Impact of Asian and Black Donor and Recipient Ethnicity on the Outcomes After Deceased Donor Kidney Transplantation in the United Kingdom.

Patients of Asian and black ethnicity face disadvantage on the renal transplant waiting list in the UK, because of lack of human leucocyte antigen and blood group matched donors from an overwhelmingly white deceased donor pool. This study evaluates outcomes of renal allografts from Asian and black donors. The UK Transplant Registry was analysed for adult deceased donor kidney only transplants performed between 2001 and 2015. Asian and black ethnicity patients constituted 12.4% and 6.7% of all deceased donor recipients but only 1.6% and 1.2% of all deceased donors, respectively. Unadjusted survival analysis demonstrated significantly inferior long-term allograft outcomes associated with Asian and black donors, compared to white donors. On Cox-regression analysis, Asian donor and black recipient ethnicities were associated with poorer outcomes than white counterparts, and on ethnicity matching, compared with the white donor-white recipient baseline group and adjusting for other donor and recipient factors, 5-year graft outcomes were significantly poorer for black donor-black recipient, Asian donor-white recipient, and white donor-black recipient combinations in decreasing order of worse unadjusted 5-year graft survival. Increased deceased donation among ethnic minorities could benefit the recipient pool by increasing available organs. However, it may require a refined approach to enhance outcomes.

Exploring adolescent girls and young women's PrEP-user profiles: qualitative insights into differentiated PrEP delivery platform selection and engagement in Cape Town, South Africa.

INTRODUCTION: Adolescent girls and young women (AGYW), a priority population for HIV prevention in Africa, show high interest but difficulty in sustained effective use of pre-exposure prophylaxis (PrEP). With ongoing PrEP scale-up focused on increasing access, it is important to understand what influences AGYW's choice of PrEP delivery platforms. METHODS: The POWER implementation study in Cape Town provided PrEP between 2017 and 2020 to AGYW (16-25 years) from four differentiated delivery platforms: mobile clinic, government facility, courier delivery or community-based youth club. Healthcare providers at government and mobile clinics provided PrEP (initiation and refills) as part of comprehensive, integrated sexual and reproductive health services. Courier and youth club platforms provided light-touch PrEP refill services incorporating rapid HIV self-testing. We conducted in-depth interviews with a purposive sample of AGYW who had ≥3 months of PrEP-use and accessed ≥2 PrEP delivery platforms. The thematic analysis explored AGYW's preferences, decision-making and habits related to PrEP access to inform market segmentation. RESULTS: We interviewed 26 AGYW (median age 20) PrEP-users between November 2020 and March 2021. AGYW PrEP-users reported accessing different services with, 24 accessing mobile clinics, 17 courier delivery, 9 government health facilities and 6 youth clubs for their PrEP refills. Qualitative findings highlighted four potential behavioural profiles. The "Social PrEP-user" preferred PrEP delivery in peer spaces, such as youth clubs or adolescent-friendly mobile clinics, seeking affirmation and social support for continued PrEP use. The "Convenient PrEP-user" favoured PrEP delivery at easily accessible locations, providing quick (courier) or integrated contraception-PrEP refill visits (mobile and government clinic). The "Independent PrEP-user" preferred PrEP delivery that offered control over delivery times that fit into their schedule, such as the courier service. The "Discreet PrEP-user" highly valued privacy regarding their PrEP use (courier delivery) and avoided delivery options where unintentional disclosure was evident (youth club). Comfort with HIV self-testing had minimal influence on PrEP delivery choice. CONCLUSIONS: Market segmentation of AGYW characterizes different types of PrEP-users and has the potential to enhance tailored messaging and campaigns to reach specific segments, with the aim of improving sustained PrEP use and HIV prevention benefits.

Natural vs. Surgical Postmenopause and Psychological Symptoms Confound the Effect of Menopause on Executive Functioning Domains of Cognitive Experience.

