Pediatric and adolescent HIV viral load coverage and suppression rates in the context of the COVID-19 pandemic in 12 PEPFAR-supported sub-Saharan African countries in 2019 and 2020.

The early period of the COVID-19 pandemic limited access to HIV services for children and adolescents living with HIV (C/ALHIV). To determine progress in providing care and treatment services, we describe viral load coverage (VLC) and suppression (VLS) (<1000 copies/ mL) rates during the COVID-19 pandemic in 12 United States President's Emergency Plan for AIDS Relief (PEPFAR)-supported countries. Data for children (0-9 years) and adolescents (10-19 years) on VLC and VLS were analyzed for 12 sub-Saharan African (SSA) countries between 2019 (pre-COVID-19) and 2020 (during COVID-19). We report the number of viral load (VL) tests, and percent change in VLC and VLS for patients on ART. For 12 countries, 181,192 children had a VL test during the pre-COVID-19 period compared with 177,683 December 2020 during COVID-19. VLC decreased from 68.8% to 68.3% overall. However, 9 countries experienced an increase ranging from a 0.7%-point increase for Tanzania and Zimbabwe to a 15.3%-point increase for Nigeria. VLS increased for all countries from 71.2% to 77.7%. For adolescents the number with a VL test increased from 377,342 to 402,792. VLC decreased from 77.4% to 77.1%. However, 7 countries experienced an increase ranging from 1.8% for Mozambique to 13.8% for Cameroon. VLS increased for all countries from 76.8% to 83.8%. This analysis shows variation in HIV VLC across 12 SSA countries. VLS consistently improved across all countries demonstrating resilience of countries during 2020. Countries should continue to improve clinical outcomes from C/ALHIV despite service disruptions that may occur during pandemic response.

Stromal cell-derived factor-1 alpha improves cardiac function in a novel diet-induced coronary atherosclerosis model, the SR-B1ΔCT/LDLR KO mouse.

BACKGROUND AND AIMS: There are a limited number of pharmacologic therapies for coronary artery disease, and few rodent models of occlusive coronary atherosclerosis and consequent myocardial infarction with which one can rapidly test new therapeutic approaches. Here, we characterize a novel, fertile, and easy-to-use HDL receptor (SR-B1)-based model of atherogenic diet-inducible, fatal coronary atherosclerosis, the SR-B1ΔCT/LDLR KO mouse. Additionally, we test intramyocardial injection of Stromal Cell-Derived Factor-1 alpha (SDF-1α), a potent angiogenic cytokine, as a possible therapy to rescue cardiac function in this mouse. METHODS: SR-B1ΔCT/LDLR KO mice were fed the Paigen diet or standard chow diet, and we determined the effects of the diets on cardiac function, histology, and survival. After two weeks of feeding either the Paigen diet (n = 24) or standard chow diet (n = 20), the mice received an intramyocardial injection of either SDF-1α or phosphate buffered saline (PBS). Cardiac function and angiogenesis were assessed two weeks later. RESULTS: When six-week-old mice were fed the Paigen diet, they began to die as early as 19 days later and 50% had died by 38 days. None of the mice maintained on the standard chow diet died by day 72. Hearts from mice on the Paigen diet showed evidence of cardiomegaly, myocardial infarction, and occlusive coronary artery disease. For the five mice that survived until day 28 that underwent an intramyocardial injection of PBS on day 15, the average ejection fraction (EF) decreased significantly from day 14 (the day before injection, 52.1 ± 4.3%) to day 28 (13 days after the injection, 30.6 ± 6.8%) (paired t-test, n = 5, p = 0.0008). Of the 11 mice fed the Paigen diet and injected with SDF-1α on day 15, 8 (72.7%) survived to day 28. The average EF for these 8 mice increased significantly from 48.2 ± 7.2% on day 14 to63.6 ± 6.9% on day 28 (Paired t-test, n = 8, p = 0.003). CONCLUSIONS: This new mouse model and treatment with the promising angiogenic cytokine SDF-1α may lead to new therapeutic approaches for ischemic heart disease.

Maternal Diet Associates with Offspring Bone Mineralization, Fracture Risk and Enamel Defects in Childhood and Influences the Prenatal Effect of High-Dose Vitamin D Supplementation.

