Birthweight, HIV exposure and infant feeding as predictors of malnutrition in Botswanan infants

Background: A better understanding of the nutritional status of infants who are HIV-Exposed-Uninfected (HEU) and HIV-Unexposed-Uninfected (HUU) during their first 1000 days is a key to improving population health, particularly in sub-Saharan Africa. Methods: A cross-sectional study compared nutritional status, feeding practices and determinants of nutritional status of HEU and HUU infants residing in representative selected districts in Botswana during their first 1000 days of life. Four hundred and thirteen infants (37.3% HIV16 exposed), aged 6-24 months attending routine child health clinics were recruited. Anthropometric, 24-hour dietary intake and socio-demographic data was collected. Anthropometric z-scores were calculated using 2006 WHO growth standards. Modelling of the determinants of malnutrition was undertaken using logistic regression. Results: Overall, prevalence of stunting, wasting and underweight were 10.4%, 11.9% and 10.2% respectively. HEU infants were more likely to be underweight (15.6% vs. 6.9%), (p<0.01) and stunted (15.6% vs. 7.3%), (p<0.05) but not wasted (p= 0.14) than HUU infants. HEU infants tended to be formula fed (89.4%) whereas HUU infants tended to breastfeed (89.6%) for the first six months (p<0.001). Significant predictors of nutritional status were HIV exposure, birthweight, birth length, Apgar score and mother/caregiver’s education with little influence of socioeconomic status. Conclusions: HEU infants aged 6-24 months had worse nutritional status compared to HUU infants. Low birthweight was the main predictor of undernutrition in this population. Optimisation of infants’ nutritional status should focus on improving birthweight. In addition, specific interventions should target HEU infants in order to eliminate growth disparity between HEU and HUU infants

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Central activity of glucocorticoids and glucocorticoid receptors in the genetically obese zucker rat (fa/fa)

SIGLEAvailable from British Library Document Supply Centre- DSC:DX96338 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Modality in the MGLAIR Architecture

Abstract The MGLAIR cognitive agent architecture includes a general model of modality and support for concurrent multimodal perception and action. It provides afferent and efferent modalities as instantiable objects used in agent implementations. Each modality is defined by a set of properties that govern its use and its integration with reasoning and acting. This paper presents the MGLAIR model of modalities and mechanisms for their use in computational cognitive agents

Effects of the glucocorticoid agonist, RU28362, and the antagonist RU486 on lung phosphatidylcholine and antioxidant enzyme development in the genetically obese Zucker rat

The biochemical maturation of the lung in late gestation and in the young animal is regulated by glucocorticoids. The present study was aimed at dissociating the different glucocorticoid receptor sites involved in these regulatory functions. The obese Zucker rat was selected as a model for this study as it exhibits hypersensitivity to glucocorticoid hormone action by virtue of its elevated receptor numbers and activity. Two synthetic steroid analogues were administered to obese animals; RU28362, a specific type II receptor agonist, and the type II antagonist RU486. RU28362 promoted a strong catabolic effect, which was associated with reduced food intake and the abolition of growth in the rats. The agonist, RU28362, attenuated developmental increases in antioxidant enzyme activities, and altered the growth of the tissue. At the age studied, development of the lung phosphatidylcholine (PC) system was almost complete, but RU28362 increased disaturated PC 16:0/16:0 concentrations by almost 2-fold, and altered the molecular composition of total pulmonary PC. RU486 attenuated the growth of the rats and reduced their food intake. Treatment with the type II antagonist attenuated lung growth and increased the activities of pulmonary copper zinc (Cu/Zn) and manganese (Mn) superoxide dismutases. RU486 had no effect on lung PC concentrations and molecular composition. The data suggest a role for type I glucocorticoid receptors in the regulation of the antioxidant enzyme system in the lung, as type II antagonism will channel endogenous glucocorticoid binding to the type I site. Type II receptor binding would appear to play a role in regulating the lung PC content