Biomarkers of systemic inflammation and growth in early infancy are associated with stunting in young Tanzanian children

Stunting can afflict up to one-third of children in resource-constrained countries. We hypothesized that low-grade systemic inflammation (defined as elevations in serum C-reactive protein or alpha-1-acid glycoprotein) in infancy suppresses the growth hormone–insulin-like growth factor (IGF) axis and is associated with subsequent stunting. Blood samples of 590 children from periurban Dar es Salaam, Tanzania, were obtained at 6 weeks and 6 months of age as part of a randomized controlled trial. Primary outcomes were stunting, underweight, and wasting (defined as length-for-age, weight-for-age and weight-for-length z-scores < −2) between randomization and endline (18 months after randomization). Cox proportional hazards models were constructed to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of time to first stunting, underweight, and wasting as outcomes, with measures of systemic inflammation, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) as exposures, adjusting for numerous demographic and clinical variables. The incidences of subsequent stunting, underweight, and wasting were 26%, 20%, and 18%, respectively. In multivariate analyses, systemic inflammation at 6 weeks of age was significantly associated with stunting (HR: 2.14, 95% CI: 1.23, 3.72; p = 0.002). Children with higher levels of IGF-1 at 6 weeks were less likely to become stunted (HR: 0.58, 95% CI: 0.37, 0.93; p for trend = 0.019); a similar trend was noted in children with higher levels of IGF-1 at 6 months of age (HR: 0.50, 95% CI: 0.22, 1.12; p for trend = 0.07). Systemic inflammation occurs as early as 6 weeks of age and is associated with the risk of future stunting among Tanzanian children.This research was funded by the National Institutes of Health (R01 HD048969, 2P30 DK040561, K24 DK104676-Dr. Duggan) and the Bill and Melinda Gates Foundation (OPP1066203-Dr. Duggan). (R01 HD048969 - National Institutes of Health; 2P30 DK040561 - National Institutes of Health; K24 DK104676 - National Institutes of Health; OPP1066203 - Bill and Melinda Gates Foundation)Accepted manuscrip

Graded Representations of Emotional Expressions in the Left Superior Temporal Sulcus

Perceptual categorization is a fundamental cognitive process that gives meaning to an often graded sensory environment. Previous research has subdivided the visual pathway into posterior regions that processes the physical properties of a stimulus, and frontal regions that process more abstract properties such as category information. The superior temporal sulcus (STS) is known to be involved in face and emotion perception, but the nature of its processing remains unknown. Here, we used targeted fMRI measurements of the STS to investigate whether its representations of facial expressions are categorical or noncategorical. Multivoxel pattern analysis showed that even though subjects were performing a categorization task, the left STS contained graded, noncategorical representations. In the right STS, representations showed evidence for both stimulus-related gradations and a categorical boundary

Task-invariant brain responses to the social value of faces

Abstract ■ In two fMRI experiments (n = 44) using tasks with different demands-approach-avoidance versus one-back recognition decisions-we measured the responses to the social value of faces. The face stimuli were produced by a parametric model of face evaluation that reduces multiple social evaluations to two orthogonal dimensions of valence and power [Oosterhof, N. N., &amp; Todorov, A. The functional basis of face evaluation

Multivitamin Supplementation Improves Haematologic Status in Children Born to HIV-positive women in Tanzania.

Anaemia is prevalent among children born to HIV-positive women, and it is associated with adverse effects on cognitive and motor development, growth, and increased risks of morbidity and mortality. To examine the effect of daily multivitamin supplementation on haematologic status and mother-to-child transmission (MTCT) of HIV through breastfeeding. A total of 2387 infants born to HIV-positive women from Dar es Salaam, Tanzania were enrolled in a randomized, double-blind, placebo-controlled trial, and provided a daily oral supplement of multivitamins (vitamin B complex, C and E) or placebo at age 6 weeks for 24 months. Among them, 2008 infants provided blood samples and had haemoglobin concentrations measured at baseline and during a follow-up period. Anaemia was defined as haemoglobin concentrations <11 g/dL and severe anaemia <8.5 g/dL. Haemoglobin concentrations among children in the treatment group were significantly higher than those in the placebo group at 12 (9.77 vs. 9.64 g/dL, p=0.03), 18 (9.76 vs. 9.57 g/dL, p=0.004), and 24 months (9.93 vs. 9.75 g/dL, p=0.02) of follow-up. Compared to those in the placebo group, children in the treatment group had a 12% lower risk of anaemia (hazard ratio (HR): 0.88; 95% CI: 0.79-0.99; p=0.03). The treatment was associated with a 28% reduced risk of severe anaemia among children born to women without anaemia (HR: 0.72; 95% CI: 0.56-0.92; p=0.008), but not among those born to women with anaemia (HR: 1.10; 95% CI: 0.79-1.54; p=0.57; p for interaction=0.007). One thousand seven hundred fifty three infants who tested HIV-negative at baseline and had HIV testing during follow-up were included in the analysis for MTCT of HIV. No association was found between multivitamin supplements and MTCT of HIV. Multivitamin supplements improve haematologic status among children born to HIV-positive women. Further trials focusing on anaemia among HIV-exposed children are warranted in the context of antiretroviral therapy

Distributed representations of dynamic facial expressions in the superior temporal sulcus.

