Optimised methods to image hepatic lipid droplets in zebrafish larvae.

The optical transparency of zebrafish larvae enables visualization of subcellular structures in intact organs, and these vertebrates are widely used to study lipid biology and liver disease. Lipid droplet (LD) presence is a prevalent feature of healthy cells but under conditions such as nutrient excess, toxicant exposure or metabolic imbalance, LD accumulation in hepatocytes can be a harbinger of more severe forms of liver disease. We undertook a comprehensive analysis of approaches useful to investigate LD distribution and dynamics in physiological and pathological conditions in the liver of zebrafish larvae. This comparative analysis of the lipid dyes oil red O (ORO), Nile Red (NR), LipidTox and LipidSpot as well as transgenic LD reporters that rely on EGFP fusions of the LD decorating protein perilipin 2 (PLIN2) demonstrate the strengths and limitations of each approach. These protocols are amenable to detection methods ranging from low resolution stereomicroscopy to confocal imaging, which enables measurements of hepatic LD size, number and dynamics at cellular resolution in live and fixed animals. This resource will benefit investigators studying LD biology in zebrafish disease models.

Adverse drug reactions and drug-related problems with supportive care medications among the oncological population.

AIM: The current study emphasizes the impact of adverse drug reactions (ADRs) and Drug-Related Problems (DRPs) caused by supportive care medications administered with chemotherapy. METHOD: This is a longitudinal observational study carried out at the Ramaiah Medical College Hospital in Bengaluru, Karnataka, India, at the Department of Oncology. The data was recorded using a specifically created data collecting form. Based on the PCNE (Pharmaceutical Care Network Europe), DRPs are identified. The WHO probability scale, Modified Hartwig and Siegel for ADR severity assessment, Naranjo's algorithm for causality assessment, Rawlins and Thompson for predictability assessment, and Modified Shumock and Thornton for preventability assessment were all utilized. The OncPal guideline was considered in terms of the precision of supportive care medications regarding the reduction of ADRs in cancer patients. RESULT: We enrolled 302 patients,166 (55%) female and 136 (45%) male (SD 14.378) (mean 49.97), patients with one comorbidity 59(19.6%) and multimorbidity (two or more) 45(14.9%), the DRPs identified were found to be 153 (50.6%); only P2 (safeties of drug therapy PCNE) were considered in this study. ADRs which are identified 175(57.9%) contributed/caused by the supportive care medications. WHO probability scale: 97 (32.1%) possible and 60 (19.9%) unlikely; Naranjo's algorithm: 97 (32.1%) unlikely and 69 (22.8%) possible; ADR severity assessment scale (Modified Hartwig and Siegel): 95 (31.5%) mild and 63 (20.9%) moderates; Rawlins and Thompson for determining predictability of an ADR: 33 (10.9%) predictable and 137 (45.5%) non-predictable; and Modified Shumock and Thornton for determining preventability of an ADR: 81 (26.8%) probably preventable and 90 (29.8%) non-preventable. The statistical comparison through preforming t-test and measuring Chi-Square between group with ADRs and without ADRs shows in some variables, significantly (Alcohol consumption status, P = .019) and Easter Cooperative Oncology Group (ECOG) performance status P < 0.001. CONCLUSION: Comprehensive assessment of supportive medications in cancer patients would enhance the patient management and therapeutic outcome. The potential adverse drug reactions (ADRs) caused by supportive care medications can contribute to longer hospital stays and interact with the systemic anti-cancer treatment. The health care professionals should be informed to monitor the patients clinically administered with supportive medications.

On the higher-order smallest ring-star network of Chialvo neurons under diffusive couplings.

