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Background This study sought to document and understand facilitators and barriers to producing, translating, and using modeled evidence in decision-making in Burkina Faso, Nigeria, India, and Kenya. We explored researcher-decision-maker engagement mechanisms as key facilitators of evidence use, with a focus on knowledge brokers and boundary organizations. Methods The study used sequential mixed methods drawing on data collected from surveys and key informant interviews, complemented by a rapid desk review to map modeling activities and actors. The survey was conducted online while the qualitative research entailed in-depth interviews with modelers, knowledge brokers, and decision-makers working in a representative variety of health fields, organizations, and levels of government. This study was approved by Health Media Lab IRB (Institutional Review Board) in the United States and a local IRB in each study country and conducted between September 2021 and June 2022. Results Informants interviewed for this study described a range of factors that facilitate and inhibit the use of modeled evidence in public health decision-making at the individual, organizational, and environmental levels. Key themes included the capacity to produce, translate, and use modeled evidence; the timing and relevance of modeling outputs; the existence of communications channels between modelers and decision-makers; the strength of underlying data systems; the role of sustained funding; and the impact of global crises. Conclusion This study highlights the importance of taking an ecosystem approach to supporting modeling activities, considering individual, organizational, and environmental factors and how different actors and interact to inform the production, translation, and use of modeled evidence. Structured interaction that promotes dialogue, debate, and joint sense making between the producers and users of evidence is critical to informing and influencing the use of evidence in decision-making.

