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BackgroundDrugs taken during pregnancy can affect maternal and child health outcomes, but few studies have compared the safety and virological efficacy of different antiretroviral therapy (ART) regimens. We report the primary safety outcomes from enrolment up to 50 weeks post partum and a secondary virological efficacy outcome at 50 weeks post partum of three commonly used ART regimens for HIV-1.MethodsIn this multicentre, open-label, randomised, controlled, phase 3 trial, we enrolled pregnant women aged 18 years or older with confirmed HIV-1 infection at 14-28 weeks of gestation. Women were enrolled at 22 clinical research sites in nine countries (Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the USA, and Zimbabwe). Participants were randomly assigned (1:1:1) to one of three oral regimens: dolutegravir, emtricitabine, and tenofovir alafenamide; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; or efavirenz, emtricitabine, and tenofovir disoproxil fumarate. Up to 14 days of antepartum ART before enrolment was permitted. Women with known multiple gestation, fetal anomalies, acute significant illness, transaminases more than 2·5 times the upper limit of normal, or estimated creatinine clearance of less than 60 mL/min were excluded. Primary safety analyses were pairwise comparisons between ART regimens of the proportion of maternal and infant adverse events of grade 3 or higher up to 50 weeks post partum. Secondary efficacy analyses at 50 weeks post partum included a comparison of the proportion of women with plasma HIV-1 RNA of less than 200 copies per mL in the combined dolutegravir-containing groups versus the efavirenz-containing group. Analyses were done in the intention-to-treat population, which included all randomly assigned participants with available data. This trial was registered with ClinicalTrials.gov, NCT03048422.FindingsBetween Jan 19, 2018, and Feb 8, 2019, we randomly assigned 643 pregnant women to the dolutegravir, emtricitabine, and tenofovir alafenamide group (n=217), the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (n=215), and the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (n=211). At enrolment, median gestational age was 21·9 weeks (IQR 18·3-25·3), median CD4 count was 466 cells per μL (308-624), and median HIV-1 RNA was 903 copies per mL (152-5183). 607 (94%) women and 566 (92%) of 617 liveborn infants completed the study. Up to the week 50 post-partum visit, the estimated probability of experiencing an adverse event of grade 3 or higher was 25% in the dolutegravir, emtricitabine, and tenofovir alafenamide group; 31% in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group; and 28% in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (no significant difference between groups). Among infants, the estimated probability of experiencing at least one adverse event of grade 3 or higher by postnatal week 50 was 28% overall, with small and non-statistically significant differences between groups. By postnatal week 50, 14 infants whose mothers were in the efavirenz-containing group (7%) died, compared with six in the combined dolutegravir groups (1%). 573 (89%) women had HIV-1 RNA data available at 50 weeks post partum: 366 (96%) in the dolutegravir-containing groups and 186 (96%) in the efavirenz-containing group had HIV-1 RNA less than 200 copies per mL, with no significant difference between groups.InterpretationSafety and efficacy data during pregnancy and up to 50 weeks post partum support the current recommendation of dolutegravir-based ART (particularly in combination with emtricitabine and tenofovir alafenamide) rather than efavirenz, emtricitabine, and tenofovir disoproxil fumarate, when started in pregnancy.FundingNational Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

BACKGROUND: Human herpesvirus 8 (HHV-8) infection occurs in early childhood and is associated with human immunodeficiency virus type 1 (HIV-1) infection and risk for Kaposi sarcoma, but behaviors associated with HHV-8 transmission are not well described. METHODS: We enrolled and followed a prospective cohort of 270 children and their household members to investigate risk factors for HHV-8 transmission in Lusaka, Zambia. RESULTS: We report an incidence of 30.07 seroconversions per 100 child-years. Independent risk factors for HHV-8 incident infection included having a child who shared utensils with a primary caregiver (hazards ratio [HR], 2.33; 95% confidence interval [CI], 1.49-7.14), having an increasing number of HHV-8-infected household members (HR, 1.27; 95% CI, 1.09-2.79), and having ≥5 siblings/children in the household (HR, 2.24; 95% CI, 1.03-4.88). Playing with >5 children a day was protective against infection (HR, 0.54; 95% CI, .33-0.89), as was increasing child age (HR, 0.96; 95% CI, .93-.99). CONCLUSIONS: This is the first study to find a temporal association between limited child feeding behaviors and risk for HHV-8 infection. Child food- and drink-sharing behaviors should be included in efforts to minimize HHV-8 transmission, and households with a large number of siblings should receive additional counseling as childhood infections occur in the home context.

