Effect of Substitution of Artemia salina Protein by Soya Protein in Clarias gariepinus Larvae Compounded Diets: Growth, Feed Efficience and Survival

Artemia salina, the main first-feeding protein source of the catfish Clarias gariepinus larvae is relatively scarce and very expensive in Côte d'Ivoire and it raises the cost of catfish fingerlings production. To reduce the feed cost, feeding trial was completed with five isonitrogenous (35%) diets formulated by substituting artemia protein in control diet by soya protein at 25% (SB25), 50% (SB50), 75% (SB75) and 100% (SB100) level. Clarias gariepinus larvae initial body weight 0.0064 ± 0.001 g were stocked at 1 larvae L-1 and fed with the experimental diets three times daily ad libitum for 49 days. At the end of the growth trial, diets SB25 and SB50 present similar growth with the control diet. The low growth recorded from fish fed SB75 and SB100 highly affected final biomass despite the best survival rate recorded. Best values of feed conversion ratio were recorded from larvae fed control diet followed by SB25, SB50. High levels of soya proteins in diets affect feed palatability and larvae growth, vigour, motility and reactivity. Compounded feeds SB25 and SB50 can be used us low cost Clarias gariepinus larvae diets without adverse effects on growth and survival compared of artemia control diet

Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits

Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3

Efficacy of APX2039 in a Rabbit Model of Cryptococcal Meningitis

Cryptococcal Meningitis (CM) is uniformly fatal if not treated, and treatment options are limited. We previously reported on the activity of APX2096, the prodrug of the novel Gwt1 inhibitor APX2039, in a mouse model of CM. Here, we investigated the efficacy of APX2039 in mouse and rabbit models of CM. In the mouse model, the controls had a mean lung fungal burden of 5.95 log10 CFU/g, whereas those in the fluconazole-, amphotericin B-, and APX2039-treated mice were 3.56, 4.59, and 1.50 log10 CFU/g, respectively. In the brain, the control mean fungal burden was 7.97 log10 CFU/g, while the burdens were 4.64, 7.16, and 1.44 log10 CFU/g for treatment with fluconazole, amphotericin B, and APX2039, respectively. In the rabbit model of CM, the oral administration of APX2039 at 50 mg/kg of body weight twice a day (BID) resulted in a rapid decrease in the cerebrospinal fluid (CSF) fungal burden, and the burden was below the limit of detection by day 10 postinfection. The effective fungicidal activity (EFA) was -0.66 log10 CFU/mL/day, decreasing from an average of 4.75 log10 CFU/mL to 0 CFU/mL, over 8 days of therapy, comparing favorably with good clinical outcomes in humans associated with reductions of the CSF fungal burden of -0.4 log10 CFU/mL/day, and, remarkably, 2-fold the EFA of amphotericin B deoxycholate in this model (-0.33 log10 CFU/mL/day). A total drug exposure of the area under the concentration-time curve from 0 to 24 h (AUC0-24) of 25 to 50 mg · h/L of APX2039 resulted in near-maximal antifungal activity. These data support the further preclinical and clinical evaluation of APX2039 as a new oral fungicidal monotherapy for the treatment of CM. IMPORTANCE Cryptococcal meningitis (CM) is a fungal disease with significant global morbidity and mortality. The gepix Gwt1 inhibitors are a new class of antifungal drugs. Here, we demonstrated the efficacy of APX2039, the second member of the gepix class, in rabbit and mouse models of cryptococcal meningitis. We also analyzed the drug levels in the blood and cerebrospinal fluid in the highly predictive rabbit model and built a mathematical model to describe the behavior of the drug with respect to the elimination of the fungal pathogen. We demonstrated that the oral administration of APX2039 resulted in a rapid decrease in the CSF fungal burden, with an effective fungicidal activity of -0.66 log10 CFU/mL/day, comparing favorably with good clinical outcomes in humans associated with reductions of -0.4 log10 CFU/mL/day. The drug APX2039 had good penetration of the central nervous system and is an excellent candidate for future clinical testing in humans for the treatment of CM