Objective: The menopause transition is associated with difficulties in executive function. However, it is unclear whether these difficulties persist past perimenopause. This study investigated whether potential confounders, including natural vs. surgical postmenopause and menopause-related psychological symptoms, influence whether executive dysfunction persists into postmenopause. Study Design: A cross-sectional sample of women aged 35-65 years (N = 1971) in one of four groups, premenopause, perimenopause, natural postmenopause, and surgical postmenopause, were surveyed. Participants self-reported executive functioning with the Brown Attention Deficit Disorder Scale (BADDS), anxiety symptom severity with the Generalized Anxiety Disorder Questionnaire (GAD-7), and depression symptom severity with the Center for Epidemiologic Studies Depression Scale (CES-D). Main Outcome Measures: We analyzed the association between group and BADDS scores using linear regression models - first, by controlling for age, education, and self-reported attention deficit hyperactivity disorder (ADHD) diagnosis (Model #1) and, second, by further controlling for current difficulty sleeping, anxiety, and depression (Model #2). Results: In both models, BADDS scores were significantly elevated (indicating more difficulties in executive function) among women in the perimenopausal and surgical postmenopausal groups compared with those in the premenopausal group. Likewise, the perimenopausal and surgical postmenopausal groups had the highest proportions of participants who reported difficulty sleeping and clinical levels of anxiety and depression. BADDS scores were significantly higher in natural postmenopausal vs. premenopausal women without controlling for difficulty sleeping, anxiety, and depression (Model #1), but not when adjusting for these variables (Model #2). Conclusions: The type of menopause and psychological symptoms are important confounders of the relationship between the menopause transition and executive dysfunction, and help explain whether executive dysfunction persists or recovers in postmenopause.Reprinted from Maturitas 2023; 170:64-73, with permission from Elsevier. Copyright © 2023.

Randomised controlled trial of population screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the SAFER trial.

INTRODUCTION: There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk. METHODS AND ANALYSIS: Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis. ETHICS AND DISSEMINATION: The London-Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee. TRIAL REGISTRATION NUMBER: ISRCTN72104369.

Harnessing technology to improve sleep in frontline healthcare workers: A pilot study of electronic noise-masking earbuds on subjective and objective sleep measures.

Objective: This pilot study assessed the effects of electronic noise-masking earbuds on subjective sleep perception and objective sleep parameters among healthcare workers (HCWs) reporting sleep difficulties during the COVID-19 pandemic. Methods: Using a pre-post design, 77 HCWs underwent 3 nights of baseline assessment followed by a 7-night intervention period. Participants wore an at-home sleep monitoring headband to assess objective sleep measures and completed subjective self-report assessments. The difference in mean sleep measures from baseline to intervention was estimated in linear mixed models. Results: Compared to baseline assessments, HCWs reported significant improvements in sleep quality as measured by the Insomnia Severity Index (ISI) (Cohen's d = 1.74, p < 0.001) and a significant reduction in perceived sleep onset latency (SOL) during the intervention (M = 17.2 minutes, SD = 7.7) compared to baseline (M = 24.7 minutes, SD = 16.1), (Cohen's d = -0.42, p = 0.001). There were no significant changes in objective SOL (p = 0.703). However, there was a significant interaction between baseline objective SOL (<20 minutes vs >20 minutes) and condition (baseline vs intervention) (p = 0.002), such that individuals with objective SOL >20 minutes experienced a significant decrease in objective SOL during the intervention period compared to baseline (p = 0.015). Conclusions: HCWs experienced a significant improvement in perceived SOL and ISI scores after using the electronic noise-masking earbuds. Our data provide preliminary evidence for a nonpharmacological intervention to improve the sleep quality of HCWs which should be confirmed by future controlled studies.

Performance of Urinalysis Parameters in Predicting Urinary Tract Infection: Does One Size Fit all?

In a multi-hospital cohort study of 3392 patients, positive urinalysis parameters had poor positive predictive value for diagnosing urinary tract infection (UTI). Combined urinalysis parameters (pyuria or nitrite) performed better than pyuria alone for ruling out UTI. However, performance of all urinalysis parameters was poor in older women.

