR: ((days supply of imatinib)/365)*100). Compliance categories were good (≥90%); medium (70–89.9%); poor (<70%). Comorbidity measure was Charlson Comorbidity Index (CCI). Outcomes were number (#) of inpatient hospital stays (IP), procedures (procs), lab tests, length of IP stay (LOS), costs of IP, procedures, labs, total medical care, and total health care (medical+pharmacy). Rates of Yr2 outcomes/person-yr within cohort and compliance category were bootstrapped (100 repetitions) to adjust for varying F/U and provide standard errors. Outcomes were compared within cohort, across compliance categories; t-tests compared mean utilization and costs. 374 CML and 91 GIST had mean age 50.8±14.1 and 57.5±12.0, respectively. 218 (58.3%) CML and 56 (61.5%) GIST pts were male. CML and GIST pts had mean F/U of 29.5±13.2 and 24.9±10.6 months, respectively. GIST pts were sicker with mean CCI 6.5±3.2 vs CCI 2.4±1.0 for CML. For almost all outcomes, pts with poor compliance had significant higher utilization and costs than pts with good compliance (Table 1,2). GIST pts with good compliance had some higher costs, likely due to small sample, high comorbidity, and wide variation in costs (vs CML). For CML pts, mean medical costs were 87% lower for good compliance vs poor in both years; mean health care costs were 45% and 54% lower for good compliance in Years 1 and 2. Pts with poor compliance had 14 times longer IP LOS, 1.4 times more labs, 2.1 times higher lab costs than good compliance, on average. Overall, good imatinib compliance was significantly associated with lower health care resource consumption. Table 1: CML Outcomes (Means) Year 1 Year 2 Compliance Good N=166 Medium N=79 Poor N=129 Good N=143 Medium N=84 Poor N=147 *0.01<p<0.05, **p<0.01 compared with good compliance # IP 0.1 0.3 1.1** 0.2 0.2 1.1** IP LOS 0.6 3.1 14.4** 0.8 2.0** 9.9** # Procs 18.4 28.3* 50.3** 18.6 18.2 56.2** # Labs 49.9 50.6 71.1* 32.2 37.5** 65.7** $ IP 307 1737 4360** 1127 392** 5745** $ Procs 5512 16483* 67328** 4613 7428** 52620** $ Labs 2570 2621 5589** 2140 1778** 4527** $ Medical 10427 23659* 83685** 9080 11101** 70940** $ Health care 47384 52693 102745** 47603 39044** 86197** Table 2: GIST Outcomes (Means) Year 1 Year 2 Compliance Good N=27 Medium N=20 Poor N=44 Good N=32 Medium N=18 Poor N=41 *0.01<p<0.05, **p<0.01 compared with good compliance # IP 0.1 0.3 1.2** 0.3 0.8** 1.5** IP LOS 0.6 1.6 14.1 1.6 2.7** 21.3** # Procs 28.8 41.1 49.1 32.1 34.5** 51.8** # Labs 34.3 29.2 33.6 31.2 25.9** 25.1** $ IP 414 324 3505 524 2163** 5064** $ Procs 12409 15223 33222* 12947 12585 26686** $ Labs 755 885 913 695 734** 953** $ Medical 15088 17991 39743* 15275 16915** 35664** $ Health care 55211 50435 55579 57745 48270** 45659**

