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Abstract Papaver bracteatum, known for its high thebaine content and absence of morphine, has emerged as a promising alternative to opium poppy for codeine production. In this study, our objective was to create a diverse panel representing the natural variation of this species in Iran. To achieve this, we employed genotyping-by-sequencing to obtain genome-wide distributed single-nucleotide polymorphisms (SNPs) for phylogeographic analysis, population structure assessment, and evaluation of genetic diversity within P. bracteatum populations. A total of 244 P. bracteatum individuals from 13 distinct populations formed seven genetic groups, along with one highly admixed population. We observed a clear split between the populations inhabiting the Alborz Mts. in the east and Zagros Mts. in the west. In between these mountain ranges, the population of Kachal Mangan exhibited a high degree of genetic admixture between both genetic groups. At or after the end of the last glacial maximum, when climate conditions rapidly changed, all P. bracteatum populations experienced a strong demographic bottleneck reducing the already small effective population sizes further before they increased to their recent strengths. Our results suggest that the ongoing climate change together with human pressure on the species’ habitats and limited seed-dispersal ability are potential factors contributing today to rising genetic isolation of P. bracteatum populations. Our results provide genetic data that can be used for conservation measures to safeguard the species’ genetic diversity as a resource for future breeding approaches in this medicinally important species.

Abstract The magnitude of the HIV-1 epidemic in Nigeria is second only to the subtype C epidemic in South Africa, yet the subtypes prevalent in Nigeria require further characterization. A panel of 50 subtype G and 18 CRF02_AG Nigerian HIV-1 pseudoviruses (PSV) was developed and envelope coreceptor usage, neutralization sensitivity and cross-clade reactivity were characterized. These PSV were neutralized by some antibodies targeting major neutralizing determinants, but potentially important differences were observed in specific sensitivities (eg. to sCD4, MPER and V2/V3 monoclonal antibodies), as well as in properties such as variable loop lengths, number of potential N-linked glycans and charge, demonstrating distinct antigenic characteristics of CRF02_AG and subtype G. There was preferential neutralization of the matched CRF/subtype when PSV from subtype G or CRF02_AG were tested using pooled plasma. These novel Nigerian PSV will be useful to study HIV-1 CRF- or subtype-specific humoral immune responses for subtype G and CRF02_AG.

Abstract Background The increasing demand for saffron metabolites in various commercial industries, including medicine, food, cosmetics, and dyeing, is driven by the discovery of their diverse applications. Saffron, derived from Crocus sativus stigmas, is the most expensive spice, and there is a need to explore additional sources to meet global consumption demands. In this study, we focused on yellow-flowering crocuses and examined their tepals to identify saffron-like compounds. Results Through metabolomic and transcriptomic approaches, our investigation provides valuable insights into the biosynthesis of compounds in yellow-tepal crocuses that are similar to those found in saffron. The results of our study support the potential use of yellow-tepal crocuses as a source of various crocins (crocetin glycosylated derivatives) and flavonoids. Conclusions Our findings suggest that yellow-tepal crocuses have the potential to serve as a viable excessive source of some saffron metabolites. The identification of crocins and flavonoids in these crocuses highlights their suitability for meeting the demands of various industries that utilize saffron compounds. Further exploration and utilization of yellow-tepal crocuses could contribute to addressing the growing global demand for saffron-related products.

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.

Der Europäische Gerichtshof für Menschenrechte (EGMR) hat im Fall „KlimaSeniorinnen" ein bemerkenswertes Urteil zugunsten einer lebenswerten Zukunft für alle gefällt. Vor allem in der Schweiz stieß das Urteil jedoch auf scharfe Kritik. Die Schweizer Volkspartei bezeichnete den Entscheid als „dreiste Einmischung fremder Richter", der Aargauer Zeitung spricht von einer „Aushebelung der Demokratie". Der Entscheid des EGMR – zumindest nach Schweizer Verständnis – wirft also zentrale Fragen der Gewaltenteilung und der Rolle der Justiz bei der Beurteilung von Menschenrechten auf.