BackgroundPregnancy outcomes of perinatally human immunodeficiency virus-infected women (PHIV) are poorly defined.MethodsWe compared preterm delivery and birth weight (BW) outcomes (low BW [LBW],

The structure of the leaf microbiome can alter host fitness and change in response to abiotic and biotic factors, like seasonality, climate, and leaf age. However, relatively few studies consider the influence of host age on microbial communities at a time scale of a few days, a short time scale relevant to microbes. To understand how host age modulates changes in the fungal and bacterial leaf microbiome on a short time scale, we ran independent field and greenhouse-based studies and characterized phyllosphere communities using next-generation sequencing approaches. Our field study characterized changes in the fungal and bacterial phyllosphere by examining leaves of different relative ages across individuals, whereas the greenhouse study examined changes in the fungal microbiome by absolute leaf age across individuals. Together, these results indicate that fungal communities are susceptible to change as a leaf ages as evidenced by shifts in the diversity of fungal taxa both in the field and the greenhouse. Similarly, there were increases in the diversity of fungal taxa by leaf age in the greenhouse. In bacterial communities in the field, we observed changes in the diversity, composition, and relative abundance of common taxa. These findings build upon previous literature characterizing host-associated communities at longer time scales and provide a foundation for targeted work examining how specific microbial taxa might interact with each other, such as fine-scale interactions between pathogenic and non-pathogenic species. [ABSTRACT FROM AUTHOR]

A pathogen arriving on a host typically encounters a diverse community of microbes that can shape priority effects, other within-host interactions and infection outcomes. In plants, environmental nutrients can drive trade-offs between host growth and defence and can mediate interactions between co-infecting pathogens. Nutrients may thus alter the outcome of pathogen priority effects for the host, but this possibility has received little experimental investigation. To disentangle the relationship between nutrient availability and co-infection dynamics, we factorially manipulated the nutrient availability and order of arrival of two foliar fungal pathogens (Rhizoctonia solani and Colletotrichum cereale) on the grass tall fescue (Lolium arundinaceum) and tracked disease outcomes. Nutrient addition did not influence infection rates, infection severity or plant biomass. Colletotrichum cereale facilitated R. solani, increasing its infection rate regardless of their order of inoculation. Additionally, simultaneous and C. cereale-first inoculations decreased plant growth and—in plants that did not receive nutrient addition—increased leaf nitrogen concentrations compared to uninoculated plants. These effects were partially, but not completely, explained by the duration and severity of pathogen infections. This study highlights the importance of understanding the intricate associations between the order of pathogen arrival, host nutrient availability and host defence to better predict infection outcomes. [ABSTRACT FROM AUTHOR]

An unprecedented extension of life expectancy observed during the past century drastically increased the number of patients diagnosed with Parkinson's diseases (PD) worldwide. Estimated costs of PD alone reached $52 billion per year, making effective neuroprotective treatments an urgent and unmet need. Current treatments of both AD and PD focus on mitigating the symptoms associated with these pathologies and are not neuroprotective. In this review, we discuss the most advanced therapeutic strategies that can be used to treat PD. We also critically review the shift of the therapeutic paradigm from a small molecule-based inhibition of protein aggregation to the utilization of natural degradation pathways and immune cells that are capable of degrading toxic amyloid deposits in the brain of PD patients. [ABSTRACT FROM AUTHOR]

Background ChatGPT is an online language-based platform designed to answer questions in a human-like way, using deep learning -technology. Objectives To examine the diagnostic capabilities of ChatGPT using real-world anonymized medical dermatology cases. Methods Clinical information from 90 consecutive patients referred to a single dermatology emergency clinic between June and December 2022 were examined. Thirty-six patients were included. Anonymized clinical information was transcribed and input into ChatGPT 4.0 followed by the question 'What is the most likely diagnosis?' The suggested diagnosis made by ChatGPT was then compared with the diagnosis made by dermatology. Results After inputting clinical history and examination data obtained by a dermatologist, ChatGPT made a correct primary diagnosis 56% of the time (n = 20). Using the clinical history and cutaneous signs recorded by nonspecialists, it was able to make a correct diagnosis 39% of the time (n = 14). This was similar to the diagnostic rate of nonspecialists (36%; n = 13), but it was much lower than that of dermatologists (83%; n = 30). There was no differential offered by referring sources 28% of the time (n = 10), unlike ChatGPT, which provided a differential diagnosis 100% of the time. Qualitative analysis showed that ChatGPT offered responses with caution, often justifying its reasoning. Conclusions This study illustrates that while ChatGPT has a diagnostic capability, in its current form it does not significantly improve the diagnostic yield in primary or secondary care. [ABSTRACT FROM AUTHOR]

Exotic species dominate many communities; however the functional significance of species' biogeographic origin remains highly contentious. This debate is fuelled in part by the lack of globally replicated, systematic data assessing the relationship between species provenance, function and response to perturbations. We examined the abundance of native and exotic plant species at 64 grasslands in 13 countries, and at a subset of the sites we experimentally tested native and exotic species responses to two fundamental drivers of invasion, mineral nutrient supplies and vertebrate herbivory. Exotic species are six times more likely to dominate communities than native species. Furthermore, while experimental nutrient addition increases the cover and richness of exotic species, nutrients decrease native diversity and cover. Native and exotic species also differ in their response to vertebrate consumer exclusion. These results suggest that species origin has functional significance, and that eutrophication will lead to increased exotic dominance in grasslands.