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A very high prevalence of multiple sclerosis (MS) has been reported in some Western European and North American countries. The few surveys of MS epidemiology in South America reveal lower prevalence rates, implying that susceptibility varies between distinct ethnic groups, thus forming an important determinant of the geographic distribution of the disease. The objective of this study is to review MS prevalence estimates in different Latin American and Caribbean countries. We reviewed surveys of regional MS prevalence from 1991 to 2011. Sources included an online database, authors’ reports and proceedings or specific lectures from regional conferences. We obtained a total of 30 prevalence surveys from 15 countries, showing low/medium MS prevalence rates. Both the number and the quality of prevalence surveys have greatly improved in this region over recent decades. This is the first collaborative study to map the regional frequency of MS. Establishment of standardized methods and joint epidemiological studies will advance future MS research in Latin America and the Caribbean. [ABSTRACT FROM PUBLISHER]

Exposure to extreme stress can negatively impact behavior and lead to prolonged fear sensitization. These processes can be studied in the lab using stress-enhanced fear learning (SEFL), where prior exposure to inescapable stress exacerbates later contextual fear conditioning. A common method to reduce conditional fear is through extinction, where a conditional stimulus once paired with an unconditional (US; e.g., a footshock) is presented alone. Previous research shows that extinction learning may not be as effective at reducing fear behavior in rodents previously exposed to stress, mirroring similar extinction impairments observed in aged rodents. Weak-shock exposure (termed US deflation) following conditioning with a strong shock has been proposed to be an alternative to extinction where presentations of weaker versions of the US would work to modify the original fear memory rather than create a new memory as in extinction and thus more precisely target the original context fear memory. While effective under normal conditions, it has yet to be studied how effective US deflation is at reducing stress-enhanced context fear. Here we aimed to test if US deflation could reduce fear in a SEFL paradigm and identify any constraints of this effect. Following 15 inescapable footshocks or matched chamber exposure, male and female Long Evans rats received 1 context-shock pairing or 5 context-shock pairings in a novel context. The next day, they were given either 10 weak footshocks (US deflation) or extinction before behavioral testing. Following training with 1 context-shock pairing, both US deflation and extinction functioned similarly in reducing freezing behavior of stressed rodents. However, following 5 context-shock pairings, only the unstressed rodents displayed a significant decrease in fear behavior, suggesting that prior stress coupled with more robust conditioning can limit the efficacy of US deflation in reducing fear behavior. Finally, we replicated the SEFL effect in aged rodents and found that they showed a significant decrease in stress-enhanced fear learning following US deflation, whereas our previous research showed impairments of traditional extinction in aged rodents. Together, these results suggest that US deflation can reduce SEFL in both adult and aged rodents following a single context-shock pairing, with additional pairings rendering this procedure ineffective at mitigating the effects of prior stress., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to determine the prevalence of pelvic floor disorders (PFDs) and associated risk factors among parous Ugandan women., Methods: We performed a cross-sectional study of parous Ugandan women. Demographics and assessment for PFD were obtained. The presence of PFD was defined by participant symptom report, standardized questionnaires, and standard physical examination (pelvic organ prolapse quantification [POP-Q] and cough stress test [CST])., Results: A total of 159 women were enrolled in the study between June 2022 and June 2023. The median age was 35 years and median parity was 4. Forty-four (28%) women in the cohort reported symptoms of urinary incontinence. No women reported symptoms of pelvic organ prolapse or anal incontinence. Seventy-two (46%) participants had a positive CST and 93 (58.3%) had stage II or greater prolapse based on the POP-Q. Cesarean section was found to have a protective effect for the development of PFD (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07-0.59, P = 0.004)., Conclusion: PFDs are prevalent among parous Ugandan women at rates similar to cohorts in other low- and middle-income countries. Cesarean section seems to be a protective factor against developing PFDs., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objective:  Current literature on the risks and outcomes of obesity in pregnancy almost exclusively utilizes prepregnancy body mass index (BMI). Given the rising obesity rate across the United States along with a paucity of available information on the relationship between delivery BMI and maternal and neonatal outcomes, our study aimed to determine the association of maternal BMI at delivery with antepartum, intrapartum, and neonatal complications at an academic referral hospital., Study Design:  This study is a secondary analysis of data collected for a prospective cohort study of Coronavirus Disease-2019 (COVID-19) in pregnancy. This analysis included all patients who delivered term singleton infants between May 1, 2020, and April 30, 2021, at the University of Iowa Hospitals and Clinics. Demographic and clinical data were obtained from the electronic medical record. The relationship between maternal BMI and maternal and neonatal characteristics of interest was assessed using logistic regression models. A statistical significance threshold of 0.05 was used for all comparisons., Results:  There were 1,996 women who delivered term singleton infants during the study period. The median BMI at delivery was 31.7 kg/m 2 (interquartile range: 27.9, 37.2), with 61.1% of women having a BMI ≥ 30.0 kg/m 2 . Increasing BMI was significantly associated with nonreassuring fetal status, unscheduled cesarean birth, overall cesarean birth rate, postpartum hemorrhage, prolonged postpartum stay, hypertensive diseases of pregnancy, neonatal hypoglycemia, neonatal intensive care unit admission, decreased APGAR score at 1 minute, and increasing neonatal birth weight. Even when controlling for preexisting hypertension in a multivariate model, increasing BMI was associated with gestational hypertension and preeclampsia., Conclusion:  Increased maternal BMI at delivery was associated with adverse perinatal outcomes. These findings have implications for clinical counseling regarding risks of pregnancy and delivery for overweight and obese patients and may help inform future studies to improve safety, especially by examining reasons for high cesarean rates., Key Points: · Sixty-one percent of delivering patients had a BMI330 kg/m2 at delivery.. · There was a higher cesarean rate with increasing delivery BMI.. · For every 5-unit increase in maternal BMI, neonatal weight increased by 0.47 g.., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction and Hypothesis: The aim was to assess the association between the degree of physical activity (PA) and the presence of pelvic floor disorders (PFDs) in a cohort of parous Ugandan women., Methods: In this cross-sectional study, PFDs were measured using symptom assessment, standardized questionnaires (Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire), and a standardized physical examination (POP-Q and cough stress test [CST]). Degree of PA was assessed using the International Physical Activity Questionnaire. Interquartile ranges were used to describe the age, parity, and body mass index (BMI) of participants. To examine the association between PA and PFDs, a log transformation was applied to the weekly minutes of PA variable and a logistic regression model was constructed with weekly minutes of moderate/vigorous PA, age, BMI, and parity as the predictors., Results: A total of 159 women were enrolled. Median age was 35 (IQR 32-37), median parity 4 (IQR 3-5), and median BMI 29.0 (IQR 24-33). The prevalence of PFD as determined by symptom assessment was 28% (n=44). The most frequent stage of prolapse identified by POP-Q was stage II (57%, n=91). Thirty-six percent of the women (n=58) reported vigorous PA. Ninety-nine percent of the cohort (n=158) reported moderate PA. When controlling for age, parity, and BMI there was a significant positive association between PFD (defined as a combination of stage II prolapse, positive CST, and urinary incontinence (UI)) and moderate PA (OR 2.20, 95% CI 1.08-5.14, p value 0.045)., Conclusions: Pelvic floor disorders are common among parous Ugandan women and are associated with moderate PA when controlling for age, BMI, and parity. Understanding the risk factors associated with PFD in this population may better equip providers to screen and care for individuals., (© 2024. The Author(s).)