Background To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of ceftazidime-avibactam in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England. Methods The health benefit of ceftazidime-avibactam was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients’ mortality risks and health-related quality of life. Patient-level costs and health-related quality of life of ceftazidime-avibactam under various usage scenarios compared with alternative management strategies in the high-value clinical scenarios were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population in quality-adjusted life-years using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for ceftazidime-avibactam. Results The clinical effectiveness of ceftazidime-avibactam relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. In the base case, ceftazidime-avibactam was associated with a statistically significantly higher susceptibility relative to colistin (odds ratio 7.24, 95% credible interval 2.58 to 20.94). The remainder of the treatments were associated with lower susceptibility than colistin (odds ratio < 1). The results were sensitive to the definition of resistance and the studies included in the analysis. In the base case, patient-level benefit of ceftazidime-avibactam was between 0.08 and 0.16 quality-adjusted life-years, depending on the site of infection and the usage scenario. There was a high degree of uncertainty surrounding the benefits of ceftazidime-avibactam across all subgroups, and the results were sensitive to assumptions in the meta-analysis used to estimate susceptibility. There was substantial uncertainty in the number of infections that are suitable for treatment with ceftazidime-avibactam, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time, and rates of emergence of resistance. The population-level benefit varied substantially across the scenarios, from 531 to 2342 quality-adjusted life-years over 20 years. Conclusion This work has provided quantitative estimates of the value of ceftazidime-avibactam within its areas of expected usage within the NHS. Limitations Given existing evidence, the estimates of the value of ceftazidime-avibactam are highly uncertain. Future work Future evaluations of antimicrobials would benefit from improvements to NHS data linkages, research to support appropriate synthesis of susceptibility studies, and application of routine data and decision modelling to assess enablement value. Study registration No registration of this study was undertaken. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Policy Research Programme (NIHR award ref: NIHR135592), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 73. See the NIHR Funding and Awards website for further award information. Plain language summary This project tested new methods for estimating the value to the NHS of an antimicrobial, ceftazidime-avibactam (CAZ-AVI), so its manufacturer could be paid fairly even if very little drug is used in order to reduce the risk of bacteria becoming resistant to the product. Clinicians said that the greatest benefit of CAZ-AVI is when used for complicated urinary tract infections (cUTI) and pneumonia acquired within hospitals caused by bacteria called Enterobacterales, with a resistance mechanism called OXA-48. Because there were no relevant clinical trial data, we estimated how effective CAZ-AVI and alternative treatments were by doing a systematic literature review of studies that grew bacteria from infections in the laboratory and tested the drugs on them. We linked this to data estimating the long-term health and survival of patients. Some evidence was obtained by asking clinicians detailed questions about what they thought the effects would be based on their experience and the available evidence. We included the side effects of the alternative treatments, some of which can cause kidney damage. We estimated how many infections there would be in the UK, whether they would increase over time and how resistance to treatments may change over time. Clinicians told us that they would also use CAZ-AVI to treat intra-abdominal and bloodstream infections. We estimated how many of these infections there would be, and assumed the same health benefits as for cUTI and HAP/VAP, respectively. The total value to the NHS was calculated using these estimates. We also considered whether we had missed any additional elements of value. We estimated that the value to the NHS was £11 million to £47 million over 20 years. This reflects the maximum the NHS could pay for use of CAZ-AVI if the health lost as a result of making these payments rather than funding other NHS services is not to exceed the health benefits of using this antimicrobial. However, these estimates are uncertain due to limitations with the evidence used to produce them and assumptions that had to be made. Scientific summary Background This evaluation is one of two performed as part of a pilot conducted by the National Institute for Health and Care Excellence (NICE), NHS England (NHSE) and NHS Improvement to assess the feasibility of innovative models that pay for antimicrobials (AMs) based on an evaluation of their value to the NHS as opposed to the volumes used. These projects informed commercial discussions regarding contract value for a period of up to 10 years. This report details the evaluation phase for ceftazidime with avibactam (CAZ-AVI, brand name Avycaz), a fixed-dose combination medication composed of ceftazidime, a cephalosporin antibiotic, and avibactam, a beta-lactamase inhibitor manufactured by Pfizer which received a marketing authorisation in June 2016 for treatment in adults and paediatric patients (> 3 months) for complicated intra-abdominal infections (cIAI), complicated UTI (cUTI), hospital-acquired pneumonia, including ventilator-associated pneumonia (HAP/VAP), bacteraemia (adults only) associated with the aforementioned infections and treatment of infections caused by aerobic Gram-negative organisms with limited treatment options. Aim and objectives The aim of this evaluation is to assess the value of CAZ-AVI to the NHS in England when used within its licensed indications. Specific objectives are: To identify two high-value clinical scenarios (HVCSs) for which CAZ-AVI is expected to impact on mortality risks and improve health-related quality of life To undertake an ‘evidence mapping’ exercise and relevant systematic literature reviews to characterise the available clinical effectiveness evidence for the use of CAZ-AVI in the HVCSs. To establish an appropriate decision-analytic model to quantify the costs and health benefits of the use of CAZ-AVI under various usage scenarios compared with usage scenarios involving other available AMs in the HVCSs. The decision-analytic model was required to estimate costs and health effects at both the individual level and the aggregate population level, providing population incremental net health effects (INHEs). Drawing on the systematic reviews and evidence synthesis, national-level data on healthcare-associated infections, and other sources as needed, identify evidence to populate the decision-analytic models. To use structured expert elicitation as necessary to supplement the available evidence to populate the decision-analytic models. To use available evidence and where necessary expert opinion to quantitatively extrapolate estimated population INHEs associated with CAZ-AVI in the HVCSs to other expected uses for the product within the product’s licensed indications. Expected usage and high-value clinical scenarios To control the spread of resistance to CAZ-AVI and to preserve its long-term viability as an effective treatment option against highly resistant pathogens, CAZ-AVI was expected to be used in a narrower group of patients than permitted by its license. This evaluation characterised the value of CAZ-AVI in two steps. First, decision modelling assessed quantitatively the value of CAZ-AVI in a set of ‘high-value clinical scenarios’ (HVCSs). Secondly, rescaling was used to provide a quantitative assessment of value in the overall population expected to receive CAZ-AVI in the English NHS, including scenarios outside the HVCSs. The HVCSs were scenarios where there was currently significant burden from resistant infections, and where CAZ-AVI was expected to offer significant improvements over existing treatments in terms of efficacy and/or safety. The HVCSs focus on the following patient populations: Empiric setting (ES): infections strongly suspected to be caused by oxacillinase-48 (OXA-48) Enterobacterales in patients with hospital-acquired pneumonia or ventilator-associated pneumonia (HAP/VAP). The pathogen, resistance mechanism and antibiotic susceptibility have not yet been established but treatment is initiated immediately due to the severity of the infection. Microbiology-directed setting (MDS): patients with an infection confirmed to be caused by OXA-48 Enterobacterales, where antibiotic susceptibility testing results were available, and where the site of infection was HAP/VAP or cUTI. The resourcing for this project was equivalent to that of a diagnostic assessment review or multiple technology assessment for NICE, but the levels of analysis extend beyond the typical focus of those evaluations, to include population-level health effects now and over time, as well as across several indications and settings. The analyses are inevitably constrained by the time and resources available for the project. Clinical evidence Methods A mapping review was undertaken to establish available evidence and ascertain which approach to estimating comparative effectiveness could inform an economic model. Reviews 1 and 2 considered RCTs and observational studies in patients with HAP/VAP or cUTI infections caused by OXA-48 Enterobacterales or suspected to be caused by carbapenem-resistant Enterobacterales. In Review 3 in vitro susceptibility studies of OXA-48 Enterobacterales isolates which reported the proportion of isolates from any infection site that were susceptible to the HVCS treatment and at least one relevant comparator (colistin, meropenem, tigecycline, aztreonam, fosfomycin, gentamicin, amikacin, tobramycin) were sought. Systematic searches across relevant databases (MEDLINE, EMBASE and Centre for Review and Dissemination (CRD) database) were conducted in March 2021. EEPRU also considered evidence submitted by Pfizer and Public Health England (PHE). After mapping, only Review 3 was pursued, since there was insufficient evidence from Reviews 1 and 2 (see details in Results below). Risk-of-bias assessment was performed using a bespoke tool developed for this evaluation. A random-effects NMA of susceptibility studies was conducted. Subgroup and sensitivity analyses were planned to investigate the impact of clinical sources of heterogeneity including: inclusion criteria (use of resistance to a comparator to select study sample); co-carriage of MBLs; the proportion who were carbapenem-sensitive; whether the sample was recruited consecutively; and what laboratory methods and breakpoints were used to assess susceptibility. Review 4 aimed to provide evidence on the link between susceptibility and clinical outcomes and Review 5 between susceptibility and long-term outcomes in the sites of interest. Review 6 aimed to assess the safety of CAZ-AVI. Results The mapping reviews of RCT and observational studies identified insufficient evidence to inform an assessment of clinical effectiveness since the RCTs included very small numbers of OXA-48 Enterobacterales infections and did not report these data as a subgroup analysis and the observational data were not reported separately for the sites of interest (cUTI and HAP/VAP), the studies were small and highly heterogeneous with respect to prognostic factors, and individual patient data (IPD) were not available within the timeframe of this evaluation. In the review of susceptibility studies, 28 data sources met the initial inclusion criteria. One, from PHE, which included isolates submitted voluntarily to the antimicrobial resistance and healthcare-associated infections (AMRHAI) reference laboratory, had high relevance, but several limitations. EEPRU therefore included a broader set of evidence synthesised using network meta-analysis (NMA). Sixteen studies and data sources met the inclusion criteria. In the synthesis, CAZ-AVI was associated with a statistically significantly higher susceptibility relative to colistin [odds ratio (OR) 7.24, 95% credible interval (CrI) 2.58 to 20.94]. The remainder of the treatments were associated with lower susceptibility than colistin (OR < 1). Heterogeneity was extremely high [standard deviation (SD) 1.56, 95% CrI 1.28 to 1.93] and sensitivity analyses were conducted to investigate the sources of heterogeneity. The evidence network using EUCAST methods and breakpoints to assess susceptibility was selected as the base-case analysis to inform the economic evaluation since heterogeneity was lower and there was a clinical rationale to support restricting to studies that had used EUCAST laboratory methods and breakpoints as these are more commonly used in England. A scenario analysis was planned to include the result from the full analysis set. A further scenario was planned restricted to studies with no-MBLs and that had used EUCAST laboratory methods and breakpoints, which left one study (Vazquez-Ucha et al.). A further scenario analysis was planned using the PHE data alone, due to its high relevance to the evaluation. Review 4 identified two studies that reported mortality or hospital length of stay conditional on susceptibility to empiric treatment and were selected for use in the ES model. No useful evidence relating to the MDS was identified. Review 5 did not identify any relevant literature, but an unpublished study (CARBAR) was submitted by Shionogi during the parallel appraisal of cefiderocol. Review 6 indicated that CAZ-AVI does not appear to increase the risk of acute kidney injury (AKI), C. difficile, or any other serious adverse events (SAE), compared to non-toxic comparators (i.e. comparators that were not colistin or an aminoglycoside). No study reported a comparison of CAZ-AVI exclusively with colistin or aminoglycosides. Event rates were generally very low or zero. Discussion of clinical evidence: there were some limitations to the approach selected and analyses done. Key limitations include: susceptibility could be considered, at best, a surrogate outcome; linking data were limited and not specific to the pathogen–mechanism combination, and expert elicitation had to be relied upon to evidence the link in the MDS; uncertainties relating to the determination and application of breakpoints and the NMA results were associated with high levels of heterogeneity. Economic evidence Methods No published existing economic evaluations that assessed the use of CAZ-AVI in the HVCSs or areas of expected usage were identified. The manufacturer’s cost-effectiveness model estimated that introduction of CAZ-AVI was associated with an expected INHE benefit of approximately 20,000 quality-adjusted life-years (QALYs) over a 10-year time horizon, based on a cost-effectiveness threshold of £30,000 per QALY. EEPRU considered the model to contain several strong assumptions and it assumed a much broader population of patients would receive CAZ-AVI than considered appropriate by clinical advisors to EEPRU. Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions developed a de novo decision-analytic model to predict the cost and health consequences (summarised as population-level INHEs) of introducing CAZ-AVI within the HVCSs. These estimates assumed CAZ-AVI was supplied free of charge to the NHS, and use an estimate of health opportunity cost of £20,000/QALY. This quantitative analysis comprises three components assessing INHEs of the HVCSs at the patient level, INHEs of the HVCSs at the population level, and how INHEs within the HVCSs might appropriately be rescaled to reflect expected usage across the English NHS. The patient-level component characterises the cost, mortality and morbidity consequences of introducing CAZ-AVI over a patient’s lifetime. Separate but related models were developed for the ES and MDS. In the ES, treatment with CAZ-AVI was compared to non-colistin/aminoglycoside-based treatment and colistin/aminoglycoside-based treatment (considered more toxic). In the MDS, outcomes in the overall microbiology-directed cohort using CAZ-AVI were compared to outcomes using existing AMs only. In the ES, outcomes were modelled both for patients in whom OXA-48 Enterobacterales suspicion was confirmed and for those in whom this suspicion turned out to be incorrect. The probability of having the suspected pathogen/resistance mechanism was informed by national surveillance data supplied by PHE. The key driver of effectiveness was in vitro susceptibility (see evidence syntheses above). A combination of evidence from the literature and structured expert elicitation informed the model. Higher rates of AKI for colistin and aminoglycoside-based therapy (compared to other agents, including CAZ-AVI) were informed by published systematic reviews. Lifetime costs, quality of life and mortality were predicted accounting for the highly comorbid nature of the patient population and the increased risk of chronic kidney disease resulting from AKI. The population-level component used a forecast-based approach to aggregate the patient-level predictions to the population-level accounting for the size of, and growth over time in, the eligible patient population within each HVCS. This component also reflects how resistance is likely to develop to CAZ-AVI and existing AMs over time. Predictions were presented for patients initiated on treatment over the next 20 years. National surveillance data were used to estimate current numbers of patients within the HVCS and to forecast growth in patient numbers over time. A series of scenarios reflect the potential emergence of resistance to CAZ-AVI. Changes in resistance to existing AMs over time were not modelled due to the sparsity of evidence available to inform these forecasts. Predicted overall population INHEs corresponding to the expected use of CAZ-AVI in the English NHS were generated by rescaling the population INHEs from the HVCSs to reflect additional areas of expected usage (known or suspected OXA-48 Enterobacterales bloodstream and intra-abdominal infections). Rescaling was based on surveillance data on population size and expert assessments of the similarity in per-patient INHEs between the HVCSs and these additional sites of interest. The literature on the economic evaluation of AMs has described a range of elements of value associated with these products that are not relevant to evaluations of other healthcare interventions. We summarised the extent to which these elements of value were captured within the quantitative estimates and, where this has not been possible, whether they were likely to substantively modify the quantitative estimates of value presented. Results Patient-level INHEs in the HVCS The benefits of CAZ-AVI are driven by similar susceptibility but improved safety compared to colistin/aminoglycoside-based treatments, and, in the ES, by higher susceptibility than non-colistin/aminoglycoside-based treatment. The two most significant sources of uncertainty relate to the ES and are (1) the susceptibility evidence and (2) the proportion of patients in the ES who are suspected of having OXA-48 Enterobacterales who are later confirmed to have this resistant pathogen. CAZ-AVI generated INHEs of 0.16 QALYs per patient in the ES (range across scenarios 0.00–0.26) and 0.08 (0.05–0.12) in the microbiology-directed settings. Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions were unable to select a base case for the population-level results. Population-level results are, therefore, presented for two different approaches to estimating current infection numbers (based on different methods to classify infections from clinical specimen sites), two alternative approaches to forecasting infections over time (based on whether observed trends are assumed to persist indefinitely or not) and three different trajectories with respect to CAZ-AVI resistance emergence (1%, 5% and 10% at 20 years). Across these scenarios, population INHEs varied from 531 to 2342 QALYs. The population size estimates are subject to additional uncertainties relating to the challenges of inferring patient population size from microbiology data and in forecasting population size in the future. Estimates were generated using a number of strong assumptions about the generalisability of patient-level INHEs between settings, for example, that patient-level INHEs for bloodstream infections can be generalised to HAP/VAP infections. These assumptions were based on discussions with clinical experts. Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions considers that it is possible that CAZ-AVI use will facilitate additional or at least more prompt receipt of required treatments/procedures for certain groups and therefore provide additional enablement value not captured within the model estimates of INHEs. The magnitude of these enablement benefits remains highly uncertain. Conclusion Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions’s quantitative assessment of value of CAZ-AVI was associated with a base-case population INHE across its areas of expected usage of 531–2342 QALYs over 20 years. These values were informed by interlinked decision-analytic models informed by systematic reviews of the literature and evidence synthesis, additional national data provided by PHE, structured expert elicitation and, where necessary, assumptions informed by clinical opinion. The quantitative estimates of the value for CAZ-AVI within the areas of expected usage within the NHS indicate that the maximum amount the NHS could pay for CAZ-AVI was £11 million to £47 million if the health lost as a result of making these payments rather than funding other NHS services is not to exceed the health benefits of using CAZ-AVI. The high level of uncertainty could be addressed via further research; however, the appropriateness of amending payments to reflect revised estimates of value requires further consideration. A broader and important question is ‘what would represent the “optimal” scope of usage for CAZ-AVI?’ Further methodological and quantitative work is required to address this question. Study registration No registration of this study was undertaken. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Policy Research Programme (NIHR award ref: NIHR135592), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 12, No. 73. See the NIHR Funding and Awards website for further award information.