IntroductionDespite the development of many successful pharmaceutical interventions, a significant subset of patients experience treatment-resistant depression (TRD). Ketamine and its derivatives constitute a novel therapeutic approach to treat TRD; however, standard tools, such as the Montgomery–Åsberg Depression Rating Scale (MADRS) are still being used to measure symptoms and track changes.MethodsThe aim of this study was to review item-level differences between rate of data change (MADRS score) and rater-weighted perception of the most useful items for assessing change in symptoms while remotely conducting the 10-item version of the MADRS in TRD in a clinical trial of rapid-acting antidepressants. Two studies of rapid-acting antidepressants in the treatment of TRD were used to identify item-scoring trends when MADRS is administered remotely and repeatedly (733 subjects across 10 visits). Scoring trends were evaluated in tandem to a rater survey completed by 75 raters. This was completed to gain insight on MADRS items’ perceived level of helpfulness when assessing change of symptoms in rapid-acting antidepressant trials.ResultsMADRS items ‘Reduced sleep’, ‘Apparent sadness’, and ‘Pessimistic thoughts’ were found to have the greatest average data change by visit, while raters ranked ‘Reported sadness’, ‘Lassitude’ and ‘Apparent sadness’ as the most helpful items when assessing symptom change.DiscussionThe diversion between rate of data-change ranking and rater perception of helpfulness could be related to difficulty in assessing specific items, to the novel treatment itself, and/or to the sensitivity to symptom change to which raters are accustomed in traditional antidepressant treatments.

This study serves as a follow-up to VanPatten's (2015a) demographic report including the makeup of many university language departments. The present study investigates what some literary and cultural studies experts self-report regarding their training in SLA/language pedagogy, term familiarity, perceptions of Communicative Language Teaching, and classroom practices. Participants included 38 university-level US Spanish and French professors with expertise in literary and cultural studies. Findings revealed a lack of familiarity with some SLA and language teaching constructs, feedback types, and the role of explicit grammar and mechanical drills. As such, we discuss the ramifications of these findings.

Abstract Genome-wide (GWAS) and copy number variant (CNV) association studies have reproducibly identified numerous risk alleles associated with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ), but biological characterization of these alleles lags gene discovery, owing to the inaccessibility of live human brain cells and inadequate animal models for human psychiatric conditions. Human-derived induced pluripotent stem cells (iPSCs) provide a renewable cellular reagent that can be differentiated into living, disease-relevant cells and 3D brain organoids carrying the full complement of genetic variants present in the donor germline. Experimental studies of iPSC-derived cells allow functional characterization of risk alleles, establishment of causal relationships between genes and neurobiology, and screening for novel therapeutics. Here we report the creation and availability of an iPSC resource comprising clinical, genomic, and cellular data obtained from genetically isolated families with BD and related conditions. Results from the first 324 study participants, 61 of whom have validated pluripotent clones, show enrichment of rare single nucleotide variants and CNVs overlapping many known risk genes and pathogenic CNVs. This growing iPSC resource is available to scientists pursuing functional genomic studies of BD and related conditions.

Abstract Pediatric high-grade gliomas of the subclass MYCN (HGG-MYCN) are highly aggressive tumors frequently carrying MYCN amplifications, TP53 mutations, or both alterations. Due to their rarity, such tumors have only recently been identified as a distinct entity, and biological as well as clinical characteristics have not been addressed specifically. To gain insights into tumorigenesis and molecular profiles of these tumors, and to ultimately suggest alternative treatment options, we generated a genetically engineered mouse model by breeding hGFAP-cre::Trp53 Fl/Fl ::lsl-MYCN mice. All mice developed aggressive forebrain tumors early in their lifetime that mimic human HGG-MYCN regarding histology, DNA methylation, and gene expression. Single-cell RNA sequencing revealed a high intratumoral heterogeneity with neuronal and oligodendroglial lineage signatures. High-throughput drug screening using both mouse and human tumor cells finally indicated high efficacy of Doxorubicin, Irinotecan, and Etoposide as possible therapy options that children with HGG-MYCN might benefit from.

Especially in Switzerland, the KlimaSeniorinnen ruling has been met with sharp criticism. The rightwing Swiss People’s party (Schweizerische Volkspartei, SVP) (predictably) accused the Court of judicial overreach and demanded that Switzerland leave the Council of Europe. The ECtHR decision directly addresses separation of powers and the role of the judiciary in adjudicating human rights, specifically in the context of climate change. This post unpacks the decision and argues that concerns about ECtHR overreach are unwarranted. It shows how the judgment forms an integral part of democratic governance (particularly in Switzerland) whilst being conducive to better laws and policies.

