Prenatal factors contribute to the emergence of kwoshiorkor or marasmus in severe undernutrition: evidence for the predictive adaptation model

Severe acute malnutrition in childhood manifests as oedematous (kwashiorkor, marasmic kwashiorkor) and non-oedematous (marasmus) syndromes with very different prognoses. Kwashiorkor differs from marasmus in the patterns of protein, amino acid and lipid metabolism when patients are acutely ill as well as after rehabilitation to ideal weight for height. Metabolic patterns among marasmic patients define them as metabolically thrifty, while kwashiorkor patients function as metabolically profligate. Such differences might underlie syndromic presentation and prognosis. However, no fundamental explanation exists for these differences in metabolism, nor clinical pictures, given similar exposures to undernutrition. We hypothesized that different developmental trajectories underlie these clinical-metabolic phenotypes: if so this would be strong evidence in support of predictive adaptation model of developmental plasticity

College Social Experiences Between First-Generation Students and Other Students Enrolled in a STEM Discipline at an HBCU

The primary purpose of this study was to determine the differences in the levels of social engagement between first-generation and other college students enrolled in a STEM discipline at a Historically Black College and University. A two-group ex post facto research design using a single questionnaire was used for the study. A stratified sample of 90 college students participated in the study. The data for the research questions were analyzed using descriptive and inferential statistics based upon the subscales of the College Student Experiences Questionnaire. These findings indicated that there were significant differences among first-generation and other college students who were enrolled in a STEM discipline at an HBCU. Statistically significant differences between first-generation and other college students were found for three items in the social integration category: “met other students,” (p = .017, η2 = .063); “used campus recreational facilities,” (p = .050, η2 = .043); and “became acquainted with students,” (p = .035, η2 = .050). Both groups felt that meeting others would happen “often.” Both groups differ for using campus recreational facilities and becoming acquainted with students whose family backgrounds were different. Firstgeneration students reported that “occasionally” and “often”; and the other college students felt “often” and “very often” that using campus recreational facilities and becoming acquainted with students whose family background was different would happen. The study documented the impact of the nurturing environment that exists at an HBCU and focused on the social engagement aspects of attending college. The study findings provide clues to ways that college administrators and researchers can assist first-generation college students enrolled in a STEM discipline at an HBCU. Implications for future research and policymakers are discussed

Predicting asthma exacerbations employing remotely monitored adherence

This Letter investigated the efficacy of a decision-support system, designed for respiratory medicine, at predicting asthma exacerbations in a multi-site longitudinal randomised control trial. Adherence to inhaler medication was acquired over 3 months from patients with asthma employing a dose counter and a remote monitoring adherence device which recorded participant\u27s inhaler use: n = 184 (23,656 audio files), 61% women, age (mean ± sd) 49.3 ± 16.4. Data on occurrence of exacerbations was collected at three clinical visits, 1 month apart. The relative risk of an asthma exacerbation for those with good and poor adherence was examined employing a univariate and multivariate modified Poisson regression approach; adjusting for age, gender and body mass index. For all months dose counter adherence was significantly (p \u3c 0.01) higher than remote monitoring adherence. Overall, those with poor adherence had a 1.38 ± 0.34 and 1.42 ± 0.39 (remotely monitored) and 1.25 ± 0.32 and 1.18 ± 0.31 (dose counter) higher relative risk of an exacerbation in model 1 and model 2, respectively. However, this was not found to be statistically significantly different. Remotely monitored adherence holds important clinical information and future research should focus on refining adherence and exacerbation measures. Decision-support systems based on remote monitoring may enhance patient-physician communication, possibly reducing preventable adverse events

Detection of a Stellar Stream Behind Open Cluster NGC 188: Another Part of the Monoceros Stream

We present results from a WIYN/OPTIC photometric and astrometric survey of the field of the open cluster NGC 188 ((l,b) = (122.8\arcdeg, 22.5\arcdeg)). We combine these results with the proper-motion and photometry catalog of Platais et al. and demonstrate the existence of a stellar overdensity in the background of NGC 188. The theoretical isochrone fits to the color-magnitude diagram of the overdensity are consistent with an age between 6 and 10 Gyr and an intermediately metal poor population ([Fe/H] = -0.5 to -1.0). The distance to the overdensity is estimated to be between 10.0 and 12.6 kpc. The proper-motions indicate that the stellar population of the overdensity is kinematically cold. The distance estimate and the absolute proper motion of the overdensity agree reasonably well with the predictions of the Pe\~{n}arrubia et al. model of the formation of the Monoceros stream. Orbits for this material constructed with plausible radial-velocity values, indicate that dynamically, this material is unlikely to belong to the thick disk. Taken together, this evidence suggests that the newly-found overdensity is part of the Monoceros stream.Comment: accepted by A

University of Missouri- St. Louis Comprehensive School Safety Initiative (UMSL CSSI)

View the website for this project here: https://www.umsl.edu/ccj/research/cssi.htm

Genetic Variation on Chromosome 6 Influences F Cell Levels in Healthy Individuals of African Descent and HbF Levels in Sickle Cell Patients

Fetal haemoglobin (HbF) is a major ameliorating factor in sickle cell disease. We investigated if a quantitative trait locus on chromosome 6q23 was significantly associated with HbF and F cell levels in individuals of African descent. Single nucleotide polymorphisms (SNPs) in a 24-kb intergenic region, 33-kb upstream of the HBS1L gene and 80-kb upstream of the MYB gene, were typed in 177 healthy Afro-Caribbean subjects (AC) of approximately 7% European admixture, 631 healthy Afro-Germans (AG, a group of African and German descendents located in rural Jamaica with about 20% European admixture), 87 West African and Afro-Caribbean individuals with sickle cell anaemia (HbSS), as well as 75 Northern Europeans, which served as a contrasting population. Association with a tag SNP for the locus was detected in all four groups (AC, P = 0.005, AG, P = 0.002, HbSS patients, P = 0.019, Europeans, P = 1.5×10−7). The association signal varied across the interval in the African-descended groups, while it is more uniform in Europeans. The 6q QTL for HbF traits is present in populations of African origin and is also acting in sickle cell anaemia patients. We have started to distinguish effects originating from European and African ancestral populations in our admixed study populations

