Chronic musculoskeletal pain among elderly individuals in a rural area of West Bengal: A mixed-method study.

Introduction: The high prevalence among elderly individuals and potential adverse impact on their overall life quality make chronic musculoskeletal pain a significant public health concern. Chronic musculoskeletal pain is an important cause of self-medication, which must be addressed to avoid various side effects and improve elderly health. This study aimed to determine the prevalence of chronic musculoskeletal pain and its associated factors among individuals (age ≥60 years) in rural West Bengal and explore their perspectives and perceived barriers regarding pain and its management. Method: This mixed-method study was conducted in rural West Bengal from December 2021 to June 2022. The quantitative strand was conducted by interviewing 255 elderly participants (age ≥60 years) using a structured questionnaire. The qualitative strand was conducted via in-depth interviews of 10 patients with chronic pain. Quantitative data were analyzed using SPSS version 16, and chronic pain-related factors were analyzed using logistic regression models. Qualitative data were analyzed thematically. Results: Among the participants, 56.8% reported chronic musculoskeletal pain. The most frequently affected site was the knee joint. Comorbidity (adjusted odds ratio [aOR]=7.47, 95% confidence interval [CI]=3.2-17.5), age (aOR=5.16, 95% CI=2.2-13.5), depression (aOR=2.96, 95% CI=1.2-6.7) and over-the-counter drug usage (aOR=2.51, 95% CI=1.1-6.4) were significantly associated with chronic pain. Analgesic dependency, lack of motivation to adopt lifestyle modifications, lack of knowledge on analgesic side effects were considered pain management barriers. Conclusion: Managing comorbidities, providing mental support, generating awareness of analgesic side effects, strengthening healthcare facilities should be prioritized for holistic chronic musculoskeletal pain management.

Spectroscopic studies on a natural biomarker for the identification of origin and quality of tea extracts for the development of a portable and field deployable prototype.

Even in the era of smart technologies and IoT enabled devices, tea testing technique continues to be a person specific subjective task. In this study, we have employed optical spectroscopy-based detection technique for the quantitative validation of tea quality. In this regard, we have employed the external quantum yield of quercetin at 450 nm (λex = 360 nm), which is an enzymatic product generated by the activity of ß-glucosidase on rutin, a naturally occurring metabolite responsible for tea-flavour (quality). We have found that a specific point in a graph representing Optical Density and external Quantum Yield as independent and dependent variables respectively of an aqueous tea extract objectively indicates a specific variety of the tea. A variety of tea samples from various geographical origin have been analysed with the developed technique and found to be useful for the tea quality assessment. The principal component analysis distinctly showed the tea samples originated from Nepal and Darjeeling having similar external quantum yield, while the tea samples from Assam region had a lower external quantum yield. Furthermore, we have employed experimental and computational biology techniques for the detection of adulteration and health benefit of the tea extracts. In order to assure the portability/field use, we have also developed a prototype which confirms the results obtained in the laboratory. We are of the opinion that the simple user interface and almost zero maintenance cost of the device will make it useful and attractive with minimally trained manpower at low resource setting.

Measuring Impact of Climate Change on Indigenous Health in the Background of Multiple Disadvantages: A Scoping Review for Equitable Public Health Policy Formulation.

How climate change is uniquely affecting Indigenous health remains a very less explored area in the existing research literature. The imperative of inclusive climate action to protect indigenous health multiplies manifolds due to their unique vulnerabilities owing to predominant dependence on natural resources and multiple disadvantages faced. The current article attempted to add to the evidence pool regarding climate change impacts on the indigenous population by systematically collecting, processing, and interpreting data as a scoping literature review for effective and inclusive climate policymaking. Twenty-Nine articles of varied study designs were identified employing a systematically organized search strategy using PubMed (Field, MeSH, and advanced search) and Google scholar; relevant data were extracted for further analysis. The Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Reviews (PRISMA-ScR) guidelines were followed. Changing climate scenarios had both direct and indirect health-related impacts on indigenous health, and altered the epidemiological triad for various health-related events, causing the emergence and re-emergence of infectious diseases, and increased prevalence of chronic diseases and mental disorders. An expanded framework was developed showcasing the variability of climate change events, multiple disadvantages, and its impacts on indigenous populations. Few studies also reported a wide range of adaptation responses of indigenous peoples towards climate change. It was substantiated that any climate-change mitigation policy must take into account the trials and tribulations of indigenous communities. Also, due to the complexity and large variability of the impacts and differences in mitigation capabilities, policies should be contextualized locally and tailored to meet the climate need of the indigenous community.

Green synthesis of zinc oxide nanoparticles using Eucalyptus lanceolata leaf litter: characterization, antimicrobial and agricultural efficacy in maize.