Introduction and Hypothesis: Pelvic floor disorders (PFDs) impact women worldwide and are assessed using instruments such as the Pelvic Floor Distress Inventory (PFDI-20) and Pelvic Floor Impact Questionnaire (PFIQ-7). There are no known valid PFD instruments in Uganda. This study's purpose was to translate and test the reliability and validity of the PFDI-20 and PFIQ-7 in Luganda. It was predicted that these instruments would be reliable and valid to assess the presence and impact of PFD in parous Luganda-speaking women., Methods: The translated PFDI-20 and PFIQ-7 were administered to parous Luganda-speaking women and readministered 4-8 months after. The Pelvic Organ Prolapse Quantification (POP-Q) examination determined the presence of pelvic organ prolapse (POP) and a cough-stress test (CST) measured urinary leakage. Analysis was completed using Cronbach's α co-efficient for internal consistency and Spearman's correlation coefficients and Wilcoxon rank sum tests for construct validity., Results: Of the 159 participants, 93 (58.3%) had stage II POP or higher. The PFDI-20 and PFIQ-7 demonstrated minimal bother and impact on activities of daily living respectively. The Urinary Distress Inventory 6 (UDI-6) scores on the PFDI-20 showed a strong positive association with the presence of urinary incontinence. When PFD was defined by responses to symptom assessment, the translated PFDI-20 and PFIQ-7 could differentiate between individuals with and without PFD., Conclusions: The UDI-6 section of the PFDI-20 was found to be valid in Luganda. The PFIQ-7 and the entirety of the PFDI-20 were not found to be reliable or valid, likely because of the low prevalence of PFDs in the study population., (© 2024. The Author(s).)

The accurate segregation of homologous chromosomes during the Meiosis I reductional division in most sexually reproducing eukaryotes requires crossing over between homologs. In baker's yeast approximately 80% of meiotic crossovers result from Mlh1-Mlh3 and Exo1 acting to resolve double-Holliday junction intermediates in a biased manner. Little is known about how Mlh1-Mlh3 is recruited to recombination intermediates to perform its role in crossover resolution. We performed a gene dosage screen in baker's yeast to identify novel genetic interactors with Mlh1-Mlh3. Specifically, we looked for genes whose lowered dosage reduced meiotic crossing over using sensitized mlh3 alleles that disrupt the stability of the Mlh1-Mlh3 complex and confer defects in mismatch repair but do not disrupt meiotic crossing over. To our surprise we identified genetic interactions between MLH3 and DMC1, the recombinase responsible for recombination between homologous chromosomes during meiosis. We then showed that Mlh3 physically interacts with Dmc1 in vitro and in vivo. Partial complementation of Mlh3 crossover functions was observed when MLH3 was expressed under the control of the CLB1 promoter (NDT80 regulon), suggesting that Mlh3 function can be provided late in meiotic prophase at some functional cost. A model for how Dmc1 could facilitate Mlh1-Mlh3's role in crossover resolution is presented., Competing Interests: Conflicts of interest The author declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Homologous recombination (HR) is a template-based DNA double-strand break repair pathway that requires the selection of an appropriate DNA sequence to facilitate repair. Selection occurs during a homology search that must be executed rapidly and with high fidelity. Failure to efficiently perform the homology search can result in complex intermediates that generate genomic rearrangements, a hallmark of human cancers. Rad54 is an ATP dependent DNA motor protein that functions during the homology search by regulating the recombinase Rad51. How this regulation reduces genomic exchanges is currently unknown. To better understand how Rad54 can reduce these outcomes, we evaluated several amino acid mutations in Rad54 that were identified in the COSMIC database. COSMIC is a collection of amino acid mutations identified in human cancers. These substitutions led to reduced Rad54 function and the discovery of a conserved motif in Rad54. Through genetic, biochemical and single-molecule approaches, we show that disruption of this motif leads to failure in stabilizing early strand invasion intermediates, causing increased crossovers between homologous chromosomes. Our study also suggests that the translocation rate of Rad54 is a determinant in balancing genetic exchange. The latch domain's conservation implies an interaction likely fundamental to eukaryotic biology., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: It was to understand HPV vaccination patterns, uptake, perceptions, and sexual risk factors in students at a Midwest public university. Participants: Students were enrolled during the spring 2024 semester at the University of Iowa. Methods: A survey was developed and emailed to 28,095 students asking demographic, general and sexual health, and HPV-related questions. Results: The response rate was 4.9%, with 76% females and a median age of 22. The HPV vaccine uptake was 82%, with 88% recommending the vaccine. Parental preference was the main reason for being unvaccinated. The median age of sexual debut was 17 years, with a median of 2 sexual partners. Vaccination was associated with female, health science, sexually active, and COVID-19/influenza vaccinated students. Conclusions: HPV vaccine uptake at University of Iowa students is higher than the national and Iowa averages. Increased education regarding HPV vaccination is still needed, particularly in males, those not having sex, and those not receiving other vaccines.

Purpose: Health care professions trainees and clinicians who perceive ambiguous situations as sources of threat (low tolerance for ambiguity [TFA]) experience greater risk for mental health disorders and professional burnout. Physical therapists likely encounter substantial ambiguity because of the biopsychosocial nature of their main therapeutic strategies. The purpose of this study was to identify student traits and experiences within the learning environment that differentiate students with high and low TFA for medicine and physical therapy (PT), and to identify areas of interprofessional overlap and distinction., Method: Graduation Questionnaire survey data from graduating PT (n = 2,727) and medical students (n = 33,159) from the 2019-2020 and 2020-2021 academic years were sorted according to student TFA score, and respondents in the highest and lowest TFA quartiles were retained for analysis. Difference-in-differences analysis was used to reduce the number of potential explanatory factors to a parimonious subset that was put into linear regression models. Inferential statistics were applied to all significant factors identified from the linear regression models., Results: For both professions, higher TFA was generally associated with more positive ratings of the learning environment (student-faculty interactions, faculty professionalism, satisfaction with career choice), lower experiences of exhaustion and disengagement (the 2 axes of academic burnout), and higher scores for the empathy domain of perspective taking. Uniquely for medical students, low TFA was associated with lower empathy scores and a lower degree of interest in working with underserved individuals., Conclusions: Findings suggest that for both professions, high TFA corresponded with better ratings of the educational experience and with traits that are advantageous for patient-centered practice and occupational resilience. Interventions to cultivate TFA among health care trainees may be an important way to meet the growing demand for humanistic health care professionals who are prepared to meet society's complex needs., (Copyright © 2024 the Association of American Medical Colleges.)

