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Objectives: We aimed to study the risks of relapse and long term disability in children with non-MS acquired demyelinating syndromes (ADS)., Methods: In this prospective, multi-centre study, from the 14 UK pediatric neurology centres, children (<16 years) experiencing a first episode of ADS were recruited from 2010 to 2014. Case report forms were collected prospectively., Results: A total of 269 children were recruited and followed up for a median of 7.2 years. Median age at onset was 9y (IQR 9.5-14.5, 126 females). At last follow-up, 46 (18 %) had MS, 4 AQP4-Ab NMOSD and 206 (80 %) had other ADS, of which 27 (13 %) relapsed. Relapsing MOGAD was the diagnosis in 12/27, 6 were seronegative and 9 did not have antibodies tested. Frequency of relapse differed according to first presentation in non-MS ADS, being least likely in transverse myelitis (p = 0.025). In the non-MS group, MOG-Ab was predictive of relapse (HR = 8.42; p < 0.001) occurring 8 times as often decreasing over time. Long-term difficulties did not differ between children with monophasic vs relapsing diseases., Conclusion: The risk of relapse in non-MS ADS depends on initial diagnosis, and MOG-Ab positivity. Long-term difficulties are observed regardless of relapses and are determined by presenting phenotype., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

MicroRNAs (miRNAs) have emerged as a prominent layer of regulation of gene expression. This article offers the salient and current aspects of machine learning (ML) tools and approaches from genome to phenome in miRNA research. First, we underline that the complexity in the analysis of miRNA function ranges from their modes of biogenesis to the target diversity in diverse biological conditions. Therefore, it is imperative to first ascertain the miRNA coding potential of genomes and understand the regulatory mechanisms of their expression. This knowledge enables the efficient classification of miRNA precursors and the identification of their mature forms and respective target genes. Second, and because one miRNA can target multiple mRNAs and vice versa , another challenge is the assessment of the miRNA-mRNA target interaction network. Furthermore, long-noncoding RNA (lncRNA)and circular RNAs (circRNAs) also contribute to this complexity. ML has been used to tackle these challenges at the high-dimensional data level. The present expert review covers more than 100 tools adopting various ML approaches pertaining to, for example, (1) miRNA promoter prediction, (2) precursor classification, (3) mature miRNA prediction, (4) miRNA target prediction, (5) miRNA- lncRNA and miRNA-circRNA interactions, (6) miRNA-mRNA expression profiling, (7) miRNA regulatory module detection, (8) miRNA-disease association, and (9) miRNA essentiality prediction. Taken together, we unpack, critically examine, and highlight the cutting-edge synergy of ML approaches and miRNA research so as to develop a dynamic and microlevel understanding of human health and diseases.

Background: Socioeconomic disparity changed healthcare seeking and management cascade of hypertension due to inequity in hypertension care cascade pathway., Objectives: The inequities in burden and treatment-seeking behavior of hypertension among reproductive age group women were studied from National Family Health Survey-4 (NFHS-4) data., Materials and Methods: We analyzed the data from NFHS-4 of women of reproductive age group between 15 and 49 years among the selected households contributing to 699,686 women. Socioeconomic inequities were assessed by expenditure quintile. Inequities in burden and treatment-seeking behavior were reported using the concentration curve and concentration index., Results: The prevalence of hypertension in India was 15% (95% confidence interval: 14.9%-15.4%). One-third (32%) of the hypertensive population received treatment and only 28% of the women had controlled blood pressure. Wealth and education-based inequalities were more in high wealth index. The inequity in screening and awareness was in the northern and northeastern regions., Conclusion: There was inequity in the overall hypertension care cascade pathway with more inequity in the northern and northeastern region., (Copyright © 2024 Copyright: © 2024 Indian Journal of Public Health.)

Protoparvovirus carnivoran1 , known commonly as feline panleukopenia virus (FPV) is a highly contagious and environmentally stable parvovirus of domestic as well as wild felids. A rapid and robust diagnostic tool will aid in implementing prompt treatment and control measures. A loop-mediated isothermal amplification (LAMP) as a point-of-care diagnostic tool for diagnosing feline panleukopenia was standardised using faecal samples of cats. The assay will reduce the cost and time required to diagnose feline panleukopenia. A set of two outer primers (F3 and B3) and two inner primers (FIP and BIP) were designed to target the viral polypeptide (VP2) gene of FPV. Optimisation of the LAMP reaction was done at 60 °C for one hour after an initial denaturation at 95 °C for five minutes. Visualisation of the result based on the addition of SYBR Green 1 dye offered an easy and reliable diagnosis. The detection limit of the standardised LAMP assay was as low as 1.25 ng/μl of the target DNA. Species specificity of the LAMP primers revealed no amplification of the non-target DNA of any other species except that of the canine parvovirus DNA template. DNA extracted from 100 PCR-positive and 20 PCR-negative faecal samples were subjected to the standardised assay and compared with PCR. Analysis of the results revealed that the LAMP assay was 100% sensitive and 90% specific compared to PCR. The LAMP assay could be a reliable tool for the point-of-care diagnosis of feline panleukopenia in limited resource settings.

Background: Violence, a notable human rights concern, has a public health impact across the globe. The study aimed to determine the prevalence and determinants of domestic violence among ever-married women aged 18-49 years in India., Methods: Secondary data analysis with National Family Health Survey 5, 2019-21 data (NFHS-5) was conducted. The complex sampling design of the survey was accounted-for during analysis. The primary outcome was domestic violence. Prevalence was reported with 95% confidence interval (CI). Prevalence ratio was reported to provide the factors associated with domestic violence using Poisson regression., Results: About 63 796 ever-married women aged 18-49 years covered under domestic violence module of NFHS-5 survey were included. Prevalence of domestic violence (12 months preceding the survey) was 31.9% (95% CI: 30.9-32.9%). Physical violence (28.3%) was the most common form followed by emotional (14.1%) and sexual violence (6.1%). Women with low education, being employed, husband being uneducated or with coercive behavior had significantly higher prevalence of domestic violence., Conclusions: One-third of the reproductive age-group women were facing some form of domestic violence. Target group interventions like violence awareness campaigns, women supportive services and stringent law enforcement should be implemented to eliminate domestic violence by year 2030., (© The Author(s) 2023. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The three-year Black Carbon (BC) aerosol measurements made during 2020, 2021, and 2022 over a rural location, namely, Panchgaon, surrounded by Aravali hillocks (elevation of about 400-600 m) have been analyzed with an aim to determine their optical and radiative characteristics, seasonal and long-term variations in mass concentration. The affinity between these parameters and associated pollutants and planetary boundary layer height (PBLH), affected by the orography, to delineate their role in mass concentration changes with time have been investigated. The coincident OPAC (Optical Properties of Aerosols and Clouds) Model-derived aerosol optical depth (AOD), and single scattering albedo (SSA) have been compared with the observed BC mass concentration, and also with synchronous satellite measurements. The year-to-year variability analysis of the data reveals that the rate of increase of BC concentration is high. The variability was low due to the reasons explained. It implies that the year-to-year variability in BC concentration at the study site depends on the source strength modulated by the valley-driven meteorology. Added, the percentage departures of BC concentration show positive values (higher concentration) during morning and evening hours, which could be due to more anthropogenic activities while it shows negative values during afternoon hours and lower boundary layer heights. The force exerted by the radiation due to BC aerosols at the bottom of the atmosphere (BOA), and in the atmosphere (ATM) are almost equal in magnitude and negative, while that at the top-of-the-atmosphere (TOA) is smaller and positive, indicating that BC aerosols in the study region cools the atmosphere at the BOA and warms the ATM and TOA, which indirectly reveals the dominant role of long-range transport phenomenon at higher levels as compared to the surface level., Competing Interests: The authors declare no conflict of interest., (© 2024 Published by Elsevier Ltd.)