High-depth African genomes inform human migration and health

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health

A second update on mapping the human genetic architecture of COVID-19

Matters Arising From: COVID-19 Host Genetics Initiative. Nature https://doi.org/10.1038/s41586-021-03767-x (2021)Data availability: Summary statistics generated by the COVID-19 HGI are available online, including per-ancestry summary statistics for African, admixed American, East Asian, European and South Asian ancestries (https://www.covid19hg.org/results/r7/). The analyses described here used the data release 7. If available, individual-level data can be requested directly from contributing studies, listed in Supplementary Table 1. We used publicly available data from GTEx (https://gtexportal.org/home/), the Neale laboratory (http://www.nealelab.is/uk-biobank/), the Finucane laboratory (https://www.finucanelab.org), the FinnGen Freeze 4 cohort (https://www.finngen.fi/en/access_results) and the eQTL catalogue release 3 (http://www.ebi.ac.uk/eqtl/).Code availability: The code for summary statistics lift-over, the projection PCA pipeline including precomputed loadings and meta-analyses (https://github.com/covid19-hg/); for heritability estimation (https://github.com/AndrewsLabUCSF/COVID19_heritability); for Mendelian randomization and genetic correlation (https://github.com/marcoralab/MRcovid); and subtype analyses (https://github.com/mjpirinen/covid19-hgi_subtypes) are available at GitHub.Reporting summary: Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article online at: https://www.nature.com/articles/s41586-023-06355-3#MOESM2 .Supplementary information is available online at: https://www.nature.com/articles/s41586-023-06355-3#Sec4 .Copyright © The Author(s) 2023. Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development1,2. Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from the COVID-19 Host Genetic Initiative (data release 7). We performed a meta-analysis of up to 219,692 cases and over 3 million controls, identifying 51 distinct genome-wide significant loci—adding 28 loci from the previous data release2. The increased number of candidate genes at the identified loci helped to map three major biological pathways that are involved in susceptibility and severity: viral entry, airway defence in mucus and type I interferon

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19(1,2), host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases(3-7). They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.Radiolog

High-depth African genomes inform human migration and health

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health

Thrombopenie severe au cours du paludisme grave de l’enfant au chu de Yopougon (Cote d’iIoire): prevalence et facteurs associes

Introduction : Parmi les critères de gravité biologique de l’OMS du paludisme grave, seule l’anémie sévère a été retenue. L’objectif de cette étude était d’évaluer la prévalence de la thrombopénie sévère et d’en déterminer les facteurs associés au cours du paludisme grave. Matériel et méthode : Il s’est agi d’une étude transversale à partir de données recueillies entre le 1er octobre 2018 et le 31 mars 2019 (6 mois) au service de pédiatrie du CHU de Yopougon. Elle a concerné les enfants de 1 mois à 15 ans atteints de paludisme grave sans autres affections associées. Les données ont été recueillies sur une fiche d’enquête standardisée. Un modèle de régression logistique a été utilisé pour déterminer les facteurs associés à la thrombopénie sévère. Le seuil de significativité était de 5%. Résultats : L’âge moyen des 312 enfants était de 32 mois (+/- 24,72). Le sex-ratio était de 1,11.Le taux médian de plaquettes était de 94 000 cellules /mm3 (IIQ = 51 500 – 190 000). Une thrombopénie sévère a été retrouvée dans 23,08% des cas. La forme hémorragique a été retrouvée 2,24% des cas. Les facteurs associés à la thrombopénie sévère étaient le sexe (p = 0,01), l’anémie sévère (p = 0,03) et l’insuffisance pondérale (p= 0,01). Elle n’était pas associée à la mortalité (p = 0,23). Conclusion : La thrombopénie sévère est relativement fréquente au cours du paludisme grave. Son pronostic controversée explique qu’il ne soit pas jusqu’ici pris en compte comme facteur de gravité du paludisme. English title: Severe thrombocytopenia during severe malaria in children at Yopougon University Hospital (Ivory Coast): prevalence and associated factors Summary Introduction: Among the WHO biological criteria of severe malaria, only severe anemia was retained. The objective of this study was to assess the prevalence of severe thrombocytopenia and to determine the associated factors during severe malaria. Material and method: This was a cross-sectional study based on data collected between October 1, 2018 and March 31, 2019 (6 months) in pediatric department of university hospital of the Yopougon. It concerned children from 1 month to 15 years old with severe malaria without other disease. The data was collected on a standardized survey form. A logistic regression model was used to determine factors associated with severe thrombocytopenia. The significance level was 5%. Results: The mean age of the 312 children was 32 months (+/- 24.72). The sex ratio was 1.11. The median platelet count was 94,000 cells / mm3 (IQR = 51,500 - 190,000). Severe thrombocytopenia was found in 23.08% of cases. The hemorrhagic form was found in 2.24% of cases. Factors associated with severe thrombocytopenia were gender (p = 0.01), severe anemia (p = 0.03) and underweight (p = 0.01). It was not associated with mortality (p = 0.23). Conclusion: Severe thrombocytopenia is relatively common in severe malaria. Its controversial prognosis explains why it has not been taken into account as a serious factor in malaria. Keywords: Severe thrombocytopenia - Severe malaria - Chil