Objective: The objective of this research was to formulate the binding energies and interaction of amino acid residues in kaempferitrin with different types of apoptotic and inflammatory proteins of colon cancer.Methods: AutoDock Vina and MGL tool were used for docking calculations. Both programs require the pdbqt input files and allow for flexibility of all the torsional bonds of small molecules. Discovery Studio Visualizer v3.5 was used for removal of water molecules and ligands and the pymol program was used to do analysis of the docking with various apoptotic proteins BAX, Bcl-2, COX-2, Protein kinase B.Results: In our study was developed binding energy scoring function of kaempferitrin docked with different types of inflammatory proteins and apoptotic proteins. Binding score values for-6.9 (BAX),-7.2 (Bcl-2),-7.3 (caspase-3),-8.8 (Cox-2),-7.4 (Cytochrome P450),-6.7 (Proteinase kinase B),-8.0 (TNF-α) and-7.2 (VEGF) kcal/mol, respectively. Amino acid interaction of kaempferitrin with proteins for ARG-25, LEU-52, ASN-54, PHE-55, GLU-17, LYS-14, TRP-22, THR-21 GLY-16 (Protein Kinase B), ASP-102, ASN-48, GLN-52, ASP-104 (BAX), GLU-176, TRP-173, GLU-132, PHE-135 (Bcl-2), SER-249, ASP-2, ASN-208, GLN-217, LEU-242 (Caspase 3), TYR-55, HIS-39, SER-49, GLU-322, GLY-326 (COX-2), SER-95, LEU-94, ARG-82, VAL-123, ALA-96 (TNF-α), ASP-414, LYS-322, GLU-326, GLU-416, GLU-438, ALA-439, GLU-437 (Cytochrome P450) and LEU-47, GLN-46, CYS-61, CYS-60, ASP-63, GLU-67, GLY-65, LEU-66 (VEGF) respectively.Conclusion: The results obtained in this research work clearly indicated the docking scores of apoptotic and Inflammatory proteins imply that kaempferitrin is an effective inhibitory compound for colon cancer.

In this study, we examine the consistency of a gravity-based predictive theory for a hydraulic jump, given by Kurihara [ Proceedings of the Report of the Research Institute for Fluid Engineering (Kyusyu Imperial University, 1946), Vol. 3, pp. 11–33]; Tani [J. Phys. Soc. Jpn. 4, 212–215 (1949)] with the phenomenological condition at the jump given by Rayleigh [Proc. R. Soc. London, Ser. A 90, 324–328 (1914)]; and Watson [J. Fluid Mech. 20, 481–499 (1964)] and show that in light of experimental evidence, the gravity-based predictive theory for the kitchen sink hydraulic jump is incompatible with the phenomenological condition, which must be valid. We also examine the solution to the downstream film and its potential influence on the hydraulic jump. We show that for all practical purposes, at normal flow conditions, the downstream liquid film remains flat and does not affect the jump, and the theory given by Bhagat et al. [J. Fluid Mech. 851, R5 (2018)] gives an excellent prediction of the jump radius. For high viscosity liquids, on a relatively large plate, the viscous dissipation in the downstream film could increase the jump height and, consequently, move the jump radius inward.

Ювенильный ревматоидный артрит (ЮРА) дошкольного возраста представлен в литературе немногочисленными наблюдениями[1,2]. Цель настоящей работы явилось изучение клинико-ла­бораторных признаков начального периода ЮРА у 60 детей в возрасте до 7 лет, а также тактика ра­циональной терапии и результаты катамнестического наблюдения за больными детьми дошкольного возраста, лечившимися в стационаре в течение 2015—2021 гг. Материал и методы: Среди наблюдаемых больных у большинства (32) заболевание нача­лось на 7-м году жизни, у 11 — в возрасте до 5 лет, у 17 — в 3 года. Подострое начало заболевания, характерное для детей дошкольного возраста, отмечено у 36 (60 %), что было обусловлено развитием у большинства больных (39, или 65%) суставной формы. Среди них большую часть составляли дети с наиболее доброкачественными вариантами — олигоартритом (19) и моноартритом (5); множественное поражение суставов было у 15 больных. Напротив, среди боль­ных с суставно-висцеральной формой (20, или 33,3%) у большей части преобладали первоначаль­но наиболее тяжелые варианты с поливисцеритами — аллергосептический синдром (у 10) и синд­ром Стилла (у 5). Результаты: В наших наблюдениях выявлена определенная зависимость характера активности ЮРА и развития деструктивных изменений в суставах от сроков на­чала целенаправленной терапии Вывод: следовательно, целенаправленная комплексная длительная терапия РА в дошкольном возрасте не толь­ко приводит к стойкому снижению активности, стабилизации процесса у большинства детей, но и позволяет избежать применения кортикостероидов, а также способствует репаративным сдвигам и реа­билитации значительной части больных (43%).

