Angiotensin-1-converting enzyme (ACE) plasma concentration is influenced by multiple ACE-linked quantitative trait nucleotides

Circulating angiotensin-1-converting enzyme (ACE) is a highly heritable trait, and a major component of the genetic variance maps to the region of the ACE gene. The strong effect of the locus, and the interest in ACE as a candidate gene for cardiovascular disorders, has led to extensive investigation of its relationship to the ACE phenotype, providing one of the most complete examples of quantitative trait locus (QTL) analysis in humans. Resequencing of ACE followed by haplotype analysis in families of British and French origin has shown that the genetic variants that are primarily associated with the ACE trait map to an 18 kb interval flanked by two intragenic, ancestral recombination breakpoints. This critical interval contains dozens of ACE-associated variants in Caucasians, but identification of which of these directly influence ACE concentration is ambiguous because of the almost complete linkage disequilibrium in European populations. In a complementary sequencing and genotyping study of individuals from West African families, we show that this population has much greater haplotype diversity across the gene. Through analysis of the contrasting relationships of the trait phenotype with haplotypes that carry different allelic combinations from those observed in Caucasians, we demonstrate that (at least) two major intragenic sites within the critical interval and (at least) one minor promoter site are associated with the ACE quantitative trait through additive effects. These results point to the importance of analysing diverse populations with different gene genealogies in gene-association studies.     

Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx?

A pilot study was designed to examine whether the outcome of embryo transfer in women with a hydrosalpinx might be improved by surgical drainage of the hydrosalpinx at the time of oocyte collection for in- vitro fertilization treatment. A comparative, controlled but retrospective analysis of the results was performed of all women with infective tubal damage aged <40 years old, who had ovulatory cycles, a normal uterus and a partner with normal spermatozoa. A standardized treatment regimen was used. A maximum of three embryos were transferred. Hydrosalpinx was defined by prior hysterosalpingography and/or laparoscopy with transcervical dye injection. A total of 237 embryo transfer cycles in women with hydrosalpinges (tubal distension not visible in 151, visible but not drained in 30 and drained in 56) were compared with 705 embryo transfer cycles in women with tubal disease but no hydrosalpinx. Results were analysed in the first three cycles but also separately in the first cycle to check for bias. Success rates were higher in the first cycle, but did not significantly influence overall differences. Implantation rates were significantly reduced overall in the hydrosalpinx group (8.0 versus 13.2% for controls; P < 0.001), being 8.3% (P < 0.01) in the subgroup without evident tubal distension and 7.5% (not significant) in the drained hydrosalpinx group. This study shows that tubal damage with distal occlusion is associated with a marked reduction in embryo implantation, even in the absence of obvious fluid distension. Surgical drainage of distended hydrosalpinges appears to offer no benefit.      

Haplotypes produced from rare variants in the promoter and coding regions of angiotensinogen contribute to variation in angiotensinogen levels

The most efficient study design to map genes underlying complex traits will be determined by assumptions about whether the genetic effects are likely to be due to relatively few common variants or multiple rare variants. To examine the possibility that rare variants may influence blood pressure, we sequenced a 6.8 kb region of the angiotensinogen (AGT) gene in 29 male Nigerians with high plasma AGT levels and 28 with low levels. The frequency of haplotypes produced from rare variants in the promoter and coding regions was significantly different between the two groups, and it is unlikely that this difference was due to the manner in which the rare variants were selected. Further analysis suggested that most of the haplotypes produced by these rare variants are found on a haplotype background created by three common SNPs. Our study confirms in an additional trait that rare variants can influence the distribution of complex traits; whether these variants can be captured by common SNPs or haplotypes requires further investigation.     

Role of pancreatic polypeptide in canine gastric acid secretion.

The interrelationships of canine pancreatic polypeptide (cPP) and gastric acid secretion were studied in dogs following infusion of histamine or pentagastrin. Pentagastrin stimulated gastric acid release 30-fold and simultaneously increased plasma cPP secretion by an average of 120 pg/ml. Although histamine stimulated gastric acid secretion to a comparable degree, it had no effect on plasma cPP levels. Three mechanisms of inhibition of acid secretion (cimetidine, duodenal acidification, and somatostatin) had different effects on pancreatic polypeptide (PP) levels. With a background infusion of pentagastrin, cimetidine did not affect cPP levels. In contrast, somatostatin dramatically inhibited both gastric fistula output and cPP release. Finally, a 10-min duodenal irrigation with 0.1 N HCl resulted in a brief spike in cPP levels (from 266 +/- 12 to 347 +/- 31 pg/ml) at the time of greatest inhibition of histamine-stimulated acid secretion. Infusions of histamine + porcine pancreatic polypeptide (pPP) at concentrations of 1.0 and 2.25 microgram/kg per h and of pentagastrin + pPP at 2.25 microgram/kg per h closely simulated postprandial cPP levels (mean 1306 +/- 18 pg/ml at 30 min) but produced no change in gastric fistula output. These studies demonstrated that PP levels and rates of gastric acid secretion are unrelated and that at physiologic concentrations PP plays no significant role in the regulation of gastric acid secretion.     

Change in knowledge of midwives and obstetricians following obstetric emergency training: a randomised controlled trial of local hospital, simulation centre and teamwork training

Objectives  To explore the effect of obstetric emergency training on knowledge. Furthermore, to assess if acquisition of knowledge is influenced by the training setting or teamwork training.
Design  A prospective randomised controlled trial.
Setting  Training was completed in six hospitals in the South West of England, UK and at the Bristol Medical Simulation Centre, UK.
Population  Midwives and obstetric doctors working for the participating hospitals were eligible for inclusion in the study. A total of 140 participants (22 junior and 23 senior doctors, 47 junior and 48 senior midwives) were studied.
Methods  Participants were randomised to one of four obstetric emergency training interventions: (1) 1-day course at local hospital, (2) 1-day course at simulation centre, (3) 2-day course with teamwork training at local hospital and (4) 2-day course with teamwork training at simulation centre.
Main outcome measures  Change in knowledge was assessed by a 185 question Multiple-Choice Questionnaire (MCQ) completed up to 3 weeks before and 3 weeks after the training intervention.
Results  There was a significant increase in knowledge following training; mean MCQ score increased by 20.6 points (95% CI 18.1–23.1, P < 0.001). Overall, 123/133 (92.5%) participants increased their MCQ score. There was no significant effect on the MCQ score of either the location of training (two-way analysis of variants P = 0.785) or the inclusion of teamwork training ( P = 0.965).
Conclusions  Practical, multiprofessional, obstetric emergency training increased midwives' and doctors' knowledge of obstetric emergency management. Furthermore, neither the location of training, in a simulation centre or in local hospitals, nor the inclusion of teamwork training made any significant difference to the acquisition of knowledge in obstetric emergencies.     

Green synthesis of ZnO coated hybrid biochar for the synchronous removal of ciprofloxacin and tetracycline in wastewater

Preparation of biochar from kaolinite and coconut husk (KCB) and further activated with HCl (KCB-A) and KOH (KCB-B) via a microwave technique for the remediation of ciprofloxacin (CIP) and tetracycline (TET) from water was carried out. Characterization using scanning electron microscopy, energy dispersive X-ray, Fourier transform infrared spectroscopy and X-ray diffraction showed the successful synthesis of functionalized biochars. Batch adsorption experiments demonstrated the potential of the adsorbents for fast and efficient removal of CIP and TET from solution. The adsorption capacities were found to be 71, 140 and 229 mg g⁻¹ for CIP and 118, 117 and 232 mg g⁻¹ for TET removal on KCB, KCB-A and KCB-B, respectively. For KCB, KCB-B and KCB-B, CIP adsorption best followed the pseudo second order kinetic model (PSOM), pseudo first order kinetic model (PFOM) and intraparticle diffusion (IDP) respectively. TET adsorption followed PSOM for KCB, IPD for KCB-B and PFOM for KCB-A. CIP adsorption on KCB, KCB-A and KCB-B best fit the Temkin, Langmuir and Brouers–Sotolongo isotherms, respectively, and TET adsorption on KCB best fit Brouers–Sotolongo while KCB-A and KCB-B best fit Langmuir–Freundlich. Adsorption of both contaminants was thermodynamically feasible showing that these materials are excellent adsorbents for the treatment of pharmaceuticals in water.

Preparation of biochar from kaolinite and coconut husk (KCB) and further activated with HCl (KCB-A) and KOH (KCB-B) via a microwave technique for the remediation of ciprofloxacin (CIP) and tetracycline (TET) from water was carried out.     

