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

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

Riesgo cardiovascular en estudiantes de medicina del municipio Puerto Padre de Las Tunas

Introduction: cardiovascular diseases are the first cause of death in Cuba; as a result, the identification of cardiovascular risks from early ages allows the implementation of health promotion and prevention strategies to reduce their impact in the futureObjective: to identify the cardiovascular risk in medical students in Puerto Padre Municipality, Las Tunas province.Methods: an observational, descriptive and cross-sectional study was conducted. The target group included 545 medical students, 237 of whom were selected by means of a simple random sample. The body mass index and waist-hip ratio were studied. Descriptive statistics was applied.Results: the predominant age group was 18-21 years old (50,2 %). The 51,47 % of the students presented a high waist-hip ratio, 54,02 % a high abdominal circumference, 52,74 % a high body mass index, and in all groups 35,44 % presented blood pressure figures lower than 120/80 mmHg; 39 % had a cardiovascular risk.Conclusions: low percentages of cardiovascular risk were identified in medical students from Puerto Padre Municipality, Las Tunas province, determined by high values of waist-hip index, body mass index and abdominal circumference.Introducción: las enfermedades cardiovasculares constituyen la primera causa de mortalidad en Cuba; por lo cual la identificación de riesgos cardiovasculares desde edades tempranas permite implementar estrategias de promoción y prevención de salud para disminuir su impacto en el futuroObjetivo: identificar el riesgo cardiovascular en estudiantes de medicina del municipio Puerto Padre de Las Tunas.Método: se realizó un estudio observacional, descriptivo y transversal. El universo estuvo constituido por 545 estudiantes de medicina, seleccionándose 237 mediante un muestreo aleatorio simple. Se estudió el índice de masa corporal, la circunferencia abdominal y la índice cintura cadera. Se empleó estadística descriptiva.Resultados: se encontró predominio del grupo etario de 18 a 21 años (50,2 %). El 51,47 % de los estudiantes presentó un índice cintura-cadera alto, el 54,02 % una circunferencia abdominal alta, el 52,74 % un índice de masa corporal alta, así como en todos los grupos el 35,44 % presentó cifras de tensión arterial inferiores a 120/80 mmHg. El 39 % presentó riesgo cardiovascular.Conclusiones: se identificaron bajos porcientos de riesgo cardiovascular en los estudiantes de medicina del municipio Puerto Padre de Las Tunas, determinado por altos valores los índice cintura-cadera, índice de masa corporal y circunferencia abdominal

Neonatal lupus erythematosus in a Nigerian infant

Systemic lupus erythematosus is a chronic inflammatory autoimmune disease that affects all organ systems and follows a relapsing and remitting course with presentation ranging from indolent to fulminant. It is an uncommon condition in children and usually manifests as the cutaneous form in the paediatric age group. We report a case of neonatal lupus erythematosus in a six-week-old Nigerian infant seen at NAUTH, Nnewi. The objective of this report is to highlight the existence of this very rare condition in infants. A 6-week-old female infant presented at the paediatric unit of our facility with a history of a pre-auricular skin eruptions of five weeks and poor suckling of three weeks duration. The skin lesions persisted unchanged after 14 days of antibiotics. A skin snip was taken for histology and a diagnosis of neonatal lupus erythematosus was made.Key words: neonatal lupsus erythematosus, infant, Nnewi