Green synthesized silver nanoparticles from Ocimum sanctum: A potent inhibitor of biofilm forming ability and efflux pumps in bacteria causing bovine mastitis.

Therapeutic management of mastitis faces significant challenges due to multidrug resistance. In the present study, multi-drug-resistant (MDR) Staphylococcus spp, Klebsiella pneumoniae, and Escherichia coli were isolated from bovine clinical mastitis cases and the phenotypic and genotypic multidrug resistance profiling was carried out. Silver nanoparticles (AgNPs) were biosynthesized using Ocimum sanctum leaf extracts and characterized via UV Vis absorption, Fourier Transform Infrared Spectroscopy, X-ray diffraction studies, Energy dispersive spectroscopy and Electron Microscopy. The determined minimum inhibitory concentration and minimum bactericidal concentration of the AgNPs against the recovered MDR isolates were 62.5 µg/ml and 125 µg/ml respectively. At a concentration of 50 µg/ml, the AgNPs demonstrated biofilm inhibitory activities of 80.35 % for MDR E. coli, 71.29 % for S. aureus and 60.18 % for MDR K. pneumoniae. Post-treatment observations revealed notable differences in biofilm formation across bacterial isolates. Furthermore, AgNP treatment led to significant downregulation of expression of the efflux pump genes acrB, acrE, acrF, and emrB in Gram-negative isolates and norB in Staphylococci isolates. This research underscores the potential for the development of an eco-friendly antimicrobial alternative in the form of green synthesized silver nanoparticles to combat drug resistance offering potential antibiofilm and efflux pump inhibitory activities.

Unravelling the complex mechanisms of multidrug resistance in bovine mastitis pathogens: Insights into antimicrobial resistance genes, biofilm dynamics, and efflux systems.

Mastitis remains a paramount economic threat to dairy livestock, with antibiotic resistance severely compromising treatment efficacy. This study provides an in-depth investigation into the multidrug resistance (MDR) mechanisms in bacterial isolates from bovine mastitis, emphasizing the roles of antimicrobial resistance genes (ARGs), biofilm formation, and active efflux systems. A total of 162 Staphylococci, eight Escherichia coli, and seven Klebsiella spp. isolates were obtained from 215 milk samples of clinical and subclinical mastitis cases. Antibiotic susceptibility testing identified Twenty Staphylococci (12.35 %), six E. coli (75 %) and seven Klebsiella (100 %) identified as MDR displaying significant resistance to ß-lactams and tetracyclines The Multiple Antibiotic Resistance (MAR) index of these isolates ranged from 0.375 to 1.0, highlighting extensive resistance. Notably, 29 of the 33 MDR isolates produced biofilms on Congo red agar, while all exhibited biofilm formation in the Microtitre Plate assay. Critical ARGs (blaZ, blaTEM, blaCTX-M, tetM, tetA, tetB, tetC, strA/B, aadA) and efflux pump genes (acrB, acrE, acrF, emrB, norB) regulating active efflux were identified. This pioneering study elucidates the synergistic contribution of ARGs, biofilm production, and efflux pump activity to MDR in bovine mastitis pathogens. To our knowledge, this comprehensive study is the first of its kind, offering novel insights into the complex resistance mechanisms. The findings underscore the imperative need for advanced antibiotic stewardship and strategic interventions in dairy farming to curb the rise of antibiotic-resistant infections, thereby protecting both animal and public health.

Diet, cardiovascular disease, and mortality in 80 countries.

AIMS: To develop a healthy diet score that is associated with health outcomes and is globally applicable using data from the Prospective Urban Rural Epidemiology (PURE) study and replicate it in five independent studies on a total of 245 000 people from 80 countries. METHODS AND RESULTS: A healthy diet score was developed in 147 642 people from the general population, from 21 countries in the PURE study, and the consistency of the associations of the score with events was examined in five large independent studies from 70 countries. The healthy diet score was developed based on six foods each of which has been associated with a significantly lower risk of mortality [i.e. fruit, vegetables, nuts, legumes, fish, and dairy (mainly whole-fat); range of scores, 0-6]. The main outcome measures were all-cause mortality and major cardiovascular events [cardiovascular disease (CVD)]. During a median follow-up of 9.3 years in PURE, compared with a diet score of ≤1 points, a diet score of ≥5 points was associated with a lower risk of mortality [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.63-0.77)], CVD (HR 0.82; 0.75-0.91), myocardial infarction (HR 0.86; 0.75-0.99), and stroke (HR 0.81; 0.71-0.93). In three independent studies in vascular patients, similar results were found, with a higher diet score being associated with lower mortality (HR 0.73; 0.66-0.81), CVD (HR 0.79; 0.72-0.87), myocardial infarction (HR 0.85; 0.71-0.99), and a non-statistically significant lower risk of stroke (HR 0.87; 0.73-1.03). Additionally, in two case-control studies, a higher diet score was associated with lower first myocardial infarction [odds ratio (OR) 0.72; 0.65-0.80] and stroke (OR 0.57; 0.50-0.65). A higher diet score was associated with a significantly lower risk of death or CVD in regions with lower than with higher gross national incomes (P for heterogeneity <0.0001). The PURE score showed slightly stronger associations with death or CVD than several other common diet scores (P < 0.001 for each comparison). CONCLUSION: A diet comprised of higher amounts of fruit, vegetables, nuts, legumes, fish, and whole-fat dairy is associated with lower CVD and mortality in all world regions, especially in countries with lower income where consumption of these foods is low.

