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Pandalid shrimp use morphological and behavioral defenses against their numerous fish and invertebrate predators. Their rapid tail-flip escape and rigid exoskeleton armor may be sensitive to changes in ocean temperature and carbon chemistry in ways that alter their efficacy and impact mortality. Here we tested the hypothesis that ocean warming and acidification conditions affect the antipredator defenses of Pandalus gurneyi. To test this hypothesis, we exposed shrimp to a combination of pH (8.0, 7.7, 7.5) and temperature (13°C, 17°C) treatments and assessed their tail-flip escape and exoskeleton armor after short-term (2 weeks) and medium-term (3 months) exposure. Results revealed complex effects on escape kinematics, with changes in different variables explained by either pH, temperature, and/or their interaction; decreased pH, for instance, primarily explains reduced acceleration while cold temperature explains increased flexion duration. Carapace mineral content (Ca and Mg) was unaffected, but warmer temperatures primarily drove enhanced mechanical properties (increased hardness and stiffness). No effects were observed in the stiffness and strength of the rostrum. Furthermore, most of the observed effects were temporary, as they occurred after short-term exposure (2 weeks), but disappeared after longer exposure (3 months). This demonstrates that P. gurneyi defenses are affected by short-term exposure to temperature and pH variations; however, they can acclimate to these conditions over time. Nonetheless, changes in the tail-flip escape kinematics may be disadvantageous when trying to flee predators and the enhanced exoskeleton armor could make them more resistant to predation during short periods of environmental change., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Background: Variations in renal veins are quite common, and most people do not experience issues due to them. However, these variations are important for healthcare professionals, especially in surgical procedures and imaging studies, as precise knowledge of vascular anatomy is essential to avoid complications during medical interventions. The purpose of this study was to expose the frequency of anatomical variations in the renal vein (RV) and detail their relationship with the retroperitoneal and renal regions. Methods: A systematic search was conducted in the Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception until January 2024. Two authors independently carried out the search, study selection, and data extraction and assessed methodological quality using a quality assurance tool for anatomical studies (AQUA). Ultimately, consolidated prevalence was estimated using a random effects model. Results: In total, 91 studies meeting the eligibility criteria were identified. This study included 91 investigations with a total of 46,664 subjects; the meta-analysis encompassed 64 studies. The overall prevalence of multiple renal veins was 5%, with a confidence interval (CI) of 4% to 5%. The prevalence of the renal vein trajectory was 5%, with a CI of 4% to 5%. The prevalence of renal vein branching was 3%, with a CI of 0% to 6%. Lastly, the prevalence of unusual renal vein origin was 2%, with a CI of 1% to 4%. Conclusions: The analysis of these variants is crucial for both surgical clinical management and the treatment of patients with renal transplant and hemodialysis.

The communicating safely policy, publicised by the catchphrase See Something, Say Something was released by the Medical Radiation Practice Board of Australia in 2019. It was developed to support medical radiation practitioners (MRPs) upholding the obligation to communicate urgent or unexpected findings in a timely manner, when identified on medical images. Prior to this policy being part of the professional capabilities, several untimely deaths occurred-the majority of whose causal factors could have been mitigated if imaging findings were urgently communicated by MRPs. This commentary summarises three coronial inquests that involved MRPs, discusses how these coronial findings are reflected in the communicating safely policy and provides some recommendations for the profession to ensure this policy is enacted in clinical practice., (© 2024 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Novel H1N2 and H3N2 swine influenza A viruses (IAVs) have recently been identified in Chile. The objective of this study was to evaluate their zoonotic potential. We perform phylogenetic analyses to determine the genetic origin and evolution of these viruses, and a serological analysis to determine the level of cross-protective antibodies in the human population. Eight genotypes were identified, all with pandemic H1N1 2009-like internal genes. H1N1 and H1N2 were the subtypes more commonly detected. Swine H1N2 and H3N2 IAVs had hemagglutinin and neuraminidase lineages genetically divergent from IAVs reported worldwide, including human vaccine strains. These genes originated from human seasonal viruses were introduced into the swine population since the mid-1980s. Serological data indicate that the general population is susceptible to the H3N2 virus and that elderly and young children also lack protective antibodies against the H1N2 strains, suggesting that these viruses could be potential zoonotic threats. Continuous IAV surveillance and monitoring of the swine and human populations is strongly recommended.IMPORTANCEIn the global context, where swine serve as crucial intermediate hosts for influenza A viruses (IAVs), this study addresses the pressing concern of the zoonotic potential of novel reassortant strains. Conducted on a large scale in Chile, it presents a comprehensive account of swine influenza A virus diversity, covering 93.8% of the country's industrialized swine farms. The findings reveal eight distinct swine IAV genotypes, all carrying a complete internal gene cassette of pandemic H1N1 2009 origin, emphasizing potential increased replication and transmission fitness. Genetic divergence of H1N2 and H3N2 IAVs from globally reported strains raises alarms, with evidence suggesting introductions from human seasonal viruses since the mid-1980s. A detailed serological analysis underscores the zoonotic threat, indicating susceptibility in the general population to swine H3N2 and a lack of protective antibodies in vulnerable demographics. These data highlight the importance of continuous surveillance, providing crucial insights for global health organizations., Competing Interests: The authors declare no conflict of interest.

