Lasmiditan: the first neurally acting anti-migraine drug

Lasmiditan is the first neurally acting drug for the treatment of acute migraine. It is a highly selective, orally acting 5-HT1F agonist that was approved in November 2019, for the acute treatment of migraine in adults, with or without aura, by USFDA. Lesmiditan may help in terminating the acute attack of migraine by inhibiting the central and peripheral neuronal activity and the release of CGRP

Evaluation of the Efficacy of a New Dichoptic Digital Platform to Treat the Anisometropic and Isometropic Amblyopia

The aim of the current study was to evaluate the results of a novel dichoptic training program using an online platform in a group of subjects with refractive amblyopia, performing a comparative analysis of unilateral and bilateral amblyopic cases. For this purpose, a retrospective study analysis of data of 161 children (4–13 years) who underwent dichoptic treatment with the Bynocs® platform (Kanohi Eye Pvt. Ltd., India) was performed. In all cases, the therapy protocol consisted of sessions of training of 30 min daily 5 times a week for 6 weeks. Best corrected visual acuity (BCVA) in the non-dominant eye improved significantly with the treatment, with a mean change of 0.39 logMAR in the whole sample (p < 0.001). Regarding binocularity, the binocular function (BF) score also experienced a significant improvement (p < 0.001), with a mean change of 1.55 with therapy in the whole sample. The BCVA of the dominant eye only improved significantly (p < 0.001) in the isometropic amblyopic subgroup. In conclusion, the use of the dichoptic therapy with the digital platform evaluated allows an effective restoration of visual acuity and binocular function in children with anisometropic and isometropic amblyopia.The author David P Piñero has been supported by the Ministry of Economy, Industry and Competitiveness of Spain within the program Ramón y Cajal, RYC‐2016‐20471

Women in the Workplace 2022

Women in the Workplace is the largest study on the state of women in corporate America. In 2015, LeanIn.Org and McKinsey & Company launched the study to give companies insights and tools to advance gender diversity in the workplace. Between 2015 and 2022, over 810 companies participated in the study, and more than 400,000 people were surveyed on their workplace experiences. This year, we collected information from 333 participating organizations employing more than 12 million people, surveyed more than 40,000 employees, and conducted interviews with women of diverse identities, including women of color, LGBTQ+ women, and women with disabilities. Our 2022 report focuses on how the pandemic has changed what women want from their companies, including the growing importance of opportunity, flexibility, employee well-being, and diversity, equity, and inclusion

Doctor YouTube’s Opinion on Seasonal Influenza: A Critical Appraisal of the Information Available to Patients

Background: Seasonal influenza is a respiratory illness caused by the influenza virus. During the 2017–2018 flu season, the Centers for Disease Control and Prevention noted approximately 959,000 hospitalizations and 79,400 deaths from influenza. We sought to evaluate the educational quality of informational videos pertaining to seasonal influenza on the popular social media forum, YouTube. Methods: Using the keywords “seasonal influenza,” all videos from 28 January to 5 February 2017 were included and analyzed for characteristics, source, and content. The source was further classified as healthcare provider, alternative-medicine provider, the patient and/or their parents, company, media, or professional society. Videos about other categories of influenza (e.g. swine or Spanish) or in foreign languages were excluded. A total of 10 blinded reviewers scored each video independently. Results: Overall, 300 videos were analyzed, with a median of 341.50 views, 1.00 likes, 0 dislikes, and 0 comments. Based on the average scores of videos by source, there was statistically significant difference in the average score among videos by video source (p \u3c 0.01). Healthcare provider videos had the highest mean scores whereas alternative medicine provider videos had the lowest. Conclusions: Although the aforementioned video sources scored higher than others, these videos did not fulfill our criteria as far as educating patients thoroughly. Our data also suggest alternative medicine and patient source videos were misleading for patients. Clinical implications: Although videos by healthcare providers were a better source of information, videos on seasonal influenza were shown to be poor sources of valid healthcare information. This study reiterates the need for higher-quality educational videos on seasonal influenza by the medical community

Polζ ablation in B cells impairs the germinal center reaction, class switch recombination, DNA break repair, and genome stability

Polζ is an error-prone DNA polymerase that is critical for embryonic development and maintenance of genome stability. To analyze its suggested role in somatic hypermutation (SHM) and possible contribution to DNA double-strand break (DSB) repair in class switch recombination (CSR), we ablated Rev3, the catalytic subunit of Polζ, selectively in mature B cells in vivo. The frequency of somatic mutation was reduced in the mutant cells but the pattern of SHM was unaffected. Rev3-deficient B cells also exhibited pronounced chromosomal instability and impaired proliferation capacity. Although the data thus argue against a direct role of Polζ in SHM, Polζ deficiency directly interfered with CSR in that activated Rev3-deficient B cells exhibited a reduced efficiency of CSR and an increased frequency of DNA breaks in the immunoglobulin H locus. Based on our results, we suggest a nonredundant role of Polζ in DNA DSB repair through nonhomologous end joining

Measuring the predictability of life outcomes with a scientific mass collaboration.

How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p