Triclosan administration to humanized UDP-glucuronosyltransferase 1 neonatal mice induces UGT1A1 through a dependence on PPARα and ATF4.

Triclosan (TCS) is an antimicrobial toxicant found in a myriad of consumer products and has been detected in human tissues, including breastmilk. We have evaluated the impact of lactational TCS on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) neonatal mice. In hUGT1 mice, expression of the hepatic UGT1A1 gene is developmentally delayed resulting in elevated total serum bilirubin (TSB) levels. We found that newborn hUGT1 mice breastfed or orally treated with TCS presented lower TSB levels along with induction of hepatic UGT1A1. Lactational and oral treatment by gavage with TCS leads to the activation of hepatic nuclear receptors constitutive androstane receptor (CAR), peroxisome proliferator-activated receptor alpha (PPARα), and stress sensor, activating transcription factor 4 (ATF4). When CAR-deficient hUGT1 mice (hUGT1/Car-/-) were treated with TCS, TSB levels were reduced with a robust induction of hepatic UGT1A1, leaving us to conclude that CAR is not tied to UGT1A1 induction. Alternatively, when PPARα-deficient hUGT1 mice (hUGT1/Pparα-/-) were treated with TCS, hepatic UGT1A1 was not induced. Additionally, we had previously demonstrated that TCS is a potent inducer of ATF4, a transcriptional factor linked to the integrated stress response. When ATF4 was deleted in liver of hUGT1 mice (hUGT1/Atf4ΔHep) and these mice treated with TCS, we observed superinduction of hepatic UGT1A1. Oxidative stress genes in livers of hUGT1/Atf4ΔHep treated with TCS were increased, suggesting that ATF4 protects liver from excessive oxidative stress. The increase oxidative stress may be associated with superinduction of UGT1A1. The expression of ATF4 in neonatal hUGT1 hepatic tissue may play a role in the developmental repression of UGT1A1.

Advancing Diversity in Microbiology: A 55-Year Retrospective Analysis.

Background For over 50 years, affirmative action helped advance equity, diversity and inclusion (EDI) in educational institutions in the United States (U.S.). However, the recent U.S. Supreme Court decision to end affirmative action in college admissions threatens the progress toward EDI. Objective This study aimed to assess the progress in promoting gender and racial diversity within the discipline of microbiology over a 55-year period. We sought to analyze the representation of women and minority groups in faculty ranks, tenure positions, and leadership to identify disparities and trends and determine who will likely be impacted most with the end of affirmative action. Materials and methods This longitudinal retrospective study utilized publicly available and non-identifiable Association of American Medical Colleges (AAMC) data on full-time microbiology faculty from 1967 to 2021. Faculty members were categorized based on academic ranks and tenure status, while gender and racial data were also considered. Results The analysis revealed a consistent dominance of white faculty, with over 60% representation across all academic ranks throughout the study period. The Asian and female faculty representation decreased in senior academic ranks. We observed a positive trend in the annual increase of women in faculty positions, academic ranks, chairs, and tenure positions. Furthermore, Asian faculty demonstrated the most robust surge in representation. However, disparities persisted for black, Hispanic, and Native American faculty members, reflecting broader challenges in their representation. Discussion Although efforts to enhance diversity within microbiology have yielded positive results, underrepresented minority groups still face obstacles in attaining leadership positions and senior academic ranks. The diminishing proportion of women at higher academic ranks raises concerns about potential attrition or lack of promotion opportunities. The end of affirmative action poses a risk of perpetuating this trend, leading to a decline in diversity among microbiology faculty.

Organizational Leadership Gender Differences in Medical Schools and Affiliated Universities.

Objective: To compare gender compositions in the leadership of the top 25 medical schools in North America with the leadership of their affiliated university senior leadership and other faculties. Materials and Methods: This retrospective cross-sectional observational study used publicly available gender data from 2018 to 2019 of universities drawn from the U.S. News Best Global Universities for Clinical Medicine Ranking report. Gender compositions in eight leadership tiers from senior leadership to medical school department directors were analyzed. Data analysis included gender compositions by leadership tier and faculty. Results: Male representation is greater at higher leadership tiers, with the largest imbalance being at the level of medical school department heads. The faculty of medicine has more men in leadership positions than the average of the other faculties (p = 0.02), though similar to schools of engineering, business, dentistry, and pharmacy. Across the eight leadership tiers, a significant trend exists between tier and proportions, indicating that male representation was greater at higher tiers (p < 0.001). No correlation was found between a university's leadership gender composition and its ranking. Conclusion: The under-representation of women is greater in medical school leadership than the leadership of their affiliated universities. The faculty of medicine has greater male over-representation than the average of the other faculties.

