CORRELATION OF TWO PYRAZOLINE MOIETY IN A SINGLE MOLECULE VIA N-LINKAGE CONTAINING FLUORINE ATOM AS A SUBSTITUENT AND THEIR BIOLOGICAL SIGNIFICANCE

Objective: The aim of the present invention is to synthesize and find out the biological importance of the series of the designed pyrazoline compounds. Methods: A series of 3-[3'-(2â€,4â€-dichloro-5â€-fluorophenyl)-5'-(2â€-furyl)-4', 5'-dihydro-1H-pyrazol-1'-yl]-5-substituted phenyl-2-pyrazolines (2a-j) and 1-Nitroso-3-[3'-(2â€,4â€-dichloro-5â€-fluorophenyl)-5'-(2â€-furyl)-4', 5'-dihydro-1H-pyrazol-1'-yl]-5-substituted phenyl-2-pyrazolines (3a-j) were prepared in moderate yields. The structures of both pyrazoline and N-nitroso pyrazoline derivatives have been characterized on the basis of physical properties of the molecule and satisfactory spectral (IR, 1H NMR) data. The antimicrobial activity of the compounds against some Gram (+) and Gram (–) bacteria is reported. Results: The Moderate yield of the proposed compounds was obtained. Spectral analysis showed the structural confirmation of the synthesized compounds. Some of the compounds showed lower to moderate level of drug-like properties. Conclusion: From the results of spectral data and microbial activity it has been concluded that the compounds were found to exhibit some functional lead properties; hence these compounds are worth to be considered as potential lead molecules for further study

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.

Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (rG) between PSC and ulcerative colitis (UC) (rG = 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (rG = 0.04) (P = 2.55 × 10-15). UC and CD were genetically more similar to each other (rG = 0.56) than either was to PSC (P < 1.0 × 10-15). Our study represents a substantial advance in understanding of the genetics of PSC

Influence of practice on visual reaction time

Background: The present study was aimed to see the effect of practice on visual information processing speed. Reaction time is one of the important physiological parameters, which gives information how fast and quickly person responses. Reaction is purposeful voluntary response to different stimuli as visual stimuli. Visual reaction time (VRT) is the time required to response to visual stimuli. Materials and Methods: The VRT was measured by the multiple choice apparatus in subjects. Simple reaction time and choice reaction time measured. Reaction time was measured in two sessions. In the first session, VRT was measured without practice of task and in the second session VRT was measured after practice of task. The results were statistically analyzed and were recorded as mean ± standard deviation and Student′s paired t-test was applied to check the level of significance. Result and Conclusion: In the present study, we found that VRT was less after practice for both simple and choice VRT tasks. Reaction time decreases by practice. Skills can be improved by practice. In daily life majority of work is done by the use of visual information. By the practice of an important task time required for stimulus identification and response can be decreased. Practice is useful for driving vehicles. It is helpful to students, as they have identification of bones, instruments, graphs and viva questions in examination of various medical subjects. Hence by practice students can identify, understand and answer quickly

Adverse drug reaction profile of oseltamivir in Indian population: A prospective observational study

