Ecological impact of pharmaceutical pollutants and options of river health improvements - A risk analysis-based approach.

Pharmaceuticals are one of the emerging pollutants (EPs) in river waters across the world. Due to their toxic effects on aquatic organisms, they have drawn the global attention of the scientific community concerned with river ecosystems. This paper reviews the existing occurrence data for various pharmaceutical pollutants (PPs) reported in river waters in some part of the world and their ecological impacts. Using algae, macroinvertebrates (MI), and fish as biotic indicator groups in water to reflect river health conditions, an attempt has been made to assess the ecological risk due to the presence of PPs in the water environment. After ascertaining the predicted no-effect concentration (PNEC) of PPs for selected groups of aquatic organisms, the risk quotient (RQ) is estimated based on their measured environmental concentration (MEC). When MEC > PNEC and RQ > 1 for any of the biotic indicator, ecologically it is 'high risk' condition. The determination of PNEC uses a minimum assessment factor (AF) of 10 due to uncertainty in data over the no observed effect level (NOEL) or lowest observed effect level (LOEL). Accordingly, MEC 10 times higher than PNEC, (RQ = 10) represents a threshold risk concentration (RCT) beyond which adverse effects may start showing observable manifestations. In the present study, a new classification system of 'high risk' conditions for RQ = 1-10 has been proposed, starting from 'moderately high' to 'severely high'. For RQ > 10, the ecological condition of the river is considered 'impaired'. For river health assessment, in the present study, the whole range of physico-chemical characteristics of river water quality has been divided into three groups based on their ease of measurement and frequency of monitoring. Dissolved oxygen related parameters (DORPs), nutrients (NTs), and EPs. PPs represent EPs in this study. A framework for calculating separate indicator group score (IGS) and the overall river health index (RHI) has been developed to predict indicator group condition (IGC) and river health condition (RHC), respectively. Color-coded hexagonal pictorial forms representing IGC and RHC provide a direct visible perception of the existing aquatic environment and a scientific basis for prioritization of corrective measures in terms of treatment technology selection for river health improvements. The analyses indicate that many rivers across the world are under 'high risk' conditions due to PPs having MEC > PNEC and RQ > 1. Up to RCT, (where RQ = 10), the 'high risk' condition varies from 'moderately high' to 'severely high'. In many instances, RQ is found much more higher than 10, indicating that the ecological condition of river may be considered as 'impaired'. Algae is the most frequently affected group of biotic indicators, followed by MI and fish. A review of treatment methods for selection of appropriate technology to reduce the pollution load, especially PPs from the wastewater streams has been summarized. It appears that constructed wetlands (CWs) are at present the most suitable nature-based solutions, particularly for the developing economies of the world, to reduce the concentrations of PPs within limits to minimize the ecological impacts of pharmaceutical compounds on biotic indicators and restore the river health condition. Some suggestive design guidelines for the CWs have also been presented to initiate the process.

Nanoemulsions a Delivery System in the Making for Tumor Targeting Therapeutics: Evaluation and Characterization to Meet Clinical Challenges.

Cancer is a complex disease characterized by the uncontrolled and unregulated growth of cells followed by invasion and proliferation from the site of origin to other sites of the body. Conventional chemotherapy largely kills rapidly expanding and dividing cancer cells by impairing DNA synthesis and mitosis. It is associated with various types of adverse effects ranging from simple nausea and appetite loss to serious ones like bone marrow depression and compromised immunity etc., due to their non-selectivity and inability to differentiate. The ideal feature of a delivery system is delivering the drug to the target place to achieve the most therapeutic impact while having the least toxicity. With the advent of novel drug delivery systems, it has been easier to deliver the drug to the target site. Utilizing new techniques and technology makes it a feasible approach to target cancer cells. Nanoemulsions are isotropic mixtures of transparent or translucent oil globules dispersed in an aqueous phase that is kinetically stable and supported by an interfacial coating of surfactant and co-surfactant molecules with droplet sizes in the nanometre range. Nanoemulsions are the delivery system of choice in case of cancer because of certain key attributes, including biodegradability, biocompatibility, large surface area nonimmunogenicity, and release behavior control. At the same time, nanoemulsions have been engineered for various reasons, including enhanced biological half-life, target-specific binding ability, and imaging capability at different therapy levels by modifying the characteristics of nanoemulsions. This review focuses on current cancer treatment challenges and the role of nanoemulsions in treating cancer with their production methods, characterization methods, application, and quality attributes, which would help them make it to the clinics where cancer treatment is going on.