Faster rehabilitation weight gain is associated with liver fat in adult survivors of childhood severe acute malnutrition

Background Nutritional rehabilitation during severe acute malnutrition (SAM) aims to quickly restore a healthy body weight, but rapid weight gain has been associated with later cardiovascular risk. We hypothesized that faster weight gain during SAM rehabilitation and post-hospitalization is associated with liver fat in adult survivors. Method Jamaican adult survivors of childhood SAM underwent abdominal CT scan to estimate liver fat as mean liver attenuation (MLA) and liver spleen ratio (L/S). Birth weight (BW) and anthropometry measured during, and post-hospitalization were abstracted from admission records. Results We studied 42 marasmus survivors (MRs) and 40 kwashiorkor survivors (KWs). MRs had a lower mean BW (SD) 2.5 (0.8) vs 3.0 (0.7) kg; p=0.01) and were more wasted (p<0.001) and stunted (p=0.03) than KWs on admission to hospital. MRs and KWs had similar rates of rehabilitation weight gain, which was inversely associated with MLA among all survivors of SM (r=-0.246, p=0.029), but only in MRs when assessed by diagnosis (r= -0.449, p=0.004). The association between rehabilitation weight gain and adult liver fat in MRs was not altered by BW, admission wasting or stunting. In KWs, post-hospitalization height gain was inversely associated with MLA (difference = -0.64, 95%CI: -0.64 to -0.13; p=0.006). Conclusions Faster rehabilitation weight gain is associated with liver fat in adult survivors of childhood severe acute malnutrition. The finding that BW did not influence these outcomes may reflect the timing of the nutritional insult in utero. Target weight gain during nutritional rehabilitation may need to be lowered to optimize long-term outcomes in these children

A protocol for a randomised clinical trial of the effect of providing feedback on inhaler technique and adherence from an electronic device in patients with poorly controlled severe asthma.

INTRODUCTION: In clinical practice, it is difficult to distinguish between patients with refractory asthma from those with poorly controlled asthma, where symptoms persist due to poor adherence, inadequate inhaler technique or comorbid diseases. We designed an audio recording device which, when attached to an inhaler, objectively identifies the time and technique of inhaler use, thereby assessing both aspects of adherence. This study will test the hypothesis that feedback on these two aspects of adherence when passed on to patients improves adherence and helps clinicians distinguish refractory from difficult-to-control asthma. METHODS: This is a single, blind, prospective, randomised, clinical trial performed at 5 research centres. Patients with partially controlled or uncontrolled severe asthma who have also had at least one severe asthma exacerbation in the prior year are eligible to participate. The effect of two types of nurse-delivered education interventions to promote adherence and inhaler technique will be assessed. The active group will receive feedback on their inhaler technique and adherence from the new device over a 3-month period. The control group will also receive training in inhaler technique and strategies to promote adherence, but no feedback from the device. The primary outcome is the difference in actual adherence, a measure that incorporates time and technique of inhaler use between groups at the end of the third month. Secondary outcomes include the number of patients who remain refractory despite good adherence, and differences in the components of adherence after the intervention. Data will be analysed on an intention-to-treat and a per-protocol basis. The sample size is 220 subjects (110 in each group), and loss to follow-up is estimated at 10% which will allow results to show a 10% difference (0.8 power) in adherence between group means with a type I error probability of 0.05. TRIAL REGISTRATION NUMBER: NCT01529697; Pre-results

Chromatin accessibility reveals insights into androgen receptor activation and transcriptional specificity

Abstract Background Epigenetic mechanisms such as chromatin accessibility impact transcription factor binding to DNA and transcriptional specificity. The androgen receptor (AR), a master regulator of the male phenotype and prostate cancer pathogenesis, acts primarily through ligand-activated transcription of target genes. Although several determinants of AR transcriptional specificity have been elucidated, our understanding of the interplay between chromatin accessibility and AR function remains incomplete. Results We used deep sequencing to assess chromatin structure via DNase I hypersensitivity and mRNA abundance, and paired these datasets with three independent AR ChIP-seq datasets. Our analysis revealed qualitative and quantitative differences in chromatin accessibility that corresponded to both AR binding and an enrichment of motifs for potential collaborating factors, one of which was identified as SP1. These quantitative differences were significantly associated with AR-regulated mRNA transcription across the genome. Base-pair resolution of the DNase I cleavage profile revealed three distinct footprinting patterns associated with the AR-DNA interaction, suggesting multiple modes of AR interaction with the genome. Conclusions In contrast with other DNA-binding factors, AR binding to the genome does not only target regions that are accessible to DNase I cleavage prior to hormone induction. AR binding is invariably associated with an increase in chromatin accessibility and, consequently, changes in gene expression. Furthermore, we present the first in vivo evidence that a significant fraction of AR binds only to half of the full AR DNA motif. These findings indicate a dynamic quantitative relationship between chromatin structure and AR-DNA binding that impacts AR transcriptional specificity

Past, Present, and Possible Future Human Infection with Influenza Virus A Subtype H7

These viruses have resulted in >100 cases of human infection since 2002, and their pandemic potential should not be underestimated