A Way of Being: A Program for Aggression Control of Male Children

Young children and adolescents that grow up in communities where violence is epidemic face great risk for pathological development (other than being violent themselves). Because growing up in a constant state of siege and apprehension makes it difficult to establish trust, spiritual values autonomy, and social competence all children need. Practical understanding of the negative effects of anger and exposure to violence on male children are presented. Furthermore, the need for interventions that are both individual centred and environmental centred along with the notion that one intervention approach does not fit all are also advanced. Detailed recommendations for effective culturally relevant psychoeducational policy initiatives and optimal anger replacement (client-based) strategies for mental health professionals, early childhood educators and violence prevention experts are offered.     

Nutritional status of public primary school children: a comparison between an upland and riverine area of Ojo LGA, Lagos State Nigeria

This cross sectional study was carried out to compare the nutritional status of public primary school children in an upland and a riverine area of Ojo Local Government Area of Lagos State, Nigeria. A multistage sampling method was used to select a total of 240 children, 120 from each of the two areas. The study population for each area had an equal sex distribution (60 boys and 60 girls). Dietary, anthropometric, clinical and laboratory methods were employed. Using the National Centre for Health Statistics (NCHS/WHO) Reference values, a malnutrition prevalence of 20.8 and 30.81 for the upland and riverine populations respectively was found. There was a stunting in 15.8% of upland and 30.0% of riverine children; 3.3% and 1.7% of them were wasted, and 14.2% in the upland and 18.3% in the rural area were underweight. The mean weights and heights for boys and girls of different ages were lower for the riverine group, although no statistically significant differences were found. Anaemia occurred among 25.0% and 29.2% of the upland and riverine groups respectively. Intestinal helminth infection was found to be significantly associated with malnutrition. Ascaris had a prevalence of 46.7% in the upland and 63.3% in the riverine area. Trichuris had a prevalence of 15.0% and 19.2% in the upland and riverine area respectively. To address the malnutrition problem in these populations, efforts should be aimed at increasing food availability and quality, personal and environmental hygiene, supply of basic amenities, prevention and treatment of infection, and general living conditions of these populations.     

Papaya (Carica papaya) consumption is unsafe in pregnancy: fact or fable? Scientific evaluation of a common belief in some parts of Asia using a rat model

Using controlled in vivo and in vitro pharmacological methods, we evaluated the safety of papaya (Carica papaya) consumption in pregnancy with reference to its common avoidance during pregnancy in some parts of Asia. Ripe papaya (Carica papaya L. (Caricaecae) blend (500 ml/l water) was freely given to four groups of Sprague-Dawley rats at different stages of gestation (days 1-5, 6-11, 12-17 and 1-20). The control group received water. The effect of ripe papaya juice and crude papaya latex on pregnant and non-pregnant rats' uteri was also evaluated using standard isolated-organ-bath methods. The daily volumes (ml) of ripe papaya blend consumed by the treated group were significantly (P<0.05) more than water consumed by the control (control 40.3 (sd 11.6) v. treated 64 (sd 19.0)). There was no significant difference in the number of implantation sites and viable fetuses in the rats given ripe papaya relative to the control. No sign of fetal or maternal toxicity was observed in all the groups. In the in vitro study, ripe papaya juice (0.1-0.8 ml) did not show any significant contractile effect on uterine smooth muscles isolated from pregnant and non-pregnant rats; conversely, crude papaya latex (0.1-3.2 mg/ml) induced spasmodic contraction of the uterine muscles similar to oxytocin (1-64 mU/ml) and prostaglandin F(2 alpha) (0.028-1.81 microm). The response of the isolated rat uterine smooth muscles to 0.2 mg crude papaya latex/ml was comparable to 0.23 microm prostaglandin F(2 alpha) and 32 mU oxytocin/ml. In the 18-19 d pregnant rat uterus, the contractile effect of crude papaya latex was characterized by tetanic spasms. The results of the present study suggest that normal consumption of ripe papaya during pregnancy may not pose any significant danger. However, the unripe or semi-ripe papaya (which contains high concentration of the latex that produces marked uterine contractions) could be unsafe in pregnancy. Though evaluation of potentially toxic agents often relies on animal experimental results to predict risk in man, further studies will be necessary to ascertain the ultimate risk of unripe papaya-semi-ripe papaya consumption during pregnancy in man.