Network dynamical systems with higher-order interactions are a current trending topic, pervasive in many applied fields. However, our focus in this work is neurodynamics. We numerically study the dynamics of the smallest higher-order network of neurons arranged in a ring-star topology. The dynamics of each node in this network is governed by the Chialvo neuron map, and they interact via linear diffusive couplings. This model is perceived to imitate the nonlinear dynamical properties exhibited by a realistic nervous system where the neurons transfer information through multi-body interactions. We deploy the higher-order coupling strength as the primary bifurcation parameter. We start by analyzing our model using standard tools from dynamical systems theory: fixed point analysis, Jacobian matrix, and bifurcation patterns. We observe the coexistence of disparate chaotic attractors. We also observe an interesting route to chaos from a fixed point via period-doubling and the appearance of cyclic quasiperiodic closed invariant curves. Furthermore, we numerically observe the existence of codimension-1 bifurcation points: saddle-node, period-doubling, and Neimark-Sacker. We also qualitatively study the typical phase portraits of the system, and numerically quantify chaos and complexity using the 0-1 test and sample entropy measure, respectively. Finally, we study the synchronization behavior among the neurons using the cross correlation coefficient and the Kuramoto order parameter. We conjecture that unfolding these patterns and behaviors of the network model will help us identify different states of the nervous system, further aiding us in dealing with various neural diseases and nervous disorders.

Impact of Migraine on Family Members - A Cross-sectional Study in Southern Part of India.

BACKGROUND: Migraine is a disabling primary headache disorder characterized by recurrent episodes of headache. Migraine not only imposes a burden on the sufferer but also imposes a burden on their family members too. A holistic approach is more essential in the management of migraine and family members should also be included in the management of migraine. There are no published studies done in India so far to look for the impact of migraine on partners and adolescent children (IMPAC). This pilot study was done to assess the IMPAC. OBJECTIVE: The objective of the study was to study the IMPAC. MATERIALS AND METHODS: In this descriptive study, 130 chronic migraine patients were observed in a row during 9 months. The impact of migraine on family members as well as migraine disability and Migraine-specific Quality of Life (MSQoL) was evaluated using validated questionnaires. RESULTS: One hundred and thirty chronic migraine patients were studied as part of this study. The mean age of the study population was 34.43 ± 9.002 years, and two-third of the participants were female. The majority of the participants had a moderate-to-severe disability due to migraine and had negatively impacted their MSQoL. The impact of migraine on family members was moderate-to-severe grade in most of the participants and affected their family life negatively both with children and spouses. The males were more significantly affected than females in terms of MSQoL, anxiety, depression, and also on migraine's impact on family members. CONCLUSION: Migraine not only affects the sufferers, it also significantly affects their family members.

Résumé Contexte:La migraine est une céphalée primaire invalidante caractérisée par des épisodes récurrents de céphalées. La migraine n'impose pas seulementun fardeau pour la victime, mais impose également un fardeau aux membres de sa famille. Une approche holistique est plus essentielle dans la gestion des la migraine et les membres de la famille doivent également être impliqués dans la prise en charge de la migraine. Il n'existe jusqu'à présent aucune étude publiée en Inde pour rechercher l'impact de la migraine sur les partenaires et les adolescents (IMPAC). Cette étude pilote a été réalisée pour évaluer l'IMPAC.Objectif:L'objectif de l'étude était d'étudier l'IMPAC.Matériels et méthodes:Dans cette étude descriptive, 130 patients migraineux chroniques ont été observés d'affilée pendant 9 mois. L'impact de la migraine sur les membres de la famille ainsi que l'incapacité migraineuse et la qualité de vie spécifique à la migraine (MSQoL) ont été évalués à l'aide de questionnaires validés.Résultats:Cent trente patients migraineux chroniques ont été étudiés dans le cadre de cette étude. L'âge moyen de la population étudiée était de 34,43 ± 9,002 ans et les deux tiers des participants étaient des femmes. La majorité des participants souffraient d'un handicap modéré à sévère dû à une migraine et avaient eu un impact négatif sur leur MSQoL. L'impact de la migraine Les effets sur les membres de la famille étaient modérés à sévères chez la plupart des participants et affectaient négativement leur vie familiale, tant avec les enfants que avec les conjoints. Les hommes ont été plus significativement touchés que les femmes en termes de MSQoL, d'anxiété, de dépression, ainsi que d'impact de la migraine sur les membres de la famille.Conclusion:La migraine n'affecte pas seulement les personnes qui en souffrent, elle affecte également de manière significative les membres de leur famille.