MicroRNAs (miRNAs) have been implicated in a variety of physiological processes, however, the function of miRNAs in insulin secretion and type 2 diabetes is still unclear. Stxbp1 plays an essential role in exocytosis, and is crucial for insulin secretion. In this study, we focused on the molecular mechanism of Stxbp1 in insulin secretion by identifying its upstream regulators: miR-218 and miR-322. The expression of Stxbp1 was significantly increased in isolated mouse islets exposed to high levels of glucose within 1 h; while two of its predicted upstream miRNAs were found to be downregulated. Further study found that miR-218 and miR-322 directly interact with Stxbp1 by targeting the 3′UTR of its mRNA. MIN6 cells overexpressing the two miRNAs showed a sharp decline in insulin secretion and a decreased sensitivity to glucose; while the inhibition of the two miRNAs promoted insulin secretion. However, islets treated with prolonged high levels of glucose, which is known as glucolipotoxicity, displayed relatively high expression of miR-218 and miR-322, and a reduced level of expression of Stxbp1 accompanied by the blocking of insulin secretion. In summary, this study identified a pathway consisting of miR-218/322 and Stxbp1 in insulin secretion, contributing to a network of β-cell function involving miRNA.

Objective: The article dedicated to debating the degree of certainty of verification of certain types of reactivation of the tuberculosis process, such as relapse, reinfection and superinfection. Analysis of native and foreign publications for the last 10 years on this issue conducted. The authors confirm that even if the outcome of a successful treatment of tuberculosis is deduced based on bacterioscopic and cultural conversion of sputum (outcome "cured"), it is not possible to claim reinfection after eradication or elimination of M. tuberculosis, because it does not exclude its presence in the parenchyma of the lungs, lymph nodes or other organs. If the outcome of successful treatment for various reasons displayed without laboratory confirmation (outcome "completed treatment"), the more so it is impossible to confirm the relapse or reinfection of the disease. Summing up the analysis of the literature, the authors point out the necessity of a differentiated approach in observations in practice and in scientific researches. The use of several costly methods of verification of the form reactivating of the tuberculosis process is not always justified. Ultimately, as recommended WHO, these cases register as new and, depending on the sensitivity to anti-tuberculosis drugs picks up the regimen of repeated chemotherapy. Keywords: Tuberculosis, reactivation, exacerbation, relapse, reinfection, superinfection..

Фразеологічний склад мови – це культурний код народу. Тому актуальним є дослідження культурного надбання Богдана Лепкого, яке акумулює основні тенденції художнього мислення від неонародництва до модернізму. У статті виокремлено структурні моделі фразем із комунікативними дієсловами у словнику «Фразеологізми у творах Богдана Лепкого». Проаналізовано дієслівні фраземи зі словника «Фразеологізми у творах Богдана Лепкого» (199 оди- ниць): комунікативні дієслова становлять 42 одиниці (21%), комунікативні дієслівні фраземи – 59 (30%). Виділено три семантичні підгрупи комунікативних дієслівних фразем: словесну, словесно-несловесну й несловесну. Словесна містить дієслова, які в складі фразеологічних одиниць мають значення, пов’язане з передаванням або отриманням інформації за допомогою вербальних засобів (20 одиниць); словесно-несловесна підгрупа – дієслова, які в складі фра- зеологічних одиниць мають значення, пов’язане з передаванням або отриманням інформації за допомогою вербаль- них і невербальних засобів (5 одиниць); несловесна – дієслова, які у складі фразеологічних одиниць мають значення, пов’язане з передаванням або отриманням інформації за допомогою невербальних засобів (17 одиниць). Виділено 17 структурних моделей фразем із комунікативними дієсловами: V + N/NP – 26 одиниць (44%); V + NP – 1 одиниця (1,7%); (Part)V + Adv – 3 одиниці (5%); V + Prep. + N /NP – 9 одиниць (15%); V+Pron. + N – 2 одиниці (3,4%); V+ Prep.+ Pron. – 3 одиниці (5%); Part.+V + N – 2 одиниці (3,4%); V+ Conj.+ (V) + N – 1 одиниця (1,7%); V+N+ Prep. + N – 1 одиниця (1,7%); V+Pron.+ Prep. + N – 2одиниці (3,4%); V+N/Pron.+Prep.+ NP – 2 одиниці (3,4%); N+Prep.+N+V – 1 одиниця (1,7%); V+ Conj.+ Prep. + N – 2 одиниці (3,4%); V+ Conj.+ Adv+ (V)+ N – 1 одиниця (1,7%); V + N + Conj. + N – 1 одиниця (1,7%); Conj.+ V+ Conj.+Part. +V – 1 одиниця (1,7%); Part.+V+N+ Prep+ Pron. – 1 одиниця (1,7%). Дві моделі є продуктивними у зазначеній групі дієслів. Перша – V + N/ NP – має такі варіанти реалізації: V + N1; V + N2/NP; V + N4/NP; V + N5 /NP. Друга – V3+ Prep. + N /NP – реалізується в таких схемах: V + Prep. + N2; V + Prep.+ N4/NP; V + Prep. + N5.

