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Chronic wounds suffer from impaired healing due to microbial attack and poor vascular growth. Thermoresponsive hydrogels gained attention in wound dressing owing to their gelation at physiological temperature enabling them to take the shape of asymmetric wounds. The present study delineates the development of thermoresponsive hydrogel (MCK), from hair-derived keratin (K) and methylcellulose (MC) in the presence of sodium sulfate. The gelation temperature (T g ) of this hydrogel is in the range of 30 °C to 33 °C. Protein-polymer interaction leading to thermoreversible sol-gel transition involved in MCK blends has been analyzed and confirmed by FTIR, XRD, and thermal studies. Keratin, has introduced antioxidant properties to the hydrogel imparted cytocompatibility towards human dermal fibroblasts (HDFs) as evidenced by both MTT and live dead assays. In vitro wound healing assessment has been shown by enhanced migration of HDFs in the presence of MCK hydrogel compared to the control. Also, CAM assay and CD31 expression by the Wistar rat model has shown increased blood vessel branching after the implantation of MCK hydrogel. Further, in vivo study, demonstrated MCK efficacy of hydrogel in accelerating full-thickness wounds with minimal scarring in Wistar rats, re-epithelialization, and reinstatement of the epidermal-dermal junction thereby exhibiting clinical relevance for chronic wounds., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

FABP3 belongs to a large family of cytoplasmic fatty acid binding proteins that are expressed in a tissue-specific manner. It is predominantly expressed in breast, muscle and heart. During our exploratory studies on the role of FABP3 in tumorigenesis and our consequent attempts to study the molecular mechanism responsible for the oncogenic potential of FABP3, we came across an unexpected role of FABP3 as an anti-bacterial protein. Presence of the protein was detected in culture media of cell lines stably over-expressing human FABP3. Conditioned medium from these FABP3 over-expressing cells exerted a distinct anti-bacterial activity against E. coli. Our results indicate that binding of FABP3 to the bacterial cell surface contributes to its anti-bacterial activity. Incubation of E. coli bacterial cells with FABP3 protein led to disruption of the physical integrity of bacterial cell membrane causing leakage of cellular components. Further, in silico analysis predicted strong binding of FABP3 to the antibiotic binding sites on the bacterial ribosome. Interestingly, we found that FABP3 is a naturally occurring secretory protein present in milk in abundance as confirmed by western blot and ELISA. Thus, our experimental data together with in silico analysis suggests that FABP3 is secreted in milk, has an anti-bacterial function, shows activity against E. coli by disrupting bacterial membrane and targeting the ribosome, and may play a protective role against bacterial infection in newborns., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Whey protein-derived carbon nanodots (WCND) were synthesized using the microwave irradiation method, and its amine-rich surface functionality was crosslinked with covalently bound Iodine functionalized 2,5-dimethoxy-2,5-dihydrofuran (DHFI) to produce WCND-DHFI. The physicochemical characterization of both WCND and WCND-DHFI was performed and compared to comprehend the consequence of iodination on the characteristics of WCND. The suitability of CND in biological environments was evaluated through in vitro cytocompatibility and Chorioallantoic Membrane (CAM) assay, as well as a hemocompatibility study. WCND-DHFI has shown enhanced cell viability against WCND. Further, the antibacterial properties of both CNDs were studied against both gram-positive and gram-negative bacterial strains, representing an enhancement in antibacterial activity after DHFI crosslinking. WCND-DHFI has depicted a stable and prominent bacteriostatic activity for up to 6 h for both strains of bacteria. WCND-DHFI has denoted a 99.996% and 99.999% loss of bacterial viability for gram-positive and negative strains, respectively. Novel surface functionalization portrays an improvement in antibacterial activity. Transmission and scanning electron microscopy represent the cell wall rupturing by the WCND-DHFI, resulting in bacterial death. The ROS-mediated bacteriostatic mechanism of WCND-DHFI has been explored through assessing lipid peroxidation and protein oxidation assay. Moreover, the oxidative damage of DNA also has been explored. WCND-DHFI is performing as a promising