Purpose: Our aim was to investigate the roles of rurality and distance to care on adverse perinatal outcomes and COVID-19 seroprevalence at the time of delivery over a 1-year period., Methods: Data were collected from the electronic medical record on all pregnant patients who delivered at a single, large, Midwest academic medical center over 1 year. Rurality was classified using standard Rural-Urban Commuting Area codes. Geographic Information System tools were used to map outcomes. Data were analyzed with univariate and multivariate models, controlling for Body Mass Index (BMI), insurance status, and parity., Findings: A total of 2,497 patients delivered during the study period; 20% of patients were rural (n = 499), 18.6% were micropolitan (n = 466), and 61.4% were metropolitan (n = 1,532). 10.4% of patients (n = 259) were COVID-19 seropositive. Rural patients did not experience higher rates of any measured adverse outcomes than metropolitan patients; micropolitan patients had increased odds of preterm labor (OR = 1.41, P = .022) and pre-eclampsia (OR = 1.78, P<.001). Patients living 30+ miles away from the medical center had increased odds of preterm labor (OR = 1.94, P<.001), pre-eclampsia (OR = 1.73, P = .002), and infant admission to the neonatal intensive care unit (OR = 2.12, P<.001), as well as lower gestational age at delivery (β = -9.2 days, P<.001) and birth weight (β = -206 grams, P<.001)., Conclusion: Distance to care, rather than rurality, was the key predictor of multiple adverse perinatal outcomes in this cohort of deliveries over a 1-year period. Our study suggests that rurality should not be used as a standalone indicator of access to care without further knowledge of the specific barriers affecting a given population., (© 2024 The Authors. The Journal of Rural Health published by Wiley Periodicals LLC on behalf of National Rural Health Association.)

Background: The high case-fatality rates among children with tuberculosis (TB) are reportedly driven by in-hospital mortality and severe forms of TB. Therefore, there is need to better understand the predictors of mortality among children hospitalised with TB. We examined the patient clinical profiles, length of hospital stay from date of admission to date of final admission outcome, and predictors of mortality among children hospitalised with TB at two tertiary hospitals in Uganda., Methods: We conducted a case-series study of children below 15 years of age hospitalised with TB, from January 1st, 2016, to December 31st, 2021. Convenience sampling was done to select TB cases from paper-based medical records at Mulago National Referral Hospital (MNRH) in urban Kampala, and Fort Portal Regional Referral Hospital (FRRH) in rural Fort Portal. We fitted linear and logistic regression models with length of stay and in-hospital mortality as key outcomes., Results: Out of the 201 children hospitalised with TB, 50 were at FRRH, and 151 at MNRH. The male to female ratio was 1.5 with median age of 2.6 years (Interquartile range-IQR 1-6). There was a high prevalence of HIV (67/171, 39%), severe malnutrition reported as weight-for-age Z-score <-3SD (51/168, 30%). Among children with pulmonary TB who initiated anti-tuberculosis therapy (ATT) either during hospitalisation or within seven days prior to hospitalisation; cough (134/143, 94%), fever (111/143, 78%), and dyspnoea (78/143, 55%) were common symptoms. Children with TB meningitis commonly presented with fever (17/24, 71%), convulsions (14/24 58%), and cough (13/24, 54%). The median length of hospital stay was 8 days (IQR 5-15). Of the 199 children with known in-hospital outcomes, 34 (17.1%) died during hospitalisation. TB meningitis was associated with in-hospital mortality (aOR = 3.50, 95% CI = 1.10-11.17, p = 0.035), while male sex was associated with reduced mortality (aOR = 0.33, 95% CI = 0.12-0.95, p = 0.035). Hospitalisation in the urban hospital predicted a 0.48-day increase in natural log-transformed length of hospital stay (ln-length of stay) (95% CI 0.15-0.82, p = 0.005), but not age, sex, HIV, malnutrition, or TB meningitis., Conclusions: In-hospital mortality was high, and significantly driven almost four times higher by TB meningitis, with longer hospital stay among children in urban hospitals. The high in-hospital mortality and long hospital stay may be reduced by timely TB diagnosis and treatment initiation among children., Competing Interests: The authors (PA, GLB, RNS, EN, AA, MJ, EW, JBJ, ARK, PE, RB) have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however, persistent infection can result in a wide array of diseases, ranging from genital warts to cancer. Most cases of cervical, anal, and oropharyngeal cancers are due to HPV infection, with cervical cancer being one of the leading causes of cancer death in women worldwide. Screening is available for HPV and cervical cancer, but is not available everywhere, particularly in lower-resource settings. HPV infection disproportionally affects individuals living with HIV, resulting in decreased clearance, increased development of cancer, and increased mortality. The development of the HPV vaccine has shown a drastic decrease in HPV-related diseases. The vaccine prevents cervical cancer with near 100% efficacy, if given prior to first sexual activity. Vaccination uptake remains low worldwide due to a lack of access and limited knowledge of HPV. Increasing awareness of HPV and access to vaccination are necessary to decrease cancer and HPV-related morbidity and mortality worldwide.

Background: Postpartum hemorrhage (PPH) remains a significant cause of maternal morbidity and mortality around the world, with rates increasing in the United States. The objective of this study was to determine predictors of, and outcomes associated with, PPH at a Midwest academic health center., Methods: Demographic and clinical data were obtained from the electronic medical record on all consecutive delivering patients between May 1, 2020, and April 30, 2021. Associations between PPH and perinatal characteristics and outcomes were assessed using logistic regression models. A significance threshold of 0.05 was used for all comparisons., Results: Of the 2497 delivering patients during the study period, 437 (18%) experienced PPH. Chronic hypertension, gestational hypertension, and preeclampsia with and without severe features were all associated with increased odds of PPH (odds rations [ORs], respectively, 1.61 (95% CI:1.13-2.24, p = 0.006), 1.62 (95% CI 1.18-2.21, p = 0.003), 1.81 (95% CI 1.14-2.80, p ≤ 0.001), and 1.92 (95% CI 1.29-2.82, p = 0.009). There were also increased odds of PPH with type I diabetes: 2.83 (95% CI 1.45-5.30, p = 0.001), type II diabetes: 2.14 (95% CI 1.15-3.82, p = 0.012), twin delivery: 3.20 (95% CI 2.11-4.81, p ≤ 0.001), cesarean delivery: 5.66 (95% CI 4.53-7.09, p ≤ 0.001), and assisted vaginal delivery: 3.12 (95% CI1.95-4.88, p ≤ 0.001). Infants of mothers with PPH had high odds of NICU admission (CI = 1.34-2.07, p < 0.001) and hypoxic ischemic encephalopathy (CI = 1.64-7.14, p < 0.001)., Conclusion: Our findings confirm previous literature that preexisting and pregnancy-related hypertension, diabetes mellitus, multiple gestation, cesarean delivery, and assisted vaginal delivery are important predictors of PPH. In addition, we found that neonates of mothers with PPH had more adverse outcomes. These results may help to inform clinical care as rates of PPH continue to rise in the United States., (© Megan Mooberry et al. 2024; Published by Mary Ann Liebert, Inc.)

Homologous recombination (HR) is a template-based DNA double-strand break repair pathway that functions to maintain genomic integrity. A vital component of the HR reaction is the identification of template DNA to be used during repair. This occurs through a mechanism known as the homology search. The homology search occurs in two steps: a collision step in which two pieces of DNA are forced to collide and a selection step that results in homologous pairing between matching DNA sequences. Selection of a homologous template is facilitated by recombinases of the RecA/Rad51 family of proteins in cooperation with helicases, translocases, and topoisomerases that determine the overall fidelity of the match. This menagerie of molecular machines acts to regulate critical intermediates during the homology search. These intermediates include recombinase filaments that probe for short stretches of homology and early strand invasion intermediates in the form of displacement loops (D-loops) that stabilize paired DNA. Here, we will discuss recent advances in understanding how these specific intermediates are regulated on the molecular level during the HR reaction. We will also discuss how the stability of these intermediates influences the ultimate outcomes of the HR reaction. Finally, we will discuss recent physiological models developed to explain how the homology search protects the genome., (© 2024 The Author(s).)