Despite being the second most often diagnosed form of cancer, lung cancers are rarely found in the general population. It is proposed in this study to employ a methodology of extracting both global and local features from CT scan images for the identification of lung cancer. Data gathering, globalised and localised training as well as testing the model are all part of this structure. This study makes use of 800 CT scan images. Images are pre-processed by warping and cropping in advance of the global testing step. Each image is represented by a feature vector employing eight distinct types of image characteristics, which are taken from the images. After creating feature vectors, three machine learning methods are employed to create detection models. Every medical image has been partitioned over a series of simple divisions throughout the training and testing process locally. To describe each block, feature vectors are derived from the image features that worked effectively in the general phase of the experiment. Similar extracted features are then used to build detection systems for all picture blocks using the learning strategies that were effective in the global stage. SVM using Haar Wavelet characteristics had an accuracy, sensitivity, and specificity of 89%, 90%, and 89%, respectively. One might get 90%‑accurate results with SVM and 91%‑sensitive and 91%‑specific results using SVM plus HOG features. Finally, the utilisation of SVM with Gabor Filter characteristics achieved the greatest correctness, specificity, and sensitivity values, particularly 87%, 86%, and 87%, respectively (Tab. 3, Fig. 7, Ref. 18). Keywords: feature extraction, support vector machine, lung cancer, classification, machine learning.

Background: Real-world data on the efficacy and safety of onasemnogene abeparvovec (OA) in spinal muscular atrophy (SMA) are needed, especially to overcome uncertainties around its use in older and heavier children. This study evaluated the efficacy and safety of OA in patients with SMA type 1 in the UK, including patients ≥2 years old and weighing ≥13.5 kg., Methods: This observational cohort study used data from patients with genetically confirmed SMA type 1 treated with OA between May 2021 and January 2023, at 6 infusion centres in the United Kingdom. Functional outcomes were assessed using age-appropriate functional scales. Safety analyses included review of liver function, platelet count, cardiac assessments, and steroid requirements., Findings: Ninety-nine patients (45 SMA therapy-naïve) were treated with OA (median age at infusion: 10 [range, 0.6-89] months; median weight: 7.86 [range, 3.2-20.2] kg; duration of follow-up: 3-22 months). After OA infusion, mean ± SD change in CHOP-INTEND score was 11.0 ± 10.3 with increased score in 66/78 patients (84.6%); patients aged <6 months had a 13.9 points higher gain in CHOP-INTEND score than patients ≥2 years (95% CI, 6.8-21.0; P  < 0.001). Asymptomatic thrombocytopenia (71/99 patients; 71.7%), asymptomatic troponin-I elevation (30/89 patients; 33.7%) and transaminitis (87/99 patients; 87.9%) were reported. No thrombotic microangiopathy was observed. Median steroid treatment duration was 97 (range, 28-548) days with dose doubled in 35/99 patients (35.4%). There were 22.5-fold increased odds of having a transaminase peak >100 U/L (95% CI, 2.3-223.7; P  = 0.008) and 21.2-fold increased odds of steroid doubling, as per treatment protocol (95% CI, 2.2-209.2; P  = 0.009) in patients weighing ≥13.5 kg versus <8.5 kg. Weight at infusion was positively correlated with steroid treatment duration (r = 0.43; P  < 0.001). Worsening transaminitis, despite doubling of oral prednisolone, led to treatment with intravenous methylprednisolone in 5 children. Steroid-sparing immunosuppressants were used in 5 children to enable steroid weaning. Two deaths apparently unrelated to OA were reported., Interpretation: OA led to functional improvements and was well tolerated with no persistent clinical complications, including in older and heavier patients., Funding: Novartis Innovative Therapies AG provided a grant for independent medical writing services., Competing Interests: Vasantha Gowda has participated in scientific advisory boards, scientific symposia and teaching initiatives for Biogen, Roche, Novartis, Wave Life Sciences, PTC therapeutics and Pfizer, received honoraria from Neurology Academy, Roche, Novartis and has been involved as principal investigator with PTC therapeutics, Wave Life Sciences and Catabasis. Mark Atherton has received conference sponsorship from Novartis. Jennie Sheehan has participated in advisory boards for Roche, received conference sponsorships from Roche and Biogen and honoraria from Novartis. Mariacristina Scoto has been involved as principal investigator in clinical trials from Roche, Biogen and Novartis and has participated in Scientific Advisory boards and teaching initiatives for Roche, Novartis and Biogen. Giovanni Baranello has been involved as principal investigator of clinical trials sponsored by Roche, Novartis, Sarepta, Pfizer, NS Pharma, Reveragen, Scholar Rock, and has received speaker and/or consulting fees from Sarepta, PTC Therapeutics, Pfizer, Biogen, Novartis Gene Therapies, Inc. (AveXis), and Roche, and grants from Sarepta, Roche and Novartis Gene Therapies. Archana Murugan has received conference sponsorship from Roche. Anil Dhawan has participated in advisory boards for Novartis, BitBio, Aspect Bio, Astellas. Michael Eyre is supported by Action Medical Research and the British Paediatric Neurology Association. Laurent Servais reports participation in advisory boards and scientific symposia from Biogen, Roche, Novartis, Scholar Rock and BioHaven and grants from the aforementioned and Zentech, Perkin Almers. Francesco Muntoni reports participation in advisory boards and scientific symposia from Biogen, Roche and Novartis and funding from Biogen and Roche for the SMA REACH National database. Min Ong has participated in advisory boards for Biogen, Novartis, Roche & CSL Behring and has received conference sponsorship from Roche and speaker fees from Biogen, and honorarium from Neurology Academy. Imelda Hughes has received honoraria from Santhera, Roche, PTC Therapeutics, Sarepta, Biogen and Novartis, conference sponsorships from PTC Therapeutics, Novartis and Biogen. Heinz Jungbluth has participated in advisory board activities for Pfizer, Astellas, Audentes and Armgo. Elizabeth Wraige has undertaken consultancy work for Novartis. Maria Vanegas has received conference sponsorship from Novartis and meeting sponsorship from SMA Europe. Sandya Tirupathi has received conference sponsorships from Novartis and PTC. Marjorie Illingworth has received conference sponsorships from Roche and Biogen. Adnan Manzur received honorarium and meeting sponsorship from Pi Healthcare. Sarah D’Urso has received conference sponsorship from Biogen. Tracey Willis has received honorarium and conference sponsorship from Novartis. Sinead Warner has received conference sponsorship from Novartis and consultancy fees from Roche. No other disclosures were reported., (© 2023 The Author(s).)

The security of civilians and high-profile officials is of the utmost importance and is often challenging during continuous surveillance carried out by security professionals. Humans have limitations like attention span, distraction, and memory of events which are vulnerabilities of any security system. An automated model that can perform intelligent real-time weapon detection is essential to ensure that such vulnerabilities are prevented from creeping into the system. This will continuously monitor the specified area and alert the security personnel in case of security breaches like the presence of unauthorized armed people. The objective of the proposed system is to detect the presence of a weapon, identify the type of weapon, and capture the image of the attackers which will be useful for further investigation. A custom weapons dataset has been constructed, consisting of five different weapons, such as an axe, knife, pistol, rifle, and sword. Using this dataset, the proposed system is employed and compared with the faster Region Based Convolution Neural Network (R-CNN) and YOLOv4. The YOLOv4 model provided a 96.04% mAP score and frames per second (FPS) of 19 on GPU (GEFORCE MX250) with an average accuracy of 73%. The R-CNN model provided an average accuracy of 71%. The result of the proposed system shows that the YOLOv4 model achieves a higher mAP score on GPU (GEFORCE MX250) for weapon detection in surveillance video cameras.