Pain Outcomes Following Endoscopic Microvascular Decompression for Trigeminal Neuralgia Based on Vascular Compression Type.

Background Arterial compression of the trigeminal nerve at the root entry zone has been the long-attributed cause of compressive trigeminal neuralgia despite numerous studies reporting distal and/or venous compression. The impact of compression type on patient outcomes has not been fully elucidated. Objective We categorized vascular compression (VC) based on vessel and location of compression to correlate pain outcomes based on compression type. Methods A retrospective video review of 217 patients undergoing endoscopic microvascular decompression for trigeminal neuralgia categorizing VC into five distinct types, proximal arterial compression (VC1), proximal venous compression (VC2), distal arterial compression (VC3), distal venous compression (VC4), and no VC (VC5). VC type was correlated with postoperative pain outcomes at 1 month ( n = 179) and last follow-up (mean = 42.9 mo, n = 134). Results At 1 month and longest follow-up, respectively, pain was rated as "much improved" or "very much improved" in 89 69% of patients with VC1, 86.6 and 62.5% of patients with VC2, 100 and 87.5% of patients with VC3, 83 and 62.5% of patients with VC4, and 100 and 100% of patients with VC5. Multivariate analysis demonstrated VC4 as a significant negative of predictor pain outcomes at 1 month, but not longest follow-up, and advanced age as a significant positive predictor. Conclusion The degree of clinical improvement in all types of VC was excellent, but at longest follow-up VC type was not a significant predictor out outcome. However distal venous compression was significantly associated with worse outcomes at 1 month.

What our children lost and gained at the time of school closure during the Covid-19 pandemic: a study on psychological distress, behavioural concerns and protective factors of resilience among preschool children in Kerala, India.

BACKGROUND: The pandemic has put at risk the social and emotional development of children on account of the paucity of arenas for social interaction. This study from Kerala, India was conducted to assess the resilience factors, behavioural concerns, psychological distress symptoms among the children aged 3 to 5 years. We also tried to look into the lost opportunities that could have aided the social and emotional development of children like peer interaction, child care hours. METHODS: The cross-sectional study was conducted among the children aged 3 to 5 years. A total of 535 children attending the immunisation clinics were enrolled by consecutive sampling. Devereux Early Childhood Assessment P2 (DECA P2) questionnaire was used to assess the levels of resilient factors and behavioural concerns in the study population. RESULTS: We observed a high proportion of children in the area of need category of protective factors under DECA P2. The proportion of children falling under area of concern was 64.5%, 49%, 68.4% for attachment/relationship, self-regulation, and initiative respectively. 24.9% study subjects have a behavioural concern score that puts them in the area of need category. The logistic regression model we created identified 'Male Gender,' 'Mothers could spend only less time for child care' and 'electronic devices used as pacifier' as significant predictors for belonging to Area of need Behavioural Concerns T score category. CONCLUSION: A large proportion of children aged between 3 to 5 years with reported behavioural concerns and lack of protective factors for socioemotional development. This can be attributed partly to the ongoing pandemic and its associated restrictions. The increased child care hours invested by parents or grandparents could have sized down the full impact that the pandemic would have had on the socio emotional development of the child. Increased time spent using electronic devices coupled with dwindled opportunities for interaction with peers have been notable challenges.

A case-cohort study of left ventricular diastolic dysfunction in patients with cirrhosis: the liver-heart axis.