cytocompatible and hemocompatible material for antibacterial applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A series of imido-heterocycle compounds were designed, synthesized, characterized, and evaluated for the anticancer potential using breast (MCF-7 and MDA-MB-231), pancreatic (PANC-1), and colon (HCT-116 and HT-29) cancer cell lines and normal cells, while normal cells showed no toxicity. Among the screened compounds, 4h exhibited the best anticancer potential with IC 50 values ranging from 1 to 5.5 μM. Compound 4h caused G2/M phase arrest and apoptosis in all the cell lines except MDA-MB-231 mammosphere formation was inhibited. In-vitro enzyme assay showed selective topoisomerase IIα inhibition by compound 4h, leading to DNA damage as observed by fluorescent staining. Cell signalling studies showed decreased expression of cell cycle promoting related proteins while apoptotic proteins were upregulated. Interestingly MDA-MB-231 cells showed only cytostatic effects upon treatment with compound 4h due to defective p53 status. Toxicity study using overexpression of dominant-negative mutant p53 in MCF-7 cells (which have wild type functional p53) showed that anticancer potential of compound 4h is positively correlated with p53 expression., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Post myocardial infarction ventricular septal rupture (PMI-VSR) is a dreaded mechanical complication of acute coronary syndromes. Given that surgical mortality approaches 50%, it is pragmatic that the risk factors for mortality and outcomes after surgical correction of PMI- VSR are carefully scrutinized., Methods: We performed a single-center, retrospective cohort study of 35 patients presenting for surgical closure of post myocardial infarction ventricular septal rupture over six years. We reviewed patient characteristics, clinical, echocardiographic, angiographic and perioperative risk factors which may affect mortality after surgical repair of PMIVSR and 30 day and one year mortality rates of these patients. Univariate and multivariate logistic and cox proportional hazard regression analysis was used to identify predictors of operative and overall mortality. Long term survival was presented with Kaplan-Meier Survival Curve., Results: Sixteen patients (46%) were in cardiogenic shock. Concomitant coronary artery bypass grafting (CABG) was done in 22 patients (63%) but did not influence survival. Preoperative thrombolysis was done in 12 patients (34%) out of which 10 (53%) survived Operative mortality was 46% and one-year mortality was 49%. Multivariate analysis identified preoperative thrombolysis: Hazards ratio, 0.12; 95% CI, 0.02-0.61; p value of 0.01, as significant independent predictor of survival in PMIVSR cohort., Conclusions: Preoperative thrombolysis is associated with decreased odds of operative and overall mortality after surgical repair in PMIVSR patients., (Copyright © 2019 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Climate change is considered as a distal determinant of public health which is increasing in importance. India, as an example, has a national action plan for climate change and human health. Sub-national (State) plans for climate change also exist, taking into account the health sector. The State of Bihar was selected for assessment because of its vulnerability (a function of exposure, sensitivity and adaptive capacity). A vulnerability framework was constructed by discussions with national and local-level specialists followed by weightage given by working in the field of climate and health with international exposure. A total of 15 districts were at a high risk of floods and these were considered for detailed analysis using the methodology for human development index as well as other examples in the field of environment. Climate health vulnerability index score were correlated with actual prevalence of flood mortality data of these 15 districts in year 2016. It was found that climate health vulnerability and flood mortality had negative low correlation of -0.25. In contrast for vector-borne diseases (VBD), both pre-flood and post-flood, the morbidity data had a correlation of 0.24 and 0.11 respectively. Possible reasons for a negative correlation for mortality could involve better preparedness by disaster district authorities. However, outbreak control is within the ambit of the health sector where a possible reason for decreased correlation coefficient in the post-flood period could be due to the impact on health facilities itself, thus leading to reduced reporting., (Copyright © 2018. Published by Elsevier B.V.)