We previously demonstrated a beneficial effect of high-dose vitamin D in pregnancy on offspring bone and dental health. Here, we investigated the effect of maternal dietary patterns during pregnancy on the risk of bone fractures, bone mineralization and enamel defects until age 6 years in the offspring. Further, the influence of diet on the effect of high-dose vitamin D was analyzed in the COPSAC2010 mother-child cohort including 623 mother-child pairs. A weighted network analysis on FFQs revealed three specific maternal dietary patterns that associated (Bonferroni p < 0.05) with both offspring bone and dental health. The effect of prenatal high-dose (2800 IU/day) vs. standard-dose (400 IU/day) vitamin D on offspring bone mineral content (adjusted mean difference (aMD): 33.29 g, 95% CI: 14.48-52.09, p < 0.001), bone mineral density (aMD: 0.02 g/cm2 (0.01-0.04), p < 0.001), fracture risk (adjusted incidence rate ratio: 0.36 (0.16-0.84), p = 0.02), and enamel defects in primary (adjusted odds ratio (aOR): 0.13 (0.03-0.58), p < 0.01) and permanent molars (aOR: 0.25; (0.10-0.63), p < 0.01) was most pronounced when mothers had lower intake of fruit, vegetables, meat, eggs, sweets, whole grain, offal and fish. This study suggests that prenatal dietary patterns influence offspring bone and dental development, and should be considered in order to obtain the full benefits of vitamin D to enhance personalized supplementation strategy.

Differences in regulation mechanisms of glutamine synthetases from methanogenic archaea unveiled by structural investigations.

Glutamine synthetases (GS) catalyze the ATP-dependent ammonium assimilation, the initial step of nitrogen acquisition that must be under tight control to fit cellular needs. While their catalytic mechanisms and regulations are well-characterized in bacteria and eukaryotes, only limited knowledge exists in archaea. Here, we solved two archaeal GS structures and unveiled unexpected differences in their regulatory mechanisms. GS from Methanothermococcus thermolithotrophicus is inactive in its resting state and switched on by 2-oxoglutarate, a sensor of cellular nitrogen deficiency. The enzyme activation overlays remarkably well with the reported cellular concentration for 2-oxoglutarate. Its binding to an allosteric pocket reconfigures the active site through long-range conformational changes. The homolog from Methermicoccus shengliensis does not harbor the 2-oxoglutarate binding motif and, consequently, is 2-oxoglutarate insensitive. Instead, it is directly feedback-inhibited through glutamine recognition by the catalytic Asp50'-loop, a mechanism common to bacterial homologs, but absent in M. thermolithotrophicus due to residue substitution. Analyses of residue conservation in archaeal GS suggest that both regulations are widespread and not mutually exclusive. While the effectors and their binding sites are surprisingly different, the molecular mechanisms underlying their mode of action on GS activity operate on the same molecular determinants in the active site.

Screening and risk factors for cervical cancer among survivors of sexual violence in conflict settings, in Eastern Democratic Republic of Congo.

This study assesses the risk that rape survivors have of developing cervical cancer in the context of conflict. A cross-sectional and descriptive study conducted in Bunyakiri and Kavumu, a conflict region in the east of the Democratic Republic of the Congo during the period from September 1 to 10, 2022, including 47 women survivors of sexual violence, 41 of whom were selected on the basis of certain criteria with age ranging from 18 to 50 years. Speculum examination was performed with visual inspection with acetic acid (VIA). After collecting data, the latter were encoded in the Excel file and grouped in the form of tables then analyzed after calculating the percentage. Ages of 21-30 years was the most represented, i.e., 56%. Among them, 34.1% were married and 31.7% were abandoned. Majority was in secondary school (46.3%) and illiterates (34.1%). 36.5% complained of pelvic pain and 36.5% reported first sexual intercourse at the age range of 13-15 years, of which 25 cases, i.e., 61% were sexually active. 39% reported having had 3 sexual partners in their life. VIA was negative in 97.5% of cases. It should be mentioned in this study that the environment of conflict zone, the circumstances of rape and the risky sexual behavior of survivors are an ecosystem that predisposes them to cervical cancer.

Cette étude évalue le risque qu'ont les survivantes de viol de développer un cancer du col de l'utérus dans un contexte de conflit. Une étude transversale et descriptive menée à Bunyakiri et Kavumu, région de conflit à l'est de la République Démocratique du Congo durant la période du 1er au 10 septembre 2022, incluant 47 femmes survivantes de violences sexuelles, dont 41 ont été sélectionnées sur la base de certains critères avec un âge allant de 18 à 50 ans. L'examen au spéculum a été réalisé avec inspection visuelle à l'acide acétique (VIA). Après collecte des données, ces dernières ont été encodées dans le fichier Excel et regroupées sous forme de tableaux puis analysées après calcul du pourcentage. La tranche d'âge de 21 à 30 ans était la plus représentée, soit 56 %. Parmi eux, 34,1% étaient mariés et 31,7% étaient abandonnés. La majorité était scolarisée dans le secondaire (46,3%) et analphabète (34,1%). 36,5% se plaignaient de douleurs pelviennes et 36,5% rapportaient leurs premiers rapports sexuels entre 13 et 15 ans, dont 25 cas, soit 61% étaient sexuellement actifs. 39 % déclarent avoir eu 3 partenaires sexuels dans leur vie. VIA était négatif dans 97,5 % des cas. Il convient de mentionner dans cette étude que l'environnement de la zone de conflit, les circonstances du viol et le comportement sexuel à risque des survivantes constituent un écosystème qui les prédispose au cancer du col de l'utérus.