Background: Suicide rates in the United States have increased recently among Black men. To address this public health crisis, smartphone-based ecological momentary assessment (EMA) platforms are a promising way to collect dynamic, real-time data that can help improve suicide prevention efforts. Despite the promise of this methodology, little is known about its suitability in detecting experiences related to suicidal thoughts and behavior (STB) among Black men., Objective: This study aims to clarify the acceptability and feasibility of using smartphone-based EMA through a pilot study that assesses the user experience among Black men., Methods: We recruited Black men aged 18 years and older using the MyChart patient portal messaging (the patient-facing side of the Epic electronic medical record system) or outpatient provider referrals. Eligible participants self-identified as Black men with a previous history of STB and ownership of an Android or iOS smartphone. Eligible participants completed a 7-day smartphone-based EMA study. They received a prompt 4 times per day to complete a brief survey detailing their STB, as well as proximal risk factors, such as depression, social isolation, and feeling like a burden to others. At the conclusion of each day, participants also received a daily diary survey detailing their sleep quality and their daily experiences of everyday discrimination. Participants completed a semistructured exit interview of 60-90 minutes at the study's conclusion., Results: In total, 10 participants completed 166 EMA surveys and 39 daily diary entries. A total of 4 of the 10 participants completed 75% (21/28) or more of the EMA surveys, while 9 (90%) out of 10 completed 25% (7/28) or more. The average completion rate of all surveys was 58% (20.3/35), with a minimum of 17% (6/35) and maximum of 100% (35/35). A total of 4 (40%) out of 10 participants completed daily diary entries for the full pilot study. No safety-related incidents were reported. On average, participants took 2.08 minutes to complete EMA prompts and 2.72 minutes for daily diary surveys. Our qualitative results generally affirm the acceptability and feasibility of the study procedures, but the participants noted difficulties with the technology and the redundancy of the survey questions. Emerging themes also addressed issues such as reduced EMA survey compliance and diminished mood related to deficit-framed questions related to suicide., Conclusions: Findings from this study will be used to clarify the suitability of EMA for Black men. Overall, our EMA pilot study demonstrated mixed feasibility and acceptability when delivered through smartphone-based apps to Black men. Specific recommendations are provided for managing safety within these study designs and for refinements in future intervention and implementation science research., International Registered Report Identifier (irrid): RR2-10.2196/31241., (©Leslie B Adams, Thomasina Watts, Aubrey DeVinney, Emily E Haroz, Johannes Thrul, Jasmin Brooks Stephens, Mia N Campbell, Denis Antoine, Benjamin Lê Cook, Sean Joe, Roland J Thorpe Jr. Originally published in JMIR Formative Research (https://formative.jmir.org), 22.01.2024.)

Our objective was to assess human immunodeficiency virus (HIV) knowledge and sexual behaviors in 294 perinatally HIV-infected youth aged 18 to 25 years from a psychosocial support group in Kampala using a self-administered survey. Seventy-nine percent reported an undetectable viral load, 9.5% detectable, and 12% did not know. Of those with sexual partners, 19% did not know the HIV status of their partner, 64% knew negative, and 22% knew positive. Sixty-two percent disclosed their HIV status to their partner. Seventy-two percent of participants previously had sex, and of those, 57% were sexually active in the last three months. Sixty-eight percent of participants used methods to prevent pregnancy. Seventy percent of participants denied physical, sexual, or emotional intimate partner violence. There was good adherence to antiretroviral therapy and a high proportion of contraceptive use, highlighting the importance of integrating these topics into psychosocial support programs for youth living with HIV., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rdh54 is a conserved DNA translocase that participates in homologous recombination (HR), DNA checkpoint adaptation, and chromosome segregation. Saccharomyces cerevisiae Rdh54 is a known target of the Mec1/Rad53 signaling axis, which globally protects genome integrity during DNA metabolism. While phosphorylation of DNA repair proteins by Mec1/Rad53 is critical for HR progression little is known about how specific post translational modifications alter HR reactions. Phosphorylation of Rdh54 is linked to protection of genomic integrity but the consequences of modification remain poorly understood. Here, we demonstrate that phosphorylation of the Rdh54 C-terminus by the effector kinase Rad53 regulates Rdh54 clustering activity as revealed by single molecule imaging. This stems from phosphorylation dependent and independent interactions between Rdh54 and Rad53. Genetic assays reveal that loss of phosphorylation leads to phenotypic changes resulting in loss-of-heterozygosity (LOH) outcomes. Our data highlight Rad53 as a key regulator of HR intermediates through activation and attenuation of Rdh54 motor function., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: It has been reported that hepatitis B virus (HBV) double mutations (A1762T, G1764A) are an aetiological factor of hepatocellular carcinoma (HCC). However, it is unclear who is prone to develop HCC, among those infected with the mutant. Exploring HBV quasispecies, which are strongly influenced by host immune pressure, may provide more information about the association of viral factors and HCC., Materials and Methods: Nine HCC cases and 10 controls were selected from the Long An cohort. Serum samples were collected in 2004 and 2019 from subjects with HBV double mutations and the complete genome of HBV was amplified and sequenced using next-generation sequencing (NGS)., Results: The Shannon entropy values increased from 2004 to 2019 in most cases and controls. There was no significant difference in mean intrahost quasispecies genetic distances between cases and controls. The change in the values of mean intrahost quasispecies genetic distances of the controls between 2004 and 2019 was significantly higher than that of the cases (P<0.05). The viral loads did not differ significantly between cases and controls in 2004(p=0.086) but differed at diagnosed in 2019 (p=0.009). Three mutations occurring with increasing frequency from 2004 to 2019 were identified in the HCC cases, including nt446 C→G, nt514 A→C and nt2857T→C. Their frequency differed significantly between the cases and controls (P<0.05)., Conclusions: The change in the values of mean intrahost quasispecies genetic distances in HCC was smaller, suggesting that HBV in HCC cases may be subject to low host immune pressure. Increasing viral loads during long-term infection are associated with the development of HCC. The novel mutations may increase the risk for HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Chen, Jia, Wang, Zhang, Huang, Harrison, Jackson, Wu and Fang.)

