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

Genome Wide Analysis of Family-1 UDP Glycosyltransferases in Populus trichocarpa Specifies Abiotic Stress Responsive Glycosylation Mechanisms

Populus trichocarpa (Black cottonwood) is a dominant timber-yielding tree that has become a notable model plant for genome-level insights in forest trees. The efficient transport and solubility of various glycoside-associated compounds is linked to Family-1 UDP-glycosyltransferase (EC 2.4.1.x; UGTs) enzymes. These glycosyltransferase enzymes play a vital role in diverse plant functions, such as regulation of hormonal homeostasis, growth and development (seed, flower, fiber, root, etc.), xenobiotic detoxification, stress response (salt, drought, and oxidative), and biosynthesis of secondary metabolites. Here, we report a genome-wide analysis of the P. trichocarpa genome that identified 191 putative UGTs distributed across all chromosomes (with the exception of chromosome 20) based on 44 conserved plant secondary product glycosyltransferase (PSPG) motif amino acid sequences. Phylogenetic analysis of the 191 Populus UGTs together with 22 referenced UGTs from Arabidopsis and maize clustered the putative UGTs into 16 major groups (A&ndash;P). Whole-genome duplication events were the dominant pattern of duplication among UGTs in Populus. A well-conserved intron insertion was detected in most intron-containing UGTs across eight examined eudicots, including Populus. Most of the UGT genes were found preferentially expressed in leaf and root tissues in general. The regulation of putative UGT expression in response to drought, salt and heat stress was observed based on microarray and available RNA sequencing datasets. Up- and down-regulated UGT expression models were designed, based on transcripts per kilobase million values, confirmed their maximally varied expression under drought, salt and heat stresses. Co-expression networking of putative UGTs indicated their maximum co-expression with cytochrome P450 genes involved in triterpenoid biosynthesis. Our results provide an important resource for the identification of functional UGT genes to manipulate abiotic stress responsive glycosylation in Populus

Using Exogenous Melatonin, Glutathione, Proline, and Glycine Betaine Treatments to Combat Abiotic Stresses in Crops

Abiotic stresses, such as drought, salinity, heat, cold, and heavy metals, are associated with global climate change and hamper plant growth and development, affecting crop yields and quality. However, the negative effects of abiotic stresses can be mitigated through exogenous treatments using small biomolecules. For example, the foliar application of melatonin provides the following: it protects the photosynthetic apparatus; it increases the antioxidant defenses, osmoprotectant, and soluble sugar levels; it prevents tissue damage and reduces electrolyte leakage; it improves reactive oxygen species (ROS) scavenging; and it increases biomass, maintains the redox and ion homeostasis, and improves gaseous exchange. Glutathione spray upregulates the glyoxalase system, reduces methylglyoxal (MG) toxicity and oxidative stress, decreases hydrogen peroxide and malondialdehyde accumulation, improves the defense mechanisms, tissue repairs, and nitrogen fixation, and upregulates the phytochelatins. The exogenous application of proline enhances growth and other physiological characteristics, upregulates osmoprotection, protects the integrity of the plasma lemma, reduces lipid peroxidation, increases photosynthetic pigments, phenolic acids, flavonoids, and amino acids, and enhances stress tolerance, carbon fixation, and leaf nitrogen content. The foliar application of glycine betaine improves growth, upregulates osmoprotection and osmoregulation, increases relative water content, net photosynthetic rate, and catalase activity, decreases photorespiration, ion leakage, and lipid peroxidation, protects the oxygen-evolving complex, and prevents chlorosis. Chemical priming has various important advantages over transgenic technology as it is typically more affordable for farmers and safe for plants, people, and animals, while being considered environmentally acceptable. Chemical priming helps to improve the quality and quantity of the yield. This review summarizes and discusses how exogenous melatonin, glutathione, proline, and glycine betaine can help crops combat abiotic stresses

Investigation of Euphorbia nivulia-HAM for Enzyme Inhibition Potential in Relation to the Phenolic and Flavonoid Contents and Radical Scavenging Activity

Euphorbia nivulia-Ham (EN) is a neglected medicinal plant traditionally used for a number of pathologies, but it has not been explored scientifically. In the current study, its various fractions were assessed for their phenolic and flavonoid content, radical scavenging, as well as its enzyme inhibitory potential. The hydro-alcoholic crude extract (ENCr) was subjected to a fractionation scheme to obtain different fractions, namely n-hexane (ENHF), chloroform (ENCF), n-butanol (ENBF), and aqueous fraction (ENAF). The obtained results revealed that the highest phenolic and flavonoid content, maximum radical scavenging potential (91 &plusmn; 0.55%), urease inhibition (54.36 &plusmn; 1.47%), and &alpha;-glucosidase inhibition (97.84 &plusmn; 1.87%) were exhibited by ENCr, while the ENBF fraction exhibited the highest acetylcholinestrase inhibition (57.32 &plusmn; 0.43%). Contrary to these, hydro-alcoholic crude as well as the other fractions showed no significant butyrylcholinestrases (BChE) and carbonic anhydrase inhibition activity. Conclusively, it was found that EN possesses a significant radical scavenging and enzyme inhibitory potential. Thus, the study may be regarded a step forward towards evidence-based phyto-medicine