Design,synthesis, evaluation,and molecular modeling studies of indolyl oxoacetamides as potential pancreatic lipase inhibitors

A series of indolyl oxoacetamide analogs was synthesized, characterized, and evaluated for their pancreatic lipase inhibitory activity using porcine pancreatic lipase (type II) and 4-nitrophenyl butyrate. Compound 8d exhibited a potent inhibition, with an IC₅₀ value of 4.53 µM, followed by 8c (IC₅₀ = 5.12 µM), compared with the standard drug, orlistat (IC₅₀ = 0.99 µM). Furthermore, analogs 8c and 8d exhibited a reversible competitive inhibition, similar to orlistat. Molecular docking studies of the compounds 7a–f and 8a – f were in agreement with the in vitro results, wherein 8d exhibited a potential MolDock score of −163.052 kcal/mol. A 10-ns molecular dynamics simulation of 8d complexed with pancreatic lipase confirmed the role of π–π stacking and π–cation interactions with the lid domain and Arg 256, respectively, in stabilizing the ligand at the active site (maximum observed root mean square deviation ≈ 2 Å). The present study led to the identification of novel indolyl oxoacetamides ( 8a – d ) as potential pancreatic lipase inhibitory leads that might further result in enhanced potency through lead optimization.     

Impact of community-based behaviour-change management on perceived neonatal morbidity: a cluster-randomized controlled trial in Shivgarh, Uttar Pradesh, India

In the context of high neonatal mortality rate (NMR) in developing country settings, a promising strategy for enhancing newborn health is promotion of preventive newborn care practices. We measured the effect of a behaviour-change intervention on perceived neonatal illnesses in rural Uttar Pradesh, India. The study was nested in a cluster-randomized controlled trial of the impact of a package of essential newborn care on NMR. We prospectively enrolled 802 mothers and administered a questionnaire on perceived neonatal morbidities. Regression analysis showed that newborns in the intervention clusters had significantly lower risk of perceived diarrhoea [adjusted relative risk (aRR) 0.67, 95% confidence interval (CI) 0.49-0.90] and skin-related complications [aRR 0.67, 95% CI 0.45-1.00] compared to newborns in the comparison area. Assuming incidence of perceived illnesses is a proxy for actual morbidity rates, we conclude that promotion of preventive care practices through behaviour-change interventions was effective in reducing neonatal morbidities.     

Oversight in Surgical Innovation: A Response to Ethical Challenges

Background

Surgical innovation has advanced outcomes in the field, but carries inherent risk for surgeons and patients alike. Oversight mechanisms exist to support surgeon-innovators through difficulties associated with the innovation process.

Methods

A literature review of ethical risks and oversight mechanisms was conducted.

Results

Oversight mechanisms range from the historical concept of surgical exceptionalism to departmental, hospital, and centralized committees. These fragmentary and non-standardized oversight mechanisms leave surgeon-innovators and patients open to significant risk of breaching the ethical principles at the core of surgical practice. A systematized approach that mitigates these risks while maintaining the independence and dignity of the surgical profession is necessary. We propose an oversight framework that incorporates multiple structures tailored toward the ethical risk introduced by different forms of innovation.

Discussion

We summarize ethical risks and current regulatory structures, and we then use these findings to outline an oversight framework that may be applied to surgical practice.

     

Neonatal health program management in a resource‐constrained setting in rural Uttar Pradesh,India

This analysis identifies salient features of team management that were critical to the efficiency of program implementation and the effectiveness of behavior change management to promote essential newborn care practices in Uttar Pradesh, India. In May 2003, the Johns Hopkins Bloomberg School of Public Health and King George Medical University initiated a cluster‐randomized, controlled neonatal health research program. In less than 2 years, the trial demonstrated rapid adoption of several evidence‐based newborn care practices and a substantial reduction in neonatal mortality in intervention clusters. Existing literature involving research program management in resource‐constrained areas of developing countries is limited and fails to provide models for team organization and empowerment. The neonatal research project examined in this paper developed a unique management strategy that provides an effective blueprint for future projects. Transferable learning points from the project include emphasizing a common vision, utilizing a live‐in field site office, prioritizing character and potential in the hiring process, implementing a learning‐by‐doing training program, creating tiers of staff recognition, encouraging staff autonomy, ensuring a broad staff knowledge base to seamlessly handle absences, and maintaining the flexibility to change partnerships or strategies. Copyright © 2009 John Wiley & Sons, Ltd.     

Impact of insurance on hospital course and readmission after resection of benign meningioma

Journal of Neuro-Oncology - We investigated multi-domain baseline neurocognition of primary brain tumor patients prior to radiotherapy (RT), including clinical predictors of function and...     

The diagnosis and management of primary and iatrogenic soft tissue sarcomas of the sella

Pituitary - Soft tissue sarcoma (STS) of the sella is exceptionally rare. We conducted a case series, literature review, and nationwide analysis of primary and iatrogenic (radiation-associated) STS...     

Community-driven impact of a newborn-focused behavioral intervention on maternal health in Shivgarh, India

ObjectiveTo assess the effect on maternal health outcomes of a community-based behavior change management intervention for essential newborn care leading to a reduction in neonatal mortality.MethodsA cluster-randomized controlled trial involving 1 control and 2 intervention arms was conducted in Shivgarh, India, between January 2004 and May 2005. Risk-enhancing domiciliary newborn care behaviors, including those posing a concomitant risk to maternal health, were targeted through home visits and community meetings. Secondary outcomes included knowledge of maternal danger signs, self-reported complications, maternal care practices, care-seeking from trained providers, and maternal mortality ratio (MMR). The intervention arms were combined for analysis, which was done by intention to treat.ResultsSignificant improvements were observed in maternal health equity and outcomes including knowledge of danger signs, care practices, self-reported complications, and timely care-seeking from trained providers. The difference in adjusted MMR was not significant (relative risk 0.44; 95% confidence interval, 0.14–1.43; P = 0.11) owing to the inadequate sample size for this outcome, but may suggest a decline in MMR given improvements in other outcomes in the causal pathway to mortality.ConclusionCommunity-based strategies focused on prevention and care-seeking effectively complemented facility-based strategies toward improving maternal health, while synergizing with newborn care interventions.     

Development of a Formability Prediction Model for Aluminium Sandwich Panels with Polymer Core

In the present work, the compatibility relationship on the failure criteria between aluminium and polymer was established, and a mechanics-based model for a three-layered sandwich panel was developed based on the M-K model to predict its Forming Limit Diagram (FLD). A case study for a sandwich panel consisting of face layers from AA5754 aluminium alloy and a core layer from polyvinylidene difluoride (PVDF) was subsequently conducted, suggesting that the loading path of aluminium was linear and independent of the punch radius, while the risk for failure of PVDF increased with a decreasing radius and an increasing strain ratio. Therefore, the developed formability model would be conducive to the safety evaluation on the plastic forming and critical failure of composite sandwich panels.