Introduction: Androgen deprivation therapy (ADT) is a mainstay treatment for prostate cancer, but many patients experience cognitive impairment in domains mediated by the medial prefrontal cortex (mPFC) and hippocampus. Prostate cancer typically occurs in older patients (>65 years). As age is often accompanied by cognitive decline, it may impact the efficacy of any treatment aimed at restoring cognitive impairment induced by ADT. Vortioxetine, a multimodal antidepressant that improves cognition in depression, has been shown to be efficacious in elderly patients. Therefore, vortioxetine may improve cognition in older patients who experience cognitive decline after ADT., Methods: Young (3 months) and middle-aged (13 months) rats were used to investigate the influence of age on treating ADT-induced cognitive decline. As our previous studies used surgical castration, we tested if vortioxetine would reverse cognitive deficits associated with more translationally relevant chemical castration using degarelix. Vortioxetine was given in the diet for 21 days. Animals underwent behavioral testing to assess visuospatial memory mediated by the hippocampus and cognitive flexibility mediated by the mPFC. We also investigated changes in afferent-evoked responses in these regions in middle-aged rats., Results: Degarelix induced impairments in both visuospatial memory and cognitive flexibility that were reversed by vortioxetine. Vortioxetine also rescued afferent-evoked responses in the mPFC and hippocampus. However, modest age-related reductions in baseline visuospatial memory limited our ability to detect further decreases induced by degarelix in middle-aged rats due to a floor effect., Conclusion: These results suggest that vortioxetine may be a treatment option for older prostate cancer patients who experience cognitive decline after ADT., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria., Methods: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment., Findings: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance., Interpretation: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy., Funding: European Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Women who are pregnant and living with HIV have traditionally been excluded from clinical trials regarding new pharmacotherapy. Immediate initiation of antiretroviral therapy (ART) is recommended for women who are pregnant and living with HIV. Integrase inhibitors (INSTIs) are first-line recommended agents as they lead to more rapid HIV viral load reduction. We conducted a retrospective study of women who are pregnant and living with HIV who received prenatal care at the University of Washington. Mothers were categorized by ART class: INSTI, protease inhibitors (PI), and non-nucleoside reverse transcriptase inhibitors (NNRTI). Chi-square and t-tests were used for the analysis of baseline characteristics, and generalized estimating equations were used to adjust for HIV viral suppression between groups. There were a total of 234 mother-infant pairs whose pregnancies progressed beyond 20 weeks. The study demonstrated that women on INSTI regimens were more likely to have a shorter time to viral load suppression than women on NNRTI regimens. Additionally, seven congenital anomalies were identified in this cohort, none of which were neural tube defects. There was no perinatal transmission of HIV to any of the infants. This small cohort of women provides high-quality data regarding the safety and efficacy of INSTI use for both mothers and infants in resource-rich settings., Competing Interests: The authors have no conflicts of interest to declare. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication.

Objective: To determine bacterial vaginosis (BV) status at multiple time points among adolescent girls and young women (AGYW) and assess the impact of pregnancy on their BV status., Design: Longitudinal cohort study., Setting: Thika, Kenya., Participants: AGYW aged 16-20 years enrolled prior to first sex or reporting only a single lifetime partner., Main Outcome Measures: The primary outcome was relative risk (RR) of BV during pregnancy compared with before pregnancy by analysing longitudinal trends in BV over time. BV risk was estimated using Poisson regression models., Results: A total of 121 AGYW became pregnant in the parent cohort and had BV results before, during or after pregnancy. Point prevalence of BV was 11.0% at visits >12 months pre-pregnancy, 13.0% at 3-12 months pre-pregnancy, 22.1% at <3 months pre-pregnancy and 13.4% during pregnancy. Compared with visits during pregnancy, RR of BV was 1.65 (95% CI: 1.00 to 2.71; p=0.05) at visits <3 months pre-pregnancy, 0.97 (95% CI: 0.62 to 1.52; p=0.90) at visits 3-12 months pre-pregnancy and 0.82 (95% CI: 0.44 to 1.53; p=0.53) at visits 12 months pre-pregnancy. An adjusted analysis including age, income, residence, date of first sex, recent sexual activity and positive sexually transmitted infection test resulted in small changes in risk estimates, with adjusted RR of BV of 1.66 (95% CI: 1.04 to 2.67; p=0.04) at visits <3 months pre-pregnancy compared with visits during pregnancy., Conclusions: BV risk during pregnancy was lower than during the immediate pre-pregnancy period. Hormonal changes in pregnancy may reduce BV., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Brain-derived neurotrophic factor (BDNF) stimulates dendrite outgrowth and synaptic plasticity by activating downstream protein kinase A (PKA) signaling. Recently, BDNF has been shown to modulate mitochondrial respiration in isolated brain mitochondria, suggesting that BDNF can modulate mitochondrial physiology. However, the molecular mechanisms by which BDNF stimulates mitochondrial function in neurons remain to be elucidated. In this study, we surmised that BDNF binds to the TrkB receptor and translocates to mitochondria to govern mitochondrial physiology in a PKA-dependent manner. Confocal microscopy and biochemical subcellular fractionation assays confirm the localization of the TrkB receptor in mitochondria. The translocation of the TrkB receptor to mitochondria was significantly enhanced upon treating primary cortical neurons with exogenous BDNF, leading to rapid PKA activation. Showing a direct role of BDNF in regulating mitochondrial structure/function, time-lapse confocal microscopy in primary cortical neurons showed that exogenous BDNF enhances mitochondrial fusion, anterograde mitochondrial trafficking, and mitochondrial content within dendrites, which led to increased basal and ATP-linked mitochondrial respiration and glycolysis as assessed by an XF24e metabolic analyzer. BDNF-mediated regulation of mitochondrial structure/function requires PKA activity as treating primary cortical neurons with a pharmacological inhibitor of PKA or transiently expressing constructs that target an inhibitor peptide of PKA (PKI) to the mitochondrion abrogated BDNF-mediated mitochondrial fusion and trafficking. Mechanistically, western/Phos-tag blots show that BDNF stimulates PKA-mediated phosphorylation of Drp1 and Miro-2 to promote mitochondrial fusion and elevate mitochondrial content in dendrites, respectively. Effects of BDNF on mitochondrial function were associated with increased resistance of neurons to oxidative stress and dendrite retraction induced by rotenone. Overall, this study revealed new mechanisms of BDNF-mediated neuroprotection, which entails enhancing mitochondrial health and function of neurons., (© 2023 International Society for Neurochemistry.)