In the present study, green synthesis of zinc oxide nanoparticles (ZnO NP) using Eucalyptus lanceolatus (leaf litter) extract was explored after characterization with UV spectrophotometery, Fourier Transform Infrared analysis, X-ray diffraction and TEM studies. ZnO NPs stability was ensured with - 32.1 mV zeta potential, while TEM showed ZnO NP as hexagonal structure (100 nm). In vitro antimicrobial activity showed potential of ZnO NP against pathogens causing diseases in maize plants. Both in vitro and in vivo studies of ZnO NP and ZnSO4 (200 ppm and 400 ppm) over a two year period (2019, 2020) were conducted on Zea mays L. var. PG2458. ZnO NP seed priming improved seed vigor index, germination percentage, shoot and root length and fresh biomass. Foliar application improved stem diameter and leaf surface area. Physiological status was relatively better, while reproductive attributes got altered to guide resource allocation for better cob growth and biomass with ZnO NP. Leaf, cob, grain and total Zn was maximum for 200 ppm ZnO NP. Translocation of Zn from leaf to cob and cob to grain was faster for ZnO NP compared to ZnSO4. Higher concentration (400 ppm) of ZnO NPs and ZnSO4 proved phytotoxic for plant growth attributes. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01136-0.

Identification of tyrosine kinase inhibitors from Panax bipinnatifidus and Panax pseudoginseng for RTK-HER2 and VEGFR2 receptors, by in silico approach.

Breast and stomach cancer is reported as a leading cause for human mortality across the world. The overexpression of receptor tyrosine kinase (RTK) proteins, namely the human epidermal growth factor receptor2 (HER2) and the vascular endothelial growth factor receptor2 (VEGFR2), is reported to be responsible for development and metastasis of breast and stomach cancer. Although several synthetic tyrosine kinase inhibitors (TKIs) as drug candidates targeting RTK-HER2 and VEGFR2 are currently available in the market, these are expensive with the reported side effects. This confers an opportunity for development of alternative novel tyrosine kinase inhibitors (TKIs) for RTK-HER2 and VEGFR2 receptors from the botanical sources. In the present study, we characterized 47 bioactive phytocompounds from the methanol extracts of the rhizomes of Asiatic traditional medicinal herbs-Panax bipinnatifidus and Panax pseudoginseng, of Indian Himalayan landraces using HPLC, GC-MS and high-sensitivity LC-MS tools. We performed molecular docking and molecular dynamics simulation analysis using Schrödinger suite 2020-3 to confirm the TKI phytocompounds showing the best binding affinity towards RTK-HER2 and VEGFR2 receptors. The results of molecular docking studies confirmed that the phytocompound (ligand) luteolin 7-O-glucoside (IHP15) showed the highest binding affinity towards receptor HER2 (PDB ID: 3PP0) with docking score and Glide g score (G-Score) of - 13.272, while chlorogenic acid (IHP12) showed the highest binding affinity towards receptor VEGFR2 (PDB ID: 4AGC) with docking score and Glide g score (G-Score) of - 10.673. Molecular dynamics (MD) simulation analysis carried out for 100 ns has confirmed strong binding interaction between the ligand and receptor complex [luteolin 7-O-glucoside (IHP15) and HER2 (PDB ID: 3PP0)] and is found to be stabilized within 40 to 100 ns of MD simulation, whereas ligand-receptor complex [chlorogenic acid (IPH12) and VEGFR2 (PDB ID: 4AGC)] also showed strong binding interaction and is found to be stabilized within 18-30 ns but slightly deviated during 100 ns of MD simulation. In silico ADME-Tox study using SwissADME revealed that the ligands luteolin 7-O-glucoside (IHP15) and chlorogenic acid (IHP12) have passed majority parameters of the common drug discovery rules. The present study has confirmed luteolin 7-O-glucoside (IHP15) and chlorogenic acid (IHP12) as potential tyrosine kinase inhibitors (TKIs) which were found to inhibit RTKs-HER2 and VEGFR2 receptor proteins, and thus paving the way for development of alternative potential TKIs (drug molecules) for treatment of HER2- and VEGFR2-positive breast and stomach cancer.

Inhibition of the ERK1/2-mTORC1 axis ameliorates proteinuria and the fibrogenic action of transforming growth factor-ß in Adriamycin-induced glomerulosclerosis.