Disorders related to defaecation are widely common in the population and are often overlooked. Patients may present with a wide variety of symptoms such as constipation, faecal incontinence, painful defaecation, incomplete defaecation, hard stools, rectal bleeding, and mass per rectum. Complete clinical examination with radiological imaging, using dynamic MR Defaecography, can help in assessing, grading, and managing posterior compartment pelvic floor disorders and complex dysfunctions. The cases reveal a spectrum of pelvic floor disorders and complex dysfunctions including spastic pelvic floor syndrome, Grade 3 anorectal descent with rectocoele and cystocoele, tri-compartmental descent with obstructed defaecation syndrome, complete external rectal prolapse with Grade 3 abnormal anorectal descent and rectal intussusception. Contribution: This case series emphasises the importance of understanding the correlation of clinical and radiological imaging findings in posterior compartment pelvic floor dysfunctions through a series of cases presenting with clinical complaints related to defaecation.

Background Appendiceal conditions continue to present diagnostic challenges due to their variable clinical presentations and the complex interplay of demographic factors. This study aims to provide a thorough analysis of the prevalence, gender distribution, and histopathological characteristics of appendiceal conditions with more attention toward mucinous lesions. Methods A detailed examination of 380 appendectomy specimens was conducted, encompassing demographic and histopathological data. Clinical diagnoses, radiological findings, and histopathological results were scrutinized to identify trends and challenges in diagnosing appendiceal conditions. Results The study unveiled a significant prevalence of appendectomies within the “21-30 years” age-group, with a pronounced male predominance (62.63%). The most prevalent diagnosis was “Acute Appendicitis” (66.32% of cases), followed by “Chronic Appendicitis” (27.37%). Notably, mucinous lesions represented 1.57% of cases, with a distinct female predominance. All six cases were reported as low-grade appendiceal mucinous neoplasm (LAMN). LAMN was the common mucinous neoplasm in our study clinically presenting as acute abdomen and radiology having varied diagnosis. It accounted for 1.57% of cases with female predominance. Mucinous lesions presented with diverse clinical and radiological characteristics and were mostly diagnosed incidentally during appendectomy. The definitive diagnosis of rare mucinous lesion was achieved through histopathological analysis. Conclusion While the main cause for acute abdomen is acute appendicitis, this study emphasizes the necessity of histopathological analysis to achieve precise diagnoses of appendiceal conditions, particularly mucinous lesions that can masquerade as acute conditions. The study emphasizes the challenges in diagnosing mucinous lesions accurately in cases with varied clinical and radiological presentations, underlining the indispensable role of histopathological examination. The findings affirm the pivotal role of histopathology in ensuring accurate clinical management and treatment decisions.

Background Osteoarthritis (OA) is a chronic degenerative joint disease that leads to disability. The prevalence of symptomatic knee OA is approximately 22% to 39% in India, which causes significant morbidity and impairment in elderly individuals. Objective To study the effects of Otago exercise versus square-stepping exercises (SSEs) on balance, fall, and functional activities in geriatric individuals with OA knee. Methods A study was carried out at Pune among 40 geriatric individuals with age over 65 years. The individuals were assigned at random to the Otago exercise group or SSE. Both groups performed exercises for 40–45 min for 10 days. The primary outcome was balance, which was measured by the Berg Balance Scale and Limits of Stability test. The secondary outcomes were risk of fall, measured by the Morse fall scale and functional activity, measured by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scale. Results Both the groups showed significant differences post intervention within the groups (P < 0.05). Between-group analysis showed that the Otago exercise group showed a higher mean difference in the primary outcomes that is in the Berg Balance Scale (19.25 > 15.24) and limits of stability. The SSE group showed a higher mean difference in Morse fall scale (18.81 > 8.8) and WOMAC scale (18.81 > 8.8). Conclusion The study concluded that, in older patients with OA knee, Otago exercise is more successful at enhancing balance but SSE is more effective at enhancing fall risk and functional activity.

Summary: Detection of nitrative stress is crucial to understanding redox signaling and pathophysiology. Dysregulated nitrative stress, which generates high levels of peroxynitrite, can damage lipid membranes and cause activation of proinflammatory pathways associated with pulmonary complications. Here, we present a protocol for implementing a peroxynitrite-sensing phospholipid to investigate nitrative stress in murine cells and lung tissue. We detail procedures for sensing ONOO– in stimulated cells, both ex vivo and in vivo, using murine models of acute lung injury (ALI).For complete details on the use and execution of this protocol, please refer to Gutierrez and Aggarwal et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The perpetual release of natural/synthetic pollutants into the environment poses major risks to ecological balance and human health. Amongst these, contaminants of emerging concern (CECs) are characterized by their recent introduction/detection in various niches, thereby causing significant hazards and necessitating their removal. Pharmaceuticals, plasticizers, cyanotoxins and emerging pesticides are major groups of CECs that are highly toxic and found to occur in various compartments of the biosphere. The sources of these compounds can be multipartite including industrial discharge, improper disposal, excretion of unmetabolized residues, eutrophication etc., while their fate and persistence are determined by factors such as physico-chemical properties, environmental conditions, biodegradability and hydrological factors. The resultant exposure of these compounds to microbiota has imposed a selection pressure and resulted in evolution of metabolic pathways for their biotransformation and/or utilization as sole source of carbon and energy. Such microbial degradation phenotype can be exploited to clean-up CECs from the environment, offering a cost-effective and eco-friendly alternative to abiotic methods of removal, thereby mitigating their toxicity. However, efficient bioprocess development for bioremediation strategies requires extensive understanding of individual components such as pathway gene clusters, proteins/enzymes, metabolites and associated regulatory mechanisms. “Omics” and “Meta-omics” techniques aid in providing crucial insights into the complex interactions and functions of these components as well as microbial community, enabling more effective and targeted bioremediation. Aside from natural isolates, metabolic engineering approaches employ the application of genetic engineering to enhance metabolic diversity and degradation rates. The integration of omics data will further aid in developing systemic-level bioremediation and metabolic engineering strategies, thereby optimising the clean-up process. This review describes bacterial catabolic pathways, genetics, and application of omics and metabolic engineering for bioremediation of four major groups of CECs: pharmaceuticals, plasticizers, cyanotoxins, and emerging pesticides.