This study aimed to determine whether autochthonous high-intensity D. repens microfilaremia leads to haematological changes in companion dogs. Dogs with hypermicrofilaremia presented to the District Veterinary Centre, Kannur were selected for the study. A total of 100 dogs were positive for hypermicrofilariaemia with D. repens based on peripheral blood smear examination and Knott's test. Of these, 3 dogs were concurrently positive for sheathed microfilaria (MF) of Brugia spp. Interestingly, an adult live worm of D. repens approximately eight cm in length was detected on a subcutaneous mass on the hind limb of a hypermicrofilaremic dog in the study. We compared the hematological parameters of 100 autochthonous hypermicrofilaremic dogs and 15 uninfected dogs. The hematological findings in the study are mild to moderate anemia, moderate to severe thrombocytopenia, leucocytosis with granulocytosis, lymphocytosis and monocytosis as compared to the uninfected group of dogs. The pathogenicity of naturally occurring hypermicrofilaremia is poorly studied, and knowledge of its epidemiology, host-parasite relationship and impact on various organs is warranted for better prevention and control, especially in hot-spot areas., Supplementary Information: The online version contains supplementary material available at 10.1007/s12639-023-01622-6., Competing Interests: Conflict of interestThere is no conflict of interest for the research findings. There is no separate funding for this research project. The authors have indicated that they have no affiliations or financial involvement with any organization or entity with a financial interest in, or in financial competition with, the subject matter or materials discussed in this article., (© Indian Society for Parasitology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Aerosol-CCN characteristics and dynamics during a pre-monsoon dust storm (April 6-11, 2015) over a high-altitude site ((17.92°N, 73.66°E, and 1348 m above mean sea level (MSL)) in Western Ghats, India, has been studied using ground-based observations, satellite, and reanalysis datasets. Spatial distribution of dust surface mass concentration along with the back trajectory analysis showed the Arabian Desert area (Rub-Al-khali desert) as the source region and strong westerly winds transported the dust particles toward the Indian subcontinent. High values noticed in the surface PM 10 (PM 2.5 ), i.e., ~ 450 (~ 130) µg m -3 , MODIS AOD 550nm (0.6), and MERRA 2 dust surface mass concentration (5 × 10 -7  kg m -3 ) along MODIS true color images confirmed the dust storm event on April 6, 2015 over the observational site. Size-segregated aerosol number concentration measured from ground-based observations showed the dominance of Aitken, accumulation, and coarse mode particles during dust period. CCN concentrations at 0.1, 0.3, 0.5, 0.7, and 0.9% SS were analyzed. A low value of CCN concentration and activation fraction (~ 0.3) near surface was noticed during dust storm day, suggesting insoluble mineral dust particle being transported. Analyzed vertical velocity during pre-dust period showed downdraft between 900 and 750 hPa, suggesting dust transport from upper altitudes toward the observational site. WRF-Chem model simulation also captured the dust storm event, and the results are in good agreement with the observation with a significance of 95% confidence level., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The COVID-19 pandemic was a global health emergency, which brought lives to a standstill. To combat this deadly virus, two vaccines were deployed widely: COVISHIELD (ChAdOx1 nCoV-19) and COVAXIN (BBV152). These were approved based on the immunological response they elicit in standardized conditions; however, the real-life scenario after deployment was completely different. Only in such situations can the true effectiveness of vaccines be assessed. The primary objective was to assess the effectiveness (VE) of COVAXIN/COVISHIELD in preventing severe pulmonary disease in RT-PCR-positive COVID-19 patients greater than 18 years of age., Materials and Methods: A case-control study was conducted among 260 subjects aged above 18 years, positive for COVID-19 through RT-PCR. 130 cases and 130 controls were enrolled. Radiological findings were obtained and subjects with >50% lung involvement were considered as cases. Subjects were interviewed about their vaccination status. Odds ratio was calculated, and the adjusted odds ratio was estimated for vaccine effectiveness, using the formula (1-adjusted ODDS ratio)*100., Results: The vaccine effectiveness for a single dose of vaccine was 55.2% (95% C.I. 11.0%-77.5%) and with two doses was 98.0% (95% C.I. 85.0%-99.7%). Hence two doses are highly effective than a single dose of vaccine in reducing lung involvement., Conclusion: Two doses of vaccine are more effective than a single dose vaccine in reducing lung involvement. Since sporadic cases of COVID-19 still persist, it is important to emphasize the role of vaccination in preventing severe COVID-19 infections, particularly in the elderly and those with comorbidities., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ravichandran et al.)

Background: Recent studies have shown a high prevalence of Type-2-diabetes (T2DM) (24%) and prediabetes (18.1%) in Kerala. There is no community based study from South Asia regarding the prevalence of type 2 diabetes and its precursors in the young adult population. This community based study was done to find the prevalence of type 2 diabetes and its precursors in South Indian adult youth (18-30 years age) of Thiruvananthapuram district., Research Design and Methods: Cross sectional design was used for this study. Multistage cluster sampling was used to enrol community dwelling youth of 18 to 30 years, residing in Thiruvananthapuram district. Six panchayath wards from rural and urban regions and 4 from coastal area were randomly selected as the primary sampling units. Trained staff nurses conducted the survey with the help of accredited-social-health-activists (ASHA). Socio-demographic data, anthropometry, clinical features of insulin resistance, and random capillary glucose (CG) and blood pressure were assessed and recorded. Oral Glucose tolerance test or HbA1c was done for participants with a CG ≥130 mg/dl for diagnosis of diabetes and prediabetes., Results: A total of 1031 participants were included from the rural ( n = 394), coastal ( n = 269) and urban ( n = 368) areas. Prevalence of hyperglycaemia i.e., T2DM and pre-diabetes was 0.48% ( n = 5) and 2.4% ( n = 25) respectively. Family-history of T2DM was present in 35.1% subjects. Prevalence of overweight, obesity and abdominal-obesity was 28.2%, 16.1% and 28.4% respectively. Clinical-features of insulin resistance (CFIR) were present in 27.1% subjects (acanthosis [17.7%], skin tags [1.7%] and PCOS phenotype [10.7%]). Among various anthropometric measurements and their derivatives, CFIR correlated best ( r = 0.24, P < 0.01) with the product of BMI and the sum of abdominal circumference and hip circumference (Trivandrum Medical College [TMC] -adiposity-index), which is a newly proposed parameter. Hyperglycaemia was more common in males, did not correlate with waist hip ratio, and correlated best again with TMC-adiposity-index (( r = 0.13, P < 0.01)., Conclusions: The burden of insulin resistance in the young South Indian population, hitherto unknown in any community based study, has been studied for the first time. The prevalence of precursors of T2DM is high in this population. Early identification of 'at risk' individuals could provide a window of opportunity for preventing or delaying future diabetes and its long term complications. TMC adiposity index could become a valuable tool in the anthropometric assessment for predicting future T2DM., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Endocrinology and Metabolism.)

The present investigation was aimed to study the anti-diabetic and hypolipidemic potential of Cinnamon cassia (Lauraceae family) bark in streptozotocin (STZ)-induced diabetic rats. The preliminary phytochemical analysis (hexane, petroleum ether, chloroform, ethanol, methanol, and aqueous extracts), GC-MS analysis (ethanol), in vitro (aqueous, ethanol and methanol), in vivo (ethanol) and in silico anti-diabetic activity with hypolipidemic effect of C. cassia bark was analysed. The ethanolic extract of the C. cassia bark has a fine inhibitory activity than the aqueous and methanolic extract. Out of 20 different compounds identified, seven compounds were biologically active, and 9-octadecenoic acid has highly interacted with PPARα/γ in docking studies. The levels of diabetic markers, enzymes, and lipid profiles were altered in STZ-induced rats, but after the treatment of C. cassia , the levels were returned to the normal. The study may prove the ethanolic extract of C. cassia has a powerful anti-diabetic and anti-hyperlipidemic activity.