Previous research on the superior temporal sulcus (STS) has shown that it responds more to facial expressions than to neutral faces. Here, we extend our understanding of the STS in two ways. First, using targeted high-resolution fMRI measurements of the lateral cortex and multivoxel pattern analysis, we show that the response to seven categories of dynamic facial expressions can be decoded in both the posterior STS (pSTS) and anterior STS (aSTS). We were also able to decode patterns corresponding to these expressions in the frontal operculum (FO), a structure that has also been shown to respond to facial expressions. Second, we measured the similarity structure of these representations and found that the similarity structure in the pSTS significantly correlated with the perceptual similarity structure of the expressions. This was the case regardless of whether we used pattern classification or more traditional correlation techniques to extract the neural similarity structure. These results suggest that distributed representations in the pSTS could underlie the perception of facial expressions

Distributed representations of dynamic facial expressions in the superior temporal sulcus.

Previous research on the superior temporal sulcus (STS) has shown that it responds more to facial expressions than to neutral faces. Here, we extend our understanding of the STS in two ways. First, using targeted high-resolution fMRI measurements of the lateral cortex and multivoxel pattern analysis, we show that the response to seven categories of dynamic facial expressions can be decoded in both the posterior STS (pSTS) and anterior STS (aSTS). We were also able to decode patterns corresponding to these expressions in the frontal operculum (FO), a structure that has also been shown to respond to facial expressions. Second, we measured the similarity structure of these representations and found that the similarity structure in the pSTS significantly correlated with the perceptual similarity structure of the expressions. This was the case regardless of whether we used pattern classification or more traditional correlation techniques to extract the neural similarity structure. These results suggest that distributed representations in the pSTS could underlie the perception of facial expressions

Effect of maternal vitamin D3 supplementation on maternal health, birth outcomes, and infant growth among HIV-infected Tanzanian pregnant women: study protocol for a randomized controlled trial

Background: Vitamin D has significant immunomodulatory effects on both adaptive and innate immune responses. Observational studies indicate that adults infected with HIV with low vitamin D status may be at increased risk of mortality, pulmonary tuberculosis, and HIV disease progression. Growing observational evidence also suggests that low vitamin D status in pregnancy may increase the risk of adverse birth and infant health outcomes. As a result, antiretroviral therapy (ART) adjunct vitamin D3 supplementation may improve the health of HIV-infected pregnant women and their children. Methods/design The Trial of Vitamins-5 (ToV5) is an individually randomized, double-blind, placebo-controlled trial of maternal vitamin D3 (cholecalciferol) supplementation conducted among 2300 HIV-infected pregnant women receiving triple-drug ART under Option B+ in Dar es Salaam, Tanzania. HIV-infected pregnant women of 12–27 weeks gestation are randomized to either: 1) 3000 IU vitamin D3 taken daily from randomization in pregnancy until trial discharge at 12 months postpartum; or 2) a matching placebo regimen. Maternal participants are followed-up at monthly clinic visits during pregnancy, at delivery, and then with their children at monthly postpartum clinic visits. The primary efficacy outcomes of the trial are: 1) maternal HIV disease progression or death; 2) risk of small-for-gestational age (SGA) births; and 3) risk of infant stunting at 1 year of age. The primary safety outcome of the trial is incident maternal hypercalcemia. Secondary outcomes include a range of clinical and biological maternal and child health outcomes. Discussion The ToV5 will provide causal evidence on the effect of vitamin D3 supplementation on HIV progression and death, SGA births, and infant stunting at 1 year of age. The results of the trial are likely generalizable to HIV-infected pregnant women and their children in similar resource-limited settings utilizing the Option B+ approach. Trial registration ClinicalTrials.gov identifier: NCT02305927. Registered on 29 October 2014. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2157-3) contains supplementary material, which is available to authorized users

Markers of systemic inflammation and environmental enteric dysfunction are not reduced by zinc or multivitamins in Tanzanian infants: a randomized, placebo-controlled trial

https://pubmed.ncbi.nlm.nih.gov/30952509/Published versio

Evolutionary Analyses of Staphylococcus aureus Identify Genetic Relationships between Nasal Carriage and Clinical Isolates

Nasal carriage of Staphylococcus aureus has long been hypothesized to be a major vector for the transmission of virulent strains throughout the community. To address this hypothesis, we have analyzed the relatedness between a cohort of nasal carriage strains and clinical isolates to understand better the genetic conformity therein. To assess the relatedness between nasal carriage and clinical isolates of S. aureus, a genetic association study was conducted using multilocus sequence typing (MLST) and typing of the hypervariable regions of clumping factor and fibronectin binding protein genes. At all loci analyzed, genetic associations between both nasal carriage and clinical isolates were observed. Computational analyses of MLST data indicate that nasal carriage and clinical isolates belong to the same genetic clusters (clades), despite differences in sequence type assignments. Genetic analyses of the hypervariable regions from the clumping factor and fibronectin binding protein genes revealed that not only do clinically relevant strains belong to identical genetic lineages as the nasal carriage isolates within our cohort, but they also exhibit 100% sequence similarity within these regions. The findings of this report indicate that strains of S. aureus being carried asymptomatically throughout the community via nasal colonization are genetically related to those responsible for high levels of morbidity and mortality

The ocean sampling day consortium.

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world's oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits