Plasma Retinoid Concentrations Are Altered in Pregnant Women

Vitamin A is vital to maternal–fetal health and pregnancy outcomes. However, little is known about pregnancy associated changes in maternal vitamin A homeostasis and concentrations of circulating retinol metabolites. The goal of this study was to characterize retinoid concentrations in healthy women (n = 23) during two stages of pregnancy (25–28 weeks gestation and 28–32 weeks gestation) as compared to ≥3 months postpartum. It was hypothesized that plasma retinol, retinol binding protein 4 (RBP4), transthyretin and albumin concentrations would decline during pregnancy and return to baseline by 3 months postpartum. At 25–28 weeks gestation, plasma retinol (−27%), 4-oxo-13-cis-retinoic acid (−34%), and albumin (−22%) concentrations were significantly lower, and all-trans-retinoic acid (+48%) concentrations were significantly higher compared to ≥3 months postpartum in healthy women. In addition, at 28–32 weeks gestation, plasma retinol (−41%), retinol binding protein 4 (RBP4; −17%), transthyretin (TTR; −21%), albumin (−26%), 13-cis-retinoic acid (−23%) and 4-oxo-13-cis-retinoic acid (−48%) concentrations were significantly lower, whereas plasma all-trans-retinoic acid concentrations (+30%) were significantly higher than ≥3 months postpartum. Collectively, the data demonstrates that in healthy pregnancies, retinol plasma concentrations are lower, but all-trans-retinoic acid concentrations are higher than postpartum.     

A meta-analysis of the prognostic significance of cardiopulmonary exercise testing in patients with heart failure

The objective of the study is to assess the role of cardiopulmonary exercise testing (CPX) variables, including peak oxygen consumption (VO₂), which is the most recognized CPX variable, the minute ventilation/carbon dioxide production (VE/VCO₂) slope, the oxygen uptake efficiency slope (OUES), and exercise oscillatory ventilation (EOV) in a current meta-analysis investigating the prognostic value of a broader list of CPX-derived variables for major adverse cardiovascular events in patients with HF. A search for relevant CPX articles was performed using standard meta-analysis methods. Of the initial 890 articles found, 30 met our inclusion criteria and were included in the final analysis. The total subject populations included were as follows: peak VO₂ (7,319), VE/VCO₂ slope (5,044), EOV (1,617), and OUES (584). Peak VO₂, the VE/VCO₂ slope and EOV were all highly significant prognostic markers (diagnostic odds ratios ≥ 4.10). The OUES also demonstrated promise as a prognostic marker (diagnostic odds ratio = 8.08) but only in a limited number of studies (n = 2). No other independent variables (including age, ejection fraction, and beta-blockade) had a significant effect on the meta-analysis results for peak VO₂ and the VE/VCO₂ slope. CPX is an important component in the prognostic assessment of patients with HF. The results of this meta-analysis strongly confirm this and support a multivariate approach to the application of CPX in this patient population.     

The role of oncogenes, tumour suppressor genes and growth factors in oral squamous cell carcinoma: a case of apoptosis versus proliferation

Mutation, deactivation and disregulated expression of oncogenes and tumour-suppressor genes may be involved in the pathogenesis of oral squamous cell carcinoma (SCC). Deactivation of the p53 tumour-suppressor gene allows cell proliferation and blocks apoptosis of malignant oral keratinocytes. Mutation in the ras oncog-ene results in persistent mitogenic signalling. Upregul-ated c-Myc expression, in the presence of growth factors, provides an additional proliferative signal. Loss of retino-blastoma tumour-suppressor gene (Rb) function may contribute to oral keratinocyte hyperproliferation and recent evidence suggests that simultaneous deactivation of both p53 and Rb is required for tumourigenesis. Enhanced Bcl-2 and reduced Fas expression inhibit tumour cell apoptosis and may convey resistance to cyto-toxic drugs and T cell-mediated cytotoxicity, respectively. Exogenous mutagens such as tobacco, alcohol and viral oncogenes may cause altered expression of oncogenes and tumour-suppressor genes in some cases of oral SCC. The impact of these mechanisms on future therapies for oral SCC is highlighted.     