Setting: Kerala State, India, implemented decentralising reforms of healthcare institutions 25 years ago through transfer of administrative control and a sizeable share of the financial allocation., Objective: To describe the main impacts of decentralisation in Kerala on local policy formulation, programme implementation and service delivery for sustainable health systems., Design: This was part of a broader qualitative study on decentralisation and health in Kerala. We conducted 25 in-depth interviews and reviewed 31 government orders or policy documents, five related transcripts and five thematic reports from the main study., Results: Liaising between health system and local governments has improved over time. A shift from welfare-centric projects to infrastructure, human resources and services was evident. Considerable heterogeneity existed due to varying degrees of involvement, capacity, resources and needs of the community. State-level discourse and recent augmentation efforts for moving towards the UN Sustainable Development Goals (SDGs) strongly uphold the role of local governments in planning, financing and implementation., Conclusion: The 25-year history of decentralised healthcare administration in Kerala indicates both successes and failures. Central support without disempowering the local governments can be a viable option to allow flexible decision-making consistent with broader system goals., Competing Interests: Conflicts of interest: none declared., (© 2023 The Union.)

Introduction: In the backdrop of the Sustainable Development Goals (SDGs), the state of Kerala, India, revamped its existing primary health centres (PHCs) into people-friendly family health centres (FHCs) in order to provide comprehensive primary care as part of a mission-based ( 'Aardram' ) initiative. It was envisioned that the mission's implementation and operation would make use of decentralised governance. The present study explored how the decentralised governance influenced reorganisation of primary care., Methods: The study adopted an exploratory approach using qualitative methods: key informant interviews ( n = 8), in-depth interviews ( n = 20) and document reviews. Thematic analysis was done following deductive coding and the themes that emerged were organised under a schema., Results: The results could be summarised under five overarching themes. Strong political commitment, combined with bureaucratic competence, facilitated implementation and functioning of 'Aardram' primary care. The insights developed through multi-sectoral training helped local governments (LGs) get involve and engage with the health system as a team in order to plan and implement interventions. The decentralised governance structures enabled re-engineering of PHCs by mobilisation of financial resources, provision of human resources, infrastructure modification, and enhanced community participation at various levels. Non-uniformity of commitment, sub-optimal engagement of urban LGs and issues of sustainability and monitoring were the shortcomings observed., Conclusion: Decentralised governance played a positive role in the re-engineering of PHCs, which was utilised as a platform to demonstrate best practices in health governance through a participatory approach. The importance of empowering LGs through capacity building to address challenges in achieving primary care SDGs is highlighted in this study., (© 2023 The Union.)

Background: The majority of Indians prefer to drive by two-wheeler. Hands are the most important interface between the rider and bike while riding a motorbike. The vibration is transferred to the physical structure by the handlebar as it travels. Long-term exposure to the vibrations may have an impact on various bodily structures., Objective: To measure and analyse the human exposure to vibration in the hand-arm system while riding a motorcycle using a vibrometer., Methods: The several types of bikes based on their cc's were evaluated in three different road conditions during this investigation (tar road, concrete road, and gravel road). The subjective and quantitative data of each participant were recorded. The RMS A(8) values were supported for every combination of motorcycles and road conditions, and vibration intensity was evaluated using a tri-axial vibrometer., Results: The exposure limit value for daily vibration exposure is 5 m/s2 according to the UK Control of Vibration at Work Regulations 2005 standards.This study suggests that the bike with the least amount of vibration be used to prevent hand-arm vibration (HAV) syndrome. This study found that bike C had the least vibration across all three types of roads, which will benefit riders by reducing health issues as they ride. Therefore, it is further examined utilising the Taguchi method with various bike C age groups. Bike C with the lowest age had the least vibration when different bike C ages were compared, hence it was recommended for riding., Conclusion: The vibration level of each bike has a huge impact, which was measured using a tri-axial vibrometer. According to the results, bike C has the least vibration across three distinct types of roads and also provides riders with less health issues while riding bikes. As a result, a moped can drive in three different road circumstances with the least amount of vibration, delivering comfort and safety while lowering vibration levels.

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/m 2 (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., Competing Interests: None

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.

Aim: To examine the incidence of cardiovascular disease (CVD), of death, and the comparative effects of 12 common modifiable risk factors for both outcomes in South Asia., Methods and Results: Prospective study of 33 583 individuals 35-70 years of age from India, Bangladesh, or Pakistan. Mean follow-up period was 11 years. Age and sex adjusted incidence of a CVD event and mortality rates were calculated for the overall cohort, by urban or rural location, by sex, and by country. For each outcome, mutually adjusted population attributable fractions (PAFs) were calculated in 32 611 individuals without prior CVD to compare risks associated with four metabolic risk factors (hypertension, diabetes, abdominal obesity, high non-HDL cholesterol), four behavioural risk factors (tobacco use, alcohol use, diet quality, physical activity), education, household air pollution, strength, and depression. Hazard ratios were calculated using Cox regression models, and average PAFs were calculated for each risk factor or groups of risk factors. Cardiovascular disease was the most common cause of death (35.5%) in South Asia. Rural areas had a higher incidence of CVD (5.41 vs. 4.73 per 1000 person-years) and a higher mortality rate (10.27 vs. 6.56 per 1000 person-years) compared with urban areas. Males had a higher incidence of CVD (6.42 vs. 3.91 per 1000 person-years) and a higher mortality rate (10.66 vs. 6.85 per 1000 person-years) compared with females. Between countries, CVD incidence was highest in Bangladesh, while the mortality rate was highest in Pakistan. The modifiable risk factors studied contributed to approximately 64% of the PAF for CVD and 69% of the PAF for death. Largest PAFs for CVD were attributable to hypertension (13.1%), high non-HDL cholesterol (11.1%), diabetes (8.9%), low education (7.7%), abdominal obesity (6.9%), and household air pollution (6.1%). Largest PAFs for death were attributable to low education (18.9%), low strength (14.6%), poor diet (6.4%), diabetes (5.8%), tobacco use (5.8%), and hypertension (5.5%)., Conclusion: In South Asia, both CVD and deaths are highest in rural areas and among men. Reducing CVD and premature mortality in the region will require investment in policies that target a broad range of health determinants., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We undertook a prescription-based study to identify the provider and institution-level factors related to achieving guideline-recommended control of hypertension and diabetes mellitus in Kerala, India., Methods: This cross-sectional study in primary and secondary care hospitals in Kerala included both public and private institutions. One practitioner was selected from each institution. Data on institutional and provider factors were collected using a structured questionnaire. Prescriptions were photographically captured and data on disease status and drugs prescribed were recorded. Factors associated with disease control were identified using binary logistic regression., Results: Totally 4679 prescriptions were included for analysis. For hypertension-only patients, control levels were 31.5% and was significantly higher in public hospitals (Adjusted odds ratio (AOR) 1.96, 95% confidence intervals (CI) 1.50-2.57). Among patients with diabetes only, diabetes control was seen in 36.6%. When both conditions were present, control was achieved in only 17.0% patients. Being prescribed two or more drugs indicated lower control, whatever the respective condition. Among antihypertensive prescriptions rationality of 26.7% were questioned, such as lack of Renin Angiotensin System (RAS) inhibitor in diabetic hypertensives, dual RAS blockage, and indication for beta-blocker monotherapy., Conclusions: In this prescription-based study in Kerala, India, a majority of hypertensive patients did not have controlled blood pressure levels, particularly if diabetes coexisted. This has serious implications as Kerala is the state with the highest burden of hypertension in India. Several prescription patterns were of questionable rationality. Further research and actions on rationality of anti-hypertensive prescriptions and barriers to treatment intensification is warranted., (Copyright © 2022 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Parkinson's disease (PD) is caused by the progressive loss of dopaminergic cells in substantia nigra pars compacta (SNc). The root cause of this cell loss in PD is still not decisively elucidated. A recent line of thinking has traced the cause of PD neurodegeneration to metabolic deficiency. Levodopa (L-DOPA), a precursor of dopamine, used as a symptom-relieving treatment for PD, leads to positive and negative outcomes. Several researchers inferred that L-DOPA might be harmful to SNc cells due to oxidative stress. The role of L-DOPA in the course of the PD pathogenesis is still debatable. We hypothesize that energy deficiency can lead to L-DOPA-induced toxicity in two ways: by promoting dopamine-induced oxidative stress and by exacerbating excitotoxicity in SNc. We present a systems-level computational model of SNc-striatum, which will help us understand the mechanism behind neurodegeneration postulated above and provide insights into developing disease-modifying therapeutics. It was observed that SNc terminals are more vulnerable to energy deficiency than SNc somas. During L-DOPA therapy, it was observed that higher L-DOPA dosage results in increased loss of terminals in SNc. It was also observed that co-administration of L-DOPA and glutathione (antioxidant) evades L-DOPA-induced toxicity in SNc neurons. Our proposed model of the SNc-striatum system is the first of its kind, where SNc neurons were modeled at a biophysical level, and striatal neurons were modeled at a spiking level. We show that our proposed model was able to capture L-DOPA-induced toxicity in SNc, caused by energy deficiency., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Muddapu, Vijayakumar, Ramakrishnan and Chakravarthy.)