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Nitrogen (N) fertiliser use on dairy pastures in south-eastern Australia has increased exponentially over the past 15 years. Concurrently, imports of supplementary feed onto dairy farms have increased, adding further nutrients to the system. These trends raise questions about the environmental effects of higher nutrient inputs to dairy farms. To gauge possible effects, annual N balances were calculated from an experiment where N inputs and losses were measured for 3 years from non-irrigated grass/clover pastures receiving either no N fertiliser (Control) or 200 kg N/ha applied annually as ammonium nitrate or urea. Estimated total N inputs, averaged over the 3 years, were 154, 314, and 321 kg N/ha.year for the control, ammonium nitrate, and urea treatments, respectively, while N outputs in meat and milk were 75, 99, and 103 kg N/ha.year, respectively. The corresponding calculated N surplus was 79, 215, and 218 kg N/ha.year for the 3 treatments, respectively, and the ratio of product N/total-N inputs for the 3 treatments ranged from 50% in the control to 32% for both N treatments. Total N losses averaged 56, 102, and 119 kg N/ha.year, leaving a positive N balance of 23, 112, and 99 kg N/ha.year for the control, ammonium nitrate, and urea treatments, respectively. The ratio of product N/total-N inputs or the N surplus may be useful in monitoring the efficiency of conversion of N into animal products and the potential environmental effect at a whole-farm scale. However, additional decision support or modelling tools are required to provide information on specific N losses for a given set of conditions and management inputs. Given the large range in N losses there is opportunity for improving N-use efficiency in dairy pastures through a range of management practices and more tactical use of grain and N fertiliser.

The structure of racemic (RS)-trichlormethiazide [systematic name: (RS)-6-chloro-3-(dichloromethyl)-1,1-dioxo-3,4-dihydro-2H-1λ6,2,4-benzothiadiazine-7-sulfonamide], C8H8Cl3N3O4S2 (RS-TCMZ), a diuretic drug used in the treatment of oedema and hypertension, was determined from laboratory X-ray powder diffraction data using DASH [David et al. (2006). J. Appl. Cryst. 39, 910–915.], refined by the Rietveld method with TOPAS-Academic [Coelho (2018). J. Appl. Cryst. 51, 210–218], and optimized using DFT-D calculations. The extended structure consists of head-to-tail dimers connected by π–π interactions which, in turn, are connected by C—Cl...π interactions. They form chains propagating along [101], further connected by N—H...O hydrogen bonds to produce layers parallel to the ac plane that stack along the b-axis direction, connected by additional N—H...O hydrogen bonds. The Hirshfeld surface analysis indicates a major contribution of H...O and H...Cl interactions (32.2 and 21.7%, respectively). Energy framework calculations confirm the major contribution of electrostatic interactions (E elec) to the total energy (E tot). A comparison with the structure of S-TCMZ is also presented.