Child's play: Harnessing play and curiosity motives to improve child handwashing in a humanitarian setting

In humanitarian emergency settings there is need for low cost and rapidly deployable interventions to protect vulnerable children, in- and out-of-school, from diarrhoeal diseases. Handwashing with soap can greatly reduce diarrhoea but interventions specifically targeting children's handwashing behaviour in humanitarian settings have not been tested. Traditional children's handwashing promotion interventions have been school-focused, resource-intensive and reliant on health-based messaging. However, recent research from non-humanitarian settings and targeting adults suggests that theory-based behaviour change interventions targeting specific motives may be more effective than traditional handwashing interventions. In this proof-of-concept study we test, for the first time, the distribution of a modified soap bar, designed to appeal to the motives of play and curiosity, in a household-level, rapidly deployable, handwashing promotion intervention for older children in a humanitarian setting - an internally displaced persons camp in Iraqi Kurdistan. Out of five total blocks within the camp, one was assigned to intervention and one to control. 40 households from each assigned block were then randomly chosen for inclusion in the study and the practice of handwashing with soap at key times was measured at baseline and four weeks after intervention delivery. Children in intervention households received transparent soaps with embedded toys, delivered within a short, fun, and interactive household session with minimal, non-health-based, messaging. The control group received plain soap delivered in a short standard, health-based, hygiene promotion session. At the 4-week follow-up, children in the intervention group were 4 times more likely to wash their hands with soap after key handwashing occasions than expected in the counterfactual (if there had been no intervention) based on the comparison to children in the control group (adjusted RR?=?3.94, 95% CI 1.59–9.79). We show that distributing soaps with toys embedded inside, in a rapidly deployable intervention, can improve child handwashing behaviour in a humanitarian emergency context. Further studies are needed to determine the longer-term behavioural and health impact of such an intervention when delivered at a greater scale in a humanitarian context.     

Mycobacterium tuberculosis--heterogeneity revealed through whole genome sequencing

The emergence of whole genome sequencing (WGS) technologies as primary research tools has allowed for the detection of genetic diversity in Mycobacterium tuberculosis (Mtb) with unprecedented resolution. WGS has been used to address a broad range of topics, including the dynamics of evolution, transmission and treatment. Here, we have analyzed 55 publically available genomes to reconstruct the phylogeny of Mtb, and we have addressed complications that arise during the analysis of publically available WGS data. Additionally, we have reviewed the application of WGS to the study of Mtb and discuss those areas still to be addressed, moving from global (phylogeography), to local (transmission chains and circulating strain diversity), to the single patient (clonal heterogeneity) and to the bacterium itself (evolutionary studies). Finally, we discuss the current WGS approaches, their strengths and limitations.     

Cancer predisposition of ataxia-telangiectasia heterozygotes

Ataxia-telangiectasia (A-T) is a progressive neurologic disorder in which there is varied immune dysfunction, an excess sensitivity to ionizing radiation, and a striking predisposition to cancer. It is the autosomal recessive syndrome for which there is the strongest evidence, derived from retrospective studies of cancer incidence and mortality in A-T families, that the heterozygote is predisposed to cancer. We present, in tabular form, the specific cancer sites or types most likely to be associated with A-T heterozygosity. These include solid tumors of the breast, pancreas, stomach, bladder, and ovary, and chronic lymphocytic leukemia. We also introduce a new method to test these associations. As soon as molecular probes for the A-T allele(s) are available, this new research design will be used to test rigorously each association, hypothesized on the basis of previous data, between a specific cancer site and A-T heterozygosity.     

Quantitative MRI volume changes in late onset schizophrenia and Alzheimer''s disease compared to normal controls

Volumes of medial and lateral temporal lobe structures were assessed using magnetic resonance imaging (MRI) in 11 patients with late-life onset schizophrenia (LOS), 18 normal elderly controls and 12 patients with moderate cognitive impairment due to Alzheimer's disease (AD) who had no non-cognitive symptoms. While both patient groups has smaller volumes of several medial temporal regions (e.g. entorhinal cortex, left hippocampus), schizophrenics had significantly smaller anterior superior temporal gyri (STG) than normal controls, but AD patients did not. We have previously demonstrated anterior STG volume to be reduced in early life onset schizophrenia.     

A continuum of care from hospital to community

This study evaluates the impact of deinstitutionalization on a multiorganizational inpatient and outpatient treatment system. Data are presented on the system's use by 613 patients over an 8 1/2 year period. Goals of a deinstitutionalization program, increasing outpatient service utilization and decreasing rehospitalization, were not clearly achieved. The needs of an inpatient and outpatient care system include effective communication between systems of care, provisions for patient drift from one community to another, and outpatient services of sufficient breadth and quantity to meet the needs of various service users, particularly the severely disabled.This research was partially supported by a NRSA training grant, No. 2 T32 MH17053-06.