<i>‘Men are not playing their roles’</i>, maternal and child nutrition in Nanoro, Burkina Faso

Objective: to collect context-specific insights into maternal and child health and nutrition issues, and to explore potential solutions in Nanoro, Burkina Faso.Design: eleven focus groups with men and women from eleven communities, facilitated by local researchers.Setting: the study took place in the Nanoro Health district, in the West-Central part of Burkina Faso.Participants: eighty-six men (18–55 years) and women by age group: 18–25; 26–34 and 35–55 years, participated in the group discussions.Results: participants described barriers to optimal nutrition of mothers and children related to a range of community factors, with gender inequality as central. Major themes in the discussions are related to poverty and challenges generated by socially and culturally determined gender roles. Sub-themes are women lacking access to food whilst pregnant and having limited access to health care and opportunities to generate income. Although communities believe that food donations should be implemented to overcome this, they also pointed out the need for enhancing their own food production, requiring improved agricultural technologies. Given the important role that women could play in reducing malnutrition, these communities felt they needed to be empowered to do so and supported by men. They also felt that this had to be carried out in the context of an enhanced health care system.Conclusions: findings reported here highlight the importance of nutrition-sensitive interventions and women’s empowerment in improving maternal and child nutrition. There is a need to integrate a sustainable multi-sectorial approach which goes beyond food support

Investing in human development and building state resilience in fragile contexts: a case study of early nutrition investments in Burkina Faso

Maternal and early malnutrition have negative health and developmental impacts over the life-course. Consequently, early nutrition support can provide significant benefits into later life, provided the later life contexts allow. This study examines the limits of siloed investments in nutrition and illustrates how ignoring life-course contextual constraints limits human development benefits and exacerbates inequality, particularly in fragile contexts. This case study focuses on Burkina Faso, a country with high rates of early malnutrition and a fragile state. We modelled the impact of scaling up 10 nutrition interventions to 80% coverage for a single year cohort on stunting, nationally and sub-nationally, using the Lives Saved Tool (LiST), and the consequent impact on earnings, without and with a complementary cash-transfer in later life. The impact on earnings was modelled utilising the well-established pathway between early nutrition, years of completed schooling and, consequent adult earnings. Productivity returns were estimated as the present value of increased income over individuals' working lives, then compared to estimates of the present value of providing the cost of nutrition interventions and cash-transfers. The cost benefit ratio at the national level for scaled nutrition alone is 1:1. Sub-nationally the worst-off region yields the lowest ratio &lt; 0.2 for every dollar spent. The combination of nutrition and cash-transfers national cost benefit is 1:12, still with regional variation but with great improvement in the poorest region. This study shows that early nutrition support alone may not be enough to address inequality and may add to state fragility. Taking a life-course perspective when priority-setting in contexts with multiple constraints on development can help to identify interventions that maximizing returns, without worsening inequality.</p