End of Affirmative Action-Who Is Impacted Most? Analysis of Race and Sex Among US Internal Medicine Faculty.

BACKGROUND: For over 50 years, the United States (US) used affirmative action as one strategy to increase diversity in higher education including medical programs, citing benefits including training future public and private sector leaders. However, the recent US Supreme Court ending affirmative action in college admissions threatens advancements in the diversity of medical college faculty. OBJECTIVE: Our study evaluated the demographic trends in Internal Medicine (IM) faculty in the US by assessing sex and race/ethnicity diversity to investigate who is likely to be impacted most with the end of affirmative action. DESIGN: Longitudinal retrospective analysis SUBJECTS: IM faculty from the Association of American Medical Colleges faculty roster from 1966 to 2021 who self-reported sex and ethnicity MAIN OUTCOMES: The primary study measurement was the annual proportion of women and racial/ethnic groups among IM faculty based on academic rank and department chairs. RESULTS: Although racial/ethnic diversity increased throughout the era of affirmative action, African American, Hispanic, and American Indian populations remain underrepresented. White physicians occupied > 50% of faculty positions across academic ranks and department chairs. Among the non-White professors, Asian faculty had the most significant increase in proportion from 1966 to 2021 (0.6 to 16.6%). The percentage of women increased in the ranks of professor, associate professor, assistant professor, and instructor by 19.5%, 27.8%, 25.6%, and 26.9%, respectively. However, the proportion of women and racial/ethnic minority faculty decreased as academic rank increased. CONCLUSION: Despite an increase in the representation of women and racial/ethnic minority IM faculty, there continues to be a predominance of White and men physicians in higher academic ranks. With the end of affirmative action, this trend has the danger of being perpetuated, resulting in decreasing diversity among IM faculty, potentially impacting patient access and health outcomes.

Terapia génica para la insuficiencia cardiaca y las miocardiopatías / Gene therapy for heart failure and cardiomyopathies

Las estrategias de terapia génica incluyen diversos enfoques, como la sustitución y la edición de genes. La sustitución proporciona una copia funcional de un gen alterado y la edición permite corregir una mutación genética preexistente. La terapia génica ya está aprobada para trastornos genéticos como la amaurosis congénita de Leber y la atrofia muscular espinal, y actualmente se estudia su uso en cardiología. En esta revisión se resume el mecanismo de las distintas estrategias de terapia génica, los sistemas de administración disponibles, los principales riesgos relacionados con la terapia génica, los ensayos clínicos en curso y los objetivos futuros, con especial atención a las miocardiopatías.(AU)

Gene therapy strategies encompass a range of approaches, including gene replacement and gene editing. Gene replacement involves providing a functional copy of a modified gene, while gene editing allows for the correction of existing genetic mutations. Gene therapy has already received approval for treating genetic disorders like Leber's congenital amaurosis and spinal muscular atrophy. Currently, research is being conducted to explore its potential use in cardiology. This review aims to summarize the mechanisms behind different gene therapy strategies, the available delivery systems, the primary risks associated with gene therapy, ongoing clinical trials, and future targets, with a particular emphasis on cardiomyopathies.(AU)

Entering the Misinformation Age: Quality and Reliability of YouTube for Patient Information on Liposuction.

Background: YouTube is currently the most popular online platform and is increasingly being utilized by patients as a resource on aesthetic surgery. Yet, its content is largely unregulated and this may result in dissemination of unreliable and inaccurate information. The objective of this study was to evaluate the quality and reliability of YouTube liposuction content available to potential patients. Methods: YouTube was screened using the keywords: "liposuction," "lipoplasty," and "body sculpting." The top 50 results for each term were screened for relevance. Videos which met the inclusion criteria were scored using the Global Quality Score (GQS) for educational value and the Journal of the American Medical Association (JAMA) criteria for video reliability. Educational value, reliability, video views, likes, dislikes, duration and publishing date were compared between authorship groups, high/low reliability, and high/low educational value. Results: A total of 150 videos were screened, of which 89 videos met the inclusion criteria. Overall, the videos had low reliability (mean JAMA score = 2.78, SD = 1.15) and low educational value (mean GQS score = 3.55, SD = 1.31). Videos uploaded by physicians accounted for 83.1% percent of included videos and had a higher mean educational value and reliability score than those by patients. Video views, likes, dislikes, comments, popularity, and length were significantly greater in videos with high reliability. Conclusions: To ensure liposuction-seeking patients are appropriately educated and informed, surgeons and their patients may benefit from an analysis of educational quality and reliability of such online content. Surgeons may wish to discuss online sources of information with patients.