Project Safe Guard: Challenges and opportunities of a universal rollout of peer-delivered lethal means safety counseling at a US military installation.

INTRODUCTION: The US Department of Defense recommends lethal means safety counseling (LMSC) to promote firearm injury prevention via secure storage of personal firearms. We describe the rollout of a universal, peer-delivered adaptation of Project Safe Guard (PSG)-a brief, single-session LMSC discussion-at a US Space Force installation. METHOD: Program evaluation data were collected via anonymous, voluntary, and online surveys. Of approximately 862 eligible active-duty service members and embedded civilians, 324 completed the preprogram survey and 68 and 37 completed the 1- and 2-month follow-ups, respectively. RESULTS: At preprogram, 69.1% agreed that peer-delivered LMSC is appropriate. After rollout, 100% of the 222 firearm locking devices available to service members were requested from the on-base Violence Prevention Integrator. The effectiveness of PSG was indeterminable due to the low survey response rates. CONCLUSIONS: Despite strong preprogram support for peer-delivered LMSC and behavioral indicators of secure firearm storage (e.g., firearm locking device requests), several challenges limited the uptake and evaluability of the PSG program in this naturalistic environment, including military survey fatigue and competing mission priorities. Additional work is needed to determine the effectiveness of peer-delivered LMSC in a military context. Sustained base support and military-civilian collaborations will be critical.

Effectiveness of Transcranial Direct Current Stimulation as an Adjuvant to Aphasia Treatment Following Stroke: Evidence From Systematic Reviews and Meta-Analyses.

PURPOSE: Transcranial direct current stimulation (tDCS) is a neuromodulation tool to amplify neural excitability and enhance outcomes associated with speech-language therapy (SLT). Stimulation currents to the left and right hemispheres vary in applying anodal (excitatory), cathodal (inhibitory), or bihemispheric signals. Several systematic reviews (SRs) and meta-analyses (MAs) have summarized the large literature examining tDCS for aphasia rehabilitation. The purpose of this project was to appraise the quality of SRs and MAs of tDCS for aphasia and examine the weight of the evidence for language outcomes in individuals with aphasia beyond SLT alone. METHOD: We searched four databases for SRs/MAs examining effects of tDCS for poststroke aphasia. We identified 16 reviews, with nine that incorporated MA to quantify results. Two reviewers reliably coded articles for methodological rigor using the AMSTAR 2 (A MeaSurement Tool to Assess Systematic Reviews, Version 2). We then summarized findings of the 16 reviews. RESULTS: The AMSTAR 2 appraisal criteria suggest that critical weaknesses were noted among all reviews except those by Elsner et al. (2015, 2019). Reviews summarized three to 48 studies, as some included only randomized crossover trials and others included all trial designs. All SRs and one MA reported improvements following tDCS stimulation for general aphasia abilities and measures of repetition and speech fluency. Five recent MAs reported significant naming improvements following tDCS using all stimulation arrays. No tDCS effects were noted for comprehension measures. CONCLUSIONS: As the tDCS literature matured, the conclusions of MAs merged with earlier SRs reporting statistically positive benefits over SLT alone. Most consistent results are reported for naming measures, leaving some to question the clinical significance of tDCS effects for functional measures of aphasia recovery. Although the tDCS literature is expansive, important questions remain before the technique can be confidently recommended for clinical practice.

Community directed assessment of pain in a northern Saskatchewan Cree community.

Indigenous Elder advisors in Pelican Narrows, a Cree community in Northern Saskatchewan, have indicated that Western pain scales may not be responsive tools for pain assessments within their community. This study employed a mixed methods research design that involved two phases. Phase one was the development of a pain scale in collaboration with an Elder and a Knowledge Keeper. Phase two was a pilot of the CDPS utilised during virtual physiotherapy sessions for chronic back pain. Twenty-seven participants completed the pre-physiotherapy treatment questionnaires, and 10 participants engaged in semi-structured interviews (9 community members; 1 healthcare provider). A weighted kappa analysis yielded k = 0.696, indicating a good agreement between the CDPS and Faces Pain Scale-Revised in terms of documenting participants' pain. Qualitative data from interviews with community members revealed three major themes: 1) Learnings Regarding Pain Scales, 2) Patient Centered Care; and 3) Strength-Based Solutions for Improving Pain Communication. Two themes were uncovered through conversations with the HCP: 1) Perspectives on CDPS and 2) Healthcare Provider Experiences Communicating about Pain. Moreover, a patient-centredcentred approach is important to ensure comprehensive pain assessments.