This Proposed work explores how machine learning can be used to diagnose conjunctivitis, a common eye ailment. The main goal of the study is to capture eye images using camera-based systems, perform image pre-processing, and employ image segmentation techniques, particularly the UNet++ and U-net models. Additionally, the study involves extracting features from the relevant areas within the segmented images and using Convolutional Neural Networks for classification. All this is carried out using TensorFlow, a well-known machine-learning platform. The research involves thorough training and assessment of both the UNet and U-net++ segmentation models. A comprehensive analysis is conducted, focusing on their accuracy and performance. The study goes further to evaluate these models using both the UBIRIS dataset and a custom dataset created for this specific research. The experimental results emphasize a substantial improvement in the quality of segmentation achieved by the U-net++ model, the model achieved an overall accuracy of 97.07. Furthermore, the UNet++ architecture displays better accuracy in comparison to the traditional U-net model. These outcomes highlight the potential of U-net++ as a valuable advancement in the field of machine learning-based conjunctivitis diagnosis.

Therapeutic Area: Other: CV Surgery Case Presentation: A 66-year-old man presented with severe symptomatic bicuspid aortic stenosis and New York Heart Association class III chronic diastolic congestive heart failure. Despite being evaluated by the heart team and considering surgical aortic valve replacement, he opted for TAVR. During his procedure, severe annular and leaflet calcification complicated the valve deployment, leading to valve migration and necessitated emergent retrieval and repositioning. Post-procedure, the patient developed hypotension and tamponade physiology, prompting emergent pericardiocentesis. Subsequently, an acute type A aortic dissection was discovered, mandating open aortic valve replacement with ascending aortic graft. Background: The decision-making process in TAVR involves weighing individual patient factors against procedural risks, underscoring the need for shared decision-making and comprehensive preoperative evaluation.The significant challenge posed by severe valve calcification, which resulted in valve migration, emphasizes the importance of intraoperative imaging for real-time visualization during transcatheter aortic valve replacement (TAVR) procedures. These imaging modalities, such as transesophageal echocardiography (TEE) or intravascular ultrasound (IVUS), enable precise assessment of anatomical structures and guide the deployment of the valve with optimal positioning. Additionally, skilled intervention is essential in navigating procedural complexities encountered during TAVR. Experienced interventionalists, as in this case, possess the expertise to address challenges promptly, such as managing calcified anatomy or addressing complications like valve migration.The development of cardiac tamponade highlights the necessity for vigilant post-procedural monitoring and prompt intervention. Timely recognition and management of complications is critical in optimizing patient outcomes. Furthermore, the discovery of an acute type A aortic dissection emphasizes the potential for catastrophic events in TAVR recipients. This case highlights the importance of maintaining a high index of suspicion for procedural complications and the readiness to escalate to open surgical intervention when necessary. Conclusions: Transcatheter aortic valve replacement (TAVR) has emerged as a viable option for select patients with severe aortic stenosis, particularly those deemed too high risk for surgical intervention. However TAVR it is not without complications, as demonstrated in our case of a 66-year-old man who underwent TAVR but encountered significant perioperative and postoperative complications.

Synovitis is a disorder that develops when the synovial tissue or joint lining becomes inflamed. The term pigmented villonodular synovitis (PVNS) refers to a form of tenosynovial giant cell neoplasm affecting the tendon and joint soft-tissue lining. We describe the rare case of a 37-year-old male presenting with complaints of swelling in the left knee following trauma. Patients have a limited range of motion. There is a previous history of an accident 1 year back for which he was operated. Recent magnetic resonance imaging (MRI) revealed anterior cruciate ligament and posterior cruciate ligament avulsion fracture. The clinical diagnosis and radiologic findings were in favor of PVNS. Histopathological examination revealed the presence of fungus. It was further confirmed by fungal culture, for which the patient was given antifungals and was further followed up in the orthopedics outpatient clinic. Thus, we diagnosed fungal synovitis in a patient who came with clinical presentation and MRI findings suggestive of PVNS.

Context: Autonomic dysfunction (AD) brings up cardiovascular morbidity/mortality and has been reported in chronic kidney disease (CKD). Still, the pattern of AD in CKD is elusive. Aim: To evaluate the distribution of cardiovascular dysautonomia in CKD. Material and Methods: This study was conducted on 33 CKD cases and 30 age and sex matched healthy controls. Five standard autonomic function tests were conducted, namely, heart rate response to Valsalva maneuver, deep breathing, and standing, and BP response to standing and sustained handgrip; based on which the patients were classified as normal, or having early parasympathetic, definite parasympathetic and combined damage. The total autonomic function score was also calculated. Results: All cases belonged to CKD stages of 3, 4, and 5; and came up with autonomic failure. The mean total autonomic function score was higher (P < 0.001) in CKD (5.09 ± 2.33) as compared to the control group (0.97 ± 0.24), using the unpaired “t” test. Most of the CKD patients (45.45%) were involved with combined damage. Of the three stages, combined damage struck stage 5 to the maximum extent (63.63%). Sympathetic failure always co occurred with parasympathetic failure. Conclusion: Combined autonomic failure is more conspicuous in late CKD, predominantly occurring in stage 5. The disease course may contort the parasympathetic system before the sympathetic system.

Angioleiomyoma (ALM) is a benign mesenchymal tumor arising from the smooth muscle cells of the vessel wall. Common sites include subcutaneous tissues of the lower extremities but can also be seen in unusual sites including the head-and-neck region, submandibular gland, uterus, ovary, and broad ligament. It is exceptionally rare in retroperitoneum. Local recurrence is extremely rare but known to occur. Imaging features are nonspecific. Differential diagnosis on the basis of radiological features is difficult. Definitive diagnosis requires histopathology examination. Angiomyolipoma and myopericytoma are considered close differentials on microscopy at retroperitoneal locations. Histopathological examination along with immunohistochemistry markers such as desmin and HMB-45 are required for definitive diagnosis. It is difficult to diagnose angioleiomoma preoperatively, considering its location, thereby we are tempted to present an extremely rare case of retroperitoneal ALM highlighting its diagnostic dilemma.

Abstract Background There is a lack of contemporary data describing global variations in vascular access for hemodialysis (HD). We used the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to highlight differences in funding and availability of hemodialysis accesses used for initiating HD across world regions. Methods Survey questions were directed at understanding the funding modules for obtaining vascular access and types of accesses used to initiate dialysis. An electronic survey was sent to national and regional key stakeholders affiliated with the ISN between June and September 2022. Countries that participated in the survey were categorized based on World Bank Income Classification (low-, lower-middle, upper-middle, and high-income) and by their regional affiliation with the ISN. Results Data on types of vascular access were available from 160 countries. Respondents from 35 countries (22% of surveyed countries) reported that > 50% of patients started HD with an arteriovenous fistula or graft (AVF or AVG). These rates were higher in Western Europe (n = 14; 64%), North & East Asia (n = 4; 67%), and among high-income countries (n = 24; 38%). The rates of > 50% of patients starting HD with a tunneled dialysis catheter were highest in North America & Caribbean region (n = 7; 58%) and lowest in South Asia and Newly Independent States and Russia (n = 0 in both regions). Respondents from 50% (n = 9) of low-income countries reported that > 75% of patients started HD using a temporary catheter, with the highest rates in Africa (n = 30; 75%) and Latin America (n = 14; 67%). Funding for the creation of vascular access was often through public funding and free at the point of delivery in high-income countries (n = 42; 67% for AVF/AVG, n = 44; 70% for central venous catheters). In low-income countries, private and out of pocket funding was reported as being more common (n = 8; 40% for AVF/AVG, n = 5; 25% for central venous catheters). Conclusions High income countries exhibit variation in the use of AVF/AVG and tunneled catheters. In low-income countries, there is a higher use of temporary dialysis catheters and private funding models for access creation.

