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

Summary 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 middleincome 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 lowincome 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 lowincome, 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

Immunomodulatory activity of Buchholzia coriacea seed methanol extract on Trypanosoma brucei brucei infected mice

Context: The seeds of Buchholzia coriacea Engler (Capparaceae) are used in Eastern Nigeria to treat feverish conditions, and to treat malaria and sleeping sickness that cause fever. Objective: The current study assesses the immunomodulatory activity of Buchholzia coriacea seed extract on Trypanosoma brucei brucei infected mice. Materials and methods: Delayed hypersensitivity reaction, humoral antibody response and in-vivo leucocyte mobilization tests were assessed in three different experiments to determine the effect of the extract on immune response. Seventy-five (75) mice (25 mice per experiment) were used for the study and were each infected with 1.00 × 106 trypanosomes intra-peritoneally. Groups A, B and C were given 250, 500 and 1000 mg/kg of the extract, respectively, group D received 7.5 mg/kg body weight of levamisole and group E was the control. Sheep RBCs were used as antigen. Results: The acute toxicity tests did not cause clinical signs or death within 24 h post treatment at all the doses tested. The extract inhibited delayed hypersensitivity reaction by 20.9 and 20.8% at 250 and 500 mg/kg, respectively, while at 1000 mg/kg, the paw size increased (−101.9%) when compared with the control. The extract elevated the antibody titre from 1.60 ± 0.40 for control to 8.00 ± 3.58 for 500 mg/kg group. The extract increased in total leucocytes counts. Discussion and conclusion: The extract has a very wide safety margin and was able to improve immune response. The results of the present study showed that Buchholzia coriacea seed methanol extract possesses immunostimulatory activity on trypanosome-infected mice

Enhanced Inorganic CsPbIBr2Perovskite Film for a Sensitive and Rapid Response Self-Powered Photodetector

Inorganic cesium lead halide CsPbIxBr3-x (x = 0-3) perovskites have recently gained considerable attention as semiconductor materials for the fabrication of photodetectors due to their high thermal and environmental stability. However, preparing high-quality CsPbIxBr3-x perovskite films using a simple spin-coating method is challenging. This study focused on enhancing the performance of a solution-processed all-inorganic CsPbIxBr3-x (x = 1, CsPbIBr2) photodetector using a silver iodide (AgI) additive. Introducing a small amount of AgI into the CsPbIBr2 precursor solution resulted in perovskite films that were more uniform and exhibited compact surface morphology that improved crystallinity and electronic properties. To further explore the influence of the AgI-modified CsPbIBr2 perovskite film on the device performance, we fabricated a self-powered photodetector with the geometry of fluorine-doped tin oxide (FTO)/compact TiO2/CsI(PbBr2)0.99(AgI)0.01/2,2′,7,7′-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9′-spirobifluorene (Spiro-OMeTAD)/Au. Photoresponse analysis revealed that the photoresponsivity, on/off ratio, and response time of the CsI(PbBr2)0.99(AgI)0.01 perovskite photodetector were improved. Notably, the CsI(PbBr2)0.99(AgI)0.01 perovskite device showed a higher responsivity and an impressive detectivity of 0.43 A/W and 2.46 × 1011 Jones, respectively, in comparison to the pristine CsPbIBr2 device. This work demonstrates the excellent potential of using inorganic CsI(PbBr2)0.99(AgI)0.01 perovskites in applications for high-performance photodetectors

Anti-hypertensive properties of 2-[N-(4-methylbenzenesulfonyl)-1-phenylformamido]-n-(4-nitrophenyl)-3-phenylpropenamide: Experimental and theoretical studies

Experimental and theoretical investigation of the anti-hypertensive activity of novel 2-[N-(4-methylbenzenesulfonyl)-1-phenylformamido]-N-(4-nitrophenyl)-3-phenylpropenamide (MBPNPP) was carried out. The experimental approach followed the dietary induction of spontaneously hypertensive adult male Wistar rats (SHRs) using 66% w/v d-fructose and the angiotensin I-converting enzyme (ACE) inhibitory activity assay while the theoretical study was achieved using DFT calculations and molecular docking against hypertension responsive proteins. The Becke-3-Paramater-Lee-Yang-Parr (B3LYP) functional/6–311G++(d,p) basis set was adopted. The molecular electronic properties such as the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) and other chemical reactivity parameters were evaluated to bring to light, the reactivity and stabilization mechanisms of MBPNPP. The highest daily oral dose of MBPNPP (10 mg/kg) significantly prevented increase in systolic blood pressure (SBP) comparable to positive and normal control groups receiving captopril (10 mg/kg/day) and distilled water (5 ml/kg) ad libitum respectively from 167.23 (negative control) to 124.50 and 120.17 (positive control). Molecular simulation was also carried out with target proteins; 2ydm, 2 × 8Y, and 3ZQZ, and the theoretical data expresses a much plausible therapeutic significance towards the control of hypertension. The frontier orbital energy gap of 3.066 eV was an indicator that the charge transfer interaction occurred within the molecule and indicates high chemical reactivity. Relative to the reference drug, Spironolactone, the compound under study showed a significant binding affinity of -9.0 kcal/mol, -8.3 kcal/mol, and -7.9 kcal/mol with the target proteins and better protein-ligand hydrogen bond interactions. The data gathered from the experimental and theoretical analysis including the docking scores showed excellent anti-hypertensive activity by MBPNPP

Health, well-being, and burnout amongst Early Career Doctors in Nigeria.

BackgroundEarly Career Doctors (ECDs) in Nigeria are faced with many individual and systemic problems, which consequently adversely affect their health, well-being, patient care and safety.ObjectiveThis study, the second phase of the Challenges of Residency Training and Early Career Doctors in Nigeria (CHARTING II) Study, sought to examine the risk factors and contributors to the health, well-being and burnout amongst Nigerian ECDs.MethodsThis was a study of health, well-being and burnout amongst Nigerian ECDs. Outcome variables included burnout, depression, and anxiety, which were respectively assessed using the Copenhagen Burnout Inventory (CBI) and Oldenburg Burnout Inventory (OLBI), Patient Health Questionnaire (PHQ-9) depression scale, and Generalized Anxiety Disorder (GAD-7) scale. The quantitative data obtained was analysed using the IBM SPSS, version 24. Associations between categorical outcome and independent variables were assessed using chi square, with level of significance set at ResultsThe mean body mass index (BMI), durations of smoking and alcohol consumption of the ECDs were 25.64 ± 4.43 kg/m2 (overweight range), 5.33 ± 5.65 years and 8.44 ± 6.43 years respectively. Less than a third (157, 26.9%) of the ECDs exercised regularly. The most common disease conditions affecting the ECDs were musculoskeletal (65/470, 13.8%) and cardiovascular diseases (39/548, 7.1%). Almost a third (192, 30.6%) of the ECDs reported experiencing anxiety. Male and lower cadre ECDs were more likely than female and higher cadre ECDs to report anxiety, burnout and depression.ConclusionThere is an urgent need to prioritize the health and well-being of Nigerian ECDs, so as to optimize patient care and improve Nigeria's healthcare indices