Objectives: To analyze the pattern of adverse drug reactions (ADRs) of oseltamivir and its comparison with available data. Materials and Methods: Suspected or confirmed cases of H1N1 influenza A on therapeutic regimen and close contacts of cases H1N1 influenza A on prophylactic regimen of oseltamivir were included. Data were collected by personal interview after obtaining written informed consent. Causality, severity, and preventability assessments were done by using Naranjo′s scale, modified Hartwig and Siegel′s scale, and modified Schumock and Thornton Scale, respectively. Data were expressed in proportions. Frequency of ADRs in therapeutic and prophylactic groups were compared with phase III trial of oseltamivir by using Chi-square test. Results: Total 294 patients were interviewed. In prophylactic group, 107 of 257 (41.63%) and in therapeutic, group 23 of 37 (62.16%) developed ADRs. ADRs reported in therapeutic group was significantly (P = 0.029) higher as compared with prophylactic group. Frequently observed ADRs in both the groups were gastritis, nausea, vomiting, diarrhea weakness, sedation, loneliness, sadness, headache, and abdominal pain. Naranjo′s algorithm showed all ADRs in probable category in prophylactic group, 27.78% probable and 72.22% possible reactions in therapeutic group. Severity assessment showed 76% mild and 24% moderate reactions in therapeutic group, 89% mild and 11% moderate reactions in prophylactic group. Severity of ADRs was significantly higher in therapeutic group. Most of ADRs were in nonpreventable category, except gastritis, nausea and vomiting were in definitely preventable category. Conclusion: Oseltamivir is well tolerated in Indian population. Gastrointestinal side effects are most common and preventable

Climate Change Adaptation: Prehospital Data Facilitate the Detection of Acute Heat Illness in India

Introduction: Extreme heat is a significant cause of morbidity and mortality, and the incidence of acute heat illness (AHI) will likely increase secondary to anthropogenic climate change. Prompt diagnosis and treatment of AHI are critical; however, relevant diagnostic and surveillance tools have received little attention. In this exploratory cross-sectional and diagnostic accuracy study, we evaluated three tools for use in the prehospital setting: 1) case definitions; 2) portable loggers to measure on-scene heat exposure; and 3) prevalence data for potential AHI risk factors.Methods: We enrolled 480 patients who presented to emergency medical services with chief complaints consistent with AHI in Ahmedabad, India, from April–June 2016 in a cross-sectional study. We evaluated AHI case definition test characteristics in reference to trained prehospital provider impressions, compared on-scene heat index measured by portable loggers to weather station measurements, and identified AHI behavioral and environmental risk factors using logistic regression.Results: The case definition for heat exhaustion was 23.8% (12.1-39.5%) sensitive and 93.6% (90.9-95.7%) specific. The positive and negative predictive values were 33.5% (20.8-49.0%) and 90.1% (88.5-91.5%), respectively. Mean scene heat index was 6.7°C higher than the mean station heat index (P &lt; 0.001), and station data systematically underestimated heat exposure, particularly for AHI cases. Heat exhaustion cases were associated with on-scene heat index ≥ 49°C (odds ratio [OR] 2.66 [1.13–6.25], P = 0.025) and a history of recent exertion (OR 3.66 [1.30–10.29], P = 0.014), while on-scene air conditioning was protective (OR 0.29 [0.10–0.85], P = 0.024).Conclusion: Systematic collection of prehospital data including recent activity history and presence of air conditioning can facilitate early AHI detection, timely intervention, and surveillance. Scene temperature data can be reliably collected and improve heat exposure and AHI risk assessment. Such data may be important elements of surveillance, clinical practice, and climate change adaptation

Effect of desiccating stress on mouse meibomian gland function

Purpose Mice exposed to standardized desiccating environmental stress to induce dry eye-like symptoms have been used as a model to study the underlying mechanisms of evaporative dry eye. While studies have shown marked inflammatory and immune changes, the effect of such stress on meibomian gland function remains largely unknown. We sought to evaluate the effects of desiccating stress on meibocyte proliferation and meibum quality. Methods Ten mice were treated with scopolamine and subjected to a drafty low humidity environment (30-35%). Five and ten days after treatment, eyelids were harvested and cryosections stained with Ki67 antibody to identify cycling cells. Sections were also imaged using stimulated Raman scattering (SRS) microscopy to characterize the gland compositional changes by detecting the vibrational signatures of methylene (lipid) and amide-I (protein). Results Desiccating stress caused a 3-fold increase in basal acinar cell proliferation from 18.3 ± 11.1% in untreated mice to 64.4 ± 19.9% and 66.6 ± 13.4% after 5 and 10 days exposure, respectively (P < .001). In addition, SRS analysis showed a wider variation in the protein-to-lipid ratio throughout the gland, suggesting alterations in meibocyte differentiation and lipid synthesis. Conclusions These data are consistent with a model that a desiccating environment may have a direct effect on meibomian gland function, leading to a significant increase in basal acinar cell proliferation, abnormal meibocyte differentiation, and altered lipid production