Transforming growth factor-ß (TGF-ß) plays crucial roles in the development of focal segmental glomerulosclerosis, but key molecular pathways remain unknown. Here, we identified the regulation of mammalian target of rapamycin complex1 (mTORC1) by TGF-ß via ERK1/2 in the Adriamycin-induced murine model of focal segmental glomerulosclerosis. Adriamycin administration elicited early activation of TGF-ß-ERK1/2-mTORC1 in podocytes, which persisted at later stages of albuminuria and glomerulosclerosis. Phosphorylation of the TGF-ß receptor-I (TGF-ßRI), Smad3, ERK1/2 and ribosomal protein S6 were evident in the glomeruli of adriamycin-treated mice. Targeting TGFß-RI and mTORC1 with pharmacological inhibitors suppressed TGF-ß signaling in glomeruli and significantly reduced albuminuria, glomerulosclerosis, protein levels of collagen 4α3, plasminogen activator inhibitor-1, and vimentin and restored mRNA levels of podocyte markers. Low dose US Food and Drug Administration (FDA)-approved MEK/ERK inhibitor trametinib/GSK1120212 blunted TGF-ß1-induced mTORC1 activation in podocytes, ameliorated up-regulation of TGF-ß, plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, fibronectin and α-smooth muscle actin and prevented albuminuria and glomerulosclerosis with improved serum albumin. In cultured podocytes, this pathway was found to be associated with translation of fibrogenic collagen 4α3 and plasminogen activator inhibitor-1, without influencing their transcription. Notably, rapamycin suppressed upstream p-TGF-ßRI, p-Smad3 and p-ERK1/2, and trametinib down-regulated upstream p-Smad3 in ex vivo and in vivo studies, indicating that harmful paracrine signaling among glomerular cells amplified the TGF-ß-ERK1/2-mTORC1 axis by forming a positive feedback loop. Thus, an accentuated TGF-ß-ERK1/2-mTORC1 pathway is suggested as a central upstream mediator to develop proteinuria and glomerulosclerosis. Hence, preventing activation of this vicious loop by trametinib may offer a new therapeutic strategy for glomerular disease treatment.

Dietary deficiency of vitamin A among rural children: A community-based survey using a food-frequency questionnaire.

BACKGROUND: Overt vitamin A deficiency has been controlled in most parts of India, but prevalence of subclinical deficiency may still be high, which may enhance susceptibility to infections, reduce growth potential and also lead to higher mortality. We aimed to: (i) assess the consumption pattern of vitamin A-rich foods in children 1-5 years of age in rural Jammu; and (ii) estimate the dietary deficiency of vitamin A leading to risk of subclinical vitamin A deficiency in cluster- villages of the study area. METHODS: In 2011, we conducted a survey of 750 children by selecting 50 from each of the 1 5 clusters. The Helen Keller International's Food-Frequency Questionnaire (HKI-FFQ) modified to the local context was used to assess past week's intake for 28 food-items, including vitamin A-rich foods. RESULTS: The study revealed that plant sources such as amaranth, carrots, etc. and animal sources such as eggs and butter were the major sources of vitamin A in the study population. Consumption of amaranth (2.7 days/week) and carrots (1.7 days/week) was moderate but that of animal foods rich in vitamin A was low to negligible (1.1 day/week for eggs and 0.2 day/week for liver and fish combined). The majority (80%) of the cluster-villages manifested inadequate intake of vitamin A-rich foods, thereby making subclinical vitamin A deficiency a public health problem for the whole area. Faulty diets, improper breastfeeding practices, low coverage of vitamin A supplementation and high prevalence of undernutrition could be related to the observed subclinical deficiency. CONCLUSION: Dietary diversification by including both plant and animal sources of vitamin A in adequate amounts along with improved breastfeeding, better implementation of mega-dose vitamin A supplementation and minimizing undernutrition may help in lowering subclinical vitamin A deficiency. The HKI-FFQ may be used as a proxy indicator of vitamin A intake/status for identifying pockets at risk of subclinical vitamin A deficiency in resource-constrained settings.

High-dose clevudine impairs mitochondrial function and glucose-stimulated insulin secretion in INS-1E cells.

BACKGROUND: Clevudine is a nucleoside analog reverse transcriptase inhibitor that exhibits potent antiviral activity against hepatitis B virus (HBV) without serious side effects. However, mitochondrial myopathy has been observed in patients with chronic HBV infection taking clevudine. Moreover, the development of diabetes was recently reported in patients receiving long-term treatment with clevudine. In this study, we investigated the effects of clevudine on mitochondrial function and insulin release in a rat clonal ß-cell line, INS-1E. METHODS: The mitochondrial DNA (mtDNA) copy number and the mRNA levels were measured by using quantitative PCR. MTT analysis, ATP/lactate measurements, and insulin assay were performed. RESULTS: Both INS-1E cells and HepG2 cells, which originated from human hepatoma, showed dose-dependent decreases in mtDNA copy number and cytochrome c oxidase-1 (Cox-1) mRNA level following culture with clevudine (10 µM-1 mM) for 4 weeks. INS-1E cells treated with clevudine had reduced total mitochondrial activities, lower cytosolic ATP contents, enhanced lactate production, and more lipid accumulation. Insulin release in response to glucose application was markedly decreased in clevudine-treated INS-1E cells, which might be a consequence of mitochondrial dysfunction. CONCLUSIONS: Our data suggest that high-dose treatment with clevudine induces mitochondrial defects associated with mtDNA depletion and impairs glucose-stimulated insulin secretion in insulin-releasing cells. These findings partly explain the development of diabetes in patients receiving clevudine who might have a high susceptibility to mitochondrial toxicity.