A decision support system for localized planning of reclaimed water around wastewater treatment plants.

Exploding population, industrialization, and an increase in water pollution has led to acute shrinkage in freshwater availability. Numerous countries have started exploring municipal wastewater as a new potential source of water to bring a paradigm shift from linearity to obtaining circularity in human water cycle management. This study aims to develop a decision support system for integrated water and wastewater management (DSS_IWWM), targeted towards reuse-focused selection of appropriate wastewater treatment technology, and localized planning around STPs in terms of reclaimed water demand identification, estimation, allocation, and sustainable pricing. The developed DSS_IWWM comprises of a repository of fourteen reuse purposes, reuse quality criteria, and 25 wastewater treatment technologies (WWTTs) in 360 combinations. It is sensitive to local resource scenarios and applies a socioeconomic and technology-focused methodology for addressing the interests of the community and investing agencies and viably. To validate the application of the DSS_IWWM, it is first tested with data from three cities in the state of Uttar Pradesh (India)-Lucknow, Prayagraj, and Agra-and then extended to nine more Indian cities with varying influent quality characteristics, resource inputs, existing STP technologies, and same target quality and decision criteria prioritization, to present a comparison of appropriate WWTTs and associated average prices obtained in different scenarios. It is concluded that influent quality, existing technology, and target quality criteria play significant role in selection of appropriate WWTTs. The traditional technologies such as UASB and ASP are required to be augmented and supplemented with high-performing WWTTs, such as BIOFOR-F with (C + F + RSF) and SBT + WP to obtain desired effluent quality. High-performing advanced oxidation process (AOP)-based systems such as A2O, SBR, and BIOFOR-F require WWTTs with relatively lower average costs (such as SBT and OP). The developed DSS_IWWM may prove to be very useful and beneficial for policymakers, government officials, engineers, and scientific community as it will facilitate rational decision-making for efficient investment planning in reuse focused wastewater treatment towards achieving circular economy in sustainable water resource management.

Biodosimetric analysis of head and neck cancer patients undergoing radiotherapy by dicentric chromosome aberration assay.

BACKGROUND: Biodosimetry is the quantification of absorbed radiation dose using biological material obtained from an exposed individual. Radiation can cause different types of chromosomal aberrations, including stable aberrations like translocations and unstable ones like micronuclei, dicentric chromosomes (DC), acentric, and ring forms. Dicentric chromosome assay has become the "gold standard" for cytogenetic biodosimetry due to its reproducibility, specificity (low baseline rates), and sensitivity to low doses. Using existing calibration curves and models obtained from in vitro irradiation of blood, the yield of DCs can be used to estimate the average whole-body absorbed dose. PURPOSE: To evaluate and compare the in vivo dose-response relation of DC aberration formation in peripheral blood lymphocytes of head and neck cancer (HNC) patients undergoing radiotherapy (RT) alone, cisplatin-based chemoradiation (CCRT), accelerated fractionation RT (AFRT), and CCRT with gefitinib (GCRT). METHODOLOGY: This prospective observational and analytical study was conducted from 2018 to 2021 in the Department of Radiation Oncology and Genetic Lab of tertiary care, teaching hospital after approval from the Institutional Ethics Committee. Biodosimetric analysis was done weekly in patients undergoing RT (n = 20) versus CCRT (n = 20), CCRT (n = 12) versus AFRT (n = 12), and CCRT (n = 6) versus GCRT (n = 6). The yield of DCs was measured in blood samples taken before starting treatment, that is, day 0 and during RT on days 6, 11, and 16 in RT alone versus CCRT; on days 7 and 13 in CCRT versus AFRT; and days 6 and 11 in CCRT versus GCRT from a blood sample drawn 1-2 h after RT. Phytohemagglutinin-stimulated lymphocytes were cultured using heparinized blood in RPMI-1640 medium supplemented with fetal bovine serum. Cells were arrested at metaphase using demecolcine, harvested by centrifugation, mounted, and stained with Giemsa. Cytogenetic analysis was performed by analyzing at least 100 metaphases with well-spread chromosomes. DC aberrations and acentric fragments were identified and recorded. To standardize the findings as per the customized field for every patient, the mean DC yield per cm2 of the irradiated area was calculated and compared. RESULTS: The mean yield of DC/cm2 in the CCRT group was greater than the RT alone group by 16.33%, 28.57%, and 18.68% on days 6, 11, and 16 of treatment, respectively. This difference between the two groups at day 6 (P = 0.001), day 11 (P < 0.001), and day 16 (P < 0.001) was found to be statistically significant. The mean yield of DC/cm2 in the CCRT group was greater than the AFRT group by 7.9% and 18.3% on days 7 and 13 of treatment, respectively. This difference at day 7 (P < 0.001) and day 13 (P < 0.001) was found to be statistically significant. The mean yield of DC/cm2 in the CCRT group was greater than the GCRT group by 22.7% and 21.8% on days 6 and 11 of treatment, respectively. The difference at day 6 (P = 0.01) was statistically significant but, on day 11 (P = 0.065) this difference was found insignificant. CONCLUSION: There is a dose-dependent increase in the yield of DCs in lymphocytes of HNC patients undergoing RT with subsequent fractions. Cisplatin-based chemoradiation is the superior method of treatment intensification radio-biologically proven by higher DC yield.

Elucidating the anti-cancer potential of Cinnamomum tamala essential oil against non-small cell lung cancer: A multifaceted approach involving GC-MS profiling, network pharmacology, and molecular dynamics simulations.

Cinnamomum tamala (Buch.-Ham.) T.Nees & Eberm., or Indian Bay Leaf, is a well-known traditional ayurvedic medicine used to treat various ailments. However, the molecular mechanism of action of Cinnamomum tamala essential oil (CTEO) against non-small cell lung cancer (NSCLC) remains elusive. The present study aims to decipher the molecular targets and mechanism of CTEO in treating NSCLC. GC-MS analysis detected 49 constituents; 44 successfully passed the drug-likeness screening and were identified as active compounds. A total of 3961 CTEO targets and 4588 anti-NSCLC-related targets were acquired. JUN, P53, IL6, MAPK3, HIF1A, and CASP3 were determined as hub genes, while cinnamaldehyde, ethyl cinnamate and acetophenone were identified as core compounds. Enrichment analysis revealed that targets were mainly involved in apoptosis, TNF, IL17, pathways in cancer and MAPK signalling pathways. mRNA expression, pathological stage, survival analysis, immune infiltrate correlation and genetic alteration analysis of the core hub genes were carried out. Kaplan-Meier overall survival (OS) curve revealed that HIF1A and CASP3 are linked to worse overall survival in Lung Adenocarcinoma (LUAD) cancer patients compared to normal patients. Ethyl cinnamate and cinnamaldehyde showed high binding energy with the MAPK3 and formed stable interactions with MAPK3 during the molecular dynamic simulations for 100 ns. The MM/PBSA analysis revealed that van der Waals (VdW) contributions predominantly account for a significant portion of the compound interactions within the binding pocket of MAPK3. Density functional theory analysis showed cinnamaldehyde as the most reactive and least stable compound. CTEO exhibited selective cytotoxicity by inhibiting the proliferation of A549 cells while sparing normal HEK293 cells. CTEO triggered apoptosis by arresting the cell cycle, increasing ROS accumulation, causing mitochondrial depolarisation, and elevating caspase-3, caspase-8 and caspase-9 levels in A549 cells. The above study provides insights into the pharmacological mechanisms of action of Cinnamomum tamala essential oil against non-small cell lung cancer treatment, suggesting its potential as an adjuvant therapy.

Redox-neutral zinc-catalyzed cascade [1,4]-H shift/annulation of diaziridines with donor-acceptor aziridines.

The coupling of diaziridines with donor-acceptor aziridines (DAAs) has been achieved using Zn-catalysis to furnish imidazopyrazole-4,4-dicarboxylates via [1,4]-hydride shift. The use of Zn-catalysis, [1,4]-hydride shift, natural product modification and a late-stage molecular docking study are important practical features.

Does the use of platelet-rich fibrin enhance the rate of orthodontic tooth movement? A systematic review and meta-analysis.

Introduction: This review synthesizes the available evidence pertinent to the effect of platelet-rich fibrin on the rate of orthodontic tooth movement during comprehensive orthodontic treatment. Method: This review followed the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Nine electronic databases were searched until January 2024 without restrictions, followed by a hand search of the reference lists. Controlled randomized split-mouth human studies assessing the effect of platelet-rich fibrin on the rate of orthodontic tooth movement were included. All relevant data from the included studies were extracted and pooled for qualitative and quantitative analysis. Risk-of-Bias was assessed using the Cochrane Risk of Bias tool. The certainty of the evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation tool. Results: From 515 studies, eleven randomized clinical trials were included for qualitative analysis and nine for quantitative analysis. The certainty of the evidence for these studies was low to moderate. The overall risk of bias for most studies was of some concern. The pooled estimate of the data from ten studies has a mean revealed difference of 1.31 (0.13-2.48) at a 95 % confidence interval with significant heterogeneity. Conclusions: This systematic review suggest that platelet-rich fibrin enhances the orthodontic tooth movement rate, but the evidence quality was moderate. Further, based on the currently available evidence, the effectiveness of platelet-rich fibrin on the acceleration of orthodontic tooth movement could not be fully established. Trial registration: PROSPERO: (CRD42021261836).

Modulation of Angiotensin-II and Angiotensin 1-7 Levels Influences Cardiac Function in Myocardial Ischemia-reperfusion Injury.

The angiotensin-converting enzyme-2 (ACE-2) alters the pathophysiology of various fatal cardiovascular diseases, including ischemic heart disease, whereas angiotensin 1-7 (Ang 1-7) exerts a wide range of actions. The effects of ischemia-reperfusion (IR) injury include damage to myocardial tissue that initiates protease action, causing cardiac cell death. Angiotensin- II (Ang-II) contributes through the renin-angiotensin system (RAS) to the IR injury, whereas Ang 1-7 paradoxically exerts a protective effect through the same. Thus, the myocardial ischemic reperfusion injury (MIRI) may be altered by the RAS of the heart. This review paper focuses on ACE-2, angiotensin-converting enzyme (ACE), and Ang 1-7 regulation in the RAS of the heart in the pathophysiology of MIRI. The treatment in such conditions using ACE-2 activator, ACE inhibitor, and Ang-II antagonists may promote vascular functions as well as cardio- protection.

Endoscopic Ultrasound-Guided Glue Embolization for Left Gastric Artery Pseudoaneurysm Presenting as Hemosuccus Pancreaticus After Failed Radiological Intervention.

Hemosuccus pancreaticus is characterized by intermittent bleeding from the ampulla of Vater due to the rupture of a pseudoaneurysm. There are significant diagnostic and therapeutic challenges associated with this rare and potentially life-threatening condition. We present a rare case in an 18-year-old man who presented with recurrent episodes of hematemesis and melena due to hemosuccus pancreaticus as a result of a left gastric artery pseudoaneurysm. Initial radiological angioembolization failed because of median arcuate ligament syndrome, and endoscopic ultrasound-guided glue embolization was successfully performed. This case further reinforces the importance of endoscopic ultrasound-guided therapy in the management of pseudoaneurysm after failed radiological treatment.

Heavy metals/-metalloids (As) phytoremediation with Landoltia punctata and Lemna sp. (duckweeds): coupling with biorefinery prospects for sustainable phytotechnologies.

Heavy metals/-metalloids can result in serious human health hazards. Phytoremediation is green bioresource technology for the remediation of heavy metals and arsenic (As). However, there exists a knowledge gap and systematic information on duckweed-based metal phytoremediation in an eco-sustainable way. Therefore, the present review offers a critical discussion on the effective use of duckweeds (genera Landoltia and Lemna)-based phytoremediation to decontaminate metallic contaminants from wastewater. Phytoextraction and rhizofiltration were the major mechanism in 'duckweed bioreactors' that can be dependent on physico-chemical factors and plant-microbe interactions. The biotechnological advances such as gene manipulations can accelerate the duckweed-based phytoremediation process. High starch and protein contents of the metal-loaded duckweed biomass facilitate their use as feedstock in biorefinery. Biorefinery prospects such as bioenergy production, value-added products, and biofertilizers can augment the circular economy approach. Coupling duckweed-based phytoremediation with biorefinery can help achieve Sustainable Development Goals (SDGs) and human well-being.

Comprehensive Review on Herbal Medicine: Emphasis on Current Therapy and Role of Phytoconstituents for Cancer Treatment.

INTRODUCTION: Cancer poses a significant public health challenge in both developed and developing nations, with a rising global incidence of patients facing the threat of death due to abnormal cell proliferation. AIM: Review explores the utilization of different parts of herbal medicinal plants and their active pharmaceutical constituents in the prevention and treatment of various types of cancer. METHODOLOGY: Various anticancer medicinal plants have been identified, demonstrating their therapeutic effects by inhibiting cancer-stimulating enzymes and hormones, activating DNA repair processes, boosting the synthesis of protective stimulants, reducing the formation of free radicals, and enhancing individual immunity. Data for this study were gathered from diverse online bibliographic and databases, including Google, Google Scholar, Mendeley, Springer Link, Research Gate, and PubMed. RESULT: Herbal drugs have a huge contribution to the inhibition of the progression of cancer.A large volume of clinical studies has reported the beneficial effects of herbal medicines on the survival, immune modulation, and quality of life (QOL) of cancer patients, when these herbal medicines are used in combination with conventional therapeutics. CONCLUSION: The latest medicines for the clinical purpose (Above 50 %) are derived from herbal products. Furthermore, combination of these herbs with nanotechnology shows promise in treating specific carcinomas.

Proximal discrepancies in intrinsic atomic interaction determines comparative in vivo biotoxicity of Chlorpyrifos and 3,5,6-trichloro-2-pyridinol in embryonic zebrafish.

Bioaccumulation of Chlorpyrifos (CP) as pesticides due to their aggrandized use in agriculture has raised serious concern on the health of ecosystem and human beings. Moreover, their degraded products like 3,5,6-trichloro-2-pyridinol (TCP) has enhanced the distress due to their unpredictable biotoxicity. This study evaluates and deduce the comparative in vivo mechanistic biotoxicity of CP and TCP with zebrafish embryos through experimental and computational approach. Experimental cellular and molecular analysis showed higher induction of morphological abnormalities, oxidative stress and apoptosis in TCP exposed embryos compared to CP exposure due to upregulation of metabolic enzymes like Zhe1a, Sod1 and p53. Computational analysis excavated the differential discrepancies in intrinsic atomic interaction as a reason of disparity in biotoxicity of CP and TCP. The mechanistic differences were deduced due to the differential accumulation and internalisation leading to variable interaction with metabolic enzymes for oxidative stress and apoptosis causing physiological and morphological abnormalities. The study unravelled the information of in vivo toxicity at cellular and molecular level to advocate the attention of taking measures for management of CP as well as TCP for environmental and human health.

Development and Validation of Brief Family Intervention for Young Adults with Substance Use Disorder: A Qualitative Study.

Background: Substance abuse is more prevalent in young adults, putting them at risk for chronic use and early onset of dependence on substances. A well-documented relationship exists between substance use and poor family functioning. Traditional family intervention approaches are time-consuming. Aim: To develop a brief family intervention for parents of young adults with substance use disorder. Methods: A qualitative research design was used. Extensive literature searches and key informant interviews (face to face) with young adults (n = 5), their parents (n = 5), and mental health professionals (n = 5) were conducted. The interviews were audio recorded. A thematic analysis was conducted using Braun and Clarke's six-step approach, and intervention strategies were identified by examining the themes. In addition, experts were consulted to ensure the content validity of the BFI. Results: The BFI program combines psychoeducation and behavioral techniques for parents. BFI involves seven sessions with parents, 45-60 min each, over one week. The BFI sessions consisted of (1) Engagement and Assessment, (2) Healthy Family Functioning, (3) Psychoeducation, (4) Relapse Prevention, (5) Communication Skill Training, (6) Problem-Solving Skill Training, and (7) Parental Monitoring and Supervision. Conclusion: Considering all stakeholders' perspectives, the BFI manual for young adults with substance use disorder has been developed. However, additional research is required to evaluate its feasibility and effectiveness.

Transition-Metal-Catalyzed Directed C-H Functionalization in/on Water.

Directing group assisted C-H bond functionalization using transition-metal-catalysis has emerged as a reliable synthetic tool for the construction of regioselective carbon-carbon/heteroatom bonds. Off late, "in/on water directed transition-metal-catalysis", though still underdeveloped, has appeared as one of the prominent themes in sustainable organic chemistry. This article covers the advancements, mechanistic insights and application of the sustainable directed C-H bond functionalization of (hetero)arenes in/on water in the presence of transition-metal-catalysis.

Game-Theoretic Analysis of Fusion Rules Over Molecular Reporting Channels.

This work adopts a game theoretic approach to analyze the behavior of transmitter nanomachines (TNMs) in a diffusive 3-dimensional (3-D) channel. In order to communicate the local observations about the region of interest (RoI) to a common supervisor nanomachine (SNM), TNMs transmit information-carrying molecules to SNM. For the production of information-carrying molecules, all the TNMs share the common food molecular budget (CFMB). The TNMs apply cooperative and greedy strategic efforts to get their share from the CFMB. In the cooperative case, all the TNMs communicate to SNM as a group, therefore they cooperatively consume the CFMB to increase the group outcome, whereas, in the greedy scenario, all TNMs decide to perform alone and thus greedily consume the CFMB to increase their individual outcomes. The performance is evaluated in terms of the average rate of success, the average probability of error, and the receiver operating characteristic (ROC) of RoI detection. The derived results are verified through Monte-Carlo and particle-based simulations (PBS).

Spatial distribution of heavy metals in the sediments of River Ganges, India: Occurrence, contamination, source identification, seasonal variations, mapping, and ecological risk evaluation.

Present study analyzed the seasonal and spatial distribution patterns, sources, and ecological risks of seven heavy metals (Cr, Fe, Ni, Cu, Zn, Cd and Pb) in the sediments of River Ganges, finding that the majority of concentrations were lithologic, except for Cd, which was significantly higher than background standards. Elevated values of geochemical indices viz. Igeo, CF, RI, Cd, mCd, HQ, mHQ, and PN suggest moderate to high ecological risk in the benthic environment and its organisms due to the synergistic effect of heavy metals. The PEC-Qmetals revealed 8-10 % toxicity in the upstream and downstream sites, due to the influence of agricultural activities. Multivariate statistical techniques (PCM and PCA) indicated that Cd and Pb predominantly originated from anthropogenic sources, while other metals primarily derived from geological background. These geochemical findings may help to understand the potential risks and recommend strategies to mitigate the effects of metallic contamination in river sediments.

Anti-Inflammatory and Antimicrobial Potential of 1, 3, 4-Oxadiazoles and its Derivatives: A Review.

1, 3, 4-oxadiazole and its derivatives have significant anti-inflammatory and antimicrobial property. Their precise mechanism of action is not known but it is postulated that they act by inhibiting the biosynthesis of certain prostaglandins. 1, 3, 4-oxadiazoles are a class of heterocyclic compounds with wide variety of biological and pharmacological activities. They have been reported to possess analgesic, antimicrobial, antipyretic and anti-inflammatory properties. These compounds are also active against a number of other inflammatory conditions such as arthritis, gout etc. A wide variety of these compounds have been synthesized and some of them are under clinical trials. In this review article, anti-inflammatory and antimicrobial activity of the 1, 3, 4- oxadiazole shall be discussed.

A descriptive study of hepatitis C in people who inject drugs.

BACKGROUND OBJECTIVES: The seroprevalence of the hepatitis C virus (HCV) in general population is higher than that of human immunodeficiency virus (HIV) in India. People who inject drugs (PWIDs) constitute a high-risk group for all blood-borne infections. Multiple behavioural surveillance surveys have provided a rich typology of HIV-infected PWIDs, but this information is missing for HCV infection. We describe awareness, transmission risk factors and the treatment continuum for HCV infection among PWID. We also report spatial clustering of HCV infection in PWIDs residing in Bengaluru. METHODS: Information from clinical records was collected and telephonic interviews of retrospectively identified PWIDs who received treatment at a tertiary-level addiction treatment facility between 2016 and 2021 were conducted. RESULTS: We identified 391 PWIDs; 220 (56.26%) received an anti-HCV antibody test (4 th Generation HCV-Tridot). Individuals reporting unsafe injection practices were more often tested than those who did not ( χ2 =44.9, df=1, P <0.01). Almost half of the tested and more than a quarter of the whole sample (109/220, 49.9%; 109/391, 27.9%) were seropositive for HCV infection. The projected seropositivity in this group was between 27.9 per cent (best case scenario, all untested assumed negative) and 71.6 per cent (worst case scenario, all untested assumed positive). Only a minority of participants interviewed were aware of HCV (27/183, 14.7%). HCV infection and its associated risk behaviour (PWID) were clustered in certain localities (Diggle and Chetwynd Test; P =0.001) in Bengaluru in the southern district of Karnataka. INTERPRETATION CONCLUSIONS: Undetected HCV infection is common in PWIDs; awareness and treatment uptake is poor in this group. Spatial clustering of infections in a district shows transmission in close networks and provides opportunities for targeted interventions.

Urinary metabolite signatures reflect the altered host metabolism in severe obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. The onset and progression of OSA are often linked with severe cardiovascular and metabolic comorbidities. At the same time, given the increasing prevalence of OSA, novel methods to screen OSA and its follow-up are needed. Untargeted metabolic profiling of OSA patients and healthy controls was planned to capture a snapshot of urinary metabolites and potential biomarkers using the gas chromatography-mass spectrometry (GC-MS) method.Polysomnography (PSG) confirmed severe OSA patients with AHI index ≥ 30 were considered for urine sample collection. The sample size was constituted of OSA (n = 36) and healthy controls (n = 36). Metabolite extraction and derivatization were performed and metabolomic analysis was performed by using GC-MS.The obtained data set was statistically analyzed using univariate and multivariate analysis. The Orthogonal partial least-squares discriminant analysis (OPLS-DA) was performed to screen differential metabolites between OSA patients and healthy controls.The metabolomic analysis revealed a total of 142 significantly altered metabolites of interest.Biomarker analysis allows for the creation of a list of putative urinary biomarkers including GABA, malic acid, glutamic acid, epichoric acid etc., with an accuracy of 99.8 % to 100 % for OSA screening. Subsequently, pathway analysis revealed that related biochemical pathways like the tricarboxylic acid cycle (TCA), glutamate/glutamine, amino acid and fatty acid metabolism, that are significantly interlinked with these metabolic biomarkers can play a crucial role in the pathogenesis of OSA. This study paves the way to undertake mass screening in a larger population to identify specific and reliable biomarkers.