Background: Left ventricular diastolic dysfunction (LVDD) is an early manifestation of cirrhotic cardiomyopathy. Few studies have addressed its clinical significance in cirrhosis. We assessed the association of LVDD with the factors affecting cirrhosis patients' severity, complications, and survival. Methods: A total of 203 cirrhosis patients were enrolled and underwent investigations, including 2-dimensional echocardiography with tissue Doppler imaging, and 139 patients with LVDD (cases) were compared with 64 patients without LVDD (controls). Logistic regression and Kaplan-Meier analysis were applied. Results: Mean age was 52.76±10 years. Among LVDD patients, 56% had grade-1, and 44% had grade-2 LVDD. Cirrhosis related to NASH had a more significant association with LVDD (P<0.001) than other etiologies. LVDD was significantly associated with a greater incidence of Child-Turcotte-Pugh (CTP) class C (P<0.001), higher model for end-stage liver disease scores (P=0.001), duration of cirrhosis >2 years since diagnosis (P=0.028), ascites (P<0.001), hepatic encephalopathy (P<0.010), hepatorenal syndrome (P<0.001), and a history of obesity (P=0.004). Multivariate analysis showed that higher CTP score, ascitic fluid protein and prolonged QTc interval were independently associated with LVDD (P=0.009; P=0.018; P=0.016, respectively). Kaplan-Meier survival analysis showed significantly poorer survival status in patients with higher grades of LVDD (P<0.001). The area under the receiver operating characteristic curve (0.78) was greatest for ascitic fluid protein in predicting LVDD, with a cutoff of >1 g/dL. Conclusions: Higher CTP score, prolonged QTc, higher ascitic fluid protein levels, and poor survival are significantly associated with LVDD. Ascitic fluid protein >1 g/dL could be an indicator for evaluating LVDD.

Physical, Chemical, Barrier, and Antioxidant Properties of Pectin/Collagen Hydrogel-Based Films Enriched with Melissa officinalis.

The essential oil extracted from Melissa officinalis (MOEO) exhibits a wide range of therapeutic properties, including antioxidant, antibacterial, and antifungal activities. The current research aimed to analyze the mechanical, barrier, chemical, and antioxidant properties of pectin and collagen-based films. Hydrogel-based films loaded with varying concentrations of MOEO (0.1%, 0.15%, and 0.2%) were prepared by solvent-casting method, and their physicochemical as well as antioxidant properties were examined. GC-MS analysis revealed the presence of major components in MOEO such as 2,6-octadienal, 3,7-dimethyl, citral, caryophyllene, geranyl acetate, caryophyllene oxide, citronellal, and linalool. Fourier transform infrared (FTIR) results revealed the interaction between components of the essential oil and polymer matrix. Scanning electron microscopy (SEM) revealed that films loaded with the highest concentration (0.2%) of MOEO showed more homogeneous structure with fewer particles, cracks, and pores as compared to control film sample. MOEO-incorporated films exhibited higher elongation at break (EAB) (30.24-36.29%) and thickness (0.068-0.073 mm); however, they displayed lower tensile strength (TS) (3.48-1.25 MPa) and transparency (87.30-82.80%). MOEO-loaded films demonstrated superior barrier properties against water vapors. According to the results, the incorporation of MOEO into pectin-collagen composite hydrogel-based films resulted in higher antioxidant properties, indicating that MOEO has the potential to be used in active food packaging material for potential applications.

Knowledge, Attitude and Practices Among Mothers of Infants Regarding Breastfeeding.

Objective: This study aims at understanding the level of knowledge, attitude, and practice of breastfeeding among mothers and the factors associated with good knowledge about breastfeeding. Materials and methods: A cross-sectional study among 251 mothers of infants admitted in the pediatric wards of SAT Hospital, Thiruvananthapuram was conducted during November-December 2019. The mothers of infants born between 37 and 42 weeks of gestation and without major birth defects were included in the study. The data were entered into an MS Excel sheet and analyzed using Statistical Package of Social Sciences version 26.0. Significance of association was tested using Chi-square test and multivariate analysis was done using binary logistic regression test. Results: The mean age of the participants was 26.25 (SD 4) years. On multivariable analysis, higher education and older age were found to be significantly associated with good knowledge. Independent sample T-Test results show that there was a statistically significant difference between the mean age of mothers with good knowledge (26.4(±4), 25.14(±3.7)), p-0.015 and statistically significant association was found between the mean attitude scores (34.07(5.58)) with current breastfeeding practices (p=0.002). Chi-square test shows that exclusive breastfeeding was significantly associated with the mother's age (p=0.006); 64.2% of women practicing exclusive breastfeeding were less than 25 years of age. This study also demonstrated a significant association between the initiation of breastfeeding within an hour and exclusive breastfeeding (p=0.003). Conclusion: This study shows that mothers with higher age and higher educational qualifications were significantly associated with good knowledge about breastfeeding. Even though mothers have good knowledge, nearly half the mothers only exclusively breastfeed their infants for six months. Improving the educational qualification of women and increasing awareness about the benefits of breastfeeding among young women will promote breastfeeding practices.

