SUPFAM: A database of sequence superfamilies of protein domains

BACKGROUND: SUPFAM database is a compilation of superfamily relationships between protein domain families of either known or unknown 3-D structure. In SUPFAM, sequence families from Pfam and structural families from SCOP are associated, using profile matching, to result in sequence superfamilies of known structure. Subsequently all-against-all family profile matches are made to deduce a list of new potential superfamilies of yet unknown structure. DESCRIPTION: The current version of SUPFAM (release 1.4) corresponds to significant enhancements and major developments compared to the earlier and basic version. In the present version we have used RPS-BLAST, which is robust and sensitive, for profile matching. The reliability of connections between protein families is ensured better than before by use of benchmarked criteria involving strict e-value cut-off and a minimal alignment length condition. An e-value based indication of reliability of connections is now presented in the database. Web access to a RPS-BLAST-based tool to associate a query sequence to one of the family profiles in SUPFAM is available with the current release. In terms of the scientific content the present release of SUPFAM is entirely reorganized with the use of 6190 Pfam families and 2317 structural families derived from SCOP. Due to a steep increase in the number of sequence and structural families used in SUPFAM the details of scientific content in the present release are almost entirely complementary to previous basic version. Of the 2286 families, we could relate 245 Pfam families with apparently no structural information to families of known 3-D structures, thus resulting in the identification of new families in the existing superfamilies. Using the profiles of 3904 Pfam families of yet unknown structure, an all-against-all comparison involving sequence-profile match resulted in clustering of 96 Pfam families into 39 new potential superfamilies. CONCLUSION: SUPFAM presents many non-trivial superfamily relationships of sequence families involved in a variety of functions and hence the information content is of interest to a wide scientific community. The grouping of related proteins without a known structure in SUPFAM is useful in identifying priority targets for structural genomics initiatives and in the assignment of putative functions. Database URL:

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

Production of conjugated linoleic acid by lactic acid bacteria in milk without any additional substrate

This study was undertaken to evaluate the production and isomeric distribution of conjugated linoleic acid (CLA) in milk fermented with lactic acid bacteria (LAB. A total of 155 cultures of LAB were analysed. Control milk samples had an average CLA content of 0.41 g/100 g of fatty acids (FA), while the lactic cultures produced CLA in the range of 0.43–1.12 g. No major changes in free fatty acids profiles were observed in milk samples fermented with CLA-producing LAB. The present study demonstrated that LAB can increase levels of CLA in nonsupplemented milk fermented for a short period of 4 h

Early time to positivity in blood cultures as an indicator of mortality in very low birth weight neonates – A retrospective observational cohort study

Introduction: Neonatal sepsis is an important cause of mortality. Blood culture is the gold standard for the diagnosis. Time to positivity (TTP) in blood cultures may help in early optimization of treatment in sick neonates.  Methods: This was an observational study. Data records were collected for all neonates who were screened for both early- and late-onset sepsis. BacT/Alert system was used for culture detection. For every positive culture, TTP was calculated as the difference between loading time and detection time. Primary outcome was correlation of TTP with mortality due to culture-proven sepsis in gestational age ≤ 34 weeks.  Results: 151 VLBW neonates with culture-proven sepsis were included in the study over a period of 22 months. Gram-negative organisms were the predominant isolates, with Klebsiella pneumoniae being the commonest organism. Median TTP was significantly lower in the mortality group (9 hours, IQR 5-24) versus the survivor group (20 hours, IQR 9-78) with a p-value < 0.001. Early-onset sepsis was significantly higher in the mortality group (60%) versus the no-mortality group (27.9%). On multivariate analysis, TTP was the only factor significant in the neonatal mortality amongst the cohort with a p-value < 0.001 and AOR 1.54, 95% CI 1.22-1.93, indicating higher odds of death in neonates with a shorter duration of TTP. Conclusions: TTP is an important predictor of neonatal mortality. Neonates with shorter TTP had higher odds of neonatal mortality due to sepsis. Thus, TTP can be used as a guide for optimal and judicious treatment in neonatal sepsis

Conjugated linoleic acid content in retail Cheddar cheeses.

Conjugated linoleic acid (CLA) refers to the isomers of linoleic acid that have the conjugated bond system. Several health benefits including anticarcinogenicity and weight loss have been associated with the intake of CLA. For healthy individuals weighing around 70 kg, CLA consumption at about 3g per day has been recommended for maintaining these health benefits. Dairy products, especially cheeses are considered rich sources of CLA. This study was undertaken to determine the CLA content in retail Cheddar cheeses available in grocery stores in a midwest region of the US. Twenty-seven samples of different brands of Cheddar cheeses were evaluated for CLA contents. These cheese samples were categorized as: Extra sharp, Sharp, and Mild/medium based on the information available on the label. Cheese samples showed CLA content in the range of 0.61-1.04, 0.62-0.87, and 0.45-1.09 g/100g fatty acids (FA), respectively. Fatty acids profiles showed minor differences for the three cheese categories