324 Background: TZ in HER2-positive breast cancer (BC) has established improved outcomes in certain Pts. TZ carries a black box warning and a recommendation for CM in all Pts prior to and during treatment (tx) Few studies have evaluated real-world CM compliance during tx. Methods: Retrospective, cross-sectional analysis was conducted to identify CM compliance among BC pts receiving TZ, using a limited data set of administrative claims data consisting of female Pts who were continuously insured over a 24-month period between Jan 1, 2019 and Dec 31, 2020, as provided through a secure portal by Blue Cross Blue Shield Association. [1] . BC diagnosis was confirmed by ICD-9 code, while tx with TZ or biosimilar was confirmed through Healthcare Common Procedure Coding System codes. A care episode spanned 14 months, including 123 days prior to first TZ dose (Index Date) and at least 307 days of follow up. Two cohorts (eligibility for both dx and continually insured status of female commercial Pts, 2018-2019 and 2019-2020) were analyzed across four tx Phases (Pre-Tx Phase [days -123-+ Index Date as day 1], Phase 1 [days 61-123], Phase 2 [days 153-215], Phase 3 [days 245-307]). Phase denominators were calculated independently, only including Pts with ongoing TZ tx for each Phase. [1] Blue Cross Blue Shield Association is an association of independent, locally operated Blue Cross and Blue Shield companies. Results: Pts in each Phase and cohort ranged from 2,304 (Full Compliance 2019-2020) to 3,263 (Pre-Tx 2019-2020). Similar results were seen in both cohorts, with highest proportion of Pts receiving CM in Pre-Tx phase. Overall compliance in Pre-Tx Phase and all subsequent Phases was low; nearly two-thirds of Pts missed one or more CM tests. Drop-off in CM testing occurred in each subsequent tx Phase (Table). Conclusions: Continued decline in CM over time suggests lack of awareness for potential late TZ cardiac toxicity. Further research regarding why Pts are not receiving recommended baseline and on-treatment CM is needed. Routine CM during TZ tx may be a quality indicator for practices, payers, and quality improvement programs.[Table: see text]

Biological response modifiers, especially tumour necrosis factor inhibitors have been proved to be very effective in the treatment of various immune mediated rheumatological, gastroenterological and dermatological diseases in the last 15 years. With their increasing use, the incidence of their adverse effects are more precisely defined. The aim of this cohort study was to analyse the adverse effects occurred within the study period in patients receiving biological therapy for rheumatological and dermatological autoimmune diseases. Methods: 324 patients within a 3 years study period were treated with biological response modifiers (adalimumab: 92, etanercept: 107, infliximab: 125). The primary diagnoses were rheumotoid arthritis (n = 174), ankylosing spondylitis (n = 60), psoriatic arthritis (n = 11), and psoriasis vulgaris (79). Results: Hypersensitive reactions were observed in 11 of the patients (3.4%), 7 of which were serious and needed treatment termination. Infections constituted the majority of side effects, which were localised to skin in 10 (3.1%) and to respiratory tract in 9 (2.8%). However, most of these were mild or moderate reactions. Malignant skin tumour developed in 1 case (0.3%) only. Drug induced inflammatory disorders occurred in some cases: onset of new psoriasis was observed in 1 and flares of the existing disease were detected in additional three. Lichenoid exanthema developed in one. (n = 5, 1.5%) Conclusion: The use of TNF-α blockers may provoke a broad spectrum of dermatological side effects. Our results suggest that the majority of these are infectious and inflammatory disorders, the latter may relatively often appear as drug induced psoriasis. The occurrence of malignancies was very low in our series. Orv. Hetil., 2011, 152, 212–220.

Introduction. The widespread adoption of Artificial Intelligence (AI) technologies forms the core of the so-called Industrial Revolution 4.0.The aim of this study is to examine qualitative changes occurring over the last two years in the development of AI through an examination of trends in PubMed publications.Materials. All abstracts with keyword “artificial intelligence” were downloaded from PubMed database https://www.ncbi.nlm.nih.gov/pubmed/ in the form of .txt files. In order to produce a generalisation of topics, we classified present applications of AI in medicine. To this end, 78,420 abstracts, 5558 reviews, 304 randomised controlled trials, 247 multicentre studies and 4137 other publication types were extracted. (Figure 1). Next, the typical applications were classified.Results. Interest in the topic of AI in publications indexed in the PubMed library is increasing according to general innovation development principles. Along with English publications, the number of non-English publications continued to increase until 2018, represented especially by Chinese, German and French languages. By 2018, the number of non-English publications had started to decrease in favour of English publications. Implementations of AI are already being adopted in contemporary practice. Thus, AI tools have moved out of the theoretical realm to find mainstream application.Conclusions. Tools for machine learning have become widely available to working scientists over the last two years. Since this includes FDA-approved tools for general clinical practice, the change not only affects to researchers but also clinical practitioners. Medical imaging and analysis applications already approved for the most part demonstrate comparable accuracy with the human specialist. A classification of developed AI applications is presented in the article.