Objectives: To assess the pattern of contraceptive use and its determinants, knowledge regarding contraceptives including oral contraceptive pills and fertility intentions among tribal women in the reproductive age group., Design: Community-based cross-sectional study., Setting: Community development blocks in a predominantly tribal district of Wayanad in Kerala, India., Participants: Women in the reproductive age group (15-49 years) from the tribal groups in the district numbering 2495., Outcome Measures: PRIMARY: Prevalence of contraceptive use and its determinants., Secondary: Knowledge regarding contraceptives in general, oral contraceptives and fertility intentions., Results: The mean age of the study participants was 30.8 years (SD=9.8) and belonged to various tribal groups such as Paniya (59.2%), Kurichiyar (13.6%) and Adiya (10.9%). Current use of contraceptive was reported by about a fourth, 658 (26.4%) (95% CI 27.9 to 24.9) of women. Following logistic regression, belonging to Paniya tribe (adjusted OR (aOR) 2.67, 95% CI 1.49 to 4.77; p<0.001) and age at menarche >13 years (aOR 1.69, 95% CI 1.14 to 2.52; p<0.009) had significantly higher use of contraceptives whereas social vulnerability as indicated by staying in a kutcha house had a lesser likelihood of use of contraceptive (aOR 0.55, 95% CI 0.31 to 0.95; p<0.03). Oral contraceptive use was low (4.8%) among this population and no abuse was observed.Less than half (47%) of the respondents had an above average knowledge on contraception. Multivariable logistic regression indicated that above average knowledge was 2.2 times more likely with higher education (95% CI 1.2 to 3.9), lesser among those who desired more than two children (aOR 0.59; 95% CI 0.38 to 0.94; p<0.02).Two children per family was the preferred choice for 1060 (42.5%) women. No gender bias in favour of the male child was observed., Conclusion: Awareness and use of contraceptives are poor though the fertility is not commensurately high. Along with developing targeted responses to contraceptive use among Indigenous people with indigenous data, awareness also requires attention. Ethnographic studies are also necessary to determine the differences in contraceptive use including traditional methods among the various Indigenous groups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Methicillin resistant Staphylococcus aureus is considered multidrug resistant bacterium due to developing biofilm formation associated with antimicrobial resistance mechanisms. Therefore, inhibition of biofilm formation is an alternative therapeutic action to control MRSA infections. The present study revealed the non-antibacterial biofilm inhibitory potential of hesperidin against ATCC strain and clinical isolates of S. aureus. Hesperidin is a flavanone glycoside commonly found in citrus fruit. Hesperidin has been shown to exhibits numerous pharmacological activities. The present study aimed to evaluate the antibiofilm and antivirulence potential of hesperidin against MRSA. Results showed that hesperidin treatment significantly impedes lipase, hemolysin, autolysin, autoaggregation and staphyloxanthin production. Reductions of staphyloxanthin production possibly increase the MRSA susceptibility rate to H 2 O 2 oxidative stress condition. In gene expression study revealed that hesperidin treatment downregulated the biofilm-associated gene (sarA), polysaccharide intracellular adhesion gene (icaA and icaD), autolysin (altA), fibronectin-binding protein (fnbA and fnbB) and staphyloxanthin production (crtM). Molecular docking analysis predicted the ability of hesperidin to interact with SarA and CrtM proteins involved in biofilm formation and staphyloxanthin production in MRSA., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

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.

Streptococcus mutans is a common pathogen present in the oral cavity and it causes dental caries for all aged groups of people, in particular, children. S. mutans have several virulence factors such as acidogenecity, aciduricity, adhesion and biofilm formation. These virulence factors are working together and lead to the development of caries in the tooth surface. The present study aimed to investigate the anticariogenic potential of 3, 5-di-tert-butylphenol (3, 5-DTBP) against S. mutans. 3, 5-DTBP biofilm inhibitory concentration (BIC) was found at 100 µg/ml concentration without any lethal effect on the growth. Moreover, 3, 5-DTBP significantly reduced water soluble and water insoluble glucans production, in concurrence with downregulation of gtfBC genes. Moreover, acidogenicity associated virulence factors such as lactate dehydrogenase and enolase enzymatic production was arrested upon 3, 5-DTBP treatment. In addition, 3, 5-DTBP greatly reduced acidtolerance ability through impedes of F 1 F 0 -ATPase. Gene expression analysis unveiled the downregulation of gtfB, gtfC, gtfD, vicRK, comDE, gbpB, smu0630 and relA upon 3, 5-DTBP treatment. The present study paves the way for exhibiting 3, 5-DTBP as a promising therapeutic agent to control S. mutans infections., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

The occurrence of resistances in Gram negative bacteria is steadily increasing to reach extremely worrying levels and one of the main causes of resistance is the massive spread of very efficient β-lactamases which render most β-lactam antibiotics useless. Herein, we report the development of a series of imino-analogues of β-lactams (namely azetidinimines) as efficient non-covalent inhibitors of β-lactamases. Despite the structural and mechanistic differences between serine-β-lactamases KPC-2 and OXA-48 and metallo-β-lactamase NDM-1, all three enzymes can be inhibited at a submicromolar level by compound 7dfm, which can also repotentiate imipenem against a resistant strain of Escherichia coli expressing NDM-1. We show that 7dfm can efficiently inhibit not only the three main clinically-relevant carbapenemases of Ambler classes A (KPC-2), B (NDM-1) and D (OXA-48) with Ki's below 0.3 μM, but also the cephalosporinase CMY-2 (class C, 86% inhibition at 10 μM). Our results pave the way for the development of a new structurally original family of non-covalent broad-spectrum inhibitors of β-lactamases., 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 © 2021 Elsevier Masson SAS. All rights reserved.)