Adverse events associated with Covishield vaccination among healthcare workers in a tertiary hospital in South India.

Background: Vaccination is the most important prophylactic measure taken to curb COVID-19 pandemics. This study was undertaken to throw light on the safety of Covishield vaccine among health care workers (HCWs) and to assess the co-variates associated with incidence of adverse events. Methods: This prospective observational study was conducted in a tertiary care center in South India as part of the HCW vaccination drive. All consenting HCWs who received the first dose of Covishield vaccine and developed ADRs were included in this study. After vaccination, all beneficiaries were monitored for AEFI for a period of half an hour and later followed up through telephone and google survey forms on day 2 and day 7 of vaccination. The data was subsequently collated into spreadsheet format and analyzed. Results: The study included 1264 consenting healthcare workers who were predominantly youth, aged 15-24 years (n = 583, 46 %) and with a female preponderance of 76 % (n = 960). Past history of COVID-19 infections was reported among 4.6 % (58) of the study population. Postvaccination symptoms were majorly reported during the first (40 %) and second day (44 %) after vaccination with a high prevalence of both local (n = 1083, 85 %) and systemic symptoms (n = 1065, 84 %). The mean duration of symptoms was observed to be 1.4 ± 0.81 days post vaccination. Symptoms were observed significantly high among females (76.7 %, p = 0.013). The prevalence of systemic (88 % vs 80 %) (p < 0.001) and allergic symptoms (7 % vs 3 %; p = 0.03) were observed to be significantly high among respondents with <25 years of age. The systemic and allergic symptoms following vaccination were reported to be low among healthcare workers who had a previous history of COVID-19 infection. Conclusion: COVID vaccination has been observed to be safe and well tolerated with more systemic symptoms reported among younger age group and females.

Adverse reaction profile of sulfasalazine and its persistence in chronic therapy of rheumatoid arthritis and spondyloarthritis: A multicentric observational study.

OBJECTIVES: Sulfasalazine has been widely used in treatment of rheumatoid arthritis and spondyloarthritis. This study aims to assess persistence with sulfasalazine and also frequency and severity of adverse drug reactions (ADRs) encountered with this very well-established disease-modifying anti-rheumatoid drug. MATERIALS AND METHODS: This retrospective study was done in 1,114 patients from medicine and rheumatology outpatient departments of six centers across India. The inclusion criteria was patients taking sulfasalazine. Patients receiving sulfasalazine for rheumatoid arthritis or spondyloarthritis were selected and details on drugs used, duration of taking sulfasalazine, ADRs to sulfasalazine and whether sulfasalazine had to be stopped due to ADRs were analyzed. RESULTS: Of the total of patients included in the study, 10.1% had ADRs with sulfasalazine, and stopped the drug. Gastritis, deranged liver enzymes, hepatitis, skin rashes were the most commonly encountered ADRs. Of the total number of patients recruited for the study, 11% were lost to follow-up, as most of the centers were army hospitals and the officers and staff were posted to other places. Sulfasalazine was taken for less than 1 month by 3.8% patients while 12.5% had taken the drug for less than 6 months. Of the study patients, 28.6% had taken the drug for 24 - 60 months and 4.6% (51 patients) had taken it for more than 5 years. It was found that ADRs were most commonly encountered within the first year of using the drug, and persistence was seen in patients on long-term therapy. CONCLUSION: Sulfasalazine is a safe option in chronic therapy of rheumatoid arthritis and spondyloarthritis. Although frequency of ADRs with patients taking sulfasalazine is minimal, it did necessitate the stoppage of drug. If not well tolerated, sulfasalazine would not have been continued for more than 12 months as evidenced from this study.

Epidemiological and clinical characterization of dengue virus serotypes during 2017-2019 in southern Kerala, India.