The Hybrid Antibiotic Thiomarinol A Overcomes Intrinsic Resistance in Escherichia coli Using a Privileged Dithiolopyrrolone Moiety.

An impermeable outer membrane and multidrug efflux pumps work in concert to provide Gram-negative bacteria with intrinsic resistance against many antibiotics. These resistance mechanisms reduce the intracellular concentrations of antibiotics and render them ineffective. The natural product thiomarinol A combines holothin, a dithiolopyrrolone antibiotic, with marinolic acid A, a close analogue of mupirocin. The hybridity of thiomarinol A converts the mupirocin scaffold from inhibiting Gram-positive bacteria to inhibiting both Gram-positive and -negative bacteria. We found that thiomarinol A accumulates significantly more than mupirocin within the Gram-negative bacterium Escherichia coli, likely contributing to its broad-spectrum activity. Antibiotic susceptibility testing of E. coli mutants reveals that thiomarinol A overcomes the intrinsic resistance mechanisms that render mupirocin inactive. Structure-activity relationship studies suggest that the dithiolopyrrolone is a privileged moiety for improving the accumulation and antibiotic activity of the mupirocin scaffold without compromising binding to isoleucyl-tRNA synthetase. These studies also highlight that accumulation is required but not sufficient for antibiotic activity. Our work reveals a role of the dithiolopyrrolone moiety in overcoming intrinsic mupirocin resistance in E. coli and provides a starting point for designing dual-acting and high-accumulating hybrid antibiotics.

Relationship of Decisional Conflict About Driving Habits Between Older Adult Drivers and Their Family Members and Close Friends.

This study examines the relationship of decisional conflict about driving habits between older adult drivers (≥70 years old) and their family members and close friends. This secondary analysis utilizes data originating from a multi-site randomized controlled trial assessing the effect of a driving decision aid (DDA) intervention. Decisional conflict about stopping or changing driving habits for drivers was measured with the Decisional Conflict Scale (DCS). Dyadic associations between drivers' and study partners' (SPs') DCS scores were analyzed using an actor-partner interdependence model. Among 228 driver-SP dyads, Dyadic DCS was correlated at baseline (r = .18, p < .01), and pre-intervention DCS was associated with post-intervention DCS (p < .001 for SPs [ß = .73] and drivers [ß = .73]). Drivers' baseline DCS and SPs' post-intervention DCS were slighly correlated (ß = .10; p = .036). Higher decisional conflict about driving among older drivers is frequently shared by their SPs. Shared decisional conflict may persist beyond intervening to support decision-making about driving cessation.

Depressed, stressed, and inflamed: C-reactive protein linked with depression symptoms in midlife women with both childhood and current life stress.