Genotype I of hepatitis B virus (HBV) was proposed recently following sequencing of complete HBV genomes from Vietnam and Laos. However, its long-term molecular evolution is unknown. The objectives of this study were to study the molecular evolution of this genotype from an asymptomatic HBsAg carrier from the Long An cohort over a 15-year period was studied using both NGS and clone-based sequencing. The number of complete genome sequences obtained in 2004, 2007, 2013, and 2019 are 17, 20, 19, and 10, respectively. All strains belong to subgenotype I1, except for six (five from 2007 and one from 2019) and 8 further strains from 2007 which form a cluster branching out from other subgenotype I sequences, supported by a 100% bootstrap value. Based on complete genome sequences, all of the estimated intragroup nucleotide divergence values between these strains and HBV subgenotypes I1-I2 exceed 4%. These strains are recombinants between genotype I1 and subgenotype C but the breakpoints vary. The median intrahost viral evolutionary rate in this carrier was 3.88E-4 substitutions per site per year. The Shannon entropy (Sn) ranged from 0.55 to 0.88 and the genetic diversity, D, ranged from 0.0022 to 0.0041. In conclusion, our data provide evidence of novel subgenotypes. Considering that the 8 strains disappeared after 2007, while one of the 6 strains appears again in 2019, we propose these 6 strains as a new subgenotype, provisionally designated HBV subgenotype I3 and the 8 strains as aberrant genotype., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Previous neurofeedback research has shown training-related frontal theta increases and performance improvements on some executive tasks in real feedback versus sham control groups. However, typical sham control groups receive false or non-contingent feedback, making it difficult to know whether observed differences between groups are associated with accurate contingent feedback or other cognitive mechanisms (motivation, control strategies, attentional engagement, fatigue, etc.). To address this question, we investigated differences between two frontal theta training groups, each receiving accurate contingent feedback, but with different top-down goals: (1) increase and (2) alternate increase/decrease. We hypothesized that the increase group would exhibit greater increases in frontal theta compared to the alternate group, which would exhibit lower frontal theta during down- versus up-modulation blocks over sessions. We also hypothesized that the alternate group would exhibit greater performance improvements on a Go-NoGo shooting task requiring alterations in behavioral activation and inhibition, as the alternate group would be trained with greater task specificity, suggesting that receiving accurate contingent feedback may be the more salient learning mechanism underlying frontal theta neurofeedback training gains. Thirty young healthy volunteers were randomly assigned to increase or alternate groups. Training consisted of an orientation session, five neurofeedback training sessions (six blocks of six 30-s trials of FCz theta modulation (4-7 Hz) separated by 10-s rest intervals), and six Go-NoGo testing sessions (four blocks of 90 trials in both Low and High time-stress conditions). Multilevel modeling revealed greater frontal theta increases in the alternate group over training sessions. Further, Go-NoGo task performance increased at a greater rate in the increase group (accuracy and reaction time, but not commission errors). Overall, these results reject our hypotheses and suggest that changes in frontal theta and performance outcomes were not explained by reinforcement learning afforded by accurate contingent feedback. We discuss our findings in terms of alternative conceptual and methodological considerations, as well as limitations of this research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

On 17 September 1683, Antonie van Leeuwenhoek, a Dutch merchant who lacked formal education and fortune, wrote a letter to the Royal Society of London describing for the first time a single-celled organism. As a tribute to this revolutionary discovery, the Portuguese Society of Microbiology with the support of the Federation of European Microbiological Societies in 2017, designated this day as International Microorganism Day (IMD), a day aiming to raise awareness about the wonderful world of microbes. Six years after the establishment of IMD, the knowledge of microbiology outreach around this celebration has expanded greatly, with 5 years of in-person and 2 years of online events. The peak of these commemorations was in 2023, with 63 parallel outreach events and more than 5000 attendees, most of which were children, and young adults. While these in-person events were occurring in the month of September, the #InternationalMicroorganismDay hashtag reached nearly 2.3 million people online, reflecting the number of users who have seen a post containing this hashtag on social media. Using a decentralized model to facilitate 63 grass-roots teams to organize events locally, IMD achieved global representation both online and offline. This paper presents details behind the organization and data on the international impact of the IMD 2022 and 2023 events, outlines plans to expand reach to more countries and audiences, and encourages readers to participate with their own events in future IMD editions so that global impact can be expanded even further., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

Direct observation of enzymes that work to promote nucleic acid metabolism is a powerful approach to understanding their biochemical and biological properties. Over several years, fluorescent optical microscopy has developed as a powerful tool for watching biological pathways as they occur in real time. Here we describe DNA curtains as an optical microscopy tool that combines engineering, biochemistry, and single molecule imaging to make direct observations of enzymes as they work on DNA in real time. We will provide a detailed methodology of this approach including information about the setup of a basic TIRF microscope, assembly of flow chambers for imaging, and the protocol for making DNA curtains. Our goal is to help the reader better understand the technical approaches to DNA curtains and to better understand the biochemical and biological applications of this approach., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To analyze the genetic features of melanocytomas and melanomas of the anterior uvea and assess the value of molecular testing for diagnosis and prognostication., Design: Retrospective case-control study., Subjects: Patients with melanocytoma (n = 16) and melanoma (n = 19) of the anterior uvea., Methods: Targeted next-generation sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue from anterior uveal melanocytic tumors and correlated with clinicopathologic features., Main Outcome Measures: Presence or absence of accompanying oncogenic alterations beyond GNAQ/GNA11 and their association with histologic features and local recurrence., Results: Hotspot missense mutations in GNAQ/GNA11 were identified in 91% (32/35) of all cases. None of the melanocytomas with or without atypia demonstrated chromosomal imbalances or additional oncogenic variants beyond GNAQ mutation, and none recurred over a median follow-up of 36 months. Additional alterations identified in a subset of melanomas include mutations in BAP1 (n = 3), EIF1AX (n = 4), SRSF2 (n = 1), PTEN (n = 1), and EP300 (n = 1); monosomy 3p (n = 6); trisomy 6p (n = 3); trisomy 8q (n = 2); and an ultraviolet mutational signature (n = 5). Local recurrences were limited to melanomas, all of which demonstrated oncogenic alterations in addition to GNAQ/GNA11 (n = 5). A single melanoma harboring GNAQ and BAP1 mutations and monosomy 3 was the only tumor that metastasized., Conclusions: In this study, anterior segment uveal melanocytomas did not display oncogenic alterations beyond GNAQ/GNA11. Therefore, they are genetically similar to uveal nevi rather than uveal melanoma based on their molecular features known from the literature. Molecular testing can be performed on borderline cases to aid risk stratification and clinical management decisions., (Published by Elsevier Inc.)

Introduction: Maternal obesity has been linked to adverse outcomes for mothers and their offspring, including, but not limited to gestational hypertension (gHTN), gestational diabetes (GDM), pre-eclampsia, fetal macrosomia, and emergency cesarean section. Recent investigations have also shown that obesity, as defined by a body mass index (BMI) ≥ 30, especially severe obesity (BMI ≥ 40), is a risk factor for both hospitalization and death from COVID-19., Objectives: The objective of this study is to determine the prevalence and association of maternal obesity at delivery with adverse antenatal, intrapartum, and neonatal outcomes in a cohort of consecutive delivering patients at a tertiary care center in Iowa from May to September 2020. A secondary objective is to determine if maternal obesity has any relationship to past or current COVID-19 infection status at the time of delivery. This is a secondary analysis of a prospective cohort study to analyze obstetric outcomes among COVID-19 infected and uninfected patients., Methods: We conducted a prospective cohort study using demographic and clinical data obtained from the electronic medical record. Excess plasma was collected from routine blood samples obtained at delivery admission to determine the seroprevalence of COVID-19 antibody using the DiaSorin and Roche antibody assays. Frequency variables were each calculated separately, and a comparison of maternal and neonatal outcomes was conducted using the generalized linear mixed modeling (GLMM) framework to account for varying distributions (normal and binary)., Results: 1001 women delivered during the study period and 89.7% met criteria for being overweight or obese; 17.9% met criteria for severe obesity. Women with obesity had 49.8% lower odds of possessing private insurance, and women with severe obesity were less than half as likely to plan to breastfeed at the time of discharge. Women with obesity of any kind had a significantly increased odds of GDM and gHTN, and an increased risk of an infant with macrosomia, hypoglycemia, and NICU admission. No significant association was found between BMI and COVID-19 infection or disease severity., Conclusion: This study provides insight into obstetric complications facing women with obesity, especially those with severe obesity. This report serves to highlight potential challenges, such as insurance status and labor complications, that impact women of high BMI to a greater degree when compared to their normal-weight counterparts.