BackgroundMultiple anal human papillomavirus (HPVs) may increase the risk of anal cancer among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). The Jaccard Similarity Index (JSI) was explored as a measure of multiple HPV persistence.MethodsThe TRUST/RV368 cohort enrolled MSM living with and without HIV in Abuja and Lagos, Nigeria. Participants with anal swabs at baseline, 3- and 12-month visits were tested for high- and low-risk HPVs using a next-generation sequencing assay. Persistence of the same HPV genotypes over time was calculated using the JSI and categorized into high, medium, and low similarity tertiles. Factors associated with higher versus lower similarity were estimated with multivariable ordinal logistic regression and reported as adjusted odds ratios (aORs) and 95% confidence intervals (CIs).ResultsOf the 225 participants, median age was 25 years (interquartile range, 22-29 years), 62% were living with HIV, median HPVs was 3 (interquartile range, 2-5), and HPV6 (28%), HPV16 (26%), HPV11 (23%), and HPV45 (20%) were most prevalent. Fifty-three percent of participants had highly similar HPVs at 3 months, and the similarity was associated with HIV (aOR, 3.11; 95% CI, 1.6-5.9) and recent receptive sex (aOR, 1.9; 95% CI, 1.0-3.5). By 12 months, 20% had highly similar HPVs, and it was associated with 12 years or longer since anal coital debut (aOR, 6.8; 95% CI, 3.1-5.2), self-reported genital warts (aOR, 3.1; 95% CI, 1.5-6.6), and 200 or less CD4 cells/mm3 (aOR, 13.3; 95% CI, 2.7-65.2) for those living with HIV.ConclusionsStudies evaluating the JSI as a predictor of high-grade intraepithelial lesions would further confirm its applicability as a quantitative measure of multiple HPV persistence.

Over the past decades, morphometric analysis of brain MRI has contributed substantially to the understanding of healthy brain structure, development and aging as well as to improved characterisation of disease related pathologies. Certified commercial tools based on normative modeling of these metrics are meanwhile available for diagnostic purposes, but they are cost intensive and their clinical evaluation is still in its infancy. Here we have compared the performance of “ScanOMetrics”, an open-source research-level tool for detection of statistical anomalies in individual MRI scans, depending on whether it is operated on the output of FreeSurfer or of the deep learning based brain morphometry tool DL + DiReCT. When applied to the public OASIS3 dataset, containing patients with Alzheimer’s disease (AD) and healthy controls (HC), cortical thickness anomalies in patient scans were mainly detected in regions that are known as predilection areas of cortical atrophy in AD, regardless of the software used for extraction of the metrics. By contrast, anomaly detections in HCs were up to twenty-fold reduced and spatially unspecific using both DL + DiReCT and FreeSurfer. Progression of the atrophy pattern with clinical dementia rating (CDR) was clearly observable with both methods. DL + DiReCT provided results in less than 25 min, more than 15 times faster than FreeSurfer. This difference in computation time might be relevant when considering application of this or similar methodology as diagnostic decision support for neuroradiologists.

Summary: Background: There is no consensus on reporting light characteristics in studies investigating non-visual responses to light. This project aimed to develop a reporting checklist for laboratory-based investigations on the impact of light on non-visual physiology. Methods: A four-step modified Delphi process (three questionnaire-based feedback rounds and one face-to-face group discussion) involving international experts was conducted to reach consensus on the items to be included in the checklist. Following the consensus process, the resulting checklist was tested in a pilot phase with independent experts. Findings: An initial list of 61 items related to reporting light-based interventions was condensed to a final checklist containing 25 items, based upon consensus among experts (final n = 60). Nine items were deemed necessary to report regardless of research question or context. A description of each item is provided in the accompanying Explanation and Elaboration (E&E) document. The independent pilot testing phase led to minor textual clarifications in the checklist and E&E document. Interpretation: The ENLIGHT Checklist is the first consensus-based checklist for documenting and reporting ocular light-based interventions for human studies. The implementation of the checklist will enhance the impact of light-based research by ensuring comprehensive documentation, enhancing reproducibility, and enabling data aggregation across studies. Funding: Network of European Institutes for Advanced Study (NETIAS) Constructive Advanced Thinking (CAT) programme; Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust, 204686/Z/16/Z); Netherlands Organisation for Health Research and Development VENI fellowship (2020–09150161910128); U.S. Department of Defense Grant (W81XWH-16-1-0223); National University of Singapore (NUHSRO/2022/038/Startup/08); and National Research Foundation Singapore (NRF2022-THE004-0002).

Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.

Family and educational institutions are the main centers of socialization in heritage language. Beyond the communicative and learning dynamics that take place in both environments, linguistic socialization also depends to a large extent on the relationship of families with educational spaces. The aim of this paper is to discuss families’ expectations regarding the intergenerational transmission of Spanish and to explore their attitudes towards heritage language and educational programs in Germany. For this purpose, the results of an exploratory study based on surveys will be presented to compare the main arguments justifying Spanish-speaking families’ decision to include heritage language courses or bilingual education spaces in their family language management in the German context. The analysis of the perception of families and their attitudes shows that the positive valuation of the family and instrumental dimension of heritage language influence families to include bilingual programs or heritage language classes in their family language management.