AbstractThe base catalyzed condensation reaction between 4-hydroxycoumarin and 3-acetylcoumarin (3-benzoylcoumarin) in water at reflux led to the formation of 1-methyl (1-phenyl)- benzopyrano[4’,3’-c]-benzo[3”,4”-ƒ ]-2,8-dioxabicyclo[3.3.1]nonane (2a, b) as final products. When 4-hydroxycoumarin and 3-acetylcoumarin reacted in a glacial acetic acid in the presence of potassium acetate the final product was 7-[3-acetyl-2-oxo-3,4-dihydro-2H-[1]benzopyran-4-yl]methyl- 6H,14H,14bH-bis-([1]benzopyrano)[4,3-b:4’,3’-d]pyran-6,14-dione (4). 4-Hydroxycoumarin and 4-(5-bromo-2-hydroxyphenyl)-3-buten-2-one were condensed in water at reflux and 1- methylcoumarino-[4’,3’-c]-bromobenzo[3”,4”-ƒ ]-2,8-dioxabicyclo[3.3.1]nonane was a final product (3).

The active implementation of digital technologies into all spheres of public life, as well as the rapid development of artificial intelligence, is assuming a serious dimension, thus requiring a special attention of the legislator. The article examines the current state of the legal regulation of the artificial intelligence. The author considers the Strategy of the Information Society Development in the Russian Federation for 2017-2030, as well as provides some clear examples of active implementation of artificial intelligence into social reality. The author also provides the McKinsey consulting group's research findings which reflect the prospects for replacing human labor by robots. It is pointed out that the issue of total computerization and the corresponding displacement of a human from the sphere of intellectual activity is rather controversial. The article also discusses the main possible problems related to the artificial intelligence technologies: the problems of responsibility that may arise in the operation of industrial robots; the continuity of digital activity can affect the psychoemotional state. The issue of a possibility for creating robots with intelligence and endowed with personality is being considered from the Philosophy perspective. The conclusion is drawn that the theoretical study of the intellect and the "electronic person" is one of the possible redirections of the Russian law development in modern conditions.

Breeding of new domestic varieties of economically useful plants for different purposes (food, fodder, technical, medicinal, decorative, etc.) is the basis for food, environmental and social security of the republic population. Therefore, preservation, study, mobilization and rational use of genetic resources in the context of global climate change and steady increase of anthropogenic pressure on nature is a planetary problem. The welfare and life of the present and future generations of mankind depends on successful solution of this problem. The paper presents history in chronicles of genetic resources preservation in the Republic of Belarus – from conception of this trend to the present day. Particular attention is paid to the presentation of the results obtained by the implementing organizations of the State Program “Plant Gene Pool” over a 17-year period (2000-2017), including 11 academic institutions and 2 higher educational institutions of the republic. The contribution of each organization to the national genetic bank formation is reflected. Basic, active, working, field, double, target, indicative, core and training collections of the main resource crops, economically significant crops and forest-forming species were formed by their efforts. The largest and most valuable genetic collections of 7 implementing organizations are included in the State Register of Scientific Objects, which constitute the national treasure of the Republic. These collections are a source of valuable genetic material and, at the same time, they are successfully used in scientific, environmental, educational and other programs. Currently, genetic collections in general include over 78,300.00 specimens belonging to 1,680.00 species of crop plants and their wild relatives. 1,016.00 varieties of crop plants were created based on them. The paper also reflects the main approaches and perspectives of preservation and rational use of the plant gene pool. Sophisticated and time-consuming processes of genetic collections formation in modern hard economic and regional natural conditions, taking into account the results of similar studies of other states, will serve as a scientific and information basis for increasing efficiency and improving work in this direction. In practical terms, the high level of species, variety and form biological diversity of genetic collections serves as a guarantee for their efficient use in crop production and selection as sources and donors of valuable genetic material.