Background: Bacterial vaginosis is a risk factor for sexually transmitted infections, including HIV. Adult African women have a high prevalence of bacterial vaginosis, but it is not known when first bacterial vaginosis occurs., Objective: This study aimed to describe bacterial vaginosis in younger African women, before and after first sex, and to determine the incidence of bacterial vaginosis and significant correlates of bacterial vaginosis incidence and recurrence., Study Design: In a prospective observational cohort study enrolling adolescents with limited sexual experience, young women aged 16 to 21 years were recruited in Thika, Kenya. Eligible participants were HIV and herpes simplex virus 2 seronegative and reported 0 or 1 lifetime sexual partner. The Nugent score was determined at quarterly visits from vaginal Gram stains. The trends in bacterial vaginosis were described over time; hazard ratios were calculated using Cox regression, and relative risk of bacterial vaginosis was estimated using generalized estimating equations and Poisson regression., Results: A total of 400 participants with a median age of 18.6 years (interquartile range, 16-21) were enrolled. Of note, 322 participants (80.5%) reported no history of sex, whereas 78 participants (19.5%) reported sex with 1 partner. At enrollment, bacterial vaginosis (Nugent score of ≥7) was uncommon (21/375 [5.6%]). Overall, 144 participants had bacterial vaginosis at least once, for an incidence rate of 16.5 cases per 100 person-years. Before first sex, bacterial vaginosis was present at 2.8% of visits, compared with 13.7% of visits after first sex. An adjusted model of bacterial vaginosis incidence observed that first sex was associated with more than a 2-fold increased bacterial vaginosis risk (adjusted hazard ratio, 2.44; 95% confidence interval, 1.25-4.76; P=.009). Chlamydia diagnosis (adjusted hazard ratio, 1.73; 95% confidence interval, 1.1-2.8; P=.02), and herpes simplex virus 2 seropositivity (adjusted hazard ratio, 2.88; 95% confidence interval, 1.17-7.09; P=.021) were both associated with incident bacterial vaginosis. A multivariate generalized estimating equation model, including all episodes of bacterial vaginosis, demonstrated risk factors, including first sex, sexually transmitted infections, urban residence, recent sex, and no income; the most important risk factor was first sex (adjusted relative risk, 1.92; 95% confidence interval, 1.12-3.31; P=.018). The probability of bacterial vaginosis increased with each subsequent episode; mean Nugent scores increased after each bacterial vaginosis episode., Conclusion: Using detailed longitudinal observation, this study found that Kenyan adolescents have almost no bacterial vaginosis before first sex and that initiation of sexual activity was the strongest risk factor for both prevalent bacterial vaginosis and incident bacterial vaginosis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

For women living with HIV (WLH) in serodiscordant partnerships, decisions about childbearing can challenge condom use and antiretroviral adherence. In a prospective cohort of 148 WLH in serodiscordant partnerships, 58 (39%) wanted more children in the future but were not currently trying to conceive (fertility desire), and 32 (22%) were currently trying to become pregnant (fertility intent). Detection of prostate specific antigen (PSA) in vaginal secretions, a marker for recent condomless sex, was lowest in women with fertility desire and highest in women with fertility intent. Detectable viral load followed a similar pattern. Risk of HIV transmission, when condomless sex and PSA detection occurred concurrently, was three to fourfold higher at visits with fertility intent compared to visits with fertility desire. Qualitative interviews underscored the importance women place on childbearing and suggested that they had limited information about the role of antiretroviral therapy in reducing sexual HIV transmission., (© 2023. The Author(s).)