Homologous recombination (HR) is a double-strand break DNA repair pathway that preserves chromosome structure. To repair damaged DNA, HR uses an intact donor DNA sequence located elsewhere in the genome. After the double-strand break is repaired, DNA sequence information can be transferred between donor and recipient DNA molecules through different mechanisms, including DNA crossovers that form between homologous chromosomes. Regulation of DNA sequence transfer is an important step in effectively completing HR and maintaining genome integrity. For example, mitotic exchange of information between homologous chromosomes can result in loss-of-heterozygosity (LOH), and in higher eukaryotes, the development of cancer. The DNA motor protein Rdh54 is a highly conserved DNA translocase that functions during HR. Several existing phenotypes in rdh54Δ strains suggest that Rdh54 may regulate effective exchange of DNA during HR. In our current study, we used a combination of biochemical and genetic techniques to dissect the role of Rdh54 on the exchange of genetic information during DNA repair. Our data indicate that RDH54 regulates DNA strand exchange by stabilizing Rad51 at an early HR intermediate called the displacement loop (D-loop). Rdh54 acts in opposition to Rad51 removal by the DNA motor protein Rad54. Furthermore, we find that expression of a catalytically inactivate allele of Rdh54, rdh54K318R, favors non-crossover outcomes. From these results, we propose a model for how Rdh54 may kinetically regulate strand exchange during homologous recombination., Competing Interests: The authors have declared that no competing interests exist.

Vaccination has been shown to stimulate remarkably high antibody levels in donors who have recovered from COVID-19. Our objective was to measure patient antibody levels before and after transfusion with COVID-19 Convalescent Plasma (CCP) and compare the antibody levels following transfusion of CCP from vaccinated and nonvaccinated donors. Plasma samples before and after transfusion were obtained from 25 recipients of CCP and COVID-19 antibody levels measured. Factors that effect changes in antibody levels were examined. In the 21 patients who received CCP from nonvaccinated donors, modest increases in antibody levels were observed. Patients who received two units were more likely to seroconvert than those receiving just one unit. The strongest predictor of changes in patient antibody level was the CCP dose, calculated by the unit volume multiplied by the donor antibody level. Using patient plasma volume and donor antibody level, the post-transfusion antibody level could be predicted with reasonable accuracy(R 2 > 0.90). In contrast, the 4 patients who received CCP from vaccinated donors all had dramatic increases in antibody levels following transfusion of a single unit. In this subset of recipients, antibody levels observed after transfusion of CCP were comparable to those seen in donors who had fully recovered from COVID-19. If available, CCP from vaccinated donors with very high antibody levels should be used. One unit of CCP from vaccinated donors increases patient antibody levels much more than 1 or 2 units of CCP from unvaccinated donors., (Copyright © 2021. Published by Elsevier Ltd.)

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is arranged as a trimer on the virus surface, composed of three S1 and three S2 subunits. Infected and vaccinated individuals generate antibodies against spike, which can neutralize the virus. Most antibodies target the receptor-binding domain (RBD) and N-terminal domain (NTD) of S1; however, antibodies against other regions of spike have also been isolated. The interhost variability in domain specificity and relative neutralization efficacy of the antibodies is still poorly characterized. To this end, we tested serum and plasma samples collected from 85 coronavirus disease 2019 (COVID-19) convalescent subjects. Samples were analyzed using seven immunoassays that employ different domains, subunits, and oligomeric forms of spike to capture the antibodies. Samples were also tested for their neutralization of pseudovirus containing SARS-CoV-2 spike and of replication-competent SARS-CoV-2. While the total amount of anti-spike antibodies produced varied among convalescent subjects, we observed an unexpectedly fixed ratio of RBD- to NTD-targeting antibodies. The relative potency of the response (defined as the measured neutralization efficacy relative to the total level of spike-targeting antibodies) also exhibited limited variation between subjects and was not associated with the overall amount of antispike antibodies produced. These studies suggest that host-to-host variation in the polyclonal response elicited against SARS-CoV-2 spike in early pandemic subjects is primarily limited to the quantity of antibodies generated rather than their domain specificity or relative neutralization potency. IMPORTANCE Infection by SARS-CoV-2 elicits antibodies against various domains of the spike protein, including the RBD and NTD of subunit S1 and against subunit S2. The antibody responses of different infected individuals exhibit different efficacies to inactivate (neutralize) the virus. Here, we show that the observed variation in the neutralizing activity of the antibody responses in COVID-19 convalescent subjects is caused by differences in the amounts of antibodies rather than their recognition properties or the potency of their antiviral activity. These findings suggest that COVID-19 vaccine strategies that focus on enhancing the overall level of the antibodies will likely elicit a more uniformly efficacious protective response.

Srs2 is a superfamily 1 (SF1) helicase that participates in several pathways necessary for the repair of damaged DNA. Srs2 regulates formation of early homologous recombination (HR) intermediates by actively removing the recombinase Rad51 from single-stranded DNA (ssDNA). It is not known whether and how Srs2 itself is down-regulated to allow for timely HR progression. Rad54 and Rdh54 are two closely related superfamily 2 (SF2) motor proteins that promote the formation of Rad51-dependent recombination intermediates. Rad54 and Rdh54 bind tightly to Rad51-ssDNA and act downstream of Srs2, suggesting that they may affect the ability of Srs2 to dismantle Rad51 filaments. Here, we used DNA curtains to determine whether Rad54 and Rdh54 alter the ability of Srs2 to disrupt Rad51 filaments. We show that Rad54 and Rdh54 act synergistically to greatly restrict the antirecombinase activity of Srs2. Our findings suggest that Srs2 may be accorded only a limited time window to act and that Rad54 and Rdh54 fulfill a role of prorecombinogenic licensing factors., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