Abstract Clinical application of cardiac magnetic resonance (CMR) is expanding but CMR assessment of LV diastolic function is still being validated. The purpose of this study was to validate assessments of left ventricular (LV) diastolic dysfunction (DD) using CMR by comparing with transthoracic echocardiography (TTE) performed on the same day. Patients with suspected or diagnosed cardiomyopathy (n = 63) and healthy volunteers (n = 24) were prospectively recruited and included in the study. CMR diastolic parameters were measured on cine images and velocity-encoded phase contrast cine images and compared with corresponding parameters measured on TTE. A contextual correlation feature tracking method was developed to calculate the mitral annular velocity curve. LV DD was classified by CMR and TTE following 2016 guidelines. Overall DD classification was 78.1% concordant between CMR and TTE (p

Abstract Current strategies to promptly, effectively, and equitably screen people with tuberculosis (TB) and link them to diagnosis and care are insufficient; new approaches are required to find the millions of people around the world with TB who are missed each year. Interventions also need to be designed considering how people interact with health care facilities and where appropriate should be suitable for use in the community. Here, the historical, new, and reemerging technologies that are being utilised for TB diagnosis globally are discussed, whilst highlighting that how we use and evaluate tests is just as important as the tests themselves.

The number of published literature on the effect of ultrasonic cavitation and advanced oxidation pretreatment on the dewatering performance of anaerobically digested sludge is very limited. This study aims at determining the optimum operating conditions of large-scale filtering centrifuges in wastewater treatment plants. The optimum dose of hydrogen peroxide, ultrasonic power, ultrasonic duration, ultrasonic pulse and particle size distribution for improved dewatering performance were determined in this study. In addition, shear stress–shear rate and viscosity–shear rate rheograms were developed to show the rheological flow properties for varying ultrasonic power and treatment duration. Optimum sonication power, time, pulse and amplitude were determined to be 14 W, 1 min, 55/5 and 20%, respectively. At a pH of 6.8, the optimum concentration of hydrogen peroxide was found to be 43.5 g/L. The optimum hydrogen peroxide dose in the combined conditioning experiments was determined to be 500 mg/L at a pH of 3. Under these optimum conditions, capillary suction time was reduced significantly by 71.1%. This study helps to reduce polymer consumption and provides the optimum pretreatment and dewatering operating conditions, and better monitoring and control in the dewatering unit has significant impact in the overall economy of wastewater treatment plants. HIGHLIGHTS Digested sludge dewatering is a cost-intensive operation in wastewater treatment plants.; The proposed ultrasonic and advanced oxidation pretreatment significantly improves the dewatering performance.; Rheological flow characteristics of digested sludge also improved after ultrasonic pretreatment.; Sonication and advanced oxidation can be used along with conventional dewatering polymers for better performance.;

National Health Mission instituted the Village Health, Sanitation, and Nutrition Committees (VHSNCs) in 2005, with an aim of ensuring health and well-being for local communities in India. There is a lack of concrete evidence on the functioning of VHSNCs at a national level. Thus, this study was undertaken to outline the roles, responsibilities, and functions of VHSNCs in India. We conducted a comprehensive data search in Medline, Cochrane Library, ScienceDirect, EMBASE, and Google Scholar between 2005 and August 2021. All peer-reviewed qualitative studies that reported the roles, responsibilities, functions, and good practices of VHSNCs from India were included in our review. Critical Appraisal Skills Programme checklist was used to assess the quality of individual studies. In total, we included 15 studies (including 1100+ VHSNCs) from various states of India. Our review highlighted that the majority of the VHSNCs functioned without a clear-cut definition of roles and responsibilities had irregular meetings and workforce shortage. There was a lack of inclusivity, accountability, and delay in the processing of untied funds. The included studies have showed that VHSNCs were involved health promotional activities such as formulation and implementation of village health plans, delivery of services through public distribution systems, ensuring safe drinking water and sanitary supervision, and identification and referral of malnourished children. Our review highlights the crucial role that VHSNCs play in improving the health outcomes of rural populations and underscores the need for continued support and capacity-building efforts to ensure their effectiveness.

Abstract The integration of the renewable energy sources (RESs) into the power grid, drives a significant transformation in the conventional power generation landscape. This transition from traditional synchronous generators to inverter based RESs introduces unique challenges in maintaining the grid frequency stability due to the reduced system inertia. The inherent stochastic nature of the RES power generation, load demand, and grid inertia includes further complexity in the assessment of frequency stability. Existing studies have limitations, including neglecting the stochastic nature of RES generation and load demand fluctuations, relying on limited metrics, and lacking a comprehensive day‐to‐day assessment. To address these shortcomings of the existing approaches, this paper introduces a novel methodology for assessing frequency stability in power grids with high RES penetration. It proposes three indices for evaluating grid frequency sensitivity, resiliency, and permissibility amidst varying RES integration. Utilizing a stochastic approach, the study incorporates uncertainties in RES generation and load demand, offering a comprehensive framework for day‐to‐day frequency stability analysis. Additionally, it presents a systematic method to ascertain the necessary inertial support for maintaining desired frequency reliability in RES‐dominated grids. The effectiveness of these methodologies is validated through a case study on a modified IEEE 39‐bus test system, demonstrating their applicability in ensuring reliable grid operation under high RES scenarios.

Aneurysms rarely present with features of ischemic stroke. The data on treatment of such strokes is limited. We present a case of multiple aneurysms and an ischemic stroke caused by distal anterior cerebral artery (DACA) aneurysm treated with flow diverter placement, the first case of endovascular treatment of DACA aneurysmal ischemic stroke reported to our knowledge.

Abstract Background Superior mesenteric artery (SMA) syndrome, also known as Wilkie’s syndrome, is a rare but serious complication following scoliosis correction surgery. It occurs as a result of mechanical compression of third part of duodenum between the SMA and aorta. This condition occurs most commonly in significantly underweight patients with deformities, and usually during the first week following spinal deformity corrective surgeries. The angle between the abdominal aorta and the SMA gets reduced following spinal lengthening during deformity correction surgery causing compression of third part of duodenum resulting in development of SMA syndrome. Case presentation. We present a case of 17-year-old male with congenital scoliosis with a 70-degree scoliotic curve who underwent spinal deformity correction surgery with posterior instrumented fusion. Post-operative course was uneventful and the patient was discharged after suture removal on post-operative day 15. The patient presented after 21-days of symptom onset on post-operative-day 51, with a 3 week history of post-prandial vomiting, abdominal pain and distension which resulted in rapid weight loss of 11 kg. A CT-angiogram showed obstruction at third part of duodenum. After reviewing clinical and radiological profile of the patient, a diagnosis of SMA syndrome was made. Conservative management was tried, but due to rapid deterioration of patient condition and symptoms of complete intestinal obstruction, the patient was treated surgically by gastro-jejunostomy and side-to-side jejuno-jejunostomy, which improved his condition. Conclusion SMA syndrome can occur much later than previously reported cases and with potentially life-threatening symptoms following scoliosis correction. Having a high index of suspicion, early recognition of condition and institution of appropriate treatment are essential to prevent occurrence of severe complications including risk of intestinal perforation and mortality. This case highlights management of delayed onset of SMA syndrome, with presentation further delayed after symptom onset, as is common in developing parts of the world, due to limited availability and accessibility of resources, and low socio-economic status of large segments of the population.