Background: Early antiretroviral therapy (ART) during infancy reduces cognitive impairment due to HIV, but the extent of benefit is unclear., Setting: Children were recruited from hospital and health centers providing HIV care and treatment in Nairobi, Kenya., Methods: Cognitive, behavioral, and motor outcomes were assessed in children with HIV and early ART (<1 year), children with HIV and late ART (1.5-6 years), and children HIV-unexposed uninfected (CHUU). Domain z scores and odds neurobehavioral impairment (≤15th percentile in CHUU) were compared in adjusted analyses., Results: Children with HIV initiated ART at median ages 0.4 (early ART) and 3.5 years (late ART). Children were assessed at median ages 6.9 (CHUU, N = 61), 6.9 (early ART, N = 54), and 13.5 (late ART; N = 27) years. Children with late ART vs. children with early ART had significantly lower z scores in 7 domains, specifically global cognition, short-term memory, visuospatial processing, learning, nonverbal test performance, executive function, and motor skills (adjusted mean differences, -0.42 to -0.62, P values ≤ 0.05), and had higher odds impairment in 7 domains (adjusted odds ratios [aORs], 2.87 to 16.22, P values ≤ 0.05). Children with early ART vs. CHUU had lower z scores in 5 domains (global cognition, short-term memory, delayed memory, processing speed, and behavioral regulation [adjusted mean differences, -0.32 to -0.88, P values < 0.05]) and higher impairment for 2 domains (short-term memory [aOR, 3.88] and behavioral regulation [aOR 3.46], P values < 0.05). Children with late ART vs. CHUU had lower z scores in 8 domains (adjusted mean differences, -0.57 to -1.05, P values ≤ 0.05), and higher impairment in 7 domains (aORs 1.98 to 2.32, P values ≤ 0.05)., Conclusion: Early ART in the first year of life attenuates but does not eliminate the neurodevelopmental compromise of HIV., Competing Interests: All authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Youth living with HIV (YLHIV) report that negative interactions with health care workers (HCWs) affects willingness to return to care. This stepped wedge randomized trial evaluated effectiveness of a standardized patient actor (SP) HCW training intervention on adolescent engagement in care in Kenya. HCWs caring for YLHIV at 24 clinics received training on adolescent care, values clarification, communication, and motivational interviewing, with 7 SP encounters followed by facilitated feedback of videotaped interactions. Facilities were randomized to timing of the intervention. The primary outcome was defined as return within 3 months after first visit (engagement) among YLHIV who were either newly enrolled or who returned to care after >3 months out of care. Visit data was abstracted from electronic medical records. Generalized linear mixed models adjusted for time, being newly enrolled, and clustering by facility. YLHIV were surveyed regarding satisfaction with care. Overall, 139 HCWs were trained, and medical records were abstracted for 4,595 YLHIV. Median YLHIV age was 21 (IQR 19-23); 82% were female, 77% were newly enrolled in care, and 75% returned within 3 months. Half (54%) of trained HCWs remained at their clinics 9 months post-training. YLHIV engagement improved over time (global Wald test, p = 0.10). In adjusted models, the intervention showed no significant effect on engagement [adjusted Prevalence Ratio (aPR) = 0.95, 95% Confidence Interval (CI): 0.88-1.02]. Newly enrolled YLHIV had significantly higher engagement than those with prior lapses in care (aPR = 1.18, 95%CI: 1.05-1.33). Continuous satisfaction with care scores were significantly higher by wave 3 compared to baseline (coefficient = 0.38, 95%CI: 0.19-0.58). Despite provider skill improvement, there was no effect of SP training on YLHIV engagement in care. This may be due to temporal improvements or turnover of trained HCWs. Strategies to retain SP-training benefits need to address HCW turnover. YLHIV with prior gaps in care may need more intensive support. Registration CT #: NCT02928900. https://clinicaltrials.gov/ct2/show/NCT02928900., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kohler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Adolescent girls and young women (AGYW) are disproportionately affected by STIs. Observation of life course events can describe behavioral and biological factors associated with STI risk., Methods: Sexually inexperienced AGYW aged 16-20 years in Kenya were followed for five years. Quarterly visits assessed for C. trachomatis (CT), N. gonorrhea (GC), and T. vaginalis (TV), bacterial vaginosis (BV), HSV-2, and HIV. Sexual activity was self-reported but amended if incongruent with results from STI, pregnancy, or any other testing. Cox regression and Generalized Estimating Equation models were used to determine hazard ratios (HRs) and relative risks (RRs) of STI., Results: During follow-up, 293 of 400 participants reported sex, 163 AGYW experienced an STI, and 72 participants had multiple STIs. Among 163 participants that experienced an STI, there were a total of 259 visits where STIs were detected, 78% (n = 201) of which included CT. Cox regression found participants with BV had over two-fold higher risk of first STI acquisition (adjusted hazard ratio (aHR): 2.35; 95% confidence interval (CI) 1.43-3.88; p = .001). Increased risk for first STI episode was associated with a new partner (aHR: 3.16; 95% CI 1.59-6.28; p = .001). AGYW who did not disclose sexual activity had the highest risk (aHR: 3.60; 95% CI 1.93-6.70; p < .001). Condom use was low, with 21% reporting condom use with sex. GEE analysis of all STIs including incident, prevalent, and recurrent, confirmed these risk factors., Discussion: During the critical years after first sex, AGYW with BV, new sexual partners, and those who did not disclose sexual activity were at highest risk for STI events, especially CT., (Copyright © 2022 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aims to investigate the diagnostic performances of Australian and Shanghai-based Chinese radiologists in reading full-field digital mammogram (FFDM) and digital breast tomosynthesis (DBT) with different levels of breast density., Approach: Eighty-two Australian radiologists interpreted a 60-case FFDM set, and 29 radiologists also reported a 35-case DBT set. Sixty Shanghai radiologists read the same FFDM set, and 32 radiologists read the DBT set. The diagnostic performances of Australian and Shanghai radiologists were assessed using truth data (cancer cases were biopsy proven) and compared overall in specificity, case sensitivity, lesion sensitivity, receiver operating characteristics (ROC) area under the curve, and jack-knife free-response receiver operating characteristics (JAFROC) figure of merit, and they were stratified by case characteristics using the Mann-Whitney U test. The Spearman rank test was used to explore the association between radiologists' performances and their work experience in mammogram interpretation., Results: There were significantly higher performances of Australian radiologists compared with Shanghai radiologists in low breast density for case sensitivity, lesion sensitivity, ROC, and JAFROC in the FFDM set ( P < 0.0001 ); in high breast density, Shanghai radiologists' performances in lesion sensitivity and JAFROC were also lower than Australian radiologists ( P < 0.0001 ). In the DBT test set, Australian radiologists performed better than Shanghai radiologists in cancer detection in both low and high breast density. The work experience of Australian radiologists was positively linked to their diagnostic performances, whereas this association was not statistically significant in Shanghai radiologists., Conclusion: There were significant variations in reading performances between Australian and Shanghai radiologists in FFDM and DBT across different levels of breast density, lesion types, and lesion sizes. An effective training initiative tailored to suit local readers is essential to enhancing the diagnostic accuracy of Shanghai radiologists., (© 2023 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Background: Adolescent girls and young women (AGYW) are at high risk of sexually transmitted infections (STIs). It is unknown whether beginning to have sexual intercourse results in changes to immune mediators in the cervicovaginal tract that contribute to this risk., Methods: We collected cervicovaginal lavages from Kenyan AGYW in the months before and after first penile-vaginal sexual intercourse and measured the concentrations of 20 immune mediators. We compared concentrations pre- and post-first sex using mixed effect models. We additionally performed a systematic review to identify similar studies and combined them with our results by meta-analysis of individual participant data., Results: We included 180 samples from 95 AGYW, with 44% providing only pre-first sex samples, 35% matched pre and post, and 21% only post. We consistently detected 19/20 immune mediators, all of which increased post-first sex (p<0.05 for 13/19; Holm-Bonferroni-adjusted p<0.05 for IL-1β, IL-2, and CXCL8). Effects remained similar after excluding samples with STIs and high Nugent scores. Concentrations increased cumulatively over time after date of first sex, with an estimated doubling time of about 5 months.Our systematic review identified two eligible studies, one of 93 Belgian participants, and the other of 18 American participants. Nine immune mediators were measured in at least two-thirds of studies. Meta-analysis confirmed higher levels post-first sex for 8/9 immune mediators (p<0.05 for six mediators, most prominently IL-1α, IL-1β, and CXCL8)., Conclusions: Cervicovaginal immune mediator concentrations were higher in women who reported that they started sexual activity. Results were consistent across three studies conducted on three different continents., Funding: This research was funded by R01 HD091996-01 (ACR), by P01 AI 030731-25 (Project 1) (AW), R01 AI116292 (FH), R03 AI154366 (FH) and by the Center for AIDS Research (CFAR) of the University of Washington/Fred Hutchinson Cancer Research Center AI027757., Competing Interests: SH, CL, FC, KM, SS, KT, BC, LO, CK, AW, MG, LH, FH, AR No competing interests declared, KN Kenneth Ngure was supported by the International AIDS Society to attend AIDS 2022. The author has no other competing interests to declare, NM Nelly R Mugo received honoraria from MERCK Ltd in support of a presentation on HPV vaccination uptake in LMIC. The author has no other competing interests to declare, (© 2022, Hughes et al.)