Climate Change Adaptation: Prehospital Data Facilitate the Detection of Acute Heat Illness in India

Introduction: Extreme heat is a significant cause of morbidity and mortality, and the incidence of acute heat illness (AHI) will likely increase secondary to anthropogenic climate change. Prompt diagnosis and treatment of AHI are critical; however, relevant diagnostic and surveillance tools have received little attention. In this exploratory cross-sectional and diagnostic accuracy study, we evaluated three tools for use in the prehospital setting: 1) case definitions; 2) portable loggers to measure on-scene heat exposure; and 3) prevalence data for potential AHI risk factors.Methods: We enrolled 480 patients who presented to emergency medical services with chief complaints consistent with AHI in Ahmedabad, India, from April–June 2016 in a cross-sectional study. We evaluated AHI case definition test characteristics in reference to trained prehospital provider impressions, compared on-scene heat index measured by portable loggers to weather station measurements, and identified AHI behavioral and environmental risk factors using logistic regression.Results: The case definition for heat exhaustion was 23.8% (12.1-39.5%) sensitive and 93.6% (90.9-95.7%) specific. The positive and negative predictive values were 33.5% (20.8-49.0%) and 90.1% (88.5-91.5%), respectively. Mean scene heat index was 6.7°C higher than the mean station heat index (P &lt; 0.001), and station data systematically underestimated heat exposure, particularly for AHI cases. Heat exhaustion cases were associated with on-scene heat index ≥ 49°C (odds ratio [OR] 2.66 [1.13–6.25], P = 0.025) and a history of recent exertion (OR 3.66 [1.30–10.29], P = 0.014), while on-scene air conditioning was protective (OR 0.29 [0.10–0.85], P = 0.024).Conclusion: Systematic collection of prehospital data including recent activity history and presence of air conditioning can facilitate early AHI detection, timely intervention, and surveillance. Scene temperature data can be reliably collected and improve heat exposure and AHI risk assessment. Such data may be important elements of surveillance, clinical practice, and climate change adaptation

Building Resilience to Climate Change: Pilot Evaluation of the Impact of India’s First Heat Action Plan on All-Cause Mortality

Background. Ahmedabad implemented South Asia’s first heat action plan (HAP) after a 2010 heatwave. This study evaluates the HAP’s impact on all-cause mortality in 2014–2015 relative to a 2007–2010 baseline. Methods. We analyzed daily maximum temperature (Tmax)-mortality relationships before and after HAP. We estimated rate ratios (RRs) for daily mortality using distributed lag nonlinear models and mortality incidence rates (IRs) for HAP warning days, comparing pre- and post-HAP periods, and calculated incidence rate ratios (IRRs). We estimated the number of deaths avoided after HAP implementation using pre- and post-HAP IRs. Results. The maximum pre-HAP RR was 2.34 (95%CI 1.98–2.76) at 47°C (lag 0), and the maximum post-HAP RR was 1.25 (1.02–1.53) estimated at 47°C (lag 0). Post-to-pre-HAP nonlagged mortality IRR for Tmax over 40°C was 0.95 (0.73–1.22) and 0.73 (0.29–1.81) for Tmax over 45°C. An estimated 1,190 (95%CI 162–2,218) average annualized deaths were avoided in the post-HAP period. Conclusion. Extreme heat and HAP warnings after implementation were associated with decreased summertime all-cause mortality rates, with largest declines at highest temperatures. Ahmedabad’s plan can serve as a guide for other cities attempting to increase resilience to extreme heat