Neural tube defects: recent advances, unsolved questions, and controversies

Neural tube defects are severe congenital malformations affecting around one in every 1000 pregnancies. An innovation in clinical management has come from the finding that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention with folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in the UK. Genetic predisposition accounts for most of the risk of neural tube defects, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but studies of mouse models of neural tube defects show that anencephaly, open spina bifida, and craniorachischisis result from failure of primary neurulation, whereas skin-covered spinal dysraphism results from defective secondary neurulation. Other malformations, such as encephalocele, are likely to be postneurulation disorders

Malaria prevention in the Buea health district in Cameroon: factors influencing Mosquito bed net use in households

Background: Insecticide treated bed nets (ITNs), though proven to be effective in preventing malaria will have little impact unless people sleep under them. Several studies have shown that owned ITNs are usually not used and that ITN use is influenced by several factors that vary between communities.Objective: To investigate the factors influencing the use of mosquito bed nets in households in the Buea Health District (BHD) in Cameroon.Material and Methods: A cross-sectional study with two-stage cluster sampling included 420 households from 35 sites. Questionnaires adapted from the Malaria Indicator Survey were used. CSPro 4.1 and Epi info 3.5.3 were used to create database and analyze respectively.Results: ITN ownership in the BHD was high (92.6%; 95% CI: 89.6%-94.9%) but ITN use was less than average (41.2%; 95% CI: 39.2%-43.3%). ITN use was least likely in the age group 5-15 years (P<0.01), in educated individuals (P<0.01) and in households with less than one ITN for two persons (P<0.01). White ITNs were less likely to be used (P<0.01). Conclusion: There is a gap between ITN ownership and use in the malaria holoendemic BHD and ITN use is associated with age of individual, level of education, colour of ITNs and household net density. Use of the highly owned ITNs could be increased by targeting the least protected 5-15 years age group and schooling individuals; by promoting school-based education on ITN use.Keywords: Insecticide-treated nets, malaria, Buea Health Distric

Ectopia cordis : a report of two cases in Cameroon

This article reports two cases of ectopia cordis in two children aged one day and twenty months respectively. A one day old newborn had complete thoracic ectopia cordis associated with an internal cardiac defect and severe thoracic and abdominal wall malformations. The centre does not have the facilities to manage complex congenital defects and prior to being transferred to a cardiac centre, the neonate died on the second day of admission. A 20-month old baby had partial ectopia of the heart and a defect in the abdominal wall. He had no major congenital cardiac defect and has remained clinically stable with no life threatening symptomspeer-reviewe

Prevalence of septicaemia and antibiotic sensitivity pattern of bacterial isolates at the University Teaching Hospital, Yaoundé, Cameroon

Bloodstream infections are important causes of mortality and morbidity. Rapid empiric antibiotic therapy is often needed. Knowledge of epidemiological data of common pathogens and their antibiotic sensitivity pattern is needed for rapid therapy. This study was aimed at determining the common causes of septicaemia and their antibiotic sensitivity pattern from the University Teaching Hospital, Yaoundé. Blood samples were collected and cultured aerobically. Isolates were identified using bacteriological and biochemical methods and antibiotic sensitivity was done using the Kirby- Bauer disc diffusion method. Results showed that of the 396 patients examined 112 (28.3%) had septicaemia. Children below the age of 15 years constituted the greatest percentage of infected subjects (63.4%) followed by patients aged between 16-30 years (10.7%) (P < 0.05). The highest incidence of septicaemia were from medicine (8.95‰), followed by paediatrics (7.04‰), surgery (6.46 ‰), out-patients (5.79‰), neonatology (5.12‰), obstetrics and gynaecology (5.05‰) and emergency (2.05‰) wards. The overall incidence of septicaemia was 5.79 per 1000 admissions. Gram-positive bacteria were encountered more often than gram negative bacteria (56.2% versus 43.8%,

Vangl2-environment interaction causes severe neural tube defects, without abnormal neuroepithelial convergent extension

Planar cell polarity (PCP) signalling is vital for initiation of mouse neurulation, with diminished convergent extension (CE) cell movements leading to craniorachischisis, a severe neural tube defect (NTD). Some humans with NTDs also have PCP gene mutations but these are heterozygous, not homozygous as in mice. Other genetic or environmental factors may interact with partial loss of PCP function in human NTDs. We found that reduced sulfation of glycosaminoglycans interacts with heterozygosity for the Lp allele of Vangl2 (a core PCP gene), to cause craniorachischisis in cultured mouse embryos, with rescue by exogenous sulphate. We hypothesised this glycosaminoglycan-PCP interaction may regulate CE but, surprisingly, DiO labeling of the embryonic node demonstrates no abnormality of midline axial extension in sulfation-depleted Lp/+ embryos. Positive-control Lp/Lp embryos show severe CE defects. Abnormalities were detected in the size and shape of somites that flank the closing neural tube in sulfation-depleted Lp/+ embryos. We conclude that failure of closure initiation can arise by a mechanism other than faulty neuroepithelial CE, with possible involvement of matrix-mediated somite expansion, adjacent to the closing neural tube

