Discovery of HC-7366: An Orally Bioavailable and Efficacious GCN2 Kinase Activator.

A series of activators of GCN2 (general control nonderepressible 2) kinase have been developed, leading to HC-7366, which has entered the clinic as an antitumor therapy. Optimization resulted in improved permeability compared to that of the original indazole hinge binding scaffold, while maintaining potency at GCN2 and selectivity over PERK (protein kinase RNA-like endoplasmic reticulum kinase). The improved ADME properties of this series led to robust compound exposure in both rats and mice, allowing HC-7366 to be dosed in xenograft models, demonstrating that activation of the GCN2 pathway by this compound leads to tumor growth inhibition.

A National Cancer Grid pooled procurement initiative, India.

In health systems with little public funding and decentralized procurement processes, the pricing and quality of anti-cancer medicines directly affects access to effective anti-cancer therapy. Factors such as differential pricing, volume-dependent negotiation and reliance on low-priced generics without any evaluation of their quality can lead to supply and demand lags, high out-of-pocket expenditures for patients and poor treatment outcomes. While pooled procurement of medicines can help address some of these challenges, monitoring of the procurement process requires considerable administrative investment.

Post-operative pain and morbidity in children who have tooth extractions under general anaesthesia: a service evaluation.

Introduction Children find dental extractions under general anaesthesia (GA) painful despite national analgesic guidelines.Aims To report on children's post-operative pain, morbidity, families' satisfaction and analgesic regime during GA dental extractions.Design A prospective service evaluation.

Device-Associated Infection Rates in 20 Cities of India, Data Summary for 2004-2013: Findings of the International Nosocomial Infection Control Consortium.

Objective: To report the International Nosocomial Infection Control Consortium surveillance data from 40 hospitals (20 cities) in India 2004-2013.

Methods: Surveillance using US National Healthcare Safety Network's criteria and definitions, and International Nosocomial Infection Control Consortium methodology.

Results: We collected data from 236,700 ICU patients for 970,713 bed-days Pooled device-associated healthcare-associated infection rates for adult and pediatric ICUs were 5.

Surgical site infection rates in six cities of India: findings of the International Nosocomial Infection Control Consortium (INICC).

Background: Surgical site infections are a threat to patient safety. However, in India, data on their rates stratified by surgical procedure are not available.

Methods: From January 2005 to December 2011, the International Nosocomial Infection Control Consortium (INICC) conducted a cohort prospective surveillance study on surgical site infections in 10 hospitals in 6 Indian cities.

Simplified basic periodontal examination (BPE) in children and adolescents: a guide for general dental practitioners.

Unlabelled: Dental plaque-induced periodontal diseases are common in children and adults. Guidelines were previously not available for the periodontal screening of under 18s. However, new guidelines have been introduced by the British Society of Periodontology and the British Society of Paediatric Dentistry which set out recommendations for the periodontal screening and management of under 18s in primary dental care.

Cytohistological features of rhinoscleroma.

Rhinoscleroma, also known as Mikulicz disease, is a chronic progressive disease caused by Klebsiella rhinoscleromatis. The disease is uncommon in Delhi. There are no cytological references of this disease.