BACKGROUND: In the context of the largest dengue outbreak in the state of Kerala, India in 2017, along with global evidence of changing epidemiology of dengue virus and its distribution, this study was planned to understand the epidemiological pattern of dengue infection and contemplate the clinical presentations of different serotypes. METHODS: This cross-sectional study was conducted in the Thiruvananthapuram and Kollam districts of Kerala, India, spanning 3 y from 2017 to 2019. We recruited adult patients based on the World Health Organization case definition of probable dengue fever to study their virological, spatial and clinical characteristics. RESULTS: Dengue infection was identified in 113 (33.9%) of the 333 probable dengue patients recruited. Dengue virus 1 (DENV1), along with its combinations (59.09%), was the predominant serotype during 2017, followed by DENV2. There was a marked increase in the proportion of DENV4 cases (34.56%) and concurrent infections (26%) in 2019. DENV3 infections were more likely to present with warning signs (adjusted relative risk 6.14 [95% confidence interval 1.3 to 29.4]) and a significantly lower platelet count (p=0.02). CONCLUSIONS: The results highlight the hyperendemicity of dengue infection in the state and the changing pattern of dengue virus predominance along with redominance. The rise in DENV4 and concurrent infections put forth the possibility of a more severe future outbreak.

A permissive epigenetic landscape facilitates distinct transcriptional signatures of activating transcription factor 6 in the liver.

Restoring homeostasis following proteostatic stress hinges on a stress-specific transcriptional signature. How these signatures are regulated is unknown. We use functional genomics to uncover how activating transcription factor 6 (ATF6), a central factor in the unfolded protein response, regulates its target genes in response to toxicant induced and physiological stress in the liver. We identified 652 conserved putative ATF6 targets (CPATs), which functioned in metabolism, development and proteostasis. Strikingly, Atf6 activation in the zebrafish liver by transgenic nAtf6 overexpression, ethanol and arsenic exposure resulted in a distinct CPAT signature for each; with only 34 CPATs differentially expressed in all conditions. In contrast, during liver regeneration in mice resulted in a dynamic differential expression pattern of 53% of CPATs. These CPATs were distinguished by residing in open chromatin, H3K4me3 occupancy and the absence of H3K27me3 on their promoters. This suggests that a permissive epigenetic landscape allows stress-specific Atf6 target gene expression.

Knowledge, Attitude and Practices Regarding Menstrual Cup Among Females in an Urban Setting of South Kerala.

Objective: This study aims to assess the knowledge, attitude, and practices regarding menstrual cups use and the factors associated with it among females of the reproductive age group in an urban setting of South Kerala. Materials and methods: We conducted a cross-sectional study from December 2021 to January 2022 among females of the reproductive age group. Data was entered in MS Excel and was analyzed using Statistical Package for Social Sciences version 26.0. The significance of association was tested using the Chi-square test. Binary logistic regression was done to predict the factors associated with knowledge levels regarding menstrual cup. Results: The mean age of study participants was 25.68(SD 6.64) years. Lack of knowledge (22.6%) and fear of insertion (56.2%) were the major reasons for not trying a menstrual cup. Out of the 350 study participants, 258(73.7%) had good knowledge scores and 92(26.3%) had poor knowledge scores. Discomfort and leakage were the most important problems reported by participants. A statistically significant association was found between younger age, educational status, socioeconomic, status, marital status of females in the reproductive age group, and knowledge about the menstrual cup. Conclusion: Most of the participants (93.4%) were aware of menstrual cups. Even though two third of the participants had good knowledge regarding menstrual cups, only 15.1% have tried to use a menstrual cup. Fear of insertion was the most common concern for not trying a menstrual cup. Discomfort and leakage were the most important problems reported by participants. Younger age and higher educational qualifications were found to be independently associated with knowledge levels regarding menstrual cups.

Obesity Burden and Physical Activity Pattern Among Doctors in South India.

