Inhibition of neuroinflammation in BV2 microglia by the biflavonoid kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism

Kolaviron is a mixture of bioflavonoids found in the nut of the West African edible seed Garcinia kola, and it has been reported to exhibit a wide range of pharmacological activities. In this study, we investigated the effects of kolaviron in neuroinflammation. The effects of kolaviron on the expression of nitric oxide/inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2)/cyclooxygenase-2, cellular reactive oxygen species (ROS) and the pro-inflammatory cytokines were examined in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Molecular mechanisms of the effects of kolaviron on NF-B and Nrf2/ARE signalling pathways were analysed by immunoblotting, binding assay, and reporter assay. RNA interference was used to investigate the role of Nrf2 in the anti-inflammatory effect of kolaviron. Neuroprotective effect of kolaviron was assessed in a BV2 microglia/HT22 hippocampal neuron co-culture. Kolaviron inhibited the protein levels of NO/iNOS, PGE2/COX-2, cellular ROS and the proinflammatory cytokines (TNFα and IL-6) in LPS-stimulated microglia. Further mechanistic studies showed that kolaviron inhibited neuroinflammation by inhibiting IB/NF-B signalling pathway in LPS-activated BV2 microglia. Kolaviron produced antioxidant effect in BV2 microglia by increasing HO-1 via the Nrf2/ antioxidant response element (ARE) pathway. RNAi experiments revealed that Nrf2 is need for the anti-inflammatory effect of kolaviron. Kolaviron protected HT22 neurons from neuroinflammation-induced toxicity. Kolaviron inhibits neuroinflammation through Nrf2-dependent mechanisms. This compound may therefore be beneficial in neuroinflammation-related neurodegenerative disorders

Variants of the FADS1 FADS2 Gene Cluster, Blood Levels of Polyunsaturated Fatty Acids and Eczema in Children within the First 2 Years of Life

Association of genetic-variants in the FADS1-FADS2-gene-cluster with fatty-acid-composition in blood of adult-populations is well established. We analyze this genetic-association in two children-cohort-studies. In addition, the association between variants in the FADS-gene-cluster and blood-fatty-acid-composition with eczema was studied. Data of two population-based-birth-cohorts in The Netherlands and Germany (KOALA, LISA) were pooled (n = 879) and analyzed by (logistic) regression regarding the mutual influence of single-nucleotide-polymorphisms (SNPs) in the FADS-gene-cluster (rs174545, rs174546, rs174556, rs174561, rs3834458), on polyunsaturated fatty acids (PUFA) in blood and parent-reported eczema until the age of 2 years. All SNPs were highly significantly associated with all PUFAs except for alpha-linolenic-acid and eicosapentaenoic-acid, also after correction for multiple-testing. All tested SNPs showed associations with eczema in the LISA-study, but not in the KOALA-study. None of the PUFAs was significantly associated with eczema neither in the pooled nor in the analyses stratified by study-cohort. PUFA-composition in young children's blood is under strong control of the FADS-gene-cluster. Inconsistent results were found for a link between these genetic-variants with eczema. PUFA in blood was not associated with eczema. Thus the hypothesis of an inflammatory-link between PUFA and eczema by the metabolic-pathway of LC-PUFAs as precursors for inflammatory prostaglandins and leukotrienes could not be confirmed by these data

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

The use of uphole method in the mapping of the thickness and velocity of the low velocity layer in parts of Eastern Niger Delta, Nigeria

Traveltimes from uphole survey operation carried out in 50 locations in the south-east Niger Delta were picked and analyzed to determine the area weathering structure using the time-intercept method. Analysis of the results shows that the thickness of the low velocity layer in the region varies from 2.6 to 13.3 m, with an average of 8.2 m. The weathering velocity ranges from 214.3 to 905.1 m/s; with an average value of 487.9 m/s. The refractor beneath it has velocities ranging from 1125.0 to 2069.1 m/s; with an average value of 1604.2 m/s. Hence it is established that the thickness and velocity of the weathering layer can vary from one shot point to another in the area of study. The resulting information is essential in oil and groundwater exploration in the area, especially in estimating static corrections and time delays during the processing of seismic reflections. Also the information could be useful in civil engineering works in the determination of the capacity of the foundation rock.Keywords: Uphole method, Traveltimes, Weathering velocity, Low velocity layer, Eastern Niger Delta

Comparison of pressure perception of static and dynamic two point discrimination in apparently healthy individuals

