Intermittent Hypoxia-Induced Cognitive Deficits Are Mediated by NADPH Oxidase Activity in a Murine Model of Sleep Apnea

Background: In rodents, exposure to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is associated with neurobehavioral impairments, increased apoptosis in the hippocampus and cortex, as well as increased oxidant stress and inflammation. Excessive NADPH oxidase activity may play a role in IH-induced CNS dysfunction. Methods and Findings: The effect of IH during light period on two forms of spatial learning in the water maze and well as markers of oxidative stress was assessed in mice lacking NADPH oxidase activity (gp91phox _/Y) and wild-type littermates. On a standard place training task, gp91phox _/Y displayed normal learning, and were protected from the spatial learning deficits observed in wild-type littermates exposed to IH. Moreover, anxiety levels were increased in wild-type mice exposed to IH as compared to room air (RA) controls, while no changes emerged in gp91phox _/Y mice. Additionally, wild-type mice, but not gp91phox _/Y mice had significantly elevated levels of NADPH oxidase expression and activity, as well as MDA and 8-OHDG in cortical and hippocampal lysates following IH exposures. Conclusions: The oxidative stress responses and neurobehavioral impairments induced by IH during sleep are mediated, at least in part, by excessive NADPH oxidase activity, and thus pharmacological agents targeting NADPH oxidase may provid

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Physical, Chemical and Sensory Properties of Baked Products from Blends of Wheat and African Yam Bean (Sphenostylis stenocarpa) Water- Extractable Proteins

Blends of wheat flour (WF) and African yam bean water-extractable proteins (AYBWEP) were processed into bread and cookies in the following ratios: 100: 0; 95: 5; 90: 10; 85: 15; 80: 20. The proximate composition, physical, chemical properties and sensory properties of bread and cookies samples from the blends were determined. Breads and cookies produced from the resultant blends were significantly higher (p &lt; 0.05) in protein (16.39% &#8211; 18.36%) than the control (11.80% &#8211; 12.58%). Carbohydrate content decreased from 60.74% with addition of AYBWEP to 52.81%following 20% substitution. The pH of bread samples prepared from whole wheat flour and blends of wheat flour and AYBWEP were significantly different (p &lt; 0.05) while bulk density and specific volume were not significantly different (p &gt; 0.05). The pH of bread samples and cookies decreased with increase in the proportion of the AYBWEP blend from 5% to 20%. The highest specific volume (3.70ml/g) was observed in bread samples prepared from the control 100: 0 blends while the 80:20 blends had the lowest specific volume (3.10 ml/g). There was no significantdifference (p &gt; 0.05) in the bulk density and thickness of the cookies. The cookies prepared using 80: 20 blends had the higher diameter (22.53 cm) and spread factor (54.03 cm) compared to the control. Generally, acceptability of the bread and cookies decreased with higher ratios of AYBWEP inclusion. The sensory acceptability scores showed the best AYBWEP substitution level for making bread and cookies was 5% and 10% of the AYBWEP respectively. The results are discussed in the context of the growing importance of promoting the processing and utilization of lesserknown local crops in baked products.enrichment

Educational Intervention to Improve the Practice of Pharmacovigilance among Traditional Medicine Practitioners in Lagos Nigeria.

In the face of the growing usage of herbs, pharmacovigilance of herbal medicine is still in its infancy. Literatures have indicated lack of awareness as one of the major barriers to pharmacovigilance. This study evaluates the impact of an educational intervention in improving the practice of pharmacovigilance among traditional medicine practitioners (TMPs) in Lagos State. A total of 237 traditional medicine practitioners attended a one day workshop on pharmacovigilance. A pre-tested questionnaire was used to obtain baseline, immediate and one month post-intervention information on knowledge, attitude and practice of pharmacovigilance among the respondents. The Paired T-Test and Analysis of Variance were used to compare the means of variables in the different phases of the study. Values of ps 0.05 were considered to be statistically significant. Mean knowledge and attitude to pharmacovigilance scores significantly improved by the end of the study from 14.4 ± 4.3 to 16.7 ± 4.8 (P = 0.003) and 4.2 ± 0.6 to 4.6 ± 0.7 (P = 0.000) respectively. Howeverthe improvementin knowledge of practice of pharmacovigilance was not sustained by the end of the study as the P value increased from 0.04 to 0.5. While educational levels of the participants significantly influenced their knowledge of pharmacovigilance (p&lt; 0.05), gender had no significant influence (p &gt; 0.05). The educational intervention had a positive impact on the knowledge, attitude and practice scores of the participants. However, the improvement on the practice knowledge of pharmacovigilance was not sustained at the end of the study. Continual improvement in the practice of pharmacovigilance of TMPs, through regular and aggressive educational interventions, is necessary for them to partiCipate effectively in the safety monitoring of herbal medicines.Key words: Educational intervention, pharmacovigilance, traditional medicine practitioners