Context: A career as a doctor makes him prone to develop health issues like obesity and obesity-related noncommunicable diseases. Aims: This study aims to find the burden and determinants of obesity among Modern Medicine doctors in Kerala. Settings and Design: We conducted a cross-sectional study among 240 doctors working in South Kerala from 2018 to 2019. Methods and Material: The sample size was calculated using a formula and stratified random sampling was done for the selection of study participants. An interviewer-administered structured questionnaire was used for data collection. Physical activity was measured using International Physical Activity Questionnaire. Statistical Analysis: Data were entered in MS Excel and was analyzed using Statistical Package for Social Sciences version 26.0. The significance of association was tested using the χ2 test. Binary logistic regression was done to predict the factors associated with overweight and obesity. Results: Out of 240 study participants, 128 (54%) were females and 112 (46%) were males. Among the 240 doctors, 54% (114) were either overweight or obese. A low level of physical activity was reported among 54.5% of doctors. Male gender odds ratio (OR) = 2.8 (95% confidence interval [CI] = 1.29-6.06), nuclear family OR = 2.7 (95% CI = 1.32-5.42), daily hours of sleep <6 hours OR = 4.92 (95% CI = 2.29-10.5), history of obesity among parents OR = 3.54 (95% CI = 1.04-12.02), reported the presence of private practice OR = 3.34 (95% CI = 1.25-8.96), and holding a graduation degree alone were found to be significantly associated with obesity. Conclusions: The study found that majority of the doctors (55%) were either overweight or obese. Awareness and behavior change communication among doctors on modifiable risk factors like having adequate sleep and reducing the hours spent in private practice is needed to reduce the burden of obesity among doctors.

Systematic Evaluation of the Effects of Toxicant Exposure on Survival in Zebrafish Embryos and Larvae.

The use of whole animal models in toxicological studies is essential for understanding the physiological responses caused by chemical exposures. However, such studies can face reproducibility challenges due to unaccounted experimental parameters that can have a marked influence on toxicological outcomes. Zebrafish embryos and larvae are a popular vertebrate animal model for studying cellular, tissue, and organ responses to toxicant exposures. Despite the popularity of this system, standardized protocols that control for the influence of various experimental parameters and culture conditions on the toxicological response in these animals have not been widely adopted, making it difficult to compare findings from different laboratories. Here, we describe a detailed approach for designing and optimizing protocols to assess the impact of chemical exposures on the development and survival of zebrafish embryos and larvae. We first describe our standard procedure to determine two key toxicological thresholds, the maximum tolerable concentration (MTC) and the lethal concentration (LC50 , defined as that in which 50% of larvae die), in response to an exposure that persists from early development through larval maturation. We then describe two protocols to systematically test how key experimental parameters, including genetic background, culture media, animal density, volume, plate material, and developmental stage in which the embryos are exposed, alter the MTC and LC50 . Finally, we provide a step-by-step guide to assess the interaction between two chemicals using this model. These protocols will guide the standardization of toxicological studies using zebrafish and maximize reproducibility. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Zebrafish embryo collection and culture, and establishment of the MTC and LC50 Basic Protocol 2: Evaluation of the impact of culture conditions on toxicant responses of zebrafish embryo and larvae Basic Protocol 3: Identification of the developmental window of sensitivity to toxicant exposure Basic Protocol 4: Testing interaction between multiple toxicants.

Strategies and challenges in Kerala's response to the initial phase of COVID-19 pandemic: a qualitative descriptive study.

OBJECTIVE: To understand the structures and strategies that helped Kerala in fighting the COVID-19 pandemic, the challenges faced by the state and how it was tackled. DESIGN: Qualitative descriptive study using focus group discussions and in-depth interviews. SETTING: State of Kerala, India. PARTICIPANTS: 29 participants: four focus group discussions and eight in-depth interviews. Participants were chosen purposively based on their involvement in decision-making and implementation of COVID-19 control activities, from the department of health and family welfare, police, revenue, local self-government and community-based organisations. Districts, panchayats (local bodies) and primary health centres (PHCs) were selected based on epidemiological features of the area like the intensity of disease transmission and preventive/containment activities carried out in that particular area to capture the wide range of activities undertaken in the state. RESULTS: The study identified five major themes that can inform best practices viz social capital, robust public health system, participation and volunteerism, health system preparedness, and challenges. This study was a real-time exploration of the intricacies of COVID-19 management in a low/middle-income country and the model can serve as an example for other states and nations to emulate or adjust accordingly. CONCLUSION: The study shows the impact of synergy of these themes towards more effective solutions; however, further research is much needed in examining the relationship between these factors and their relevance in policy decisions.