Physical experiments allow to obtain maximum information on a studied process at minimal cost, ensuring its higher accuracy comparing with data, obtained by mathematical simulation and avoiding risks, which can occur at industrial testing of new technological modes. Results of studies of deformation in the process of pipes production by extrusion presented. The studies were accomplished at laboratory test units, developed by specialists of the laboratory of drawing and extrusion of JSC “RusNITI”. One of the basic problems at pipes production by extrusion is ensuring minimal possible wall non-uniform thickness. It was noted that the relation between plunger die moving speeds during sleeve pressing-out and immediate pipe extrusion has a significant effect on pipe wall non-uniform thickness. Computer simulation of the pipe extrusion process, accomplished by application QForm program shown that minimal values of wall non-uniform thickness corresponded to relation abovementioned speeds as 0.5–0.8. To check the data, a physical simulation of extrusion process of lead cylinder samples, having outside diameter of 18.94 mm and wall thickness 5.19–5.32 mm was accomplished. For the extrusion, a universal servohydraulic system of dynamic test Shimadzu Servopulser was used. Within the physical experiment a dependence was established between pipe wall non-uniform thickness on relation between speeds of pressing-out and extrusion. The revealed regularity was confirmed during pilot production of a pipe lot at the 55 MN force extrusion line. Another physical simulation of extrusion of 10.0×2.0 mm pipe-samples made of C1 grade lead was accomplished with one- and twothread helical ribbing of internal surface. For its accomplishment an experimental module was designed and manufactured. It was established that rotation speed of the extrusion mandrel had no significant effect on extrusion force. Metallographic studies shown that the extrusion mandrel rotation speed contributes to considerable increase of pipes surface hardness and obtaining finer grain comparing with the classic extrusion method. The technical ability of pipes production with internal helical ribbing by hot extrusion method was confirmed. The results of the study became a base for elaboration of a technology of pipes production at Volzhsky pipe plant according to ТУ 14-3Р-157–2018 “Steel seamless hot-extruded pipes with helical ribbing of internal surface for steam boilers”. Results of physical simulation of pipe drawing process at self-adjusting mandrel with application of lubricant materials of various viscosity. The data obtained were used for elaboration of a technology for production of cold-deformed pipes with internal diameter of 6.0–12.0 mm at Sinarsky pipe plant.

AbstractThe high-temperature polymorph of the trisulfide Cs2S3, which has been synthesized from Cs2S2 and elemental sulfur, crystallizes in a new structure type (monoclinic, space group P21/c, a=999.97(4), b=1029.30(5), c=2642.07(12) pm, β=90.083(2)°, Z=16, R1=0.0324). The structure contains four crystallographically independent angled ${\rm{S}}_3^{2 - }$ trisulfide ions with S–S distances of 205.7–208.3 pm. The distorted b.c.c. packing of the anions and their insertion in the five-membered rings of 3.53+3.5.3.5. (1:1) Cs nets are similarly found in the r.t. form (Cmc21, K2S3-type structure) and the two polymorphs differ mainly in the orientation of the S3 groups. The second title compound, K37Te28, was synthesized from stoichiometric melts of the elements. It forms a complex (3+1)D modulated tetragonal structure (space group I41/amd (00σ3)s0s0, q=(0, 0, 0.5143), a=1923.22(2), c=2626.66(4) pm, Z=4, R1all=0.0837). According to K37Te28=K37[Te(1X)]8[Te(2X)2]6[Te(3X)8] the structure contains three different types of Te anions: The two crystallographically different isolated telluride anions [Te(1X)]2− are coordinated by 9/10 K+ cations. Three [Te(2X)2]2− dumbbells (dTe-Te=277.9/286.4 pm) are arranged to ‘hexamers’. The Te(31) and Te(32) atoms are located in columns of face-sharing K square antiprisms. Their z position modulation, which is accompanied by a smaller shift of the surrounding K+ cations, results in the decomposition of the [Te(3X)8]2 chain in a sequence |:Te3–Te2–Te2–Te3–Te2–Te2–Te2:| of dumbbells Te22− (dTe–Te=304 pm) and hypervalent linear trimers Te34− (dTe–Te=325 pm).