Importin 8, encoded by IPO8, is a ubiquitously expressed member of the importin-β protein family that translocates cargo molecules such as proteins, RNAs, and ribonucleoprotein complexes into the nucleus in a RanGTP-dependent manner. Current knowledge of the cargoes of importin 8 is limited, but TGF-β signaling components such as SMAD1-4 have been suggested to be among them. Here, we report that bi-allelic loss-of-function variants in IPO8 cause a syndromic form of thoracic aortic aneurysm (TAA) with clinical overlap with Loeys-Dietz and Shprintzen-Goldberg syndromes. Seven individuals from six unrelated families showed a consistent phenotype with early-onset TAA, motor developmental delay, connective tissue findings, and craniofacial dysmorphic features. A C57BL/6N Ipo8 knockout mouse model recapitulates TAA development from 8-12 weeks onward in both sexes but most prominently shows ascending aorta dilatation with a propensity for dissection in males. Compliance assays suggest augmented passive stiffness of the ascending aorta in male Ipo8 -/- mice throughout life. Immunohistological investigation of mutant aortic walls reveals elastic fiber disorganization and fragmentation along with a signature of increased TGF-β signaling, as evidenced by nuclear pSmad2 accumulation. RT-qPCR assays of the aortic wall in male Ipo8 -/- mice demonstrate decreased Smad6/7 and increased Mmp2 and Ccn2 (Ctgf) expression, reinforcing a role for dysregulation of the TGF-β signaling pathway in TAA development. Because importin 8 is the most downstream TGF-β-related effector implicated in TAA pathogenesis so far, it offers opportunities for future mechanistic studies and represents a candidate drug target for TAA., (Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

This work investigated the interaction of indole with SARS-CoV-2. Indole is widely used as a medical material owing to its astounding biological activities. Indole and its derivatives belong to a significant category of heterocyclic compounds that have been used as a crucial component for several syntheses of medicine. A straightforward one-pot three-component synthesis of indole, coupled with Mannich base derivatives 1a-1j, was synthesized without a catalyst. The products were confirmed by IR, 1 H-NMR, 13 C-NMR, mass spectra, and elemental analysis. The indole derivatives were tested for cytotoxic activity, using three cancer cell lines and normal cell lines of Human embryonic kidney cell (HEK293), liver cell (LO2), and lung cell (MRC5) by MTT assay using doxorubicin as the standard drug. The result of cytotoxicity indole compound 1c (HepG2, LC 50 -0.9 μm, MCF-7, LC 50 -0.55 μm, HeLa, LC 50 -0.50 μm) was found to have high activity compared with other compounds used for the same purpose. The synthesized derivatives have revealed their safety by exhibiting significantly less cytotoxicity against the normal cell line (HEK-293), (LO2), and (MRC5) with IC 50 > 100 μg/ml. Besides, we report an in silico study with spike glycoprotein (SARS-CoV-2-S). The selective molecules of compound 1c exhibited the highest docking score -2.808 (kcal/mol) compared to other compounds. This research work was successful in synthesizing a few compounds with potential as anticancer agents. Furthermore, we have tried to emphasize the anticipated role of indole scaffolds in designing and discovering the much-awaited anti-SARS CoV-2 therapy by exploring the research articles depicting indole moieties as targeting SARS CoV-2 coronavirus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gobinath, Packialakshmi, Ali, Alarifi, Alotaibi, Idhayadhulla and Surendrakumar.)

Importance: Cohort studies report inconsistent associations between fish consumption, a major source of long-chain ω-3 fatty acids, and risk of cardiovascular disease (CVD) and mortality. Whether the associations vary between those with and those without vascular disease is unknown., Objective: To examine whether the associations of fish consumption with risk of CVD or of mortality differ between individuals with and individuals without vascular disease., Design, Setting, and Participants: This pooled analysis of individual participant data involved 191 558 individuals from 4 cohort studies-147 645 individuals (139 827 without CVD and 7818 with CVD) from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study and 43 413 patients with vascular disease in 3 prospective studies from 40 countries. Adjusted hazard ratios (HRs) were calculated by multilevel Cox regression separately within each study and then pooled using random-effects meta-analysis. This analysis was conducted from January to June 2020., Exposures: Fish consumption was recorded using validated food frequency questionnaires. In 1 of the cohorts with vascular disease, a separate qualitative food frequency questionnaire was used to assess intake of individual types of fish., Main Outcomes and Measures: Mortality and major CVD events (including myocardial infarction, stroke, congestive heart failure, or sudden death)., Results: Overall, 191 558 participants with a mean (SD) age of 54.1 (8.0) years (91 666 [47.9%] male) were included in the present analysis. During 9.1 years of follow-up in PURE, compared with little or no fish intake (≤50 g/mo), an intake of 350 g/wk or more was not associated with risk of major CVD (HR, 0.95; 95% CI, 0.86-1.04) or total mortality (HR, 0.96; 0.88-1.05). By contrast, in the 3 cohorts of patients with vascular disease, the HR for risk of major CVD (HR, 0.84; 95% CI, 0.73-0.96) and total mortality (HR, 0.82; 95% CI, 0.74-0.91) was lowest with intakes of at least 175 g/wk (or approximately 2 servings/wk) compared with 50 g/mo or lower, with no further apparent decrease in HR with consumption of 350 g/wk or higher. Fish with higher amounts of ω-3 fatty acids were strongly associated with a lower risk of CVD (HR, 0.94; 95% CI, 0.92-0.97 per 5-g increment of intake), whereas other fish were neutral (collected in 1 cohort of patients with vascular disease). The association between fish intake and each outcome varied by CVD status, with a lower risk found among patients with vascular disease but not in general populations (for major CVD, I2 = 82.6 [P = .02]; for death, I2 = 90.8 [P = .001])., Conclusions and Relevance: Findings of this pooled analysis of 4 cohort studies indicated that a minimal fish intake of 175 g (approximately 2 servings) weekly is associated with lower risk of major CVD and mortality among patients with prior CVD but not in general populations. The consumption of fish (especially oily fish) should be evaluated in randomized trials of clinical outcomes among people with vascular disease.

The present study was aimed to investigate the antibiofilm activity of 5-hydroxymethylfurfural against Acinetobacter baumanni and Vellar estuary isolates v3 (Acinetobacter nosocomialis). The biofilm inhibitory concentration (BIC) of 5HMF against A. baumannii and v3 (A. nosocomialis) was found to be 100 µg/ml) exhibited non-bactericidal concentration-dependent antibiofilm activities against Acinetobacter species. The present study found that 5HMF treatment is very effective in the initial stage of A. baumannii biofilms and it significantly disrupted the mature biofilms. Moreover, 5HMF treatment inhibited the extracellular polymeric substances (EPS), including polysaccharides and proteins production. Results from gene expression and in vitro assays further demonstrated the 5HMF treatment downregulated the expression of bfmR, bap, csuA/B, ompA and katE virulence genes, which consistently affects biofilm formation and its mediated virulence property. The present study suggests that 5HMF unveil its antibiofilm activity by interfering initial biofilm formation and suppressing the virulence regulator genes in A. baumannii. Further studies are required to explore the 5HMF mode of action responsible for the antibiofilm activity.

Background: Menopause characterized by a gradual decline in ovarian hormones takes its toll on the women both physically and mentally. These health problems can negatively impact the mental status. Hence, the current study was done to determine the level of stress and its associated factors among postmenopausal women in urban Puducherry, India., Materials and Methods: A facility-based cross-sectional study was done among 219 postmenopausal women attending the outpatient department in urban primary health center during May 2017-June 2017. Information regarding sociodemographic profile was collected using pretested semi-structured questionnaire and Cohen's Perceived Stress Scale was used to assess the stress level. We calculated adjusted prevalence ratios (aPRs) to identify the determinants of stress., Results: Among 219 participants, 46.6% were in the age group of 60-74 years; 32.9% had primary to secondary level of education; 56.2% were unemployed; 42.5% belonged to lower socioeconomic class; and 32.9% had both diabetes mellitus and hypertension. The prevalence of stress among the postmenopausal women was 26.0% (95% confidence interval: 20.7-32.2). Postmenopausal woman with higher education (aPR - 2.18), belonging to nuclear family (aPR - 1.93), lesser parity (aPR - 1.18), and current alcohol/tobacco users (aPR-2.32) were found to have a significant association with stress among the study participants., Conclusion: The current study showed that more than one-fourth of the postmenopausal women had high to very high level of stress. Education, religion, parity, and substance abuse were the significant determinants of stress. However, further longitudinal research needs to be done to determine whether the factors informed in the current study are truly associated with stress and develop interventions accordingly., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Mid-life Health.)