An update on the use of inositols in preventing gestational diabetes mellitus (GDM) and neural tube defects (NTDs)

INTRODUCTION: Obstetric history and maternal body composition and lifestyle may be associated with serious complications both for the mother, such as gestational diabetes mellitus (GDM), and for the fetus, including congenital malformations such as neural tube defects (NTDs). AREAS COVERED: In view of the recent knowledge, changes of nutritional and physical activity habits ameliorate glycemic control during pregnancy and in turn improve maternal and neonatal health outcomes. Recently, a series of small clinical and experimental studies indicated that supplementation with inositols, a family of insulin sensitizers, was associated with beneficial impact for both GDM and NTDs. EXPERT OPINION: Herein, we discuss the most significant scientific evidence supporting myo-inositol administration as a prophylaxis for the above-mentioned conditions

A Machine Learning Approach for Micro-Credit Scoring

© 2021 by the authors. In micro-lending markets, lack of recorded credit history is a significant impediment to assessing individual borrowers’ creditworthiness and therefore deciding fair interest rates. This research compares various machine learning algorithms on real micro-lending data to test their efficacy at classifying borrowers into various credit categories. We demonstrate that off-the-shelf multi-class classifiers such as random forest algorithms can perform this task very well, using readily available data about customers (such as age, occupation, and location). This presents inexpensive and reliable means to micro-lending institutions around the developing world with which to assess creditworthiness in the absence of credit history or central credit databases

Essential prescribing tips for GP Associates-in-Training

Prescribing is an essential role in general practice but it is also, at times, a high risk activity. GP Associates-in-Training (GP AiTs) have been highlighted as needing further support to reduce the risk of prescribing errors. This article highlights some common prescribing errors to help GP AiTs to review their prescribing and develop prescribing habits to avoid errors. The general practice workforce is changing and there are more pharmacists working in general practice. This article describes the role of clinical pharmacists in prescribing safety and in supporting GP AiTs

Dolutegravir in pregnant mice is associated with increased rates of fetal defects at therapeutic but not at supratherapeutic levels

BACKGROUND: Dolutegravir (DTG) is a preferred regimen for all people with HIV including pregnant women, but its effects on the fetus are not fully understood. Periconceptional exposure to DTG has been associated with increased rates of neural tube defects (NTDs), although it is unknown whether this is a causal relationship. This has led to uncertainty around the use of DTG in women of reproductive potential. METHODS: Pregnant C57BL/6J mice were randomly allocated to control (water), 1x-DTG (2.5 mg/kg-peak plasma concentration ~3000 ng/ml - therapeutic level), or 5x-DTG (12.5 mg/kg-peak plasma concentration ~12,000 ng/ml - supratherapeutic level), once daily from gestational day 0.5 until sacrifice. DTG was administered with 50 mg/kg tenofovir+33.3 mg/kg emtricitabine. Fetal phenotypes were determined, and maternal and fetal folate levels were quantified by mass-spectrometry. FINDINGS: 352 litters (91 control, 150 1x-DTG, 111 5x-DTG) yielding 2776 fetuses (747 control, 1174 1x-DTG, 855 5x-DTG) were assessed. Litter size and viability rates were similar between groups. Fetal and placenta weights were lower in the 1x-DTG vs. control. Placental weight was higher in the 5x-DTG vs. control. Five NTDs were observed, all in the 1x-DTG group. Fetal defects, including microphthalmia, severe edema, and vascular/bleeding defects were more frequent in the 1x-DTG group. In contrast, defect rates in the 5x-DTG were similar to control. Fetal folate levels were similar between control and 1x-DTG, but were significantly higher in the 5x-DTG group. INTERPRETATION: Our findings support a causal relationship of DTG at therapeutic doses with increased risk for fetal defects, including NTDs at a rate that is similar that reported in the Tsepamo study for women exposed to DTG-based ART from conception. The non-monotonic dose-response relationship between DTG and fetal anomalies could explain the previous lack of fetal toxicity findings from pre-clinical DTG studies. The fetal folate levels suggest that DTG is unlikely to be an inhibitor of folate uptake. FUNDING: This project has been funded with Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN275201800001I