Synthesis and studying the antitumor activity of novel 5-(2-methylbenzimidazol-5-yl)-1,3,4-oxadiazole-2(3H)-thiones

The influence of the incorporation of 1,3,4-oxadiazole ring into 2-methyl-1H-benzimidazole derivatives producing a series of substituted 5(6)-(2-methylbenzimidazol-5-yl)-1,3,4-oxadiazoles on the antitumor activity was studied in this study. The antitumor activity of the new compounds was tested against breast cancer cell line MCF-7 and lung cancer cell line A549. S-5-(2-methyl-1H-benzo[d]imidazol-5-yl)-1,3,4-oxadiazol-2-yl 2-nitrobenzenesulfonothioate (9) showed potent activity against both MCF-7 and A549 cell lines. Whereas, compounds 7, 11-13 and 15-17 have moderate growth inhibitory activity on the two cell lines

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

The epidemiology of renal replacement therapy in two different parts of the worldThe Latin American Dialysis and Transplant Registry versus the European Renal Association-European Dialysis and Transplant Association Registry

Publisher Copyright: © 2018 Pan American Health Organization. All rights reserved.Objective: To compare the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in Latin America and Europe, as well as to study differences in macro-economic indicators, demographic and clinical patient characteristics, mortality rates, and causes of death between these two populations. Methods: We used data from 20 Latin American and 49 European national and subnational renal registries that had provided data to the Latin American Dialysis and Renal Transplant Registry (RLADTR) and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry, respectively. The incidence and prevalence of RRT in 2013 were calculated per million population (pmp), overall and by subcategories of age, sex, primary renal disease, and treatment modality. The correlation between gross domestic product and the prevalence of RRT was analyzed using linear regression. Trends in the prevalence of RRT between 2004 and 2013 were assessed using Joinpoint regression analysis. Results: In 2013, the overall incidence at day 91 after the onset of RRT was 181 pmp for Latin American countries and 130 pmp for European countries. The overall prevalence was 660 pmp for Latin America and 782 pmp for Europe. In the Latin American countries, the annual increase in the prevalence averaged 4.0% (95% confdence interval (CI): 2.5%-5.6%) from 2004 to 2013, while the European countries showed an average annual increase of 2.2% (95% CI: 2.0%-2.4%) for the same time period. The crude mortality rate was higher in Latin America than in Europe (112 versus 100 deaths per 1 000 patient-years), and cardiovascular disease was the main cause of death in both of those regions. Conclusions. There are considerable differences between Latin America and Europe in the epidemiology of RRT for ESRD. Further research is needed to explore the reasons for these differences.Peer reviewe

New indices for quantification of the power spectrum of heart rate variability time series without the need of any frequency band definition

This paper presents a new family of indices for the frequency domain analysis of heart rate variability time series that do not need any frequency band definition. After proper detrending of the time series, a cumulated power spectrum is obtained and frequencies that contain a certain percentage of the power below them are identified, so median frequency, bandwidth and a measure of the power spectrum asymmetry are proposed to complement or improve the classical spectral indices as the ratio of the powers of LF and HF bands (LF/HF). In normal conditions the median frequency provides similar information as the classical indices, while the bandwidth and asymmetry can be complementary measures of the physiological state of the tested subject. The proposed indices seem to be a good choice for tracking changes in the power spectrum in exercise stress, and they can guide in the determination of frequency band limits in other animal species.Peer Reviewe

The Evolutionary Landscape of SARS-CoV-2 Variant B.1.1.519 and Its Clinical Impact in Mexico City

The SARS-CoV-2 pandemic is one of the most concerning health problems around the globe. We reported the emergence of SARS-CoV-2 variant B.1.1.519 in Mexico City. We reported the effective reproduction number (Rt) of B.1.1.519 and presented evidence of its geographical origin based on phylogenetic analysis. We also studied its evolution via haplotype analysis and identified the most recurrent haplotypes. Finally, we studied the clinical impact of B.1.1.519. The B.1.1.519 variant was predominant between November 2020 and May 2021, reaching 90% of all cases sequenced in February 2021. It is characterized by three amino acid changes in the spike protein: T478K, P681H, and T732A. Its Rt varies between 0.5 and 2.9. Its geographical origin remain to be investigated. Patients infected with variant B.1.1.519 showed a highly significant adjusted odds ratio (aOR) increase of 1.85 over non-B.1.1.519 patients for developing a severe/critical outcome (p = 0.000296, 1.33–2.6 95% CI) and a 2.35-fold increase for hospitalization (p = 0.005, 1.32–4.34 95% CI). The continuous monitoring of this and other variants will be required to control the ongoing pandemic as it evolves

The Evolutionary Landscape of SARS-CoV-2 Variant B.1.1.519 and Its Clinical Impact in Mexico City

The SARS-CoV-2 pandemic is one of the most concerning health problems around the globe. We reported the emergence of SARS-CoV-2 variant B.1.1.519 in Mexico City. We reported the effective reproduction number (Rt) of B.1.1.519 and presented evidence of its geographical origin based on phylogenetic analysis. We also studied its evolution via haplotype analysis and identified the most recurrent haplotypes. Finally, we studied the clinical impact of B.1.1.519. The B.1.1.519 variant was predominant between November 2020 and May 2021, reaching 90% of all cases sequenced in February 2021. It is characterized by three amino acid changes in the spike protein: T478K, P681H, and T732A. Its Rt varies between 0.5 and 2.9. Its geographical origin remain to be investigated. Patients infected with variant B.1.1.519 showed a highly significant adjusted odds ratio (aOR) increase of 1.85 over non-B.1.1.519 patients for developing a severe/critical outcome (p = 0.000296, 1.33–2.6 95% CI) and a 2.35-fold increase for hospitalization (p = 0.005, 1.32–4.34 95% CI). The continuous monitoring of this and other variants will be required to control the ongoing pandemic as it evolves

Persistence, Magnitude, and Patterns of Postacute Symptoms and Quality of Life Following Onset of SARS-CoV-2 Infection: Cohort Description and Approaches for Measurement.

BackgroundThere is mounting evidence for the presence of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), but there is limited information on the spectrum, magnitude, duration, and patterns of these sequelae as well as their influence on quality of life.MethodsWe assembled a cohort of adults with a documented history of SARS-CoV-2 RNA positivity at ≥2 weeks past onset of coronavirus disease 2019 (COVID-19) symptoms or, if asymptomatic, first positive test. At 4-month intervals, we queried physical and mental health symptoms and quality of life.ResultsOf the first 179 participants enrolled, 10 were asymptomatic during the acute phase of SARS-CoV-2 infection, 125 were symptomatic but not hospitalized, and 44 were symptomatic and hospitalized. During the postacute phase, fatigue, shortness of breath, concentration problems, headaches, trouble sleeping, and anosmia/dysgeusia were most common through 8 months of observation. Symptoms were typically at least somewhat bothersome and sometimes exhibited a waxing-and-waning course. Some participants experienced symptoms of depression, anxiety, and post-traumatic stress, as well as difficulties with performance of usual activities. The median visual analogue scale rating of general health was lower at 4 and 8 months compared with pre-COVID-19. Two clusters of symptom domains were identified.ConclusionsMany participants report bothersome symptoms following onset of COVID-19 with variable patterns of persistence and impact on quality of life. The substantial variability suggests the existence of multiple subphenotypes of PASC. A rigorous approach to the prospective measurement of symptoms and functional manifestations sets the stage for the next phase of research focusing on the pathophysiologic causes of the various subgroups of PASC

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least 4 m. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the 6.5 m James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 yr, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit