Performance of health and wellness centre in providing primary care services in Chhattisgarh, India.

INTRODUCTION: Primary health care has regained its importance in global policy making. In 2018, the Government of India initiated the Ayushman Bharat - Comprehensive Primary Health Care (AB-CPHC) programme. It was based on upgrading the existing primary health facilities into Health and Wellness Centers (HWCs). The current study aimed to assess the readiness and performance of HWCs in providing comprehensive primary health care services in India's Chhattisgarh state. METHODS: We conducted a cross-sectional health facility assessment with a state-representative sample of 404 HWCs. A standardized health facility survey tool was used to collect information on essential inputs and service outputs of HWCs. The expected population healthcare needs were estimated using secondary sources. The performance of HWCs was assessed by comparing the volume of services provided against the expected population need for outpatient care. RESULTS: On an average, 358 outpatients including 128 non-communicable disease (NCD) patients were treated monthly at an HWC. HWCs were able to cover 31% of the total population's health need for outpatient care, 26% for hypertension, and 21% for diabetes care. In addition to services for reproductive and child health, HWCs provided services for common acute ailments (cold, cough, fever, aches and pains); infections of skin, eye, ear, and reproductive tract, and minor injuries. HWCs were also contributing significantly to national disease control programmes. Acute ailments followed by NCDs and communicable diseases had the largest share among services provided. The key gaps were in coverage of mental illnesses and chronic respiratory diseases. Most of the HWCs showed adequate readiness for the availability of required human resources, supplies, and infrastructure. CONCLUSION: HWCs were able to provide a comprehensive range of primary care services and able to cater to a sizable portion of the rural population's acute and chronic health care needs. The performance was made possible by the adequate availability of medicines, staff, training programmes and tele-consultation linkages. If HWCs in other states are able to reach a similar level of performance, the initiative will prove to be a game changer for equitable primary care in India.

Effects of α-olefin sulfonate (AOS) on Tubifex tubifex: toxicodynamic-toxicokinetic inferences from the general unified threshold (GUTS) model, biomarker responses and molecular docking predictions.

We investigated the potential ecological risks and harm to aquatic organisms posed by anionic surfactants such as α-olefin sulfonate (AOS), which are commonly found in industrial and consumer products, including detergents. This study assessed acute (96-h) and subchronic (14-day) responses using antioxidant activity, protein levels, and histopathological changes in Tubifex tubifex exposed to different AOS concentrations (10% of the LC50, 20% of the LC50, and a control). Molecular docking was used to investigate the potential interactions between the key stress biomarker enzymes (superoxide dismutase, catalase, and cytochrome c oxidase) of Tubifex tubifex. Acute AOS exposure showed a concentration-dependent decrease in survival, and the general unified threshold (GUTS) model revealed that survivorship is linked to individual response patterns rather than random (stochastic) fluctuations. The GUTS model also revealed dose-dependent toxicity patterns in Tubifex tubifex exposed to α-olefin sulfonate (AOS), with adaptive mechanisms at lower concentrations but significant increases in mortality beyond a certain threshold, emphasizing the role of the AOS concentration in shaping its toxicological impact. Exposure to AOS disrupted antioxidant activity, inducing oxidative stress, with GST and GPx showing positive associations with surfactant concentration and increased lipid peroxidation (elevated MDA levels); moreover, AOS exposure decreased protein concentration, signifying disturbances in vital cellular processes. Histopathological examinations revealed various tissue-level alterations, including cellular vacuolation, cytoplasmic swelling, inflammation, necrosis, and apoptosis. Molecular docking analysis demonstrated interactions between AOS and enzymes (-catalase, superoxide dismutase, and cytochrome c oxidase) in Tubifex tubifex, including hydrophobic and hydrogen bond interactions, with the potential to disrupt enzyme structures and activities, leading to cellular process disruptions, oxidative stress, and tissue damage. According to the species sensitivity distribution (SSD), the difference in toxicity between Tilapia melanopleura (higher sensitivity) and Daphnia magna (low sensitivity) to AOS suggests distinct toxicokinetic and toxicodynamic mechanisms attributable to more complex physiology in Tilapia and efficient detoxification in Daphnia due to its smaller size.

Pathological and ultrastructural changes of Bellamya bengalensis under chronic carboxylic acid exposure at environmentally relevant levels: Inferences from general unified threshold model for survival (GUTS) predictions and hepatopancreatic integrity assessment.

This study aimed to understand the effects of freshwater acidification, driven by industrial runoff, agricultural activities, and atmospheric deposition, on the freshwater mollusk Bellamya bengalensis. By systematically investigating the impact of two common carboxylic acids, acetic acid (AA) and benzoic acid (BA), this research employed diverse toxicological, pathological, and ecological assessments. We explored survival predictions through the generic unified threshold model of survival (GUTS-SD), examined oxidative stress responses, and investigated hepatopancreatic alterations. In the experimental design, Bellamya bengalensis were subjected to environmentally relevant sublethal concentrations (10%, 20% LC50) of AA (39.77 and 79.54 mg/l) and BA (31.41 and 62.82 mg/l) over 28 days. Acute toxicity tests revealed increased LC50 values, indicating heightened toxicity with prolonged exposure, particularly due to the greater potency of benzoic acid compared to acetic acid. The GUTS-SD model provided accurate predictions of time-specific effects on populations, presenting long-term exposure (100 days) LC50 values for AA (263.7 mg/l) and BA (330.9 mg/l). Sequentially, the integrated biomarker response (IBR) analysis across study intervals highlighted the 28-day interval as the most sensitive, with GST emerging as the most responsive enzyme to oxidative stress induced by AA and BA. Histopathological and ultrastructural assessments of the hepatopancreas showed severe alterations, including necrosis, vacuolation and disrupted micro-villi, which were especially pronounced in higher BA exposure concentrations. These findings highlight the health and survival impacts of carboxylic acid toxicity on Bellamya bengalensis, emphasizing the need for proactive measures to mitigate acidification in aquatic ecosystems. The broader ecological implications underscore the importance of effective management and conservation strategies to address ongoing environmental challenges.

Fluorene-induced stress in the benthic oligochaete Tubifex tubifex: A multi-biomarker assessment of toxicological pathways and mechanisms under acute and subchronic exposures.

This study examined the multifaceted impacts of fluorene exposure on Tubifex tubifex, encompassing acute (survival analysis and behavioral responses) and subchronic exposure regimens (antioxidant enzyme response and histopathology), molecular docking studies, and generalized read-across analysis. Survival analysis revealed concentration-dependent increases in toxicity over varying time intervals, with LC50 values decreasing from 30.072 mg/L at 24 h to 12.365 mg/L at 96 h, emphasizing the time-sensitive and concentration-responsive nature of the stressor. Behavioral responses were both concentration- and duration-dependent. While Erratic Movement and Clumping Tendency exhibited earlier responses (within 24 h) at lower concentrations, the wrinkling effect and mucus secretion) exhibited delayed onset, suggesting intricate regulatory mechanisms underlying adaptability to environmental challenges; moreover, the wrinkling effect was consistently induced at higher concentrations, indicating greater sensitivity to the toxic effects of fluorene. With sublethal environmentally relevant concentrations-1.24 mg/l and 2.47 mg/L i.e., 10% and 20% 96 h, respectively-the antioxidant enzyme response (i.e., upregulation of SOD, CAT, and GST) with increasing fluorene concentration, revealing a nonlinear, hormetic response, suggested adaptive protection at lower doses but inhibition at higher concentrations. Histopathological examination indicated that higher fluorene concentrations caused cellular proliferation, inflammation, and severe tissue damage in the digestive tract and body wall. Molecular docking studies demonstrated robust interactions between fluorene and major stress biomarker enzymes, disrupting their functions and inducing oxidative stress. Interactions with cytochrome c oxidase suggested interference with cellular energy production. Generalized Read-Across (GenRA) analysis unveiled shared toxicity mechanisms among fluorene and its analogs, involving the formation of reactive epoxides and the influence of cytochrome P450 enzymes. The diverse functional groups of these analogs, particularly chlorine-containing compounds, were implicated in toxicity through lipid peroxidation and membrane damage. Adverse outcome pathways and broader consequences for aquatic ecosystem health are discussed.

Behavioral toxicity, histopathological alterations and oxidative stress in Tubifex tubifex exposed to aromatic carboxylic acids- acetic acid and benzoic acid: A comparative time-dependent toxicity assessment.

This study evaluated Acetic acid (AA) and Benzoic acid's (BA) acute and sublethal toxicity by observing mortality, behavioral responses, and changes in the levels of oxidative stress enzymes in Tubifex tubifex. Exposure-induced changes in antioxidant activity (Catalase, Superoxide dismutase), oxidative stress (Malondialdehyde concentrations), and histopathological alterations in the tubificid worms were also noted across exposure intervals. The 96 h LC50 values of AA and BA to T. tubifex were 74.99 and 37.15 mg/l, respectively. Severity in behavioral alterations (including increased mucus production, wrinkling, and reduction in clumping) and autotomy showed concentration-dependent trends for both toxicants. Although histopathological effects also showed marked degeneration in the alimentary and integumentary systems in highest exposure groups (worms exposed to 14.99 mg/l for AA and 7.42 mg/l for BA) for both toxicants. Antioxidant enzymes (catalase and superoxide dismutase) also showed a marked increase of up to 8-fold and 10-fold for the highest exposure group of AA and BA respectively. While species sensitivity distribution analysis revealed T. tubifex as most sensitive to AA and BA compared to other freshwater vertebrates and invertebrates, General Unified Threshold model of Survival (GUTS) predicted individual tolerance effects (GUTS-IT), with slower potential for toxicodynamic recovery, as a more likely pathway for population mortality. Study findings demonstrate BA with greater potential for ecological effects compared to AA within 24 h of exposure. Furthermore, ecological risks to critical detritus feeders like T. tubifex may have severe implications for ecosystem services and nutrient availability within freshwater habitats.

Recent updates on the role of phytochemicals in the treatment of glioblastoma multiforme.

ABSTRACTS: Glioblastoma multiforme (GBM) is a malignant type of glioma. This malignant brain tumor is a devastating disease and is often fatal. The spectrum of illness and poor prognosis associated with brain tumors extract a terrible toll on patients and their families. The inoperability of these tumors and resistance to radiation and chemotherapy contribute to the fatal outcome of this disease. Thus, scientists are hunting for the new drug candidate and safer chemoprevention, especially the phytochemicals that possess potent anti-tumor properties. We have summarized the cellular and biochemical impacts of different phytochemicals that can successfully encounter GBM via induction of apoptosis and active interference in different cell and molecular pathways associated with GBM in brain tumors. The in silico predictive model determining the blood-brain barrier permeability of the compound and their potential druggability are discussed in the review.

Mechanistic insights to lactic and formic acid toxicity on benthic oligochaete worm Tubifex tubifex.

Lactic and formic acid are two commonly found monocarboxylic organic acids. Lactic acid is discharged into the water bodies as acidic industrial effluent from the food, cosmetic, chemical, and pharmaceutical industries, whereas formic acid is discharged from various paper, leather tanning, and textile processing industries. The present study investigated the toxicity of both organic acids upon the benthic oligochaete worm Tubifex tubifex. The 96-h median lethal concentration (LC50) values for lactic and formic acid are determined as 143.81 mg/l and 57.99 mg/l respectively. The effects of two sublethal concentrations (10% and 30% of 96 h LC50) of these acids on differential expression of oxidative stress enzymes are investigated. The comparative analysis of acute toxicity demonstrates that formic acid exposure is more detrimental to T. tubifex than lactic acid. The in silico structural analysis predicts that formic acid can interact with cytochrome c oxidase of the electron transport system and thereby inhibits its functionality and induces reactive oxygen species production. Integrated biomarker response (IBR) analysis illustrates that overall oxidative stress of formic acid to T. tubifex is significantly higher than that of lactic acid, which supports the structural analysis. It is concluded from this study that toxicokinetic-toxicodynamic and species sensitivity distributions studies are helpful for ecological risk management of environmental toxicants.

Quercetin: a silent retarder of fatty acid oxidation in breast cancer metastasis through steering of mitochondrial CPT1.

BACKGROUND: Recent evidence confirmed that the maximum energy in metastatic breast cancer progression is supplied by fatty acid oxidation (FAO) governed by a rate-limiting enzyme, carnitine palmitoyltransferase 1 (CPT1). Therefore, the active limitation of FAO could be an emerging aspect to inhibit breast cancer progression. Herein, for the first time, we have introduced quercetin (QT) from a non-dietary source (Mikania micrantha Kunth) to limit the FAO in triple-negative breast cancer cells (TNBC) through an active targeting of CPT1. METHODS: Molecular quantification of QT was confirmed through high-performance thin-layer chromatography (HPTLC). Computational docking analyses predicted the binding affinity of QT to CPT1. Cell-based seahorse energy efflux investigated the mitochondrial respiration rate, glycolytic function and ATP production rate. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) investigated the FAO-associated gene expression. Matrigel cell invasion and fluorescence-activated cell sorting analyses investigated anti-metastatic and apoptotic cell death induction activities, respectively. In vivo antitumor activities were checked using the female breast cancer mice (BALB/c) model. RESULTS: QT resulted in a significant reduction in the intracellular mitochondrial respiration and glycolytic function, limiting extensive ATP production. In turn, QT elevated the reactive oxygen species (ROS) and depleted antioxidant levels to induce anti-metastatic and cell apoptosis activities. qRT-PCR resulted in active healing of altered FAO-associated gene expression which was well predicted through the successful in silico molecular binding potentiality of QT to CPT1. Subsequently, QT has shown excellent in vivo antitumor activities through the altered lipid profile and oxidative stress-healing capabilities. CONCLUSIONS: All the obtained data significantly grounded the fact that QT could be a promising metabolism-targeted breast cancer therapeutic.

COVID-19 rhapsody: Rage towards advanced diagnostics and therapeutic strategy.

The deadly global outbreak of coronavirus disease-2019 (COVID-19) has forged an unrivaled threat to human civilization. Contemplating its profuse impact, initial risk management and therapies are needed, as well as rapid detection strategies alongside treatments with existing drugs or traditional treatments to provide better clinical support for critical patients. Conventional detection techniques have been considered but do not sufficiently meet the current challenges of effective COVID-19 diagnosis. Therefore, several modern techniques including point-of-care diagnosis with a biosensor, clustered regularly interspaced short palindromic repeats (CRISPR)-associated proteins that function as nuclease (Cas) technology, next-generation sequencing, serological, digital, and imaging approaches have delivered improved and noteworthy success compared to that using traditional strategies. Conventional drug treatment, plasma therapy, and vaccine development are also ongoing. However, alternative medicines including Ayurveda, herbal drugs, homeopathy, and Unani have also been enlisted as prominent treatment strategies for developing herd immunity and physical defenses against COVID-19. All considered, this review can help develop rapid and simplified diagnostic strategies, as well as advanced evidence-based modern therapeutic approaches that will aid in combating the global pandemic.

Recent trends in analytical and digital techniques for the detection of the SARS-Cov-2.

The current global outbreak of COVID-19 due to SARS-CoV-2 is an unprecedented humanitarian crisis. Considering the gravity of its impact there is an immediate need to develop a detection technique that is sensitive, specific, fast, and affordable for the clinical diagnosis of the disease. Real time Polymerase Chain Reaction (RT-PCR)-based detection platforms are contemplated to be the gold standard to detect viral RNA. However, that may be susceptible to errors, and there is a risk of obtaining false results, which ultimately compromises the strategy of efficient disease management. Several modern techniques exhibiting assured results with enhanced sensitivity and specificity against the SARS-CoV-2 associated viral components or immune response against it have been developed and may be implemented. The review deals with the conventional RT-PCR detection techniques and compares them to other detection platforms viz., biosensor based detection of antigens, fluorescent or colorimetric detection systems including CRISPR-Cas 13 based SHERLOCK kit, CRISPR Cas-9 based FELUDA test kit, CRISPR DETECTR kit, Next Generation Sequencing or microarray-based kits. These modern techniques are great as a point of care detection methods but should be followed by RT PCR based detection for the confirmation of COVID-19 status.

COVID-19 rhapsody:Rage towards advanced diagnostics and therapeutic strategy / 药物分析学报

The deadly global outbreak of coronavirus disease-2019(COVID-19)has forged an unrivaled threat to human civilization.Contemplating its profuse impact,initial risk management and therapies are needed,as well as rapid detection strategies alongside treatments with existing drugs or traditional treatments to provide better clinical support for critical patients.Conventional detection techniques have been considered but do not sufficiently meet the current challenges of effective COVID-19 diagnosis.Therefore,several modern techniques including point-of-care diagnosis with a biosensor,clustered regularly interspaced short palindromic repeats(CRISPR)-associated proteins that function as nuclease(Cas)technology,next-generation sequencing,serological,digital,and imaging approaches have delivered improved and noteworthy success compared to that using traditional strategies.Conventional drug treatment,plasma therapy,and vaccine development are also ongoing.However,alternative medicines including Ayurveda,herbal drugs,homeopathy,and Unani have also been enlisted as prominent treat-ment strategies for developing herd immunity and physical defenses against COVID-19.All considered,this review can help develop rapid and simplified diagnostic strategies,as well as advanced evidence-based modern therapeutic approaches that will aid in combating the global pandemic.