It has been reported that some mutations in the genome of hepatitis B virus (HBV) may predict the outcome of the virus infection. However, evolutionary data derived from long-term longitudinal analysis of entire HBV genomes using next generation sequencing (NGS) remain rare. In this study, serum samples were collected from asymptomatic hepatitis B surface antigen (HBsAg) carriers from a long-term prospective cohort. The entire HBV genome was amplified by polymerase chain reaction (PCR) and sequenced using NGS. Twenty-eight time series serum samples from nine subjects were successfully analysed. The Shannon entropy (Sn) ranged from 0 to 0.89, with a median value of 0.76, and the genetic diversity (D) ranged from 0 to 0.013, with a median value of 0.004. Intrahost HBV viral evolutionary rates ranged from 2.39E-04 to 3.11E-03. Double mutations at nt1762(A → T) and 1764(G → A) and a stop mutation at nt1896(G → A) were seen in all sequences from subject BO129 in 2007. However, in 2019, most sequences were wild type at these positions. Deletions between nt 2920-3040 were seen in all sequences from subject TS115 in 2007 and 2013 but these were not present in 2004 or 2019. Some sequences from subject CC246 had predicted escape substitutions (T123N, G145R) in the surface protein in 2004, 2013 and 2019 but none of the sequences from 2007 had these changes. In conclusion, HBV mutations may revert to wild type in natural infection. Clinicians should be wary of predicting long-term prognoses on the basis of the presence of mutations., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Epstein-Barr virus (EBV) is the cause of infectious mononucleosis, which disproportionately affects university students. This population has the potential to benefit from a prophylactic EBV vaccine trial. Our objectives were to determine EBV infection status and associated demographic/lifestyle factors among first year undergraduate university students at the beginning and end of first year., Methods: EBV infection status was assessed by testing for circulating IgG class antibodies against EBV viral capsid antigen., Results: Of 198 starting students; 56.1% were positive for EBV antibodies with a higher rate in women (64.8%) than male (41.1%); p = 0.002. A history of deep kissing was associated with a higher rate of EBV antibody positivity. On follow-up 8 months later at the end of freshman year, 22.4% had acquired EBV antibodies for a primary infection incidence of 33.6/100 person years., Conclusion: These findings indicate that our first year undergraduate population contains sufficient EBV-naïve subjects for a prophylactic vaccine trial.

This article analyzes the decisionmaking, communication, and outcomes of collaboration between the West Virginia National Guard (WVNG) and state and county organizations in hosting state-prioritized COVID-19 testing site events from May 22 to December 30, 2020. The United States Census Bureau designated 34 of the 55 counties in West Virginia as rural. For this study, we classified 23 counties as rural-identified counties, 14 counties as minority-identified counties and 14 counties as both rural and minority-identified counties. This resulted in a total 51 of the 55 counties receiving a rural, minority, or both rural and minority-identified county designation. Through collaboration between the WVNG and public health partners, 98,846 COVID-19 tests were conducted between May 22 and December 30, 2020, making up 7% of the total of 1,414,373 COVID-19 tests conducted in the entire state of West Virginia during that time frame. A total of 349 (68.2%) of the 512 WVNG-supported testing sites occurred in either rural or minority-identified counties: 185 (36.1%) in rural counties, 134 (26.2%) in minority-identified counties, and 30 (5.9%) in counties designated as both rural and minority-identified. The novel use of the WVNG to support county health departments in rural and minority-identified counties allowed more COVID-19 testing site events to occur. This demonstrates the use of the National Guard as a force multiplier, helping to reach the state's most vulnerable and underserved populations.

Rad54 and Rdh54 are Snf2 DNA motor proteins that function during maintenance of genomic integrity. Though highly related, Rad54 and Rdh54 have different biochemical and genetic functions during maintenance of genomic integrity. Rad54 functions primarily during the homology search and strand invasion steps of homologous recombination, while Rdh54 appears to play a minor role in these processes. More recently it has been shown that Rdh54 functions as a pathway branch point at HR intermediates, and as has a role in cell cycle recovery. Here we will explore recent advances that have improved our understanding of the role these two DNA motor proteins play during DNA repair., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to estimate the prevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) among pregnant patients at the time of delivery in a rural Midwest tertiary care hospital and to examine demographics, clinical factors, and maternal and neonatal outcomes associated with SARS-CoV-2 infection during pregnancy., Study Design: This prospective cohort study included all delivering patients between May 1 and September 22, 2020 at the University of Iowa Hospitals and Clinics. Plasma SARS-CoV-2 antibody testing was performed. SARS-CoV-2 viral reverse-transcription polymerase chain reaction (RT-PCR) results and maternal and neonatal outcomes were collected from the electronic medical record. Data were analyzed using univariate statistical methods with clustering for multiple births., Results: In total, 1,000 patients delivered between May 1 and September 22, 2020. Fifty-eight (5.8%) were SARS-CoV-2 antibody positive. Twenty-three also tested viral positive during pregnancy. Three of 1,000 (0.3%) were viral positive on admission but antibody negative. The median age was 30 years (interquartile range [IQR]: 26-33 years) and body mass index was 31.75 kg/m 2 (IQR 27.7-37.5 kg/m 2 ). The cesarean delivery rate was 34.0%. The study population was primarily white (71.6%); however, 41.0% of SARS-CoV-2 infected patients identified as Black, 18.0% as Hispanic/Latino, 3.3% as Native Hawaiian/Pacific Islander, and only 27.9% as White ( p  < 0.0001). SARS-CoV-2 infection was more likely in patients without private insurance ( p  = 0.0243). Adverse maternal and/or neonatal outcomes were not more likely in patients with evidence of infection during pregnancy. Two SARS-CoV-2 infected patients were admitted to the intensive care unit. There were no maternal deaths during the study period., Conclusion: In this largely rural Midwest population, 6.1% of delivering patients had evidence of past or current SARS-CoV-2 infection. Rates of SARS-CoV-2 during pregnancy were higher among racial and ethnic minorities and patients without private insurance. The SARS-CoV-2 infected patients and their neonates were not found to be at increased risk for adverse outcomes., Key Points: · SARS-CoV-2 seroprevalence rate in pregnant population in Iowa is 5.8%.. · Infections are higher among minorities, non-English speakers, and patients without private insurance.. · No increased adverse maternal/neonatal outcomes observed for SARS-CoV-2 infected mothers.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: While molecular techniques remain the gold standard for diagnosis of acute SARS-CoV-2 infection, serological tests have the unique potential to ascertain how much of the population has been exposed to the COVID-19 pathogen. There have been limited published studies to date documenting the performance of SARS-CoV-2 antibody assays., Methods: We compared the DiaSorin Liaison SARS-CoV-2 S1/S2 IgG and Roche Diagnostics Elecsys Anti-SARS-CoV-2 assays using 228 samples spanning patients with positive PCR for SARS-CoV-2, patients with compatible symptoms but negative PCR, pre-COVID specimens, and potential cross-reactives., Results: Both assays detected antibodies in 18/19 samples collected at least one week after a positive PCR result. Neither method consistently detected antibodies in specimens collected within one week of a positive PCR result (sensitivity < 50%), but antibodies were detected by only Roche in four samples in this time frame. Using 139 pre-COVID and 35 PCR-negative samples, the Roche and DiaSorin assays demonstrated specificities of 100.0% and 98.9%, respectively. Neither assay demonstrated cross-reactivity from other coronaviruses (229E, HKU1, NL63, OC43), respiratory pathogens (adenovirus, metapneumovirus, rhinovirus/enterovirus), or antibodies to other viruses (HIV, EBV, CMV, HBV, HCV, HAV)., Discussion: Overall, the qualitative interpretations afforded by the Roche and DiaSorin assays agreed for 97% of samples evaluated. Minor discrepancies in sensitivity and specificity were observed between methods, with the differences in specificity more clinically significant for our low-prevalence population. For the DiaSorin assay, all disagreements with the Roche assay occurred in samples with quantitative signals near the cut-off determining positivity., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Rad54 and Rdh54 are closely related ATP-dependent motor proteins that participate in homologous recombination (HR). During HR, these enzymes functionally interact with the Rad51 presynaptic complex (PSC). Despite their importance, we know little about how they are organized within the PSC, or how their organization affects PSC function. Here, we use single-molecule optical microscopy and genetic analysis of chimeric protein constructs to evaluate the binding distributions of Rad54 and Rdh54 within the PSC. We find that Rad54 and Rdh54 have distinct binding sites within the PSC, which allow these proteins to act cooperatively as DNA sequences are aligned during homology search. Our data also reveal that Rad54 must bind to a specific location within the PSC, whereas Rdh54 retains its function in the repair of MMS-induced DNA damage even when recruited to the incorrect location. These findings support a model in which the relative binding sites of Rad54 and Rdh54 help to define their functions during mitotic HR., (© 2020 The Authors.)