To determine whether the relationship between inflammatory factors and clinically significant depression symptoms is moderated by high exposure to adverse childhood experiences and current life stressors in a longitudinal community cohort of midlife women. Methods: Participants from the Penn Ovarian Ageing Study community cohort (age at baseline: M = 45.3 [SD = 3.8]) were included in analyses if they had a blood sample measuring basal inflammatory markers during at least one visit where depression symptom severity and current stressful life events were also assessed (N = 142, average number of visits per participant = 1.75 [SD = 0.92]). Approximately annually over the course of 16 years, participants self-reported depression symptom severity using the Centre for Epidemiologic Studies Depression (CESD) Scale, provided menstrual diaries to determine menopause stage, and contributed blood samples. Residual blood samples were assayed for interleukin (IL)-6, IL 1-beta (IL-1ß), tumour necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hsCRP). Early life stress was quantified using the Adverse Childhood Experiences questionnaire (low [0-1 experience(s)] versus high [≥ 2 experiences]). Current stressful life events were assessed using a structured interview (low [0-1 events] vs. high [≥ 2 events]). Generalised estimating equation models were used to model associations with the outcome of interest-clinically significant depression symptoms (CESD ≥16)-and risk factors: inflammatory marker levels (log transformed), adverse childhood experiences group, and current life stressors group. Covariates included menopause stage, age at study baseline, body mass index, race, and smoking status. We found a significant three-way interaction between log hsCRP levels, adverse childhood experiences group, and current life stressors group on likelihood of experiencing clinically significant depression symptoms (OR: 4.33; 95% CI: 1.22, 15.46; p = 0.024) after adjusting for covariates. Solely for women with high adverse childhood experiences and with high current life stressors, higher hsCRP was associated with higher odds of having clinically significant depression symptoms (OR: 1.46; 95% CI 1.07, 1.98; p = 0.016). This three-way interaction was not significant for IL-6, IL-1ß, or TNF-α. For women in midlife with exposure to high adverse childhood experiences and multiple current life stressors, elevated levels of CRP were uniquely associated with clinically significant depression symptoms. Early life adversity and current life stressors represent identifiable individual risk factors whose negative impact may be curtailed with inventions to target inflammation in midlife women.

Structural insight into selectivity of amylin and calcitonin receptor agonists.

Amylin receptors (AMYRs), heterodimers of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins, are promising obesity targets. A hallmark of AMYR activation by Amy is the formation of a 'bypass' secondary structural motif (residues S19-P25). This study explored potential tuning of peptide selectivity through modification to residues 19-22, resulting in a selective AMYR agonist, San385, as well as nonselective dual amylin and calcitonin receptor agonists (DACRAs), with San45 being an exemplar. We determined the structure and dynamics of San385-bound AMY3R, and San45 bound to AMY3R or CTR. San45, via its conjugated lipid at position 21, was anchored at the edge of the receptor bundle, enabling a stable, alternative binding mode when bound to the CTR, in addition to the bypass mode of binding to AMY3R. Targeted lipid modification may provide a single intervention strategy for design of long-acting, nonselective, Amy-based DACRAs with potential anti-obesity effects.

Perinatal Telehealth: Meeting Patients Where They Are.

INTRODUCTION: Prior to the coronavirus disease 2019 (COVID-19) pandemic, studies of innovative telehealth perinatal care models showed similar clinical outcomes and perceived quality of care between groups receiving a combination of virtual video and in-person visits. However, these studies included primarily White, English-speaking participants, excluding those who were economically disenfranchised or did not speak English. The purpose of this qualitative study was to describe perinatal patients' and providers' experiences with telehealth during and after the acute phase of the COVID-19 pandemic to inform future utilization of telehealth to drive the delivery of high-quality, accessible, and equitable perinatal care to diverse communities. METHODS: This descriptive qualitative study included a purposive sample of 14 patients and 17 providers who received or provided perinatal care via telehealth in either a certified nurse-midwifery practice or the nurse-family partnership care model between March 2020 and April 2022. Maximum variation sampling offered a diverse population based on race, ethnicity, and rurality. Researchers conducted 2 rounds of semistructured interviews with a focus on understanding social and geographic context. RESULTS: Six themes were identified through inductive analysis: (1) unexpected advantages of telehealth, (2) patient empowerment, (3) providers' fear of adverse outcomes, (4) concern for equitable care, (5) strategies to enhance the telehealth experience, and (6) strategies to address access to perinatal telehealth. Patients appreciated the increased ease and reduced cost of accessing visits, which led to fewer missed appointments. Health care providers saw great opportunity in telehealth but expressed concerns about accessibility for patients with language barriers or limited resources. DISCUSSION: This study provides insight into priorities for continued telehealth utilization focused on providing equitable access to perinatal care. Rather than returning to practices from before the COVID-19 pandemic formed from longstanding routines and perceived limitations, providers are encouraged to capitalize on the rapid innovations in telehealth to build a more effective, equitable, and patient-centered approach to perinatal care.

