Identification of novel inhibitors targeting TIRAP interactions with BTK and PKCδ in inflammation through an in silico approach.

Advanced computational tools focusing on protein-protein interaction (PPI) based drug development is a powerful platform to accelerate the therapeutic development of small lead molecules and repurposed drugs. Toll/interleukin-1 receptor (TIR) domain-containing adapter protein (TIRAP) and its interactions with other proteins in macrophages signalling are crucial components of severe or persistent inflammation. TIRAP activation through Bruton's tyrosine kinase (BTK) and Protein Kinase C delta (PKCδ) is essential for downstream inflammatory signalling. We created homology-based structural models of BTK and PKCδ in MODELLER 9.24. TIRAP interactions with BTK and PKCδ in its non-phosphorylated and phosphorylated states were determined by multiple docking tools including HADDOCK 2.4, pyDockWEB and ClusPro 2.0. Food and Drug Administration (FDA)-approved drugs were virtually screened through Discovery Studio LibDock and Autodock Vina tools to target the common TIR domain residues of TIRAP, which interact with both BTK and PKC at the identified interfacial sites of the complexes. Four FDA-approved drugs were identified and found to have stable interactions over a range of 100 ns MD simulation timescales. These drugs block the interactions of both kinases with TIRAP in silico. Hence, these drugs have the potential to dampen downstream inflammatory signalling and inflammation-mediated disease.

Double zero tillage and foliar phosphorus fertilization coupled with microbial inoculants enhance maize productivity and quality in a maize-wheat rotation.

Maize is an important industrial crop where yield and quality enhancement both assume greater importance. Clean production technologies like conservation agriculture and integrated nutrient management hold the key to enhance productivity and quality besides improving soil health and environment. Hence, maize productivity and quality were assessed under a maize-wheat cropping system (MWCS) using four crop-establishment and tillage management practices [FBCT-FBCT (Flat bed-conventional tillage both in maize and wheat); RBCT-RBZT (Raised bed-CT in maize and raised bed-zero tillage in wheat); FBZT-FBZT (FBZT both in maize and wheat); PRBZT-PRBZT (Permanent raised bed-ZT both in maize and wheat], and five P-fertilization practices [P100 (100% soil applied-P); P50 + 2FSP (50% soil applied-P + 2 foliar-sprays of P through 2% DAP both in maize and wheat); P50 + PSB + AM-fungi; P50 + PSB + AMF + 2FSP; and P0 (100% NK with no-P)] in split-plot design replicated-thrice. Double zero-tilled PRBZT-PRBZT system significantly enhanced the maize grain, starch, protein and oil yield by 13.1-19% over conventional FBCT-FBCT. P50 + PSB + AMF + 2FSP, integrating soil applied-P, microbial-inoculants and foliar-P, had significantly higher grain, starch, protein and oil yield by 12.5-17.2% over P100 besides saving 34.7% fertilizer-P both in maize and on cropping-system basis. P50 + PSB + AMF + 2FSP again had significantly higher starch, lysine and tryptophan content by 4.6-10.4% over P100 due to sustained and synchronized P-bioavailability. Higher amylose content (24.1%) was observed in grains under P50 + PSB + AMF + 2FSP, a beneficial trait due to its lower glycemic-index highly required for diabetic patients, where current COVID-19 pandemic further necessitated the use of such dietary ingredients. Double zero-tilled PRBZT-PRBZT reported greater MUFA (oleic acid, 37.1%), MUFA: PUFA ratio and P/S index with 6.9% higher P/S index in corn-oil (an oil quality parameter highly required for heart-health) over RBCT-RBCT. MUFA, MUFA: PUFA ratio and P/S index were also higher under P50 + PSB + AMF + 2FSP; avowing the obvious role of foliar-P and microbial-inoculants in influencing maize fatty acid composition. Overall, double zero-tilled PRBZT-PRBZT with crop residue retention at 6 t/ha per year along with P50 + PSB + AMF + 2FSP while saving 34.7% fertilizer-P in MWCS, may prove beneficial in enhancing maize productivity and quality so as to reinforce the food and nutritional security besides boosting food, corn-oil and starch industry in south-Asia and collateral arid agro-ecologies across the globe.

Hand hygiene compliance of patients' family members in India: importance of educating the unofficial 'fourth category' of healthcare personnel.

INTRODUCTION: In India, due to manpower constraints, patients' family members are often actively involved in healthcare activities of their near and dear ones. They have significant contact with the patient at all World Health Organization (WHO) 'five moments for hand hygiene'. This study analysed the impact of decade-long awareness campaigns on the hand hygiene compliance (HHC) by our patients' carers. METHODS: Trained infection control nurses observed the HHC at each of the five moments for patients' attendants in different hospital settings from January 2014 to December 2018. Compliance was calculated as percentage of events divided by total opportunities. FINDINGS: A total of 7302 opportunities were observed with an overall compliance of 46.1% (35.5% in 2014 to 48.2% in 2018, P < 0.0001). Compliance at WHO moments 1, 2, 3, 4, and 5 was 51.0%, 47.4%, 67.6%, 48.8%, and 24.3% respectively. Among family members, mothers of newborns had a much higher HHC (77%) than others (44.5%) (P < 0.0001). Also, the compliance was higher in medical versus surgical wards and in paediatric wards versus adult wards (P < 0.0001 in both). CONCLUSION: This is the first study on family members' HHC in a hospital setting in a low- and middle-income country. The study shows that family members, once trained, exhibit fairly good HHC while caring for their patients, especially mothers of newborns. It is worthwhile empowering and educating patient attendants about the importance and process of hand hygiene as it is likely to result in immense benefit for patients.