Abstract Chickpea is a highly nutritious protein-rich source and one of the major crops to alleviate global malnutrition, but poor seed quality affects its productivity. Seed quality is essential for better crop establishment and higher yields, particularly in the uncertain climate change. The present study investigated the impact of botanical priming versus hydropriming and bavistin seed treatment on chickpea seeds. A detailed physiological (germination percentage, root and shoot length, vigour index) and biochemical (amylase, protease, dehydrogenase, phytase, and lipid peroxidation) analysis was carried out in order to assess the effect of priming treatments. Turmeric-primed seeds showed better germination rate (94.5%), seedling length, enzyme activity, and lower malondialdehyde (MDA) content. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed the expression of minor polypeptides of albumin and globulin in the primed seeds. Moreover, field experiments indicated increased crop growth, vigour, days to 50% flowering, yield and its attributing traits in turmeric-primed seeds. Botanical priming can increase chickpea yield by up to 16% over the control group. This low-cost and eco-friendly technique enhances seed and crop performance, making it a powerful tool for augmenting chickpea growth. Therefore, chickpea growers must adopt botanical priming techniques to enhance the quality of seed and crop performance. Moreover, this approach is environmentally sustainable and can help conserve natural resources in the long term. Therefore, this new approach must be widely adopted across the agricultural industry to ensure sustainable and profitable farming practices.

Abstract Alzheimer’s disease (AD) is associated with cognitive deficits and epigenetic deacetylation that can be modulated by natural products. The role of natural oxyresveratrol-β-cyclodextrin (ORV) on cognition and histone deacetylase activity in AD is unclear. Herein, in-silico docking and molecular dynamics simulation analysis determined that oxyresveratrol potentially targets histone deacetylase-2 (HDAC2). We therefore evaluated the in vivo ameliorative effect of ORV against cognitive deficit, cerebral and hippocampal expression of HDAC in experimental AD rats. Intracerebroventricular injection of STZ (3 mg/kg) induced experimental AD and the rats were treated with low dose (200 mg/kg), high dose (400 mg/kg) of ORV and donepezil (10 mg/kg) for 21 days. The STZ-induced AD caused cognitive and behavioural deficits demonstrated by considerable increases in acetylcholinesterase activity and escape latency compared to sham control. The levels of malondialdehyde (MDA) and HDAC activity were significantly increased in AD disease group comparison to the sham. Interestingly, the ORV reversed the cognitive-behavioural deficit and prominently reduced the MDA and HDAC levels comparable to the effect of the standard drug, donepezil. The findings suggest anti-AD role of ORV via antioxidant effect and inhibition of HDAC in the hippocampal and frontal cortical area of rats for AD.

Purpose: To compare the changes encountered in corneal biomechanics and aberration profile following accelerated corneal collagen cross-linking (CXL) using hypo-osmolar and iso-osmolar riboflavin in corneal thicknesses of 400 microns, respectively. Methods: This is a prospective, interventional, comparative study involving 100 eyes of 75 patients with progressive keratoconus. Eyes were divided into two groups based on corneal thickness: group 1 included eyes with a corneal thickness of 400 microns who underwent iso-osmolar CXL. Corneal biomechanical and aberration profiles were evaluated and compared between groups. Results: In group 1, all higher-order aberrations (HOA) except secondary astigmatism significantly decreased from baseline; however, in group 2, only coma and trefoil decreased. The corneal resistance factor and corneal hysteresis significantly improved in both groups, which was significantly greater in group 2 than in group 1. The change in inverse radius, deformation amplitude, and tomographic biomechanical index was significantly improved in group 2 as compared to group 1. Conclusion: Improvement in corrected distance visual acuity and decrease in HOA were significantly better in the hypo-osmolar CXL group; however, the improvement in biomechanical strength of the cornea was significantly better in the iso-osmolar group.

Purpose: To assess the safety and efficacy of intravitreal Aflibercept (IVA) versus dexamethasone (DEX) implant for treating recalcitrant diabetic macular edema (DME) in pseudophakic eyes at 1-year follow-up. Design: Retrospective comparative case series. Participants: Data of all patients diagnosed with DME between January 2019 and December 2021, who underwent 4-monthly doses of intravitreal ranibizumab but had persistent DME [central macular thickness (CMT) within 10% of baseline value] were extracted from a computerized database. Of these, only pseudophakic eyes that underwent either IVA or DEX implant and had at least 1-year follow-up were included for analysis. Methods: DEX implant was preferred before December 2020 and IVA after this time point. In the IVA group, patients were followed up every month while DEX were followed at least every 3 months. Reinjections were considered when vision dropped by at least 1 Snellen’s line or CMT increased by at least 10% from the previous visit in both groups. Main Outcome Measures: Comparison of change in vision and CMT at 1-year follow-up in DEX versus IVA groups. Results: Eighty-four eyes of 84 patients aged 54.4 + 4.4 years were included, 39 (46%) received DEX and 45 (54%) received IVA. Groups were comparable for baseline vision and CMT. Vision improved equally in both groups from 0.83 + 0.15 logMAR to 0.52 + 0.10 logMAR at 3 months (P < 0.01) and then stabilized till 1 year. However, eyes in the IVA group were 6.5 times more likely (Odds ratio = 6.45, 95% CI = 1.3 – 31.9) to achieve >3-line improvement in vision. The CMT reduction was also comparable between groups (-169 + 51 in DEX vs. -174 + 49 in IVA, P = 0.67). More eyes in the IVA group required >3 injections (91% vs. 69% in DEX, P = 0.01). The IOP was significantly higher at 6 and 9 months in the DEX group and 5 eyes (13%) required IOP lowering medications. Conclusion: In pseudophakic eyes with recalcitrant DME not responding to ranibizumab, switching to IVA or DEX implant results in equal visual improvement and CMT reduction. Though >3-line improvement occurs more frequently with IVA, this comes at the expense of a greater number of injections and follow-up visits.

Tuberculosis being endemic in country like India can affect any organ though pulmonary tuberculosis is rampant and extrapulmonary is rare. Tuberculosis affecting parotid gland is a rare occurrence, usually unilateral. However, Mycobacterium tuberculosis causing cold abscess in bilateral parotid glands is even rarer. Here, we present a case of a young female presented with bilateral slow-growing swelling in the parotid region with evening raise of temperature for two months. On clinical examination, no signs of inflammation were seen. Ultrasonography showed thick-walled hypoechoic collection with septae and internal echoes within involving both superficial and deep lobes of the parotid gland. Fine-needle aspiration cytology (FNAC) suggested a caseating granuloma and acid fast bacilli were detected on ZN staining, thereby confirming the diagnosis of cold abscess. She was put on antitubercular drugs and there was a drastic reduction in the size of swelling.

Oxalate Nephropathy (ON) represents a serious condition characterized by a decline in renal function associated with calcium oxalate crystal deposition within renal tubules. It can arise from Primary Hyperoxaluria (PH) due to genetic defects or secondary causes such as increased dietary oxalate intake. We present a case of a 46-year-old male with facial puffiness, abdominal pain, and pedal oedema, diagnosed with acute kidney injury superimposed on probable chronic kidney disease. Diagnostic investigations revealed bilateral renal echogenicity and severe acute tubular injury with calcium oxalate crystal deposition on renal biopsy. A24-hour urinary oxalate analysis confirmed ON. Despite the absence of identifiable risk factors, the patient was categorized as probable primary oxalate nephropathy, pending genetic testing results. Management included thrice-weekly haemodialysis and assessment for liver-kidney transplant. Early identification and intervention are crucial in ON to prevent progression to renal failure, emphasizing the need for heightened clinical suspicion and timely management strategies.

Bullous emphysema is a chronic obstructive pulmonary disease (COPD) that results from chronic inflammation of the lung parenchyma leading to alveolar destruction. Etiology includes tobacco smoking and alpha-1 antitrypsin deficiency. In this article, we present a rare case of bullous emphysema in a nonsmoker with no genetic predisposition or social risk factors presenting with productive cough, fatigue, and shortness of breath. The patient was diagnosed with bullous emphysema with superimposed pneumonia based on clinical and radiological findings. The patients acute complaints were treated successfully with antibiotics, supplemental oxygen, systemic steroids, and, nebulizer treatments. With this case report the authors highlight an unusual presentation of pneumonia in a patient with underlying bullous emphysema. Environmental exposure is often overlooked and the outcomes cannot be turned to favor without a comprehensive approach in patient management from history and physical to deciding the right treatment and follow-up protocols.