Background: Nutrient supplements are widely used for type 2 diabetes (T2D), yet evidence-based guidance for clinicians is lacking. Methods: We searched the four electronic databases from November 2015−December 2021. The most recent, most comprehensive, high-ranked systematic reviews, meta-analyses, and/or umbrella reviews of randomised controlled trials in adults with T2D were included. Data were extracted on study characteristics, aggregate outcome measures per group (glycaemic control, measures of insulin sensitivity and secretion), adverse events, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessments. Quality was assessed using A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2). Results: Twelve meta-analyses and one umbrella review were included. There was very low certainty evidence that chromium, Vitamin C, and omega-3 polyunsaturated fatty acids (Ω-3 PUFAs) were superior to placebo for the primary outcome of glycated hemoglobin (HbA1c) (Mean Difference/MD −0.54, −0.54 and ES −0.27, respectively). Probiotics were superior to placebo for HbA1c (Weighted Mean Difference/WMD −0.43%). There was very low certainty evidence that Vitamin D was superior to placebo for lowering HbA1c in trials of <6 months (MD −0.17%). Magnesium, zinc, Vitamin C, probiotics, and polyphenols were superior to placebo for FBG. Vitamin D was superior to placebo for insulin resistance. Data on safety was limited. Conclusions: Future research should identify who may benefit from nutrient supplementation, safety, and optimal regimens and formulations.