Tujuan penelitian ini untuk mengetahui perilaku pencarian informasi pemustaka menggunakan Model Ellis, kendala yang dialami pemustaka, dan pemanfaatan sebagai sarana pendukung perkuliahan. Penelitian ini menggunakan pendekatan kuantitatif jenis deskriptif. Populasi pada penelitian ini anggota aktif Perpustakaan UKMC sampai tahun 2018 sebanyak 1.979 pemustaka dan jumlah sampel sebanyak 98 responden. Hasil penelitian ini ada 3: pertama, perilaku pencarian informasi pemustaka Perpustakaan UKMC melakukan/mengikuti tahapan model Ellis meskipun ada tahapan jarang atau tidak selalu dilakukan, secara berturut-turut rata-rata nilai setiap tahapannya, yaitu starting 3,2 dan 2,8; chaining 3,1 dan 2,6; browsing 3,4 dan 2,4; differentiating 2,9 dan 2,7; monitoring 2,7 dan 2,8; extracting 2,8 dan 2,8; verifying 2,9 dan 3,1; ending 3,2 dan 3,1. Kedua, kendala yang dialami pemustaka adalah pada kategori koleksi dan fasilitas. Ketiga, pemanfaatan Perpustakaan UKMC sebagai pendukung perkuliahan:persentase pemanfaatan sebesar 76%.

Deregulation of NOTCH1-signalling pathway is common in chronic lymphocytic leukemia (CLL). The most of studies are focused on detection of the hotspot c.7541_7542delCT NOTCH1 mutations in exon 34, while studies of mutations in the 3′UTR region are rare. The aims of work were to evaluate the frequencies of mutations in the 3′UTR region of the NOTCH1 gene (9:136,495553-136,495994) in Ukrainian CLL patients, the distribution of rs3124591 genotypes located in that area, and association of NOTCH1 mutations with structure of B-cell receptor. Materials and Methods: Detection of mutations in the 3′UTR region of the NOTCH1 was performed by direct sequencing in 87 previously untreated CLL patients (from the total group of 237 CLL patients) with unmutated immunoglobulin heavy-chain variable (UM IGHV) genes and without mutations in hotspot regions of TP53, SF3B1, and exon 34 of NOTCH1 genes. Results: Mutations in the 3′UTR region of the NOTCH1 were revealed in three of 87 CLL patients (3.4%). Two cases with non-coding mutations were related to subset #1 of stereotyped B-cell receptors, and one case belonged to stereotyped subset #28a. Analysis with inclusion of 30 UM IGHV cases with previously detected c.7544_7545delCT mutations revealed that the frequency of UM IGHV genes of I phylogenetic clan (except IGHV1-69) was significantly increased, and the frequency of UM IGHV3 and IGHV4 genes, on the contrary, was reduced in NOTCH1-mutated cases comparing with NOTCH1-unmutated cases (p = 0.002) and the general group (p = 0.013). SNP rs3124591 did not affect the risk of CLL and survival parameters of the patients. At the same time, differences were found in the frequency of IGHV gene usage and in the structure of HCDR3 in carriers of individual genotypes. Conclusion: The frequency of NOTCH1 mutations in 3′UTR region was low. Our findings confirmed current data on the association between the structure of the B-cell receptor and the appearance of NOTCH1 mutations. Some features of HCDR3 structure were identified in carriers of TT and CC genotypes of rs3124591.

Levels of lead-210, polonium-210, radium-226, and uranium are reported for 10 plant species (2 conifer, 4 shrub, 3 lichen, and 1 moss species) and soils in northern Saskatchewan. Two localities were studied in each of two regions, one uraniferous, the other not. Nonvascular species showed the highest levels of lead-210, polonium-210, and uranium, and the shrubs, the highest levels of radium-226. The lichen and moss species show no significant difference in accumulation of lead-210 and polonium-210 among regions, reflecting the assumed atmospheric distribution and particulate accumulation of these radionuclides. Seven of eight species for which comparisons could be made showed significant differences in uranium accumulation among regions. High levels in the lichen and moss species suggest that the primary source of uranium in these species is not directly from the soil. In contrast to the other radionuclides, radium-226 only showed significant differences among localities within regions, this being due to high accumulations occurring at one locality in the nonuraniferous region.