Objective: The study was carried out to compare the perception of Static and Dynamic two point discrimination sensibility in the index finger and investigate the influence of some demographic characteristics such as age, gender and limb dominance on two point discrimination sensibility.Methods: One hundred and thirty-eight apparently healthy subjects (68 males and 70 females) aged between 20 and 90 years, recruited by the purposive consecutive sampling technique, participated in the study and were grouped into 3 age groups of 20-39years (Group 1), 40-59 years (Group 2), and &ge;60 years (Group 3). The study design was ex post facto; subjects were screened for previous sensory abnormalities through history taking and physical examination. An improvised discriminator on which a 5g monofilament fibre mounted was used to determine limits of static and dynamic two point discrimination sensitivity at the tips of both index fingers.Results: Mean values of static two point discrimination in the right and left index fingers respectively were 1.77&plusmn;0.79mm and 1.86&plusmn;1.02mm in group 1, 1.58&plusmn;0.70mm and 1.63&plusmn;0.77mm in group 2, and 2.21&plusmn;0.81mm and 2.02&plusmn;0.80mm in group 3. There was a significant difference between static and dynamic two point discrimination within each of the groups (p&lt;0.05) but none across the groups (p&gt;0.05). Mean two point discrimination values between males and females were not significantly different in all groups (p&gt;0.05). Static and dynamic two point discrimination values showed significant difference between the right and left index finger (p&lt;0.05).Conclusion: Age and gender did not affect the perception of static and dynamic two point discrimination while the limb side (left or right) affected the perception of static and dynamic two point discrimination. The index finger is also more sensitive to moving rather static sensations

Prevalence of selected fall variables and relationship among them in a Nigerian stroke population

Objectives- This study investigated the relationships among the three fall indices of fall incidence (FI), fall risk (FR) and fear of falling (FOF)among stroke survivors in a Nigerian population.Design: Ex-post facto study with co-relational designMethods-This correlation study involved 26 stroke survivors (17 males, 9 females) recruited through consecutive non-probability samplingtechnique from two South-Eastern Nigeria teaching hospitals. The Modified Falls Efficacy Scale (MFES), Berg Balance Scale (BBS) and oralinterview were respectively used to assess fear, risk and incidence of falls of participants.Results- FOF prevalence in the studied population was 81% while actual fall prevalence was 19.2% within the 6months period preceding datacollection. Risk of falling was also present in about 70% of participants. FOF and FR both significantly correlated (

Selected socio-demographic variables and their effect on the quality of life of elderly individuals in a Southeast community of Nigeria.

Background : The aim of this study was to determine the effect of some socio demographic variables on the quality of life of elderly individuals aged 60 to 75years in Nnewi North Local Government area of Anambra State, Southeastern Nigeria.Method: A total of 169 subjects which included 80 females and 89 males who were elderly individuals participated in this study. A cross-sectional survey was conducted to measure quality of life (QOL).QOL was assessed using the WHOQOL-BREF and WHOQOL-OLD. Data were analysed using descriptive statistics, Kruskal Wallis Test and Mann Whitney test at 0.05 alpha level of Significance.Result : Seventy one percent (71.0%) were married, thirteen percent (13.0%) had Post-graduate education, twenty nine percent (29.0%) had Primary education and only twenty four percent (24%) earned monthly income of more than 30,000 Naira and above. Among the selected social demographic variables, Level of Education and income had significant difference (p-value=0.000) in all domains of WHOQOL-BREF and WHOQOL-OLD.Conclusion: High educational level and income had significant effect on the Physical, Psychological ,Social and Enviromental Health Domains of WHOQOL-BREF as well as QOL in WHO-OLD. However Gender and Marital status had no significant effect on all WHOQOL BREF and OLD Domains. Age had significant effect on Psychological health but no significant effect on other domains of WHOQOL-BREF and OLD.Keywords: Quality of life, elderly, Socioeconomic, WHObref, WHOol

Fatty acid desaturase 2 promoter mutation is not responsible for Delta6-desaturase deficiency

Dietary essential polyunsaturated fatty acids (PUFAs) require fatty acid desaturases (FADS) for conversion to long-chain PUFAs (LCPUFAs), which are critical for many aspects of human health. A Δ6-desaturase deficiency in a single patient was attributed to an insertion mutation in the FADS2 promoter. Later population studies have shown this thymidine nucleotide (T) insertion to be a common polymorphism (rs3834458). We examined correlations between rs3834458 variants and fatty acid evidence of FADS2 activity in a cohort of rheumatoid arthritis patients selected for low or nil consumption of n-3 LCPUFA as fish or fish oil. The presence of the T allele was associated with higher FADS2 activity, as indicated by higher conversion of plasma n-3 PUFA to LCPUFA. However, the T-insertion/deletion polymorphism did not affect FADS2 promoter activity in luciferase reporter assays in HepG2 or NIH/3T3 cells. Our results indicate that the polymorphism rs3834458 does not appear to directly affect FADS2 promoter activity and is not responsible for a previously reported Δ6-desaturase deficiency.Melissa K Gregory, Susan E Lester, Rebecca J Cook-Johnson, Robert A Gibson, Susanna M Proudman, Leslie G Cleland and Michael J Jame