Background: Perinatal HIV and antiretroviral therapy exposure may influence neurocognitive outcomes, although evidence is mixed and most studies are limited to outcomes in the first 24 months. We compared neurocognitive outcomes in school-aged children who were HIV exposed uninfected (CHEU) with those in children who were HIV unexposed uninfected (CHUU)., Setting: Children were recruited from a health center in Nairobi, Kenya., Methods: Key inclusion criteria were children aged 5-12 years and confirmed child and maternal HIV status; for CHEU, mothers reported knowing HIV-positive status before or at delivery of the index child. Children underwent a detailed battery of neuropsychological tests and behavioral assessment, and comparisons of scores between CHEU and CHUU were conducted using linear regression., Results: Among 56 CHEU and 65 CHUU, the median age and sex distributions were 6.8 and 7.0 years (P = 0.8) and 48% and 60% girls (P = 0.2), respectively. In analyses adjusted for child's age and sex and caregiver's age, education, and household rent, CHEU had significantly lower mean z scores for global cognitive ability than CHUU [-0.35, 95% confidence interval (CI): -0.64 to -0.05; P = 0.02], short-term memory (-0.44, 95% CI: -0.76 to -0.12; P = 0.008), delayed memory (-0.43, 95% CI: -0.79 to -0.08; P = 0.02), attention (-0.41, 95% CI: -0.78 to -0.05; P = 0.03), and processing speed (-0.76, 95% CI: -1.37 to -0.16; P = 0.01). Models adjusted for child nutritional status, household food security, and orphanhood yielded similar results., Conclusions: Children exposed to HIV had poorer long-term neurocognitive outcomes than CHUU. These data suggest that long-term studies of neurocognitive and educational attainment in CHEU are warranted., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Breast cancer incidence is rapidly increasing throughout South East Asia, highlighting the need for high-quality early diagnosis and treatment. This study aims to investigate the efficacy of mammography detection in Hanoi and Ho Chi Minh City (HCMC), Vietnam, using data from Australian radiologists as a benchmark; factors that influence performance will be highlighted., Methods: A total of 53, 35 and 52 clinicians from Australia, HCMC and Hanoi, respectively, examined and diagnosed a test set of 60 mammograms, 20 of which contained cancers. Each clinician completed an accompanying questionnaire establishing demographic and experiential characteristics. The performance metrics of specificity, sensitivity, area under the receiver operating characteristic curve (AUC), location sensitivity and Jackknife free-response ROC (JAFROC) figure of merit were used to evaluate clinicians performance. Mann-Whitney and Kruskal-Wallis statistical methods were employed to establish significance., Results: Vietnamese radiologists demonstrated significantly lower sensitivity, AUC, lesion sensitivity and JAFROC scores compared to Australian radiologists. There was no difference in performance between clinicians from Hanoi and HCMC. However, certain performance features (older and more experienced clinicians compared with their younger, less experienced counterparts, readers who read more compared with fewer mammograms per week, clinicians with greater radiological experience and clinicians that completed a fellowship) demonstrated significantly better performances., Conclusions: The significant difference in diagnostic efficacy of mammograms between Vietnam and Australia identifies the need for improvements in breast radiology training, management and practice. Cost-effective solutions are available that can improve the reading efficacy of clinicians, and consequently health outcomes for Vietnamese women., (© 2020 John Wiley & Sons Australia, Ltd.)

Competing Interests: Competing interests: None declared.

Background: The vaginal microbiome plays a key role in women's reproductive health. Use of exogenous hormones, such as intramuscular depot medroxyprogesterone acetate (DMPA-IM), may alter the composition of vaginal bacterial community., Methods: Vaginal swab samples were collected from postpartum Kenyan women initiating DMPA-IM or nonhormonal contraception (non-HC). Bacterial vaginosis was assessed by Nugent score (Nugent-BV) and bacterial community composition was evaluated using broad-range 16S ribosomal RNA gene polymerase chain reaction with high-throughput sequencing. Changes in Nugent score, alpha diversity (Shannon diversity index), and total bacterial load between contraceptive groups from enrollment to 3 months after initiation were estimated using multivariable linear mixed effects regression., Results: Among 54 human immunodeficiency virus-negative women, 33 choosing DMPA-IM and 21 choosing non-HC, Nugent-BV was more common among DMPA-IM users at enrollment. At follow-up, Nugent score had decreased significantly among DMPA-IM users (change, -1.89; 95% confidence interval [CI], -3.53 to -.25; P = .02) while alpha diversity remained stable (0.03; -.24 to .30; P = .83). Conversely, Nugent score remained relatively stable among non-HC users (change, -0.73; 95% CI, -2.18 to .73; P = .33) while alpha diversity decreased (-0.34; -.67 to -.001; P = .05). The total bacterial load decreased slightly in DMPA-IM users and increased slightly among non-HC users, resulting in a significant difference in change between the contraceptive groups (difference, -0.64 log10 gene copies per swab sample; 95% CI, -1.19 to -.08; P = .02). While significant changes in Nugent score and alpha diversity were observed within contraceptive groups, changes between groups were not significantly different., Conclusions: Postpartum vaginal bacterial diversity did not change in DMPA-IM users despite a reduction in Nugent-BV, but it decreased significantly among women using non-HC. Choice of contraception may influence Lactobacillus recovery in postpartum women., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Identifying determinants of human immunodeficiency virus (HIV) reservoir levels may inform novel viral eradication strategies. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) coinfections were assessed as predictors of HIV proviral DNA level in 26 HIV RNA-suppressed Kenyan children starting antiretroviral therapy before 7 months of age. Earlier acquisition of CMV and EBV and higher cumulative burden of systemic EBV DNA viremia were each associated with higher HIV DNA level in the reservoir after 24 months of antiretroviral therapy, independent of HIV RNA levels over time. These data suggest that delaying or containing CMV and EBV viremia may be novel strategies to limit HIV reservoir formation., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