Introduction: Tuberculosis (TB) is one of the leading causes of death due to infectious diseases in the world. Kerala a southern state in India aims to eliminate TB in the near future. In order to achieve its goal Kerala is providing various social support services to TB patients to ensure their smooth transition as they pass through the treatment cascade. Therefore, the objective of the current study was to qualitatively analyse the support systems provided for TB patients in Kerala and to assess the enablers and challenges faced during the provision of these services., Methodology: A qualitative study using grounded theory approach was carried out among TB survivors, current TB patients and healthcare workers from all 14 districts of Kerala along with district health officials. A total of 14 in depth interviews were conducted among healthcare workers from all the districts of Kerala. Three FGDs were conducted, out of which two were among TB survivors and another one among current TB patients. The data was collected till data saturation was reached. The audio recorded data was transcribed, translated, manually coded and emerging themes and sub themes were identified. Using data triangulation, conclusions were made., Results: It was observed that different TB support services were being provided across all the 14 districts of Kerala. Each of these initiatives were found to be unique in their own way for bridging the gaps in the in the continuum of care provided for TB patients. The main domains identified were grouped as support services provided for getting diagnosis, services provided after diagnosis of TB, prevention of TB and support provided to the patients reaching private sector. Under each of these domains a wide range of TB support initiatives that facilitated early diagnosis, good adherence to treatment, minimising patient inconveniences, stigma reduction, prevention out of pocket expenditure and emotional support were identified. Majority of these supportive measures were found not to be uniform throughout. Those are locally customised initiatives, evolved at different time periods with common objective of patient support. Community ownership, proactive health care system and political commitment contributed to these patient support systems., Conclusion: These support services offered to TB patients were found to be very effective in paving the way towards the goal of TB elimination in Kerala., Competing Interests: Declaration of competing interest The authors have none to declare., (Copyright © 2020 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: Edasalonexent (CAT-1004) is an orally-administered novel small molecule drug designed to inhibit NF-κB and potentially reduce inflammation and fibrosis to improve muscle function and thereby slow disease progression and muscle decline in Duchenne muscular dystrophy (DMD)., Objective: This international, randomized 2 : 1, placebo-controlled, phase 3 study in patients ≥4 - < 8 years old with DMD due to any dystrophin mutation examined the effect of edasalonexent (100 mg/kg/day) compared to placebo over 52 weeks., Methods: Endpoints were changes in the North Star Ambulatory Assessment (NSAA; primary) and timed function tests (TFTs; secondary). Assessment of health-related function used the Pediatric Outcomes Data Collection tool (PODCI)., Results: One hundred thirty one patients received edasalonexent (n = 88) and placebo (n = 43). At week 52, differences between edasalonexent and placebo for NSAA total score and TFTs were not statistically significant, although there were consistently less functional declines in the edasalonexent group. A pre-specified analysis by age demonstrated that younger patients (≤6.0 years) showed more robust and statistically significant differences between edasalonexent and placebo for some assessments. Treatment was well-tolerated and the majority of adverse events were mild, and most commonly involved the gastrointestinal system (primarily diarrhea)., Conclusions: Edasalonexent was generally well-tolerated with a manageable safety profile at the dose of 100 mg/kg/day. Although edasalonexent did not achieve statistical significance for improvement in primary and secondary functional endpoints for assessment of DMD, subgroup analysis suggested that edasalonexent may slow disease progression if initiated before 6 years of age. (NCT03703882).

Introduction: It is estimated that 10 million people fall ill with Tuberculosis (TB) every year worldwide. TB continues to be in the top 10 causes of death globally with India being the home to the world's largest number of TB patients. One of the major factors attributing to this is the presence of comorbidities such as Diabetes Mellitus and HIV/AIDS., Aim: The aim of this study was to determine the prevalence of comorbidities such as Diabetes mellitus & HIV/AIDS among the newly diagnosed TB patients in Kerala in 2019 and also to determine the factors associated with it., Materials and Methods: A cross-sectional study was carried out using the secondary data from NIKSHAY portal. There were a total of 16,527 cases of pulmonary and extrapulmonary TB cases reported from 14 districts of Kerala from January to September 2019. Using a checklist, data regarding the age, gender, type of case, Type of patient, site of disease, drug resistance were collected separately for TB patients suffering from Diabetes mellitus and HIV/AIDS. The data was then entered into Excel sheet and was analyzed using SPSS version 23., Results: Out of the total 16,527 study population, most of the patients were elderly above the age of 60 years (28.6%). The prevalence of Diabetes mellitus (22.6%) was higher among TB patients when compared to HIV/AIDS (1.2%). Males in the age group between 50-59 years were found to be significantly associated with TB- Diabetes Mellitus comorbidities. Diabetes was significantly associated with Pulmonary TB patients, while HIV/AIDS was significantly associated with extrapulmonary TB., Conclusion: Both Diabetes Mellitus and HIV/AIDS are comorbidities that have a strong impact on the diagnosis and management of Tuberculosis patients. Therefore, there is an urgent need to prevent these comorbidities from occurring along with the implementation of early diagnosis and appropriate management strategies. This study is of prime importance especially among Primary care Physicians who are treating TB patients on routine basis. They are particularly important in TB control since they are usually the first to meet a TB suspect, before diagnosis occurs. Both HIV/AIDS and Diabetes mellitus are immunocompromised conditions and these comorbidities can affect the treatment outcomes of TB. Primary care physicians are essential in detecting TB suspects and treating them, thus contribute significantly to reducing the burden of TB., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Family Medicine and Primary Care.)

Objective: The present investigation was aimed to evaluate the hepatoprotective potential of ethanolic extract of Psidium guajava ( P. guajva ) and its isolated quercetin fraction on carbon tetrachloride (CCl 4 )-induced hepatotoxicity., Materials and Methods: The rats were divided into 6 groups and each group contained 6 rats. CCl 4 (1.5 ml/kg b.w.) was used to induce the hepatotoxicity. Ethanolic extract of P. guajava (300 mg/kg b.w.), isolated quercetin fraction (20 mg/kg b.w.) were used as a treatment and silymarin (25 mg/kg b.w.) was used as a standard drug. After the study period, the liver tissues were collected and evaluate the levels of liver functional markers, mitochondrial enzymes, histopathological analysis and the expressions of inflammatory markers., Results: The levels of liver functional markers were increased and protein, albumin and A/G ratio levels were decreased and the decreased levels of mitochondrial enzymes were noted in CCl 4 -induced rats and the levels were restored near to normal significantly when the administration ethanolic extract of P. guajava , isolated quercetin fraction and silymarin. The normal architecture of liver tissues were altered and the mRNA expressions were up-regulated in CCl 4 -induced rats and the liver tissues were normalized and the mRNA and protein expressions were down-regulated near to normal significantly when the administration of ethanolic extract of P. guajava , isolated quercetin fraction and silymarin., Conclusion: From these results, the isolated quercetin fractions have better activity than that of the ethanolic extract of P. guajava leaves. Hence, the isolated quercetin may be used as the safest drug for hepatotoxicity in future.

