Preventive measures in infancy to reduce under-five mortality: a case-control study in The Gambia.

OBJECTIVE: To investigate the relationship between child mortality and common preventive interventions: vaccination, trained birthing attendants, tetanus toxoid during pregnancy, breastfeeding and vitamin A supplementation. METHODS: Case-control study in a population under demographic surveillance. Cases (n = 141) were children under five who died. Each was age and sex-matched to five controls (n = 705). Information was gathered by interviewing primary caregivers. RESULTS: All but one of the interventions - whether the mother had received tetanus toxoid during pregnancy - were protective against child mortality after multivariate analysis. Having a trained person assisting at child birth (OR 0.2 95% CI 0.1-0.4), receiving all vaccinations by 9 months of age (OR 0.1; 95% CI 0.01-0.3), being breastfed for more than 12 months (Children breastfed between 13 and 24 months OR 0.1 95% CI 0.03-0.3, more than 25 months OR 0.1 95% CI 0.01-0.5) and receiving vitamin A supplementation at or after 6 months of age (OR 0.05; 95% CI 0.01-0.2) were protective against child death. CONCLUSIONS: This study confirms the value of at least four available interventions in the prevention of under-five death in The Gambia. It is now important to identify those who are not receiving them and why, and to intervene to improve coverage across the population

A Model of Basic Surgical Skills Course to Supplement the Training of Foundation-Year Doctors by Efficient Use of Local Resources

INTRODUCTION: This study investigates the efficiency of teaching basic surgical skills to foundation-year doctors and medical students by using local resources. METHODS: A course comprising 4 workshops, once a week, of 3 hours duration per session was delivered using local education center facilities and using the local faculty of consultants and surgical trainees. Teaching methods include practical skill stations supplemented with short didactic lectures and group discussion. Precourse and postcourse assessments were completed by candidates and analyzed to measure outcomes of the course both subjectively and objectively. RESULTS: A total number of 20 participants completed the course. On completion of the course, (1) participants' theoretical knowledge improved significantly (p < 0.0001), as measured by multiple-choice questions, and scores improved by 35% (mean 44%, standard deviation = 16%) before the course compared to (mean = 79%, standard deviation = 13) after the course; (2) the level of confidence in knowledge and skills was measured by a questionnaire on a scale of 1 to 5, and there was a significant (p < 0.0001) improvement on postcourse assessment (mean difference = 1.5, 95% CI: 0.7-2.4); and (3) practical skills such as suture position, knot tying, and wound apposition significantly improved after the course, χ(2) (2) = 16, p < 0.001; χ(2) (2) = 18, p < 0.001; and χ(2) (2) = 22, p < 0.0001, respectively. CONCLUSION: Effective delivery of basic surgical skills to foundation-year doctors by using local resources can be achieved at low cost

Linking the Urban Environment and Health: An Innovative Methodology for Measuring Individual-Level Environmental Exposures

Environmental exposures (EE) are increasingly recognised as important determinants of health and well-being. Understanding the influences of EE on health is critical for effective policymaking, but better-quality spatial data is needed. This article outlines the theoretical and technical foundations used for the construction of individual-level environmental exposure measurements for the population of a northern English city, Bradford. The work supports ‘Connected Bradford’, an entire population database linking health, education, social care, environmental and other local government data over a period of forty years. We argue that our current understanding of environmental effects on health outcomes is limited both by methodological shortcomings in the quantification of the environment and by a lack of consistency in the measurement of built environment features. To address these shortcomings, we measure the environmental exposure for a series of different domains including air quality, greenspace and greenness, public transport, walkability, traffic, buildings and the built form, street centrality, land-use intensity, and food environments as well as indoor dwelling qualities. We utilise general practitioners’ historical patient information to identify the precise geolocation and duration of a person’s residence. We model a person’s local neighbourhood, and the probable routes to key urban functions aggregated across the city. We outline the specific geospatial procedure used to quantify the environmental exposure for each domain and use the example of exposure to fast-food outlets to illustrate the methodological challenges in the creation of city and nationwide environmental exposure databases. The proposed EE measures will enable critical research into the relationship and causal links between the built environment and health, informing planning and policy-making

Giardia assemblage A: human genotype in muskoxen in the Canadian Arctic

As part of an ongoing program assessing the biodiversity and impacts of parasites in Arctic ungulates we examined 72 fecal samples from muskoxen on Banks Island, Northwest Territories, Canada for Giardia and Cryptosporidium. Cryptosporidium spp. were not detected, but 21% of the samples were positive for Giardia. Sequencing of four isolates of Giardia demonstrated G. duodenalis, Assemblage A, a zoonotic genotype

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

Etiology of severe childhood pneumonia in the Gambia, West Africa, determined by conventional and molecular microbiological analyses of lung and pleural aspirate samples.

Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae

Urinary MicroRNA Profiling in the Nephropathy of Type 1 Diabetes

Background: Patients with Type 1 Diabetes (T1D) are particularly vulnerable to development of Diabetic nephropathy (DN) leading to End Stage Renal Disease. Hence a better understanding of the factors affecting kidney disease progression in T1D is urgently needed. In recent years microRNAs have emerged as important post-transcriptional regulators of gene expression in many different health conditions. We hypothesized that urinary microRNA profile of patients will differ in the different stages of diabetic renal disease. Methods and Findings: We studied urine microRNA profiles with qPCR in 40 T1D with >20 year follow up 10 who never developed renal disease (N) matched against 10 patients who went on to develop overt nephropathy (DN), 10 patients with intermittent microalbuminuria (IMA) matched against 10 patients with persistent (PMA) microalbuminuria. A Bayesian procedure was used to normalize and convert raw signals to expression ratios. We applied formal statistical techniques to translate fold changes to profiles of microRNA targets which were then used to make inferences about biological pathways in the Gene Ontology and REACTOME structured vocabularies. A total of 27 microRNAs were found to be present at significantly different levels in different stages of untreated nephropathy. These microRNAs mapped to overlapping pathways pertaining to growth factor signaling and renal fibrosis known to be targeted in diabetic kidney disease. Conclusions: Urinary microRNA profiles differ across the different stages of diabetic nephropathy. Previous work using experimental, clinical chemistry or biopsy samples has demonstrated differential expression of many of these microRNAs in a variety of chronic renal conditions and diabetes. Combining expression ratios of microRNAs with formal inferences about their predicted mRNA targets and associated biological pathways may yield useful markers for early diagnosis and risk stratification of DN in T1D by inferring the alteration of renal molecular processes. © 2013 Argyropoulos et al

Cuprizone demyelination of the corpus callosum in mice correlates with altered social interaction and impaired bilateral sensorimotor coordination

For studies of remyelination in demyelinating diseases, the cuprizone model of CC (corpus callosum) demyelination has experimental advantages that include overall size, proximity to neural stem cells of the subventricular zone, and correlation with a lesion predilection site in multiple sclerosis. In addition, cuprizone treatment can be ended to allow more direct analysis of remyelination than with viral or autoimmune models. However, CC demyelination lacks a useful functional correlate in rodents for longitudinal analysis throughout the course of demyelination and remyelination. In the present study, we tested two distinct behavioural measurements in mice fed 0.2% cuprizone. Running on a ‘complex' wheel with varied rung intervals requires integration between cerebral hemispheres for rapid bilateral sensorimotor coordination. Maximum running velocity on the ‘complex' wheel decreased during acute (6 week) and chronic (12 week) cuprizone demyelination. Running velocity on the complex wheel distinguished treated (for 6 weeks) from non-treated mice, even after a 6-week recovery period for spontaneous remyelination. A second behavioural assessment was a resident–intruder test of social interaction. The frequency of interactive behaviours increased among resident mice after acute or chronic demyelination. Differences in both sensorimotor coordination and social interaction correlated with demonstrated CC demyelination. The wheel assay is applicable for longitudinal studies. The resident–intruder assay provides a complementary assessment of a distinct modality at a specific time point. These behavioural measurements are sufficiently robust for small cohorts as a non-invasive assessment of demyelination to facilitate analysis of subsequent remyelination. These measurements may also identify CC involvement in other mouse models of central nervous system injuries and disorders

The effect of the systemic inflammatory response on plasma vitamin 25 (OH) D concentrations adjusted for albumin

&lt;b&gt;Aim&lt;/b&gt;&lt;p&gt;&lt;/p&gt; To examine the relationship between plasma 25(OH)D, CRP and albumin concentrations in two patient cohorts.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; 5327 patients referred for nutritional assessment and 117 patients with critical illness were examined. Plasma 25 (OH) D concentrations were measured using standard methods. Intra and between assay imprecision was &#60;10%.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Result&lt;/b&gt;&lt;p&gt;&lt;/p&gt; In the large cohort, plasma 25 (OH) D was significantly associated with CRP (rs = −0.113, p&#60;0.001) and albumin (rs = 0.192, p&#60;0.001). 3711 patients had CRP concentrations ≤10 mg/L; with decreasing albumin concentrations ≥35, 25–34 and &#60;25 g/l, median concentrations of 25 (OH) D were significantly lower from 35 to 28 to 14 nmol/l (p&#60;0.001). This decrease was significant when albumin concentrations were reduced between 25–34 g/L (p&#60;0.001) and when albumin &#60;25 g/L (p&#60;0.001). 1271 patients had CRP concentrations between 11–80 mg/L; with decreasing albumin concentrations ≥35, 25–34 and &#60;25 g/l, median concentrations of 25 (OH) D were significantly lower from 31 to 24 to 19 nmol/l (p&#60;0.001). This decrease was significant when albumin concentration were 25–34 g/L (p&#60;0.001) and when albumin &#60;25 g/L (p&#60;0.001). 345 patients had CRP concentrations &#62;80 mg/L; with decreasing albumin concentrations ≥35, 25–34 and &#60;25 g/l, median concentrations of 25 (OH) D were not significantly altered varying from 19 to 23 to 23 nmol/l. Similar relationships were also obtained in the cohort of patients with critical illness.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Plasma concentrations of 25(OH) D were independently associated with both CRP and albumin and consistent with the systemic inflammatory response as a major confounding factor in determining vitamin D status.&lt;p&gt;&lt;/p&gt