ANTIFUNGAL ACTIVITY OF BIPHENYL-2,6-DIETHANONE DERIVATIVES

Objective: The objective of the study was to evaluate the antifungal activity of biphenyl-2,6-diethanone derivatives against Cryptococcus neoformans.Methods: Antifungal activity of biphenyl derivatives were evaluated against C. neoformans. Zone of inhibition by disc diffusion method and minimum inhibitory concentration (MIC) using micro-broth dilution method was performed as per clinical and laboratory standard institute (CLSI). Melanin was extracted using 1M KOH, purified using 6M HCL and its reduction was assayed spectrophotometrically at 530 nm. Laccase activity was measured using L-DOPA as substrate and was assayed spectrophotometrically at 480 nm. Time kill assay was also performed to compare the antifungal potency of the test compound against azole drug.Results: Zone of inhibition of 12 mm diameter was estimated against C. neoformans. MIC80 of compound 1e was calculated as 50µg/ml. 63.67% decrease in melanization and 57.44% laccase activity reduction was determined. The Time-kill assay illustrated that the compound 1e inhibited the growth of C. neoformans cells in almost the same duration as observed in fluconazole.Conclusion: The outcome of in vitro antifungal studies indicated that compound 1e demonstrated maximum reduction of melanin and laccase activity in C. neoformans. In conclusion, biphenyl-2,6-diethanone derivatives possess significant antifungal property which can be explored further for lead generation.Â

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Optogenetic control of kinesins -1, -2, -3 and dynein reveals their specific roles in vesicular transport

Each cargo in a cell employs a unique set of motor proteins for its transport. Often multiple types of kinesins are bound to the same cargo. It is puzzling why several types of motors are required for robust transport. To dissect the roles of each type of motor, we developed optogenetic inhibitors of kinesin-1, -2, -3 and dynein. This system allows us to control the activity of the endogenous set of motor proteins that are bound to intracellular cargoes. We examined the effect of optogenetic inhibition of kinesins-1, -2, and -3 and dynein on the transport of early endosomes, late endosomes, and lysosomes. While kinesin-1, kinesin-3, and dynein transport vesicles at all stages of endocytosis, kinesin-2 primarily drives late endosomes and lysosomes. In agreement with previous studies, sustained inhibition of either kinesins or dynein results in reduced motility in both directions. However, transient, optogenetic inhibition of kinesin-1 or dynein causes both early and late endosomes to move more processively by relieving competition with opposing motors. In contrast, optogenetic inhibition of kinesin-2 reduces the motility of late endosomes and lysosomes, and inhibition of kinesin-3 reduces the motility of endosomes and lysosomes. These results suggest that the directionality of transport is likely controlled through regulating kinesin-1 and dynein activity. On vesicles transported by several kinesin and dynein motors, motility can be directed by modulating the activity of a single type of motor on the cargo

The impact of primary open-angle glaucoma: Quality of life in Indian patients

Purpose: Glaucoma significantly affects the quality of life (QoL) of a patient. Despite the huge number of glaucoma patients in India, not many, QoL studies have been carried out. The purpose of the present study was to evaluate the QoL in Indian patients with varying severity of glaucoma. Methods: This was a hospital-based, cross-sectional, analytical study of 180 patients. The QoL was assessed using orally administered QoL instruments comprising of two glaucoma-specific instruments; Glaucoma Quality of Life-15 (GQL-15) and Viswanathan 10 instrument, and 1 vision-specific instrument; National Eye Institute Visual Function Questionnaire-25 (NEIVFQ25). Results: Using NEIVFQ25, the difference between mean QoL scores among cases (88.34 ± 4.53) and controls (95.32 ± 5.76) was statistically significant. In GQL-15, there was a statistically significant difference between mean scores of cases (22.58 ± 5.23) and controls (16.52 ± 1.24). The difference in mean scores with Viswanathan 10 instrument in cases (7.92 ± 0.54) and controls (9.475 ± 0.505) was also statistically significant. QoL scores also showed moderate correlation with mean deviation, pattern standard deviation, and vertical cup-disc ratio. Conclusion: In our study, all the three instruments showed decrease in QoL in glaucoma patients compared to controls. With the increase in severity of glaucoma, corresponding decrease in QoL was observed. It is important for ophthalmologists to understand about the QoL in glaucoma patients so as to have a more holistic approach to patients and for effective delivery of treatment

Cigarette Smoking Behavior and Associated Psychosocial Determinants Among School Going Adolescents in Panchkula, India

Introduction: Seventy percent of premature deaths in adults occur owing to harmful behavioral patterns such as smoking that emerged in adolescence. The rising trend of adolescent addiction to cigarettes is a cause for worry. Aim: To assess the prevalence of cigarette smoking in adolescents and to investigate the different psychosocial determinants which influence them to either smoke or not to smoke. Materials and Methods: A cross-sectional study was conducted in higher secondary schools of Panchkula, India. A self-structured questionnaire was used to assess the smoking behavior and other associated factors among 584 school going adolescents in the age group of 14–19 years. The proportion, the chi-square test, and bivariate and multivariate logistic regressions were applied. All analyses were done using the Statistical Package for Social Sciences, version 17.0 software. Results: The prevalence of ever smokers was 13.5% including 10.5% males and 3% females. Male students were more likely to ever smoke than females [odds ratio (OR) = 4.01; 95% confidence interval (CI): 2.84–6.14]. Subjects in the late adolescence were more likely to ever smoke than the middle adolescents (OR = 2.18; 95% CI: 1.18–3.67). Students in grade 12 had more than four times the odds of ever smoke than those in grade 10 (OR = 3.83; 95% CI: 2.34–5.67). Cigarette smoking was six times more likely if students had seen their sibling ever smoke (OR = 6.3; 95% CI: 3.16–9.69), three times more likely if a best friend smoked (OR = 3.18; 95% CI: 1.82–5.67), and two times more likely in students who had seen their father smoking (OR = 2.18; 95% CI: 1.67–2.84). Conclusion: A strong association exists between cigarette smoking behavior and different psychosocial factors, highlighting the need for efforts from parents, siblings, teachers, and peer groups to discourage smoking behavior

The shifting care and outcomes for patients with endangered limbs - Critical limb ischemia (SCOPE-CLI) registry overview of study design and rationale.

Background: Critical limb ischemia (CLI), the most severe form of peripheral artery disease, is associated with pain, poor wound healing, high rates of amputation, and mortality (>20% at 1 year). Little is known about the processes of care, patients preferences, or outcomes, as seen from patients perspectives. The SCOPE-CLI study was co-designed with patients to holistically document patient characteristics, treatment preferences, patterns of care, and patient-centered outcomes for CLI. Methods: This 11-center prospective observational registry will enroll and interview 816 patients from multispecialty, interdisciplinary vascular centers in the United States and Australia. Patients will be followed up at 1, 2, 6, and 12 months regarding their psychosocial factors and health status. Hospitalizations, interventions, and outcomes will be captured for 12 months with vital status extending to 5 years. Pilot data were collected between January and July of 2021 from 3 centers. Results: A total of 70 patients have been enrolled. The mean age was 68.4 ± 11.3 years, 31.4% were female, and 20.0% were African American. Conclusions: SCOPE-CLI is uniquely co-designed with patients who have CLI to capture the care experiences, treatment preferences, and health status outcomes of this vulnerable population and will provide much needed information to understand and address gaps in the quality of CLI care and outcomes.ClinicalTrials.gov identifier (NCT Number): NCT04710563 https://clinicaltrials.gov/ct2/show/NCT04710563