Historique : YouTube est actuellement la plateforme la plus populaire en ligne. Les patients l'utilisent de plus en plus comme ressource en chirurgie plastique. Pourtant, son contenu est en grande partie non réglementé, ce qui peut entraîner la diffusion d'information peu fiable et inexacte. La présente étude vise à évaluer la qualité et la fiabilité du contenu de YouTube sur la liposuccion à la disposition de patients éventuels. Méthodologie : Les chercheurs ont fait une recherche dans YouTube à l'aide des mots-clés liposuction, lipoplasty et body sculpting. Ils ont examiné les 50 premiers résultats de chaque terme pour en déterminer la pertinence. Ils ont classé les vidéos qui respectaient les critères d'inclusion d'après le score de qualité globale (SGQ) pour leur valeur éducative et les critères du Journal of the American Medical Association (JAMA) pour la fiabilité des vidéos. Ils ont comparé la valeur éducative, leur fiabilité, le nombre de visionnements, les « J'aime ¼, les « Je n'aime pas ¼, la durée et la date de publication entre groupes d'auteur, la forte et la faible fiabilité et la valeur éducative élevée ou basse. Résultats : Les chercheurs ont visionné 150 vidéos, dont 89 respectaient les critères d'inclusion. Dans l'ensemble, elles avaient une faible fiabilité (score JAMA moyen = 2.78, ÉT = 1.15) et une faible valeur éducative (SQG moyen = 3.55, ÉT = 1.31). Les vidéos téléversées par des médecins formaient 83,1% du contenu et présentaient une valeur éducative moyenne et un score de fiabilité plus élevés que celles des patients. Les visionnements, les « J'aime ¼, les « Je n'aime pas ¼, les commentaires, la popularité et la durée étaient beaucoup plus élevés lorsque les vidéos avaient une forte viabilité. Conclusions : Pour que les patients qui veulent subir une liposuccion reçoivent la bonne information, les chercheurs et leurs patients peuvent profiter d'une analyse de la qualité et de la fiabilité du contenu en ligne. Les chirurgiens pourraient souhaiter parler des sources d'information en ligne avec leurs patients.

The Genetic Evaluation of Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is a common cause of heart failure and is the primary indication for heart transplantation. A genetic etiology can be found in 20-35% of patients with DCM, especially in those with a family history of cardiomyopathy or sudden cardiac death at an early age. With advancements in genome sequencing, the understanding of genotype-phenotype relationships in DCM has expanded with over 60 genes implicated in the disease. Subsequently, these findings have increased adoption of genetic testing in the management of DCM, which has allowed for improved risk stratification and identification of at risk family members. In this review, we discuss the genetic evaluation of DCM with a focus on practical genetic testing considerations, genotype-phenotype associations, and insights into upcoming personalized therapies.

Gene therapy for heart failure and cardiomyopathies.

Gene therapy strategies encompass a range of approaches, including gene replacement and gene editing. Gene replacement involves providing a functional copy of a modified gene, while gene editing allows for the correction of existing genetic mutations. Gene therapy has already received approval for treating genetic disorders like Leber's congenital amaurosis and spinal muscular atrophy. Currently, research is being conducted to explore its potential use in cardiology. This review aims to summarize the mechanisms behind different gene therapy strategies, the available delivery systems, the primary risks associated with gene therapy, ongoing clinical trials, and future targets, with a particular emphasis on cardiomyopathies.

American Society of Emergency Radiology (ASER) social media committee workgroup: best practices for the use of social media in emergency radiology.

Social media has become integrated within the profession of medicine, and emergency radiology has inevitably felt the impact of its presence. Emergency radiologists are encouraged to consider the advantages of embracing the digital era and the benefits it may bring to our careers. We aim to present the best practice guidelines for emergency radiologists and radiology departments. This paper is a product of the American Society of Emergency Radiology Social Media (ASER) Committee workgroup and represents the best practices of the society.

Lactational delivery of Triclosan promotes non-alcoholic fatty liver disease in newborn mice.

