Design, synthesis, molecular docking and DFT studies on novel melatonin and isatin based azole derivatives.

In order to address the pressing demand for newer broad-spectrum antifungal medicines with enhanced activity, computer modelling was utilised to rationally develop newer antifungal azole-based drugs. Based on the drug and active sites of the Lanosterol 14 alpha-Demethylases (LAD) of the prominent fungal pathogen Candida albicans interaction, Novel triazole-linked melatonin and isatin derivatives 7a-d and 8a-d were synthesised using bioisosterism. Besides the experimental synthesis and subsequent characterization, the present study focused on obtaining optimised geometries, frequency calculations, and TD-DFT studies of the synthesised molecules. We also performed molecular docking studies to explore the inhibitory ability of the synthesised compounds against the active sites of the Lanosterol 14 alpha-Demethylases (LAD) of the prominent fungal pathogen Candida albicans. The binding interactions resulted in positive findings, demonstrating the involvement of the synthesised compounds in the suppression of fungal growth. Comparative analysis of the binding potential of the synthesised molecules and commercially available drug fluconazole revealed a remarkable note: the docking scores for the designed drugs 7b, 7c, and 8c are much greater than those of the fluconazole molecule. The in silico study of the designed series of drug molecules serves as an important guideline for further exploration in the quest for potent antifungal agents.

Targeting Insect Olfaction in vivo and in vitro Using Functional Imaging.

Insects decode volatile chemical signals from its surrounding environment with the help of its olfactory system, in a fast and reliable manner for its survival. In order to accomplish this task, odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs) in the fly's antenna process such odor information. In order to study such a sophisticated process, we require access to the sensory neurons to perform functional imaging. In this article, we present different preparations to monitor odor information processing in Drosophila melanogaster OSNs using functional imaging of their Ca2+ dynamics. First, we established an in vivo preparation to image specific OSN population expressing the fluorescent Ca2+ reporter GCaMP3 during OR activation with airborne odors. Next, we developed a method to extract and to embed OSNs in a silica hydrogel with OR activation by dissolved odors. The odor response dynamics under these different conditions was qualitatively similar which indicates that the reduction of complexity did not affect the concentration dependence of odor responses at OSN level.

Calmodulin regulates the olfactory performance in Drosophila melanogaster.

Insect odorant receptors (ORs) detect volatile chemical cues with high sensitivity. These ORs operate as ligand-gated ion channels and are formed by heptahelical OrX and Orco (co-receptor) proteins. A highly conserved calmodulin (CaM) binding site (CBS) 336SAIKYWVER344 within the second intracellular loop of Drosophila melanogaster Orco constitutes a target for regulating OR performance. Here we asked how a point mutation K339N in this CBS affects the olfactory performance of Drosophila melanogaster. We first asked how this mutation would affect the odor responses of olfactory sensory neurons (OSNs). Using Ca2+ imaging in an ex-vivo antenna preparation, we activated all OR (OrX/Orco) expressing neurons using the synthetic agonist VUAA1. In a next attempt, we restricted the OR spectrum to Or22a expressing neurons (Or22a/Orco) and stimulated these OSNs with the ligand ethyl hexanoate. In both approaches, we found that flies carrying the K339N point mutation in Orco display a reduced olfactory response. We also found that the mutation abolishes the capability of OSNs to sensitize by repeated weak odor stimuli. Next, we asked whether OrcoK339N might affect the odor localization performance. Using a wind tunnel bioassay, we found that odor localization in flies carrying the OrcoK339N mutation was severely diminished.

A study of prevalence of intestinal worm infestation and efficacy of anthelminthic drugs.

BACKGROUND: Intestinal worm infestation is a global health problem. Soil-transmitted helminth (STH) infections form the most important group of intestinal worms affecting two billion people worldwide, causing considerable morbidity and suffering, though entirely preventable. The present study was undertaken to measure the parasite load in the target population and evaluate the efficacy of anthelminthic drugs. METHODS: Current study was undertaken from 01 July 2012 to 30 June 2013. All outdoor as well as indoor patients advised stool examination formed the study population and it included 2656 males and 76 females (including 6 children). Investigations included stool examination and blood counts. A single-oral dose of anthelminthic drug was given to all positive cases. Stool tests were repeated after 14-21 days to evaluate cure rate. RESULTS: Overall prevalence of intestinal worm infection was found to be 49.38%. Ascaris was the most common parasite (46.88%), followed by Taenia (2.1%) and Hymenolepis nana (0.21%). Cure rate was found to be 66% for Ascaris and 100% in other cases. CONCLUSION: The study reveals high prevalence of intestinal helminths in our subject population and calls for immediate control measures, including preventive chemotherapy and treatment of entire 'at risk' population and improvement of their living conditions including provision of potable water.

Study on relation of metabolic syndrome with menopause.

This study is carried out to determine the prevalence of metabolic syndrome (MS) in 148 women between 36 to 65 years using the International Diabetes Federation criteria in the North-Eastern part of India. The prevalence of MS and all its individual components were found to be significantly higher among postmenopausal as compared to premenopausal and perimenopausal women. Various components of MS except waist circumference shows a significant increase and homeostasis model assessment index for insulin resistance also showed significant differences between the three groups. All the MS diagnostic markers (except serum high density lipoprotein) showed a strong positive correlation with MS score among the groups. Further MS score correlated with indicators of insulin resistance evaluated. This study concluded that MS is highly prevalent among North-East Indian postmenopausal women seeking primary health care and its determinant factors related to age and sedentary habits. Thus recognizing and treating MS early with proper intervention can minimize complication.

Legal awareness and responsibilities of nursing staff in administration of patient care in a trust hospital.

INTRODUCTION: The enactment of various legal provisions like Consumer Protection Act, Right to Information Act and standardization of procedures and practices have brought nursing care under legal ambit. Needless to say, the level of legal awareness amidst nursing staff in India is abysmally low. Present study was undertaken to assess the level of legal awareness and responsibilities of nursing staff in administration of patient care at a trust hospital. METHODS: An open ended questionnaire was prepared to assess the level of legal awareness among the nursing staff. The GNM and ANM nursing staff deployed at the nursing home and general wards only were randomly screened and specialty nurses were exempted. RESULTS: The knowledge on various legal provisions, as was applicable to nursing, across all categories of nurses which were under review, was found to be poor. The nursing staff had poor knowledge on patients' rights and also on their legal obligations towards patients. The GNM nurses fared better than ANM nurses. However, 46.67 % of nurses were found to be aware about cases of omission or commission. CONCLUSION: This study substantiated the fact that nurses had poor knowledge on the law that governed their profession and that in days to come, it would become increasingly difficult for them to avoid law suits which were prepared against them, unless remedial actions were taken.

Beneficial effects of carvedilol as a concomitant therapy to angiotensin-converting enzyme inhibitor in patients with ischemic left ventricular systolic dysfunction.

Studies are scant on the effects of short-term carvedilol treatment as an adjuvant to angiotensin-converting enzyme (ACE) inhibitor in patients with left ventricular (LV) systolic dysfunction. The objective of this study was to find the effects of short-term treatment of carvedilol on patients with ischemic LV systolic dysfunction (defined as LV ejection fraction (LVEF)