Abstract Safflower (Carthamus tinctorius, Asteraceae) is a source of high-quality edible oil growing in moisture-limited environments. Despite its economic importance, the relationships to close wild species in Carthamus and the presence and relationships of ecotypes within safflower are still not fully clarified. Here we use genotyping-by-sequencing to identify the wild progenitor of C. tinctorius, infer phylogenetic relationship within the series Carthamus and identify groups of closely related lineages within cultivated safflower. Phylogenetic and population genomic analyses found C. palaestinus to be the closest relative and single progenitor of C. tinctorius, which confirms the Levant as the area of domestication of the crop. Flow cytometry showed all analyzed samples of C. oxyacantha, C. palaestinus and C. tinctorius to be diploid (2n = 2x = 24) with 2C genome sizes of 2.4–2.7 pg. Analyses of a set of 114 worldwide distributed safflower accessions arrived at two to five genetic groups, which showed, however, no correlation with the geographic origins of these accessions. From this, we conclude that the trade of safflower seeds resulted in multiple introductions of genotypes from the Levant into other areas with suitable climate conditions for the plant, as well as exchange of genotypes among these areas.

BackgroundHIV and malaria are associated with immunological perturbations and neurocognitive disorders even when asymptomatic. However, the effect of asymptomatic malaria (AM) in HIV-infected adults on neurocognitive impairment (NCI) is not well understood. This study investigated the biomarkers of systemic inflammation and neurocognition in dually infected Nigerian adults.MethodsWe assessed the HIV and AM status of 269 adults and measured their global and domain-specific neurocognition and depression using standardized measures. Blood levels of sCD14 and sCD163 were also measured.ResultsThe mean age of the participants (n = 269) was 33 years, 62% were women, and AM among HIV+ and HIV- was similar (36% versus 37%). NCI was found in 23% (62/269) of participants. HIV+/AM+ had a higher prevalence of impaired learning and executive functions and were more depressed than HIV-/AM- or HIV+/AM-. HIV+ with CD4 T-cell counts ≤200/µL were more impaired in the learning domain than those with >200/µL. HIV+/AM+ group had higher levels of sCD14 compared to the other 3 groups and higher levels of sCD163 than the HIV-/AM- group. Higher levels of sCD14 and sCD163 were each associated with NCI. The sCD163 (log10) levels were higher for those with 1+ versus 2+ parasitemia level.ConclusionsHIV and AM coinfection was associated with an increased risk of reduced learning and executive functions, and elevated systemic inflammation. Mood was more depressed in HIV patients with than those without AM. The mechanisms and long-term effects on neurocognition and depression among HIV+/AM+ individuals should be studied because this coinfection is common globally.

Introduction There is considerable variation in the structure and resources of New Zealand (NZ) rural hospitals; however, these have not been recently quantified and their effects on healthcare outcomes are poorly understood. Importantly, there is no standardised description of each rural hospital’s catchment boundary and the characteristics of the population living within this area. Aim To define and describe a catchment population for each of New Zealand’s rural hospitals. Methods An exploratory approach to developing catchments was employed. Geographic Information Systems were used to develop drive-time-based geographic catchments, and administrative health data (National Minimum Data Set and Primary Health Organisation Data Set) informed service utilisation-based catchments. Catchments were defined at both the Statistical Area 2 (SA2) and domicile levels, and linked to census-based population data, the Geographic Classification for Health, and the area-level New Zealand Index of Socioeconomic Deprivation (NZDep2018). Results Our results highlight considerable heterogeneity in the size (max: 57 564, min: 5226) and characteristics of populations served by rural hospitals. Substantial differences in the age structure, ethnic composition, socio-economic profile, ‘remoteness’ and projected future populations, are noted. Discussion In providing a standardised description of each rural hospital’s catchment boundary and its population characteristics, the considerable heterogeneity of the communities served by rural hospitals, both in size, rurality and socio-demographic characteristics, is highlighted. The findings provide a platform on which to build further research regarding NZ’s rural hospitals and inform the delivery of high-quality, cost-effective and equitable health care for people living in rural NZ.