Cardiovascular Changes in Menopause.

Menopause is associated with changes consistent with cardiovascular aging. The effects of cardiac disease are multifaceted, affecting endothelial function, coronary artery physiology and metabolic dysfunction leading to structural changes in the coronary anatomy. A systematic review of literature from 1986 to 2019 was conducted using PubMed and Google Scholar. The search was directed to retrieve papers that addressed the changes in cardiovascular physiology in menopause and the current therapies available to treat cardiovascular manifestations of menopause. The metabolic and clinical factors secondary to menopause, such as dyslipidemia, insulin resistance, fat redistribution and systemic hypertension, contribute to the accelerated risk for cardiovascular aging and disease. Atherosclerosis appears to be the end result of the interaction between cardiovascular risk factors and their accentuation during the perimenopausal period. Additionally, complex interactions between oxidative stress and levels of L-arginine and ADMA may also influence endothelial dysfunction in menopause. The increased cardiovascular risk in menopause stems from the exaggerated effects of changing physiology on the cardiovascular system affecting peripheral, cardiac and cerebrovascular beds. The differential effects of menopause on cardiovascular disease at the subclinical, biochemical and molecular levels form the highlights of this review.

Arsenic induced redox imbalance triggers the unfolded protein response in the liver of zebrafish.

Inorganic arsenic (iAs) is one of the most endemic toxicants worldwide and oxidative stress is a key cellular pathway underlying iAs toxicity. Other cellular stress response pathways, such as the unfolded protein response (UPR), are also impacted by iAs exposure, however it is not known how these pathways intersect to cause disease. We optimized the use of zebrafish larvae to identify the relationship between these cellular stress response pathways and arsenic toxicity. We found that the window of iAs susceptibility during zebrafish development corresponds with the development of the liver, and that even a 24-h exposure can cause lethality if administered to mature larvae, but not to early embryos. Acute exposure of larvae to iAs generates reactive oxygen species (ROS), an antioxidant response, endoplasmic reticulum (ER) stress and UPR activation in the liver. An in vivo assay using transgenic larvae expressing a GFP-tagged secreted glycoprotein in hepatocytes (Tg(fabp10a:Gc-EGFP)) revealed acute iAs exposure selectively decreased expression of Gc-EGFP, indicating that iAs impairs secretory protein folding in the liver. The transcriptional output of UPR activation is preceded by ROS production and activation of genes involved in the oxidative stress response. These studies implicate redox imbalance as the mechanism of iAs-induced ER stress and suggest that crosstalk between these pathways underlie iAs-induced hepatic toxicity.

Covalent Organic Framework Embedded with Magnetic Nanoparticles for MRI and Chemo-Thermotherapy.

Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide nanoparticles (γ-Fe2O3 NPs), and stabilized with a shell of poly(l-lysine) cationic polymer (PLL) for simultaneous synergistic thermo-chemotherapy treatment and MRI imaging. The pH responsivity of the resulting nanoagents (γ-SD/PLL) allowed the release of the drug selectively within the acidic microenvironment of late endosomes and lysosomes of cancer cells (pH 5.4) and not in physiological conditions (pH 7.4). γ-SD/PLL could efficiently generate high heat (48 °C) upon exposure to an alternating magnetic field due to the nCOF porous structure that facilitates the heat conduction, making γ-SD/PLL excellent heat mediators in an aqueous solution. The drug-loaded magnetic nCOF composites were cytotoxic due to the synergistic toxicity of Dox and the effects of hyperthermia in vitro on glioblastoma U251-MG cells and in vivo on zebrafish embryos, but they were not significantly toxic to noncancerous cells (HEK293). To the best of our knowledge, this is the first report of multimodal MRI probe and chemo-thermotherapeutic magnetic nCOF composites.