Transcription factor 4 promotes increased corneal endothelial cellular migration by altering microtubules in Fuchs endothelial corneal dystrophy.

Fuchs endothelial corneal dystrophy (FECD) is a complex corneal disease characterized by the progressive decline and morphological changes of corneal endothelial cells (CECs) that leads to corneal edema and vision loss. The most common mutation in FECD is an intronic CTG repeat expansion in transcription factor 4 (TCF4) that leads to its altered expression. Corneal endothelial wound healing occurs primarily through cell enlargement and migration, and FECD CECs have been shown to display increased migration speeds. In this study, we aim to determine whether TCF4 can promote cellular migration in FECD CECs. We generated stable CEC lines derived from FECD patients that overexpressed different TCF4 isoforms and investigated epithelial-to-mesenchymal (EMT) expression, morphological analysis and cellular migration speeds. We found that full length TCF4-B isoform overexpression promotes cellular migration in FECD CECs in an EMT-independent manner. RNA-sequencing identified several pathways including the negative regulation of microtubules, with TUBB4A (tubulin beta 4A class IVa) as the top upregulated gene. TUBB4A expression was increased in FECD ex vivo specimens, and there was altered expression of cytoskeleton proteins, tubulin and actin, compared to normal healthy donor ex vivo specimens. Additionally, there was increased acetylation and detyrosination of microtubules in FECD supporting that microtubule stability is altered in FECD and could promote cellular migration. Future studies could be aimed at investigating if targeting the cytoskeleton and microtubules would have therapeutic potential for FECD by promoting cellular migration and regeneration.

Subsequent pregnancy outcomes after second trimester miscarriage or termination for medical/fetal reason: A systematic review and meta-analysis of observational studies.

INTRODUCTION: Women with a prior stillbirth or a history of recurrent first trimester miscarriages are at increased risk of adverse pregnancy outcomes. However, little is known about the impact of a second trimester pregnancy loss on subsequent pregnancy outcome. This review investigated if second trimester miscarriage or termination for medical reason or fetal anomaly (TFMR/TOPFA) is associated with future adverse pregnancy outcomes. MATERIAL AND METHODS: A systematic review of observational studies was conducted. Eligible studies included women with a history of a second trimester miscarriage or termination for medical reasons and their pregnancy outcomes in the subsequent pregnancy. Where comparative studies were identified, studies which compared subsequent pregnancy outcomes for women with and without a history of second trimester loss or TFMR/TOPFA were included. The primary outcome was livebirth, and secondary outcomes included: miscarriage (first and second trimester), termination of pregnancy, fetal growth restriction, cesarean section, preterm birth, pre-eclampsia, antepartum hemorrhage, stillbirth and neonatal death. Studies were excluded if exposure was nonmedical termination or if related to twins or higher multiple pregnancies. Electronic searches were conducted using the online databases (MEDLINE, Embase, PubMed and The Cochrane Library) and searches were last updated on June 16, 2023. Risk of bias was assessed using the Newcastle-Ottawa scale. Where possible, meta-analysis was undertaken. PROSPERO registration: CRD42023375033. RESULTS: Ten studies were included, reporting on 12 004 subsequent pregnancies after a second trimester pregnancy miscarriage. No studies were found on outcomes after second trimester TFMR/TOPFA. Overall, available data were of "very low quality" using GRADE assessment. Meta-analysis of cohort studies generated estimated outcome frequencies for women with a previous second trimester loss as follows: live birth 81% (95% CI: 64-94), miscarriage 15% (95% CI: 4-30, preterm birth 13% [95% CI: 6-23]).The pooled odds ratio for preterm birth in subsequent pregnancy after second trimester loss in case-control studies was OR 4.52 (95% CI: 3.03-6.74). CONCLUSIONS: Very low certainty evidence suggests there may be an increased risk of preterm birth in a subsequent pregnancy after a late miscarriage. However, evidence is limited. Larger, higher quality cohort studies are needed to investigate this potential association.