Bioelectrocatalytic CO2 Reduction by Mo-Dependent Formylmethanofuran Dehydrogenase.

Massive efforts are invested in developing innovative CO2 -sequestration strategies to counter climate change and transform CO2 into higher-value products. CO2 -capture by reduction is a chemical challenge, and attention is turned toward biological systems that selectively and efficiently catalyse this reaction under mild conditions and in aqueous solvents. While a few reports have evaluated the effectiveness of isolated bacterial formate dehydrogenases as catalysts for the reversible electrochemical reduction of CO2 , it is imperative to explore other enzymes among the natural reservoir of potential models that might exhibit higher turnover rates or preferential directionality for the reductive reaction. Here, we present electroenzymatic catalysis of formylmethanofuran dehydrogenase, a CO2 -reducing-and-fixing biomachinery isolated from a thermophilic methanogen, which was deposited on a graphite rod electrode to enable direct electron transfer for electroenzymatic CO2 reduction. The gas is reduced with a high Faradaic efficiency (109±1 %), where a low affinity for formate prevents its electrochemical reoxidation and favours formate accumulation. These properties make the enzyme an excellent tool for electroenzymatic CO2 -fixation and inspiration for protein engineering that would be beneficial for biotechnological purposes to convert the greenhouse gas into stable formate that can subsequently be safely stored, transported, and used for power generation without energy loss.

Structural and biochemical elucidation of class I hybrid cluster protein natively extracted from a marine methanogenic archaeon.

Whilst widespread in the microbial world, the hybrid cluster protein (HCP) has been paradoxically a long-time riddle for microbiologists. During three decades, numerous studies on a few model organisms unravelled its structure and dissected its metal-containing catalyst, but the physiological function of the enzyme remained elusive. Recent studies on bacteria point towards a nitric oxide reductase activity involved in resistance during nitrate and nitrite reduction as well as host infection. In this study, we isolated and characterised a naturally highly produced HCP class I from a marine methanogenic archaeon grown on ammonia. The crystal structures of the enzyme in a reduced and partially oxidised state, obtained at a resolution of 1.45 and 1.36-Å, respectively, offered a precise picture of the archaeal enzyme intimacy. There are striking similarities with the well-studied enzymes from Desulfovibrio species regarding sequence, kinetic parameters, structure, catalyst conformations, and internal channelling systems. The close phylogenetic relationship between the enzymes from Methanococcales and many Bacteria corroborates this similarity. Indeed, Methanococcales HCPs are closer to these bacterial homologues than to any other archaeal enzymes. The relatively high constitutive production of HCP in M. thermolithotrophicus, in the absence of a notable nitric oxide source, questions the physiological function of the enzyme in these ancient anaerobes.

A role for heritable transcriptomic variation in maize adaptation to temperate environments.

BACKGROUND: Transcription bridges genetic information and phenotypes. Here, we evaluated how changes in transcriptional regulation enable maize (Zea mays), a crop originally domesticated in the tropics, to adapt to temperate environments. RESULT: We generated 572 unique RNA-seq datasets from the roots of 340 maize genotypes. Genes involved in core processes such as cell division, chromosome organization and cytoskeleton organization showed lower heritability of gene expression, while genes involved in anti-oxidation activity exhibited higher expression heritability. An expression genome-wide association study (eGWAS) identified 19,602 expression quantitative trait loci (eQTLs) associated with the expression of 11,444 genes. A GWAS for alternative splicing identified 49,897 splicing QTLs (sQTLs) for 7614 genes. Genes harboring both cis-eQTLs and cis-sQTLs in linkage disequilibrium were disproportionately likely to encode transcription factors or were annotated as responding to one or more stresses. Independent component analysis of gene expression data identified loci regulating co-expression modules involved in oxidation reduction, response to water deprivation, plastid biogenesis, protein biogenesis, and plant-pathogen interaction. Several genes involved in cell proliferation, flower development, DNA replication, and gene silencing showed lower gene expression variation explained by genetic factors between temperate and tropical maize lines. A GWAS of 27 previously published phenotypes identified several candidate genes overlapping with genomic intervals showing signatures of selection during adaptation to temperate environments. CONCLUSION: Our results illustrate how maize transcriptional regulatory networks enable changes in transcriptional regulation to adapt to temperate regions.