The present study evaluated the quebrachitol (QBC) antibiofilm and antivirulence potential against methicillin-resistant Staphylococcus aureus (MRSA). QBC inhibited MRSA biofilm formation at concentration dependent manner without affecting the bacterial growth. Then, QBC biofilm efficacy was confirmed with light and confocal laser scanning microscopy analysis. QBC treatment significantly inhibited the biofilm formation on stainless steel, titanium and silicone surfaces. Besides, QBC treatment significantly reduced the MRSA virulence productions such as lipase and hemolysis. Moreover, it reduced MRSA survival rate in the presence of hydrogen peroxide. QBC treatment inhibited the MRSA adherence on hydrophobic, hydrophilic, collagen coating and fibrinogen coating surfaces. As well as it significantly reduced the autolysin and bacterial aggregation progress. The real-time PCR analysis revealed the ability of QBC downregulated the virulence genes expression including global regulator sarA, agr and polysaccharide intracellular adhesion (PIA) encode ica. The cumulative results of the present study suggest that QBC as a potential agent to combat against MRSA pathogenesis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., Competing Interests: None

Introduction. Streptococcus pyogenes is a diverse virulent synthesis pathogen responsible for invasive systemic infections. Establishment of antibiotic resistance in the pathogen has produced a need for new antibiofilm agents to control the biofilm formation and reduce biofilm-associated resistance development. Aim. The present study investigates the in vitro antibiofilm activity of eucalyptol against S. pyogenes . Methodology. The antibiofilm potential of eucalyptol was assessed using a microdilution method and their biofilm inhibition efficacy was visualized by microscopic analysis. The biochemical assays were performed to assess the influence of eucalyptol on virulence productions. Real-time PCR analysis was performed to evaluate the expression profile of the virulence genes. Results. Eucalyptol showed significant antibiofilm potential in a dose-dependent manner without affecting bacterial growth. Eucalyptol at 300 µg ml -1 (biofilm inhibitory concentration) significantly inhibited the initial stage of biofilm formation in S. pyogenes . However, eucalyptol failed to diminish the mature biofilms of S. pyogenes at biofilm inhibitory concentration and it effectively reduced the biofilm formation on stainless steel, titanium, and silicone surfaces. The biochemical assay results revealed that eucalyptol greatly affects the cell-surface hydrophobicity, auto-aggregation, extracellular protease, haemolysis and hyaluronic acid synthesis. Further, the gene-expression analysis results showed significant downregulation of virulence gene expression upon eucalyptol treatment. Conclusion. The present study suggests that eucalyptol applies its antibiofilm assets by intruding the initial biofilm formation of S. pyogenes . Supplementary studies are needed to understand the mode of action involved in biofilm inhibition.

Competing Interests: None

creativecommons.org/licenses/by-nc-sa/3.0/. Cells assemble stress granules (SGs) to protect their RNAs from exposure to harmful chemical reactions induced by environmental stress. These SGs release RNAs, which resume translation once the stress is relieved. During stem cell differentiation, gene expression is altered to allow cells to adopt various functional and morphological features necessary to differentiate. This process induces stress within a cell, and cells that cannot overcome this stress die. Here, we investigated the role of SGs in the progression of stem cell differentiation. SGs aggregated during the neuronal differentiation of human bone marrow-mesenchymal stem cells, and not in cell lines that could not undergo differentiation. SGs were observed between one and three hours post-induction; RNA translation was restrained at the same time. Immediately after disassembly of SGs, the expression of the neuronal marker neurofilament-M (NFM) gradually increased. Assembled SGs that persisted in cells were exposed to salubrinal, which inhibited the dephosphorylation of eukaryotic translation initiation factor 2 subunit 1 (eIF2α), and in eIF2α/S51D mutant cells. When eIF2α/S51A mutant cells differentiated, SGs were not assembled. In all experiments, the disruption of SGs was accompanied by delayed NF-M expression and the number of neuronally differentiated cells was decreased. Decreased differentiation was accompanied by decreased cell viability, indicating the necessity of SGs for preventing cell death during neuronal differentiation. Collectively, these results demonstrate the essential role of SGs during the neuronal differentiation of stem cells.

Background: Chronic obstructive pulmonary disease (COPD) is the second leading cause of mortality in India; however, there are no programs for COPD in India at primary care level. Kerala became the first state in India to implement a program at primary care for COPD, called the Step Wise Approach to Airway Syndrome program., Objective: The objective of the study was to evaluate and document the implementation status of a program for obstructive airway disease (OAD) in Trivandrum district of Kerala state in India and compare the treatment characteristics of patients with OAD seeking care from the centers implementing and not implementing this program for OADs., Methods: A cross-sectional study was done as early evaluation of a program for OAD implemented in Kerala state, India, from October 2018 to February 2019., Results: A reflection of the health-seeking behavior due to better facilities at the FHCs. There was no difference in the hospital visits or emergency department visits between the two groups. However, there was a statistically significant difference in the average number of visits per patient to health center for taking injectable drugs and visits for nebulization. Forty-nine (94%) of the COPD and 36 (100%) of the asthma patients underwent spirometry from implementing center itself. A higher proportion of patients receiving care from implementing centers (30.9%) never had to buy inhalers from outside., Conclusion: This is the first time that a public health programme for chronic respiratory disease management at primary care level was evaluated in India. The study has provided valuable insights on the need for strengthening the training for health care providers as well as patient education in bringing about a change in patient attitudes., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Family Medicine and Primary Care.)

Objective: The current study was done to determine the prevalence, determinants, disclosure status and help-seeking behaviour of spousal violence using a nationally representative sample of ever-married women in India., Methods: We have analysed the most recent National Family Health Survey-4 data (2015-2016) gathered from the Demographic Health Survey programme. Stratification and clustering in the sample design were accounted using svyset command. Point estimates were reported as proportions with 95% CI., Results: A total of 66 013 ever-married women aged 15-49 years were included. Lifetime prevalence of spousal violence in India was 31% (95% CI 30.4% to 31.7%). Physical violence was the most common form accounting for 27.4% of victims followed by emotional (12.7%) and sexual violence (6.7%). Higher women's age, Muslim religion, low education, employed women, lower socioeconomic status, presence of substance use among women and husbands, lower education and unemployed husbands, history of family violence and women in Central and Eastern states had a significant association with one or more forms of spousal violence with significant p value. Prevalence of help-seeking behaviour among women who faced spousal violence in India was 13.5% (95% CI 12.8% to 14.2%). Widowed/separated/divorced women, employed and highly educated women, and women in Northern states had significantly higher prevalence of help-seeking behaviour with respect to all the forms of spousal violence (p<0.001)., Conclusion: One in three women in India faces spousal violence. Only 1 in 10 women seeks help following violence. Efforts should be made to ensure people working in formal institutions screen for spousal violence and know how to respond to women facing it., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: TB and HIV/AIDS are the two major public health problems. Stigma and discrimination has an enormous impact on the sufferers. The impact is felt at home, in workplace, and at the institutions. The objective of the current study was to measure the stigma and discrimination associated with TB and HIV/AIDS and to determine the underlying factors related to it among women self-help group members in Kochi city Kerala., Methods: A cross-sectional study was carried out among the women self-help group members in Kochi city. A total of 135 participants were included in the study. The study tool was a pretested self-administered questionnaire which captured information regarding the sociodemographic profile and stigma towards TB and HIV/AIDS., Result: All the respondents were women with mean age group 47.1(SD- 10.7). Majority (60%) belonged to APL category and were Hindus (52.1%). All the members have heard about HIV/AIDS and TB. The respondents reported that they would not send their children for playing with infected people (TB-49.3%; HIV-37.1%), would stay away from infected people (TB-84.3%; HIV-67.1%), and had discomfort while approaching those are infected (TB-62.1%; HIV-59.3%). Stigma toward TB and HIV was found not to have any association with any of the socio demographic factors. Correlation was observed between stigma scores of TB and HIV/AIDS ( r = 0.853; P = <0.001)., Conclusion: Stigma toward TB and HIV still exists as a major issue even among women self-help group members in Kochi. It was observed that those who had stigma toward TB also had stigma toward HIV/AIDS. Therefore is need to create holistic awareness about these diseases among women self-help groups., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Family Medicine and Primary Care.)

IgG4-related disease of the stomach is a rare disorder, and only a few cases have been reported. We present two cases that were identified over a 2-month period in our center. Two male patients aged 52 and 48 years presented with mass lesion in the stomach, which were clinically thought to be gastrointestinal stromal tumor, and they underwent excision of the lesion. Microscopic examination revealed marked fibrosis, which was storiform in one case, associated with diffuse lymphoplasmacytic infiltration and an increase in IgG4-positive plasma cells on immunohistochemistry. Serum IgG4 level was markedly elevated. Although rare, IgG4-related disease should be considered in the differential diagnosis of gastric submucosal mass lesions.