PurposeAnal cancer risk is substantially higher among HIV-infected men who have sex with men (MSM) as compared with other reproductive-age adults, but screening is rare across sub-Saharan Africa. We report the use of high-resolution anoscopy (HRA) as a first-line screening tool and the resulting early outcomes among MSM in Abuja, Nigeria.MethodsFrom August 2016 to August 2017, 424 MSM enrolled in an anal cancer screening substudy of TRUST/RV368, a combined HIV prevention and treatment cohort. HRA-directed biopsies were diagnosed by histology, and ablative treatment was offered for high-grade squamous intraepithelial lesions (HSIL). HRA proficiency was assessed by evaluating the detection of squamous intraepithelial lesions (SIL) over time and the proportion biopsied. Prevalence estimates of low-grade squamous intraepithelial lesions and HSIL with 95% CIs were calculated. Multinomial logistic regression was used to identify those at the highest risk of SIL.ResultsMedian age was 25 years (interquartile range [IQR], 22-29), median time since sexual debut was 8 years (IQR, 4-12), and 59% (95% CI, 54.2% to 63.6%) were HIV infected. Rate of detection of any SIL stabilized after 200 screenings, and less than 20% had two or more biopsies. Preliminary prevalence estimates of low-grade squamous intraepithelial lesions and HSIL were 50.0% (95% CI, 44.7% to 55.3%) and 6.3% (95% CI, 4.0% to 9.3%). HIV infection, at least 8 years since anal coital debut, concurrency, and external warts were independently statistically associated with SIL.ConclusionProficiency with HRA increased with experience over time. However, HSIL detection rates were low, potentially affected by obstructed views from internal warts and low biopsy rates, highlighting the need for ongoing evaluation and mentoring to validate this finding. HRA is a feasible first-line screening tool at an MSM-friendly health care facility. Years since anal coital debut and external warts could prioritize screening.

Abstract The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.

Abstract The Euro-Siberian steppe flora consists of warm- and cold-adapted species, which may have responded differently to Pleistocene glacials and interglacials. Genotyping-by-sequencing individuals from across the distribution range of the pheasant’s eye (Adonis vernalis), we aimed to gain insight into steppe florogenesis based on the species’ evolutionary history. Although the primary area of origin of the species group comprising A. vernalis, A. villosa and A. volgensis is in Asia, our results indicate that recent populations of A. vernalis are not of Asian origin but evolved in the southern part of Europe during the Pleistocene, with Spanish populations clearly genetically distinct from the Southeastern European populations. We inferred that A. vernalis migrated eastwards from the sub-Mediterranean forest-steppes of Southeastern Europe into the continental forest-steppe zone. Eastern European populations had the highest private allelic richness, indicating long-term large population sizes in this region. As a thermophilic species, A. vernalis seems unlikely to have survived in the cold deserts of the Last Glacial Maximum in Western Siberia, so this region was likely (re)colonized postglacially. Overall, our results reinforce the importance of identifying the area of origin and the corresponding ecological requirements of steppe plants in order to understand the composition of today’s steppe flora.

Increasingly, youth development advocates, educators, and communities recognize the importance of out-of-school time (OST) activities for academic achievement and youth well-being. This study situates OST work in the workforce sector the career development literature calls "care workers". Working within that framework, the authors surveyed OST line staff and site directors to attempt to quantify factors that led them to be more or less dedicated to their care work. The findings have implications for staff recruitment, training, and retention, and for the institutional and policy development of OST programs.

BackgroundRisk of cognitive impairment is increased among persons with high or low body mass index in HIV- and HIV+ populations in resource-rich settings. We examined this association among HIV+ patients in 3 resource-limited settings.MethodsThis secondary analysis included data of 761 HIV+ volunteers pooled from 3 prospective cohort studies conducted in China (n = 404; 53%), India (n = 200; 26%), and Nigeria (n = 157; 21%). World Health Organization (WHO) weight classifications were based on body mass index. T scores, adjusted for demographics and practice effects, were derived from a 7-domain neuropsychological battery. Neurocognitive impairment (NCI) was defined as global deficit score of ≥0.5.ResultsOverall, prevalence of NCI at baseline was 27.7% (similar across all cohorts). The overweight/obese and underweight constituted 37.3% and 15.5% of the total participants, respectively. In a multivariable logistic regression of pooled longitudinal data, adjusting for clinical and demographic variables, the odds of global NCI were 38% higher among the overweight/obese as compared to normal weight participants [odds ratio: 1.38 (95% confidence interval: 1.1 to 1.72); P = 0.005]. Similarly, the odds of global NCI were 39% higher among the underweight as compared to normal weight participants [odds ratio: 1.39 (95% confidence interval: 1.03 to 1.87); P = 0.029].ConclusionsNCI among HIV-1-infected patients was more prevalent in both overweight/obese and underweight than normal weight individuals in 3 resource-limited settings, confirming observations in resource-rich settings. Mechanisms underlying these associations are unclear but likely differ for underweight and overweight persons.