The main objective of this investigation is to study the effect of post weld heat treatments (PWHTs) on tensile properties, hardness, and microstructure of pulsed CMT–MIG (cold metal transfer arc–metal inert gas) welded AA20214-T6 aluminum alloy joints. The welded joints were subjected to PWHT of artificial aging (AA), solution annealing treatment (ST) and ST + aging (STA). The tensile properties and microhardness of joints were evaluated. The microstructure of joints was studied using optical microscope (OM) and transmission electron microscope (TEM). The fractured surface of tensile specimens was analyzed using scanning electron microscope (SEM). Results showed that the tensile properties and hardness of as welded and PWHT joints are inferior compared to base metal (BM). This mainly refers to the microstructural heterogeneity in different regions of joints and softening of heat affected zone (HAZ) induced by the weld thermal cycle. The PWHTs of AA and ST did not show significant effect on tensile strength and hardness of AW joints. However, the slight reduction in elongation was observed in AA and ST joints. The STA joints showed higher joint efficiency of 71.6%, than other joints by compromising on the elongation. This refers to the greater precipitation of hardening precipitates in STA joints compared to AA and ST joints. It exhibited the higher tensile and yield strength of 326 MPa and 266 MPa and the lowest elongation of 3.8%. The STA joints showed 28.35%, 38.28% and 57.77% reduction in tensile strength, yield strength and elongation compared to BM respectively. All the tensile specimens of joints failed in HAZ owing to the lower hardness. This refers to dissolution of precipitates in HAZ. However, the HAZ softening is less severe in STA joints than AW, AA, and ST joints.

Background: This review aimed to comprehensively investigate the impact of Hormone Replacement Therapy (HRT) on implant osseointegration and bone loss. The study considered factors such as HRT type, osteoporosis, smoking, and diabetes mellitus, and analysed the available literature to provide insights into the association between HRT and implant outcomes. Methods: Multiple databases were utilized, and studies with diverse designs and methodologies were included that examined the relationship between HRT and implant osseointegration. The selected studies were analyzed and relevant data on implant success rates, bone loss, and other correlations was extracted. Results: The review findings indicate that HRT has a detrimental impact on implant osseointegration, as evidenced by lower implant success rates and increased bone loss in HRT-treated individuals. The odds ratio analysis further strengthens this association, with significant values of 0.59 (95% CI: 0.50–0.70) and 0.64 (95% CI: 0.54–0.76), indicating a higher likelihood of implant failure in HRT-treated patients., highlighting the need for caution when considering HRT as a treatment option in patients undergoing implant procedures. Smoking and diabetes mellitus were also found to significantly affect implant outcomes, emphasizing the importance of addressing these factors in patient management. Conclusion: The assessments demonstrate that HRT adversely affects implant osseointegration and increases bone loss. The results suggest the importance of considering the potential negative impact of HRT on implant outcomes and the need for thorough patient evaluation and management. Further research is warranted to explore the underlying mechanisms, assess the impact of specific HRT types and dosages, and evaluate preventive strategies to mitigate the detrimental effects of HRT on implant success.

This article furnishes a brief review of the geochemistry of waters produced during coal bed methane and shale gas exploration. Stable deuterium and oxygen isotopes of produced waters, as well as the stable carbon isotope of dissolved inorganic carbon in these waters, are influenced by groundwater recharge, methanogenic pathways, the mixing of formation water with saline water, water–rock interactions, well completion, contamination from water from adjacent litho-units, and coal bed dewatering, among many others. Apart from the isotopic fingerprints, significant attention should be given to the chemistry of produced waters. These waters comprise natural saturated and aromatic organic functionalities, metals, radioisotopes, salts, inorganic ions, and synthetic chemicals introduced during hydraulic fracturing. Hence, to circumvent their adverse environmental effects, produced waters are treated with several technologies, like electro-coagulation, media filtration, the coupling of chemical precipitation and dissolved air flotation, electrochemical Fe+2/HClO oxidation, membrane distillation coupled with the walnut shell filtration, etc. Although produced water treatment incurs high costs, some of these techniques are economically feasible and sustain unconventional hydrocarbon exploitation.

Multidrug-resistant yeast Candida auris is a serious threat to public health with documented survival in various hospital niches. The dynamics of this survival benefit and its trade off with drug resistance are still unknown for this pathogen. In this study we investigate the oxidative stress response (OSR) in fluconazole-resistant C. auris and compare its relative fitness with fluconazole-susceptible strains. A total of 351 C. auris clinical isolates (61 fluconazole-susceptible and 290 fluconazole-resistant) were screened for stress tolerance by spot assay and 95.08 % fluconazole-susceptible isolates were hyper-resistant to oxidative stress while majority (94.5 %) fluconazole-resistant isolates had lower oxidative tolerance. Expression of Hog1 and Cta1 gene transcript levels and cellular catalase levels were significantly higher in fluconazole-susceptible isolates and a corresponding higher intracellular reactive oxygen species level (iROS) was accumulated in the fluconazole-resistant isolates. Biofilm formation and cell viability under oxidative stress revealed higher biofilm formation and better viability in fluconazole-susceptible isolates. Fluconazole-resistant isolates had higher basal cell wall chitin. On comparison of virulence, the % cytotoxicity in A549 cell line was higher in fluconazole-susceptible isolates and the median survival of the infected larvae in G. mellonella infection model was higher in fluconazole-resistant (5; IQR:4.5–5 days) vs. fluconazole-susceptible C. auris (2; IQR:1.5–2.5 days). All organisms evolve with changes in their environmental conditions, to ensure an optimal balance between proliferation and survival. Development of tolerance to a certain kind of stress example antifungal exposure in yeast can leads to a compensatory decrease in tolerance for other stresses. This study provides useful insights into the comparative fitness and antifungal susceptibility trade off in C. auris. We report a negative association between H2O2 tolerance and fluconazole susceptibility. Using in-vitro cell cytotoxicity and in-vivo survival assays we also demonstrate the higher virulence potential of fluconazole-susceptible C. auris isolates corroborating the negative correlation between susceptibility and pathogen survival or virulence. These findings could also be translated to clinical practice by investigating the possibility of using molecules targeting stress response and fitness regulating pathways for management of this serious infection.

The P91 martensitic steel and 304L austenitic stainless steels are two mainly used structural steels in power plants. The major problem in conventional multipass tungsten inert gas (TIG) welding of P91/304L steel is high heat input and joint distortion, increased cost and time associated with V groove preparation, filler rod requirement, preheating and welding in multiple passes, and labor efforts. Hence, in this study, a novel approach of robotically operated activated flux TIG (A-TIG) welding process and thin AlCoCrFeNi2.1 eutectic high entropy alloy (EHEA) sheet as the interlayer was used to weld 6.14 mm thick P91 and 304L steel plates with 02 passes in butt joint configuration. The joints were qualified using visual examination, macro-etching, X-ray radiography testing and angular distortion measurement. The angular distortion of the joints was measured using a coordinate measuring machine (CMM) integrated with Samiso 7.5 software. The quality of the A-TIG welded joints was compared to the joints made employing multipass-TIG welding process and Inconel 82 filler rod in 07 passes. The A-TIG welded joints showed significant reduction in angular distortion and higher productivity. It showed a 55% reduction in angular distortion and 80% reduction in welding cost and time compared to the multipass-TIG welded joints.

Titanium (Ti) is widely used in structural, maritime, aerospace, and biomedical applications because of its outstanding strength-to-weight ratio, superior corrosion resistance, and excellent biocompatibility. However, the lower surface hardness and inferior wear resistance of the Ti and Ti alloys limit their industrial applications. Coating Ti surfaces can initiate new possibilities to give unique characteristics with significant improvement in the Ti component’s functionality. The current research designed and synthesized titanium nitride (TiN), titanium carbide (TiC), titanium carbonitride (TiCN), tantalum nitride (TaN), and niobium nitride (NbN) ceramic coating layers (400 µm) over a Ti substrate using a spark plasma sintering process (SPS). The coatings on the Ti substrate were compact and consolidated at an SPS temperature of 1500 °C, pressure of 50 MPa, and 5 min of holding time in a controlled argon atmosphere. Microstructure investigation revealed a defect-less coating-substrate interface formation with a transition/diffusion zone ranging from 10 µm to 20 µm. Among all of the ceramic coatings, titanium carbide showed the highest improvement in surface hardness, equal to 1817 ± 25 HV, and the lowest coefficient of friction, equal to 0.28 for NbN.