Migraine headaches are associated with motor vehicle crashes and driving habits among older drivers: Prospective cohort study.

BACKGROUND: Migraine headache is common in older adults, often causing symptoms that may affect driving safety. This study examined associations of migraine with motor vehicle crashes (MVCs) and driving habits in older drivers and assessed modification of associations by medication use. METHODS: In a multi-site, prospective cohort study of active drivers aged 65-79 (53% female), we assessed prevalent migraine (i.e., ever had migraine, reported at enrollment), incident migraine (diagnosis first reported at a follow-up visit), and medications typically used for migraine prophylaxis and treatment. During 2-year follow-up, we recorded self-reported MVCs and measured driving habits using in-vehicle GPS devices. Associations of prevalent migraine with driving outcomes were estimated in multivariable mixed models. Using a matched design, associations of incident migraine with MVCs in the subsequent year were estimated with conditional logistic regression. Interactions between migraine and medications were tested in all models. RESULTS: Of 2589 drivers, 324 (12.5%) reported prevalent migraine and 34 (1.3%) incident migraine. Interactions between migraine and medications were not statistically significant in any models. Prevalent migraine was not associated with MVCs in the subsequent 2 years (adjusted OR [aOR] = 0.98; 95% CI: 0.72, 1.35), whereas incident migraine significantly increased the odds of having an MVC within 1 year (aOR = 3.27; 1.21, 8.82). Prevalent migraine was associated with small reductions in driving days and trips per month and increases in hard braking events in adjusted models. CONCLUSION: Our results suggest substantially increased likelihood of MVCs in the year after newly diagnosed migraine, indicating a potential need for driving safety interventions in these patients. We found little evidence for MVC risk or substantial changes in driving habits associated with prevalent migraine. Future research should examine timing, frequency, and severity of migraine diagnosis and symptoms, and use of medications specifically prescribed for migraine, in relation to driving outcomes.

Considerations in the assessment and management of ADHD within the TGDNB population.

AIMS: In this article we consider current literature around Attention Deficit Hyperactivity Disorder (ADHD) in the transgender, gender diverse and non-binary (TGDNB) population. METHODS: Literature review. RESULTS: N/A conclusions: We outline specific considerations pertaining to the assessment and treatment of ADHD in this group and highlight evidential gaps and avenues for future research. We conclude that TGDNB individuals should be considered a "special population" with regards to ADHD and encourage mental health practitioners to consider specific TGDNB mental health needs beyond capacity assessments and gender-affirming care.

High levels of alpha-gal with large variation in the salivary glands of lone star ticks fed on human blood.

Tick bites, associated with the secretion of tick saliva containing the xenoglycan galactose-alpha-1, 3-galactose (alpha-gal or aGal), are recognized as the causal factors of alpha-Gal syndrome (AGS; or red meat allergy) in humans. AGS occurs after the increased production of IgE antibodies against aGal, which is found in most mammalian cells, except for the Old World monkey and humans. The aGal sensitization event has been linked to an initial tick bite, followed by consumption of red meat containing the aGal glycan, which triggers the onset of the allergic response resulting in urticaria, anaphylaxis, or even death. In North America, the lone star tick, Amblyomma americanum, has been identified as the main culprit for AGS. However, only a subset of the human population exposed to lone star tick bites develops AGS. This suggests the presence of unidentified variables associated with the sensitization event. To evaluate the quantitative variations of the aGal in ticks, we evaluated the differences in aGal levels in different strains of A. americanum ticks partially fed on different blood sources using an artificial feeding system and animal hosts. We found significantly higher aGal levels in the female ticks fed on human blood than those fed on the blood of other mammals with large variations among different tick populations and individuals. We propose that host-specific genetic components in the A. americanum ticks are involved in the production of high aGal epitope in the tick saliva, which provides a part of the explanation for the variables associated with the AGS sensitization event of the tick bite.