Predictive value of medical school ranking in the academic scholarship of ophthalmology residents.

Objective: To determine whether a resident's medical school ranking predicts their scholarship during residency. Design: The authors stratified ophthalmology residents in ACGME accredited programs into tiers based off their medical school background's US News & World Report ranking: T1 (schools 1-20), T2 (21-50), and T3 (51-90). Investigators queried PubMed and Scopus for number of total publications, first/second author publications, publications in the top 10 impact factor journals in ophthalmology, and publications with the senior author affiliated with the resident's residency program/medical school. Authors collected data from start of ophthalmology residency to December 5th, 2021, and performed Pearson chi squared, ANOVA, Eta squared, Tukey, and multivariable logistic regression tests. Results: 1054 residents were included for analysis, with 370 from T1 schools, 296 from T2 schools, and 388 from T3 schools. T3 residents had a significantly decreased likelihood of publishing at least one (OR = 0.659;95%CI = 0.481,0.905;p = .010), two (OR = 0.643;95%CI = 0.436,0.949;p = .026), or five (OR = 0.407;95%CI = 0.187,0.886;p = .024) total publications compared to T1 residents. T3 residents also were partially predicted to publish fewer first author works, high impact journal articles, and articles with senior authors affiliated with their medical school. T2 residents were more likely to publish at least one second author work than T1 residents (OR = 1.604;95%CI = 1.101,2.337;p = .014). There was no significant difference between tiers in publications with senior authors affiliated with the same residency program. Conclusions: The authors observed little difference in scholarship between residents from T1 and T2 schools, but some differences may exist between T3 and T1/T2 residents. Merit of rankings should be further explored.

Short-term trivalent arsenic and hexavalent chromium exposures induce gut dysbiosis and transcriptional alteration in adipose tissue of mice.

BACKGROUND: Inorganic arsenic [As(III)] and hexavalent chromium [Cr(VI)] can potentially affect metabolic functions. These heavy metal(s)/metalloids can also affect the gut microbial architecture which affects metabolic health. Here, we assessed the effects of short-term exposure of As(III) and Cr(VI) on key transcription factors in adipose tissues and on selected gut microbial abundances to understand the possible modulatory role of these toxicants on host metabolic health. METHODS AND RESULTS: qRT-PCR based relative bacterial abundance studies in cecal samples, gene expression analysis for gut wall integrity in ileum and colon and adipogenesis, lipolysis, and thermogenic genes in gonadal white and brown adipose tissue (gWAT and BAT), along with tissue oxidative stress parameters have been performed. As(III) and Cr(VI) exposure reduced beneficial Lactobacilli, Bifidobacteria, Akkermansia, Lachenospiraceae, Fecalibacterium, Eubacterium, and clostridium coccoid group while increasing lipopolysaccharides producing Enterobacteriaceae abundances. It also impaired structural features and expression of key tight junction and mucin production genes in ileum and colon (Cld-2, Cld-4, ZO-1, ZO-2, MUC-2 and - 4). In gWAT it inhibited adipogenesis (PPARγ, FASN, SREBP1a), lipolysis (HSL, ACOX-1), and thermogenesis (UCP-1, PGC1a, PRDM-16, PPARa) related genes expression, whereas in BAT, it enhanced adipogenesis and reduced thermogenesis. These exposures also reduces the endogenous antioxidants levels in these tissues and promote pro-inflammatory cytokines genes expression (TLRs, IL-6, MCP-1). The combinatorial exposure appears to have more deleterious effects. CONCLUSION: These effects of As(III) and Cr(VI) may not directly be linked to their known toxicological effects, instead, more intriguing crosstalk with gut microbial ecosystem hold the key.

Perceptions and Knowledge towards COVID-19 Vaccine Hesitancy among a Subpopulation of Adults in Kenya: An English Survey at Six Healthcare Facilities.