Background: In ST-elevation myocardial infarction (STEMI), prehospital delay is a significant factor, decreasing likelihood of revascularization and increasing mortality. Prehospital delays are substantive in Indian patients with STEMI. Our study aimed to investigate factors associated with prehospital delay in patients with STEMI., Methods: A multicentric prospective analysis was conducted at five major cardiac care referral centers in Punjab including a tertiary care teaching hospital over a period of 1 year from January 2015 to December 2015. Patients presenting with STEMI were included in the study. A structured questionnaire was used to gather patient characteristics and factors responsible for prehospital delay., Results: Of the 619 patients included in the study, 42% presented with more than 6 h of prehospital delay. On univariate analysis, delay was significantly higher among elderly (p = 0.01), illiterate patients (p = 0.02), and patients residing in rural areas (p = 0.04). Recognizing symptoms as cardiac in origin (p < 0.001), hospital as initial medical contact, and availability of prehospital electrocardiogram (ECG) (p = 0.001) were associated with shorter delays. On multivariate analysis, prehospital delay was significant in elderly patients, initial point of care as outpatient clinic, and patients without access to prehospital ECG., Conclusion: Our study concludes that demographic and socioeconomic barriers exist that impede rapid care seeking and highlights the need for utilization of prehospital ECG to decrease prehospital delay. Possibilities include, educating the public on the importance of early emergency medical services contact or creating emergency stations in rural areas with ECG capabilities. Our study also invites further research, regarding role of telemedicine to triage patients derived from prehospital ECGs to decrease prehospital delay., (Copyright © 2018 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

A number of pyrimidine bridged combretastatin derivatives were designed, synthesized and evaluated for anticancer activities against breast cancer (MCF-7) and lung cancer (A549) cell lines using MTT assays. Most of the synthesized compounds displayed good anticancer activity with IC 50 values in low micro-molar range. Compounds 4a and 4p were found most potent in the series with IC 50 values of 4.67 µM & 3.38 µM and 4.63 µM & 3.71 µM against MCF7 and A549 cancer cell lines, respectively. Biological evaluation of these compounds showed that selective cancer cell toxicity (in vitro using human lung and breast cancer cell lines) might be due to the inhibition of antioxidant enzymes instigating elevated ROS levels which triggers intrinsic apoptotic pathways. These compounds were found nontoxic to the normal human primary cells. Compound 4a, was found to be competitive inhibitor of colchicine and in the tubulin binding assay it showed tubulin polymerization inhibition potential comparable to colchicine. The molecular modeling studies also showed that the synthesized compounds fit well in the colchicine-binding pocket., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: Previous reports from our laboratory have established that morphine-6-O-sulfate (M6S) is a mixed μ/δ opioid receptor (OR) agonist and a potential improved alternative to morphine for treatment of chronic multimodal pain in non-diabetic rats. This study extends the antinociceptive effects of M6S and morphine in STZ-induced diabetic rats., Materials and Methods: Effects of morphine and M6S were studied across a range of pain modalities, using hot plate threshold (HPT), pinprick sensitivity threshold (PST) and paw pressure threshold (PPT) tests., Key Findings: Acutely, M6S was 3- to 5-fold more potent and 2- to 3-fold more efficacious than morphine in HPT and PST tests. No differences in analgesic drug potency/efficacy were detected in the PPT test. After 7-9days of chronic treatment, tolerance developed to the antinociceptive effects of morphine, but not to M6S, in all three pain tests. Furthermore, morphine-tolerant rats were not cross-tolerant to M6S. The selective δ-OR antagonist, naltrindole, blocked M6S-induced antinociception by 62±3% in the HPT test, 93±5% in the PST test, and 30±17% in the PPT test when examined acutely., Significance: These studies provide additional confirmation for the mixed μ/δ activity of M6S and demonstrate potential improved clinical utility for dual μ/δ agonists relative to morphine in treatment of diabetic neuropathy across multiple pain domains., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In recent years, cultural competence has appeared on the agendas of the medical profession as well as other health care providers. Through semistructured interviews with staff at different types of health care institutions, we explored the motivation for and barriers against the implementation of cultural competence training. The findings show that while some progress has been made, there is still work to be done in making cultural competency an integral part of the organizational fabric of health care. National organizations need to consider their leadership role in helping health care organizations translate broad statements of cultural competence into meaningful action.