High traffic volume is one of the main contributors to wildlife-vehicle collision (WVC) and wildlife mortality on roads. Government shelter-in-place (SIP) orders have been used to help mitigate the spread of COVID-19, resulting in unprecedented reductions in global traffic volumes. Using traffic and collision data from four US states (California, Idaho, Maine, and Washington), we investigated changes in total WVC, following the state and local SIP orders. From mid-March to mid-April 2020, these orders have resulted in up to 71%, 63%, 73%, and 72% reduction in driving, as measured by vehicle miles traveled (VMT), in CA, ID, ME, and WA respectively. The daily WVC rates from the 4 weeks prior to SIP orders going into effect, to the 4 weeks after, declined 34%, with 21, 36, 44, and 33% declines for CA, ID, ME, and WA, respectively. For mountain lions ( Puma concolor) in CA, there was a 58% decline in mortality during the traffic reduction. The changes in WVC from 1 month pre-SIP orders to 1 month post-order only occurred in 2020 and not 2015, 2016, 2017, 2018, or 2019, suggesting that the reductions were associated with the reductions in traffic. The measured declines in WVC reversed in ME and WA during May, June and July 2020, paralleling reversals in traffic volumes. A 34% reduction in WVC would potentially equate to 10s of millions fewer vertebrates killed on US roadways during one month of traffic reduction, representing an unintentional conservation action unprecedented in modern times., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier Ltd. All rights reserved.)

Background: Long-acting injectable (LAI) antiretroviral therapy (ART) may offer persons living with HIV (PLWH) an attractive alternative to pill-based treatment options, yet acceptability data remain scant, especially in sub-Saharan Africa., Methods: We conducted 6 focus group discussions with PLWH, including key stake holder groups, and analyzed data with content analysis., Results: Initial reactions to the idea of LAI-ART were often positive. The primary advantages voiced were potential to facilitate improved adherence and alleviate the burden of daily pill-taking while avoiding inadvertent disclosure and HIV stigma. Potential side effects were a particular concern of the women. Most participants preferred clinic-based administration over self-injections at home due to concerns about safety, privacy, and potential need for refrigeration., Conclusions: LAI-ART may be acceptable in Kenya, provided injections are infrequent and delivered in a clinic setting. However, HIV stigma, fear of potential side effects, and limited clinical capacity would need to be addressed.

Aim: To examine the impact of the time of day on radiologists' mammography reading performance., Materials and Methods: Retrospective mammographic reading assessment data were collected from the BreastScreen Reader Assessment Strategy database and included timestamps of the readings and reader-specific demographic data of 197 radiologists. The radiologists performed the readings in a workshop setting with test case sets enriched with malignancies (one-third of cases were malignant). The collected data were evaluated with an analysis of covariance to determine whether time of day influenced radiologists' specificity, lesion sensitivity or the jackknife alternative free-response receiver operating characteristic (JAFROC)., Results: After adjusting for radiologist experience and fellowship, specificity varied significantly by time of day (p=0.027), but there was no evidence of any significant impact on lesion sensitivity (p=0.441) or JAFROC (p=0.120). The collected data demonstrated that specificity during the late morning (10.00-12.00) was 71.7%; this was significantly lower than in the early morning (08.00-10.00) and mid-afternoon (14.00-16.00), which were 82.74% (p=0.003) and 81.39% (p=0.031), respectively. Specificity during the late afternoon (16.00-18.00) was 73.95%; this was significantly lower than in the early morning (08.00-10.00) and mid-afternoon (14.00-16.00), which were 82.74% (p=0.003) and 81.39% (p=0.031), respectively., Conclusion: The results indicated that the time of day may influence radiologists' performance, specifically their ability to identify normal images correctly., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