Here we show that Triclosan (TCS), a high-volume antimicrobial additive that has been detected in human breastmilk, can be efficiently transferred by lactation to newborn mice, causing significant fatty liver (FL) during the suckling period. These findings are relevant since pediatric non-alcoholic fatty liver disease (NAFLD) is escalating in the United States, with a limited mechanistic understanding. Lactational delivery stimulated hepatosteatosis, triglyceride accumulation, endoplasmic reticulum (ER) stress, signs of inflammation, and liver fibrosis. De novo lipogenesis (DNL) induced by lactational TCS exposure is shown to be mediated in a PERK-eIF2α-ATF4-PPARα cascade. The administration of obeticholic acid (OCA), a potent FXR agonist, as well as activation of intestinal mucosal-regenerative gp130 signaling, led to reduced liver ATF4 expression, PPARα signaling, and DNL when neonates were exposed to TCS. It is yet to be investigated but mother to child transmission of TCS or similar toxicants may underlie the recent increases in pediatric NAFLD.

Subscription-based and open access dermatology journals: the publication model dilemma.

Medical journalism and the dissemination of peer-reviewed research serve to promote and protect the integrity of scholarship. We evaluated the publication models of dermatology journals to provide a snapshot of the current state of publishing. A total of 106 actively-publishing dermatology journals were identified using the SCImago Journal Rankings (SJR) citation database. Journals were classified by publication model (subscription-based and open-access), publishing company, publisher type (commercial, professional society, and university), MEDLINE-indexing status, and SJR indicator. Of these, 65 (61.32%) dermatology journals were subscription-based and 41 (38.68%) were open-access. In addition, 59 (55.66%) journals were indexed in MEDLINE and most were subscription-based (N=51) and published by commercial entities (N=54). MEDLINE-indexing status was significantly different across publisher types (P<0.001), access-types (P<0.001), and the top four publishers (P=0.016). Distribution of SJR indicator was significantly different across publisher types (P<0.001) and access-types (all journals, P=0.001; indexed journals only, P=0.046). More than 91% of MEDLINE-indexed titles were published by commercial entities, and among them, four companies controlled the vast majority. Discontinuation of access to any one of the top publishers in dermatology can significantly and disproportionately impact education and scholarship.

Influences of the Social Media Continuum Model in Radiology: Theory and Reality.

Social media utilization has been growing exponentially worldwide and has created a thriving venue for radiologists and the profession of radiology to engage in on both the academic and social levels. The aim of this article is to conduct updated literature review and address a gap in the literature by introducing a simple classification for social media utilization and a new theoretical model to outline the role and potential value of social media in the realm of radiology. We propose classifying social media through usage-driven and access-driven indices. Furthermore, we discuss the interdependency of radiologists, other physicians and non-physician stakeholders, scientific journals, conferences/meetings and the general public in an integrated social media continuum model. With the ongoing sub-specialization of radiology, social media helps mitigate the physical barriers of making connections with peers and audiences which would have otherwise been unfeasible. The constant evolution and diversification of social media platforms necessitates a novel approach to better understand its role through a radiological lens. With the looming fear of 'ancillary service' labelling, social media could be the golden plate to halt the path towards commoditization of radiology.

Investigating Gender Differences in Canadian Plastic Surgery Online Patient Education.

BACKGROUND: The public interest and demand for cosmetic surgery is growing in North America. As practices continue to advertise cosmetic procedures, male consumers must also be given fair consideration in a market targeted mostly towards women. OBJECTIVES: This study investigated the advertising trends of plastic surgery clinics to assess for prevailing gender differences among online Canadian plastic surgery practice advertising. METHODS: The 2021 College of Physicians and Surgeons directory for each province and territory was utilized to identify all practicing plastic surgeons. A systematic search with Google (Mountain View, CA) was conducted to analyze the websites of Canadian plastic surgery centers in the following manner: "[physician name] [province of practice]." RESULTS: A total of 209 websites and 13,838 images were identified and analyzed. Of these images, 12,386 (90%) were female and 1452 (10%) were male patients or models. Although only 20% had a male services page, 62% of all centers offered gynecomastia procedures. The most common procedures targeting men were blepharoplasty (95%), liposuction (93%), and abdominoplasty (93%). The Prairies region had significantly fewer websites with male-only pages compared with all other Canadian regions. CONCLUSIONS: Despite the increase in cosmetic surgery procedures for males, the market for cosmetic surgery procedures targeted towards males remains insignificant. An increase in the advertising of in-demand male cosmetic procedures can allow for a broader consumer market and a subsequent increase in benefits for plastic surgeons.