Acute toxicity studies and protective effects of Cinnamon cassia bark extract in streptozotocin-induced diabetic rats.

The medicinal properties of Cinnamon cassia (C. cassia) bark have been reported for their clinical importance for many diseases including diabetes. However, there is no clear evidence so far regarding dose selection for its hepato- and nephroprotective effect in diabetic condition. Hence, the present study aims at evaluating in vitro antioxidant activity, the acute toxicity, and dose fixation of C. cassia bark for their effective medicinal values in streptozotocin (STZ)-induced rats. All the extracts exhibited potential in vitro antioxidant activity and showed a dose-dependent (1000, 2000, 3000, 4000, and 5000 mg/kg BW) acute toxicity by in vivo model. The levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), urea, and creatinine showed a significant elevation in animals treated with the highest dose. In further studies along with histopathological studies, animals treated with STZ (60 mg/kg BW) followed by a different dose (300, 400, and 500 mg/kg BW) of ethanolic extract of the C. cassia bark and glibenclamide (3 mg/kg BW) revealed that the altered level of mitochondrial enzymes, hepatic, and renal marker in STZ-induced animals were restored in C. cassia bark extract-treated group as of control. These results could be of scientific support for the use of the ethanolic extract of the C. cassia bark in folk medicine for the management of diabetes and its associated complications.

Automatic detection of breast cancer in ultrasound images using Mayfly algorithm optimized handcrafted features.

BACKGROUND: The incidence rates of breast cancer in women community is progressively raising and the premature diagnosis is necessary to detect and cure the disease. OBJECTIVE: To develop a novel automated disuse detection framework to examine the Breast-Ultrasound-Images (BUI). METHODS: This scheme includes the following stages; (i) Image acquisition and resizing, (ii) Gaussian filter-based pre-processing, (iii) Handcrafted features extraction, (iv) Optimal feature selection with Mayfly Algorithm (MA), (v) Binary classification and validation. The dataset includes BUI extracted from 133 normal, 445 benign and 210 malignant cases. Each BUI is resized to 256×256×1 pixels and the resized BUIs are used to develop and test the new scheme. Handcrafted feature-based cancer detection is employed and the parameters, such as Entropies, Local-Binary-Pattern (LBP) and Hu moments are considered. To avoid the over-fitting problem, a feature reduction procedure is also implemented with MA and the reduced feature sub-set is used to train and validate the classifiers developed in this research. RESULTS: The experiments were performed to classify BUIs between (i) normal and benign, (ii) normal and malignant, and (iii) benign and malignant cases. The results show that classification accuracy of > 94%, precision of > 92%, sensitivity of > 92% and specificity of > 90% are achieved applying the developed new schemes or framework. CONCLUSION: In this work, a machine-learning scheme is employed to detect/classify the disease using BUI and achieves promising results. In future, we will test the feasibility of implementing deep-learning method to this framework to further improve detection accuracy.

Glycemic control and its determinants among people with type 2 diabetes mellitus in Ernakulam district, Kerala.

Background: Diabetes is a public health problem of colossal proportions. The National Family Health Survey 5 (2019-2020) has found high blood sugar levels among 13.5% of women and 15.6% of men in India. The high morbidity and mortality in diabetes mellitus are due to uncontrolled hyperglycemia resulting in micro- and macrovascular changes affecting multiple organs in the body. The objectives of this study were to estimate glycemic control and its determinants among type 2 diabetics in the Ernakulam district. Methods: A community-based cross-sectional study was conducted among 364 type 2 diabetics who had the disease for at least 5 years duration in the Ernakulam district of Kerala. Probability proportional to size cluster sampling technique was adopted. A semi-structured questionnaire was used to collect sociodemographic and behavioral profiles. Participants' HbA1c levels were assessed to determine glycemic control. Results: The proportion of people with good glycemic control was 21.4%. Determinants such as female gender adjusted odds ratio (aOR = 2.36, P = 0.005), body mass index >23 kg/m2 (aOR = 2.71, P = 0.002), combined drug treatment with Oral Hypoglycaemic agents (OHA) and insulin (aOR = 3.76, P = 0.004), and poor compliance with medications (aOR = 1.93, P = 0.030) were found to be significantly associated with poor glycemic control. Conclusions: Poor compliance with medications and unhealthy lifestyle choices has resulted in a high proportion of diabetics with poor glycemic control in the district. Women are particularly more vulnerable to uncontrolled hyperglycemia than males. Type 2 diabetes mellitus people should be encouraged to maintain strict glycemic control, which is an important measure for secondary prevention of complications.

Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study.

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Cost analysis of dengue from a State in south India.

BACKGROUND & OBJECTIVES: Improved dengue cost estimates offer the potential to provide a baseline measure to determine the cost-effectiveness of interventions. The objective of this study was to estimate the cost of dengue prevention, treatment and fatalities in Kerala, India, over a period of one year. METHODS: The study was done in Kerala, a southern State in India. Costing of treatment was done from a family perspective. It was found by primary data collection in a sample of 83 dengue patients from Thiruvananthapuram district and estimated for Kerala using the reported number of cases in 2016. Costing of prevention was done from the government perspective for the entire State. In-depth interviews with State programme officers and experts in the field were conducted. The present value of lifetime earnings was used to value lives. RESULTS: The cost of treatment of dengue in the State was ₹137 milion (2.16 million US$). The cost of prevention in the State was ₹535 million (8.3 million US$). The cost of fatalities was the highest among costs at ₹1760 million (27.7 million US$). US$ 38 million was the least possible estimate of total cost of dengue. The total out-of-pocket spending (OOPS) of >60 yr was significantly (P<0.05) higher than other age groups. The total OOPS was significantly (P<0.001) higher in private sector compared to public. INTERPRETATION & CONCLUSIONS: Although deaths due to dengue were few, the cost of fatalities was 12 times more than the cost of treatment and three times the cost of prevention. Focusing on mortality reduction and disease prevention in elderly would be beneficial.

Bridging the gap in outreach and compliance with mass drug administration for lymphatic filariasis elimination in an endemic district in Kerala, India: an intervention research approach.

Lymphatic filariasis (LF), a neglected tropical disease is targeted for elimination globally by 2020. National Health Policy of India set the goal by 2017 and annual single-dose mass drug administration (MDA) with anti-filarial drugs is in operation in endemic districts since 2004. Performance and effectiveness of MDA was diverse across the nation and prevalence of infection continues above threshold level in 50% of endemic districts which requires alternative strategies. National programme aims at achieving >65% consumption for transmission control. Post 10 rounds of MDA in an endemic district of Kerala state, a three-arm study identified determinants in gap in outreach and consumption, based on which context-dependent intervention using social group work and networking (SGWN) was implemented and impact assessed. A spill over effect with overall increase in coverage and consumption rates irrespective of arms apparently is due to inclusive improvement in MDA programme whereas, significant relative improvement in intervention arm reflects effectiveness of SGWN strategy. Though reduction in microfilaria prevalence in all arms was observed, it was significant between intervention and comparison arm. This study highlights need for context-dependent communication strategy to improve MDA for accelerating LF elimination by the targeted 2020.

Implementation of Software Agents and Advanced AoA for Disease Data Analysis.

To eliminate the possibilities of getting various contradicting solutions to a single problem during diagnosis, a single regular Agent oriented Approach (AoA) is replaced by Intelligent Artificial Agents that act like human and even dynamically decide in any situations known as Intelligent Searching Approach (ISA) is proposed. These agents are used to analyse the medical forums and results or findings are derived accurately than any manual approach. Multiple Agents have been used to analyse the blogs by dividing the work areas and communicating themselves using Agent Communication Language (ACL) and FIPA. The local solutions thus formed are forwarded to a global agent. This Global Agent controls all operations and makes the decision about the best solution. As the Global Agent controls all other agents, it eradicates unwanted and ineffective communication between the various local agents and hence keeping the time taken for communication at the minimum level. Based on these solutions a prioritization matrix is formed using advanced clustering techniques to create a prioritized content of suggested best solutions. Once the decision is made, the refining process runs several times recursively checking for all possible better solutions solving the input. On completion of this process, the Global Agent returns the exact result of the discussion. This process saves time rather than researching the entire blog for result data. This advanced approach lights a different way of obtaining solution keeping the time taken for discussion and intercommunication between the agents to the minimal level but not compromising on the perfection of the solution at the same time.