With long-acting injectable antiretroviral therapy likely to be a treatment option for people living with HIV (PLWH), it is critical to assess its acceptability among potential end-users. Based on formative qualitative work and our own ongoing development of targeted long-acting products in nanosuspension formulations, we created eight hypothetical medication scenarios varying along six dichotomous attributes: administration location (home versus [vs.] clinic), dosing frequency (every 2 weeks vs. 1 week), injections per dose (one vs. two), injection pain (mild vs. moderate), injection site reaction (mild vs. moderate), and effectiveness (better vs. same as pills). PLWH from three outpatient care clinics in Seattle, WA and Riverside, CA rated acceptability (i.e., willingness to try each hypothetical medication) from 0 (very unlikely) to 100 (very likely). In conjoint analyses, we examined level and correlates of acceptability, the impact of each attribute on overall acceptability, and moderators of this effect. Participants (median age 52 years; 71% male, 34% White, 36% Black/African American, 20% Hispanic) rated acceptability of the 8 scenarios from 47.8 (standard deviation [SD] = 37.0) to 68.8 (SD = 34.1), with effectiveness (impact score = 7.3, SD = 18.7, p = 0.005) and dosing frequency (impact score = 5.7, SD = 19.6, p = 0.034) the only attributes with a significant impact on acceptability. There were no statistically significant differences in overall acceptability according to any participant socio-demographic or other characteristic; however, gender, education, employment status, and experience with and hatred/avoidance of injections moderated some effects. Overall acceptability for targeted long-acting antiretroviral treatment as proposed was modest, with superior effectiveness and lower dosing frequency most impactful on acceptability. Future acceptability research should continue to evaluate specific products in development with a full range of conjoint analytic and other techniques.

Background: The ECHO trial has relieved apprehension about intramuscular depot medroxyprogesterone acetate (DMPA-IM), however it is still important to understand how DMPA-IM affects the vaginal environment. We sought to describe how DMPA-IM initiation influences vaginal bacteria associated with HIV acquisition in postpartum women., Methods: Vaginal swabs were collected for Nugent score determination and taxon-specific quantitative PCR of eight bacteria. Enrollment occurred at contraceptive initiation (DMPA-IM or non-hormonal contraception (non-HC)) and repeat vaginal swabs were collected after three months. Generalized estimating equations were used to estimate changes in Nugent score, total bacterial load, and taxa concentrations among contraceptive groups., Results: Women who chose DMPA-IM (n = 33) were more likely to be married (97%vs.67%) and have resumed intercourse since delivery (52%vs.29%) compared to women who chose non-HC (n = 21). After three months, significant decreases in the concentrations of Sneathia species, Mycoplasma hominis, and Parvimonas species Type 1 were seen among non-HC users, however concentrations remained stable among DMPA-IM users; contraceptive method was associated with significantly different changes in M. hominis concentration between groups (p = 0.010)., Conclusions: Our findings suggest that postpartum use of DMPA-IM and non-HC may have differential impacts on the vaginal concentrations of some bacteria that have previously been associated with HIV acquisition., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: David N. Fredricks has a financial relationship with BD for licensure of molecular diagnosis of BV. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Accurate interpretation of radiological images involves a complex visual search that relies on several cognitive processes, including selective attention, working memory, and decision-making. Patient outcomes often depend on the accuracy of image interpretations, and yet research has revealed that conclusions vary significantly from one radiologist to another. A myriad of factors has been shown to contribute to the likelihood of interpretative errors and discrepancies, including the radiologist's level of experience and fatigue, and these factors are well reported elsewhere; however, a potentially important factor that has been given little previous consideration is how radiologists' interpretations might be impacted by the time of day at which the reading takes place, a factor that other disciplines have shown to be a determinant of competency. The available literature shows that while the time of day is known to significantly impact some cognitive functions that likely relate to reading competence, including selective visual attention and visual working memory, little is known about the impact of the time of day on radiology interpretation performance. This review explores the evidence regarding the relationship between time of day and performance, with a particular emphasis on radiological activities., (Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Breast Screen Reader Assessment Strategy (BREAST) is an innovative training and research program for radiologists in Australia and New Zealand. The aim of this study is to evaluate the efficacy of BREAST test sets in improving readers' performance in detecting cancers on mammograms., Materials and Methods: Between 2011 and 2018, 50 radiologists (40 fellows, 10 registrars) completed three BREAST test sets and 17 radiologists completed four test sets. Each test set contained 20 biopsy-proven cancer and 40 normal cases. Immediate image-based feedback was available to readers after they completed each test set which allowed the comparison of their selections with the truth. Case specificity, case sensitivity, lesion sensitivity, the Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) and Jackknife Free-Response Receiver Operating Characteristic (JAFROC) Figure of Merit (FOM) were calculated for each reader. Kruskal-Wallis test was utilized to compare scores of the radiologist and registrars across all test-sets whilst Wilcoxon signed rank test was to compare the scores between pairs of test sets., Results: Significant improvements in lesion sensitivity ranging from 21% to 31% were found in radiologists completing later test sets compared to first test set (p ≤ 0.01). Eighty three percent of radiologists achieved higher performance in lesion sensitivity after they completed the first read. Registrars had significantly better scores in the third test set compared to the first set with mean increases of 79% in lesion sensitivity (p = 0.005) and 37% in JAFROC (p = 0.02). Sixty percent and 100% of registrars increased their scores in lesion sensitivity in the second and third reads compared to the first read while the percentage of registrars with higher scores in JAFROC was 80%., Conclusion: Introduction of BREAST into national training programs appears to have an important impact in promoting diagnostic efficacy amongst radiologists and radiology registrars undergoing mammographic readings., (Copyright © 2019. Published by Elsevier Inc.)