Background: Vaccine hesitancy, as defined by the WHO, is the reluctance or refusal to vaccinate despite the availability of vaccines and is one of the ten threats to global health in 2019. Vaccine hesitancy remains a complex matter influenced by multiple factors, especially in sub-Saharan Africa. Methods: We conducted a cross-sectional study between November 2021 and January 2022 among the general adult public seeking care at six different healthcare facilities in Kenya. The survey, in English, consisted of questions based on demographics, knowledge, and attitudes, including hesitancy towards the COVID-19 vaccine. Results: Of the 3996 surveys collected, 55.1% were from private, 19.5% from faith-based and 25.3% from government facilities., Approximately 81.0% of all the participants reported it was important to get a vaccine to protect other people from COVID-19, 79.9% reported they would take a vaccine to protect against COVID-19, yet 40.5% reported being hesitant to take the vaccine primarily due to side effects. Most of the variables were associated with receiving a vaccine. Only 52.1% of those seeking care from the government facility and 54.5% of those seeking care from the faith-based facility were vaccinated, compared to 81.5% seeking care from the private facilities (p < 0.001). More participants from private facilities felt that vaccines are safe as compared to those at the faith-based and government facilities (p < 0.001). Conclusion: Vaccine hesitancy in Kenya, even though much lower than reported in other countries, remains a dynamic problem. Mitigating strategies specific to Africa need to be developed to help address vaccine hesitancy in this part of the continent.

Use of Telemedicine to Expedite and Expand Care During COVID-19.

INTRODUCTION: The novel coronavirus disease 2019 (COVID-19) created challenges with access to care including increased burden on healthcare systems and potential exposure risks for vulnerable patients. To address these needs, Rush University Medical Center created a virtual, urgent care program specifically designed to address these challenges during the COVID-19 pandemic. METHODS: This was a retrospective study analyzing adult patients with COVID-19-related telemedicine visits performed between March 1-June 30, 2020. COVID-19-related telemedicine visits refer to those who used the "Concern for Coronavirus" module. We assessed the total number of telemedicine visits using this module, percentage with a subsequent emergency department (ED) visit within seven days, and outcomes (ie, hospitalization status, intubation, and death) of patients who presented to the ED for evaluation. Data are presented using descriptive statistics. RESULTS: A total of 2,974 adult patients accessed the program via the COVID-19 module over the four-month period. Of those, 142 patients (4.8%) had an ED visit within seven days. Only 14 patients (0.5%) required admission. One patient was intubated, and there were no deaths among the telemedicine population. CONCLUSION: The data suggests that telemedicine may be a safe and effective way to screen and treat patients with possible COVID-19, while reducing potential burdens on EDs.

Factors Associated With Poor Sleep in Older Women Diagnosed With Breast Cancer

OBJECTIVES: To determine the relationship among gait, grip strength, cognition, depression, pain, and fatigue, and to identify which variables are most predictive of poor sleep. SAMPLE & SETTING: 60 women with breast cancer aged 69 years or older who were receiving treatment in the Senior Adult Oncology Program at the James Cancer Hospital at the Ohio State University. METHODS & VARIABLES: The variables were gait and grip strength (functional domains), cognition, depression, pain, and fatigue. Patients were tested using the Timed Up and Go Test (TUG), Jamar Hydraulic Hand Dynamometer, Mini-Cog, Numeric Pain Rating Scale, Brief Fatigue Inventory, Geriatric Depression Scale, and Pittsburgh Sleep Quality Index. Pearson correlation coefficients and logistic regression models were used. RESULTS: The mean age of the sample was 78 years. Pain and fatigue, depression and pain, and depression and fatigue each were positively related, and grip strength and TUG scores were negatively related. Fatigue was the strongest predictor of poor sleep. IMPLICATIONS FOR NURSING: These findings are important to the comprehensive care of older women diagnosed with breast cancer. Understanding symptoms associated with poor sleep helps nurses develop comprehensive care plans for older adults with breast cancer.