Homologous recombination (HR) helps maintain genome integrity, and HR defects give rise to disease, especially cancer. During HR, damaged DNA must be aligned with an undamaged template through a process referred to as the homology search. Despite decades of study, key aspects of this search remain undefined. Here, we use single-molecule imaging to demonstrate that Rad54, a conserved Snf2-like protein found in all eukaryotes, switches the search from the diffusion-based pathways characteristic of the basal HR machinery to an active process in which DNA sequences are aligned via an ATP-dependent molecular motor-driven mechanism. We further demonstrate that Rad54 disrupts the donor template strands, enabling the search to take place within a migrating DNA bubble-like structure that is bound by replication protein A (RPA). Our results reveal that Rad54, working together with RPA, fundamentally alters how DNA sequences are aligned during HR., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Total NIH funding dollars have increased from 2009-2018. We questioned whether this growth has occurred proportionately around the country and throughout allopathic medical schools. Therefore, we compared the trend in NIH grant funding from 2009 to 2018 for United States allopathic medical schools among historically top-funded schools, private and public schools, and by region of the country. Changes in both unadjusted and real funding dollars over time revealed a significant difference. Region was the only significant factor for mean percent change in funding from 2009-2018, with the Western region showing a 33.79% increase in purchasing power. The Northeastern region showed a -6.64% decrease in purchasing power while the Central and Southern regions reported changes of 2.46% and -6.08%, respectively. The mean percent increases were more proportional and nonsignificant in the public vs. private institutions comparison, at -3.41% and 4.75%, respectively. Likewise, the top-funded institutions vs. other institutions comparisons demonstrated modest, nonsignificant differences. However, although the relative changes might be proportional, the absolute increases evidence a pattern of growing cumulative advantage that favor the highest-funded institutions and private institutions. The potential consequences of this disproportionate increase include health science education, biomedical research, and patient access disparities in large parts of the country. The NIH and the scientific community should explore potential solutions in its funding models., Competing Interests: The authors have declared that no competing interests exist.

Background: Conservative treatment for carpal tunnel syndrome (CTS) often includes wrist orthosis. However, there is no consensus on whether commercial or custom-made wrist orthosis is better for the treatment., Purpose: To assess feasibility of a study comparing nocturnal use of commercial versus custom-made wrist orthosis in the treatment of mild/moderate CTS and estimate their potential effects on function and symptoms., Study Design: Randomized clinical trial., Methods: Twenty-four individuals with mild/moderate CTS were randomized to wear either a commercial orthosis (n = 12) or a custom-made orthosis (n = 12). Participants used the assigned orthosis at night for 45 days and performed gliding exercises at home/work. We collected data on access to eligible population and feasibility of protocol. Data on use of orthosis, performance of exercises, and symptoms were collected through a dairy filled by the participant. Outcomes were pain (using Numeric Pain Rating Scale), symptom severity and functional status (using Boston Questionnaire), pinch strength (by dynamometry), and electromyographic activity of forearm muscles (sampled during a reach-to-grasp task). Outcomes were measured before and after the intervention., Results: There were no loses to follow-up in either intervention group. After treatment, we found increased tripod pinch strength and better symptoms and function in both orthosis groups, with better outcomes for the custom-made orthosis, although the differences were not statistically significant., Conclusions: The preliminary results showed a potential for better outcomes from the custom-made orthosis. We established that a larger study would be feasible and could be designed and conducted based on the estimates provided by this study., Trial Registration: Brazilian Registry of Clinical Trials (ReBEC) - registration number: RBR-74rqnz., Competing Interests: Declarations of competing interest No conflicts of interest have been reported by the authors of this study., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Rad52 is a key factor for homologous recombination (HR) in yeast. Rad52 helps assemble Rad51-ssDNA nucleoprotein filaments that catalyze DNA strand exchange, and it mediates single-strand DNA annealing. We find that Rad52 has an even earlier function in HR in restricting DNA double-stranded break ends resection that generates 3' single-stranded DNA (ssDNA) tails. In fission yeast, Exo1 is the primary resection nuclease, with the helicase Rqh1 playing a minor role. We demonstrate that the choice of two extensive resection pathways is regulated by Rad52. In rad52 cells, the resection rate increases from ∼3-5 kb/h up to ∼10-20 kb/h in an Rqh1-dependent manner, while Exo1 becomes dispensable. Budding yeast Rad52 similarly inhibits Sgs1-dependent resection. Single-molecule analysis with purified budding yeast proteins shows that Rad52 competes with Sgs1 for DNA end binding and inhibits Sgs1 translocation along DNA. These results identify a role for Rad52 in limiting ssDNA generated by end resection., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The vast majority of eukaryotes possess two DNA recombinases: Rad51, which is ubiquitously expressed, and Dmc1, which is meiosis-specific. The evolutionary origins of this two-recombinase system remain poorly understood. Interestingly, Dmc1 can stabilize mismatch-containing base triplets, whereas Rad51 cannot. Here, we demonstrate that this difference can be attributed to three amino acids conserved only within the Dmc1 lineage of the Rad51/RecA family. Chimeric Rad51 mutants harboring Dmc1-specific amino acids gain the ability to stabilize heteroduplex DNA joints with mismatch-containing base triplets, whereas Dmc1 mutants with Rad51-specific amino acids lose this ability. Remarkably, RAD-51 from Caenorhabditis elegans , an organism without Dmc1, has acquired "Dmc1-like" amino acids. Chimeric C. elegans RAD-51 harboring "canonical" Rad51 amino acids gives rise to toxic recombination intermediates, which must be actively dismantled to permit normal meiotic progression. We propose that Dmc1 lineage-specific amino acids involved in the stabilization of heteroduplex DNA joints with mismatch-containing base triplets may contribute to normal meiotic recombination., (© 2019 Steinfeld et al.; Published by Cold Spring Harbor Laboratory Press.)

DNA helicases of the RecQ family are conserved among the three domains of life and play essential roles in genome maintenance. Mutations in several human RecQ helicases lead to diseases that are marked by cancer predisposition. The Saccharomyces cerevisiae RecQ helicase Sgs1 is orthologous to human BLM, defects in which cause the cancer-prone Bloom's Syndrome. Here, we use single-molecule imaging to provide a quantitative mechanistic understanding of Sgs1 activities on single stranded DNA (ssDNA), which is a central intermediate in all aspects of DNA metabolism. We show that Sgs1 acts upon ssDNA bound by either replication protein A (RPA) or the recombinase Rad51. Surprisingly, we find that Sgs1 utilizes a novel motor mechanism for disrupting ssDNA intermediates bound by the recombinase protein Rad51. The ability of Sgs1 to disrupt Rad51-ssDNA filaments may explain some of the defects engendered by RECQ helicase deficiencies in human cells., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)