Comparison of verbal fluency performance in Kannada-speaking adults with and without euthymic bipolar disorder type 1.

Individuals with euthymic bipolar disorder (BD) type I exhibit deficits in executive functions. Although less explored in the BD population, the tasks of verbal fluency (VF) have shown great potential in understanding semantic organization. This study provides an extensive exploration across the letter and semantic VF tasks in 27 demographically matched euthymic BD-I and healthy controls (HC). The groups were compared on measures of the total number of correct words (TNCW), temporal pattern analysis, number of clusters (NC), mean cluster size (MCS), number of switches (NS), and error pattern. An overall reduction in letter fluency scores (the TNCW, number of switches, and NC) as compared to semantic fluency scores was noted for both groups, with a significantly greater decrease in the BD-1 group. The MCS and temporal pattern were relatively similar across the two groups. The influence of education with no gender difference was observed between groups with error types prevalent in both groups. The study findings call attention toward assessing the VF performance in persons with BD in terms of error production and the strategies employed (clustering-switching).

A Permissive Amide N-Methyltransferase for Dithiolopyrrolones.

Amide N-methylation is important for the activity and permeability of bioactive compounds but can be challenging to perform selectively. The broad-spectrum antimicrobial natural products thiolutin and holomycin differ only by an N-methyl group at the endocyclic amide of thiolutin, but only thiolutin exhibits antifungal activity. The enzyme responsible for amide N--methylation in thiolutin biosynthesis has remained elusive. Here, we identified and characterized the amide N-methyltransferase DtpM that is encoded >400 kb outside of the thiolutin gene cluster. DtpM catalyzes efficient conversion of holomycin to thiolutin, exhibits broad substrate scope toward dithiolopyrrolones, and has high thermal stability. In addition, sequence similarity network analysis suggests DtpM is more closely related to phenol O-methyltransferases than some amide methyltransferases. This study expands the limited examples of amide N-methyltransferases and may facilitate chemoenzymatic synthesis of diverse dithiolopyrrolone compounds as potential therapeutics.

Family influences on oral PrEP use among adolescent girls and young women in Kenya and South Africa.

INTRODUCTION: Effective use of oral HIV pre-exposure prophylaxis (PrEP) has been lower among African adolescent girls and young women (AGYW) than among older women, young men who have sex with men, and serodiscordant heterosexual couples in the region. Efforts to build PrEP support have centered around peers and male partners, but the family may also play an important role. This qualitative study aimed to describe family influence on PrEP use among AGYW in in three African cities. METHODS: POWER (Prevention Options for Women Evaluation Research) was a PrEP demonstration project among 2550 AGYW (16-25 years old) in Johannesburg and Cape Town, South Africa and Kisumu, Kenya conducted from 2017 to 2020. In-depth interviews and focus group discussions were conducted with 136 AGYW participants to explore their PrEP views and experiences, including awareness and interest in PrEP; barriers and facilitators to uptake and use; the influence of family, peers, intimate partners, and community; and the key types of support for their PrEP use. Transcripts were coded and analysed thematically. RESULTS: The decision to initiate PrEP was associated with fear and anxiety linked to anticipated stigma from family members, and with family's lived HIV experience. Family disclosure, especially to mothers, was important to participants, as most lived with their families and considered it essential for them to obtain their mother's approval to use PrEP. Most family members, particularly mothers, provided instrumental, emotional, informational and appraisal support to participants using PrEP, including reminders, encouragement, and problem-solving. Participants reported that family members with insufficient information about PrEP safety and efficacy and who voiced concerns were a substantial barrier to their use. However, they often became supportive after receiving more PrEP information. CONCLUSION: Families, particularly mothers, can play an important role in supporting PrEP use. PrEP programmes should leverage family support to help with PrEP persistence by providing basic information to families about PrEP safety and efficacy. AGYW using PrEP should be encouraged to selectively disclose PrEP use to build support and counseled on how to disclose and address family concerns.