ABSTRACT Pseudomonas bharatica CSV86T displays the unique property of preferential utilization of aromatic compounds over simple carbon sources like glucose and glycerol and their co-metabolism with organic acids. Well-characterized growth conditions, aromatic compound metabolic pathways and their regulation, genome sequence, and advantageous eco-physiological traits (indole acetic acid production, alginate production, fusaric acid resistance, organic sulfur utilization, and siderophore production) make it an ideal host for metabolic engineering. Strain CSV86T was engineered for Carbaryl (1-naphthyl-N-methylcarbamate) degradation via salicylate-catechol route by expression of a Carbaryl hydrolase (CH) and a 1-naphthol 2-hydroxylase (1NH). Additionally, the engineered strain exhibited faster growth on Carbaryl upon expression of the McbT protein (encoded by the mcbT gene, a part of Carbaryl degradation upper operon of Pseudomonas sp. C5pp). Bioinformatic analyses predict McbT to be an outer membrane protein, and Carbaryl-dependent expression suggests its probable role in Carbaryl uptake. Enzyme activity and protein analyses suggested periplasmic localization of CH (carrying transmembrane domain plus signal peptide sequence at the N-terminus) and 1NH, enabling compartmentalization of the pathway. Enzyme activity, whole-cell oxygen uptake, spent media analyses, and qPCR results suggest that the engineered strain preferentially utilizes Carbaryl over glucose. The plasmid-encoded degradation property was stable for 75–90 generations even in the absence of selection pressure (kanamycin or Carbaryl). These results indicate the utility of P. bharatica CSV86T as a potential host for engineering various aromatic compound degradation pathways.IMPORTANCEThe current study describes engineering of Carbaryl metabolic pathway in Pseudomonas bharatica CSV86T. Carbaryl, a naphthalene-derived carbamate pesticide, is known to act as an endocrine disruptor, mutagen, cytotoxin, and carcinogen. Removal of xenobiotics from the environment using bioremediation faces challenges, such as slow degradation rates, instability of the degradation phenotype, and presence of simple carbon sources in the environment. The engineered CSV86-MEC2 overcomes these disadvantages as Carbaryl was degraded preferentially over glucose. Furthermore, the plasmid-borne degradation phenotype is stable, and presence of glucose and organic acids does not repress Carbaryl metabolism in the strain. The study suggests the role of outer membrane protein McbT in Carbaryl transport. This work highlights the suitability of P. bharatica CSV86T as an ideal host for engineering aromatic pollutant degradation pathways.

Abstract In this study, we analyze the spatiotemporal patterns of propagation of pre‐monsoon heatwaves and their drivers in India. Using complex networks, we find that heatwaves originate most frequently in northwest India and propagate in the northeast or southeast direction. Heatwaves propagating in the northeast direction have a higher intensity, lower moving distance, smaller areal coverage, and shorter duration than heatwaves moving in the southeast. We find that the larger area and duration of heatwaves propagating southeast are a result of development of larger and more persistent high‐pressure systems extending over entire northern and eastern India, which are influenced by El Niño Southern Oscillation. On the other hand, higher radiative fluxes and larger heat entrainment in the boundary layer in the heatwaves propagating northeast contribute to their higher intensities.

Abstract Background The highly variable occurrence of primary liver cancers across the United States emphasize the relevance of location‐based factors. Social determinants such as income, educational attainment, housing, and other factors may contribute to regional variations in outcomes. To evaluate their impact, this study identified and analyzed clusters of high mortality from primary liver cancers and the association of location‐based determinants with mortality across the contiguous United States. Methods A geospatial analysis of age‐adjusted incidence and standardized mortality rates from primary liver cancers from 2000 to 2020 was performed. Local indicators of spatial association identified hot‐spots, clusters of counties with significantly higher mortality. Temporal analysis of locations with persistent poverty, defined as high (>20%) poverty for at least 30 years, was performed. Social determinants were analyzed individually or globally using composite measures such as the social vulnerability index or social deprivation index. Disparities in county level social determinants between hot‐spots and non‐hot‐spots were analyzed by univariate and multivariate logistic regression. Results There are distinct clusters of liver cancer incidence and mortality, with hotspots in east Texas and Louisiana. The percentage of people living below the poverty line or Hispanics had a significantly higher odds ratio for being in the top quintile for mortality rates in comparison to other quintiles and were highly connected with mortality rates. Current and persistent poverty were both associated with an evolution from non‐hotspots to new hotspots of mortality. Hotspots were predominantly associated with locations with significant levels of socioeconomic vulnerability or deprivation. Conclusions Poverty at a county level is associated with mortality from primary liver cancer and clusters of higher mortality. These findings emphasize the importance of addressing poverty and related socio‐economic determinants as modifiable factors in public health policies and interventions aimed at reducing mortality from primary liver cancers.

Obesity is a known risk factor for many chronic diseases and a substantial threat to public health. We investigated the effects of figs sourced from Ficus hispida on a high fat-fed experimental rat model. We found that a 500-mg dose of ethanolic extract of figs (EFH) reduced oxidative stress markers nitric oxide (NO), malondialdehyde (MDA), and advanced oxidation protein products (AOPP), which were increased in high fat-fed rats. Antioxidant enzymes superoxide dismutase (SOD), catalase, reduced glutathione (GSH), and myeloperoxidase (MPO), found elevated in high fat-fed rats, were also normalized to nearly regular levels by fig treatment. Administration of EFH further reduced fat deposition and expression of adipogenic genes leptin, fatty acid synthase (FAS), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol regulatory element-binding protein-1c (SERBP-1c). Our results suggest that figs have significant effects on reducing oxidative stress and mitigating obesity-associated liver and adipose tissue abnormalities via suppressing adipogenesis. Thus, we propose that F. hispida has potential benefits in reducing obesity.

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by inflammatory assaults on the central nervous system (CNS), particularly on the optic nerves and spinal cord. In recent years, a wider range of clinical manifestations of this complex disease have been observed, emphasizing the importance of gaining a more profound understanding beyond optic neuritis (ON) and transverse myelitis (TM). Current knowledge This study explores the many clinical symptoms of NMOSD, including common and uncommon presentations. Distinctive aspects of ON, TM, and diencephalic/brainstem syndromes are examined, highlighting their unique characteristics in contrast to conditions such as multiple sclerosis. We also discuss extra‐CNS involvement, such as unusual signs, including muscle involvement, retinal injury, auditory impairment, and rhinological symptoms. Aims and objectives Our study intends to highlight the wide range and complexity of NMOSD presentations, emphasizing the significance of identifying unusual symptoms for precise diagnosis and prompt management. The specific processes that contribute to the varied clinical presentation of NMOSD are not well understood despite existing information. This emphasizes the necessity for more study to clarify the mechanisms that cause different symptoms and discover new treatment targets for this complex autoimmune disorder. Conclusion It is essential to acknowledge the complex and varied clinical manifestations of NMOSD to enhance diagnosis, treatment, and patient results. By enhancing our comprehension of the fundamental processes and investigating innovative therapeutic approaches, we may aim to enhance the quality of life for persons impacted by this illness.

Aim: The present study assessed the three-dimensional bone loss, at three different levels, around implants placed immediately after extraction using the socket shield method versus immediate implant placement. Materials and Methods: A non-randomized clinical trial was conducted in 30 cases divided into two groups: socket shield method and immediate implant placement (15 cases each). Horizontal bone width (HBW) (at three different levels from baseline) and vertical bone level (VBL) (mesial and distal surfaces of the implant) were measured preoperatively and 6 months postoperatively by using cone beam computed tomography and radio visio graphy. Results: The mean difference at 2-mm and 8-mm HBW from the baseline was better in the socket shield technique, although the results were not significant. Significant results were found in Levene’s test for equality of error variances. The VBL was significant at both the distal and mesial surfaces of the implant. Conclusion: The socket shield approach demonstrated promising clinical outcomes in preserving alveolar ridge morphology. It can be utilized as a substitute for the typical instantaneous implant placement in the aesthetic zone.

Background Onion thrips (Thrips tabaci) is a complex of cryptic species with subtle morphological differences and distinct genetic backgrounds; thus, species identification using traditional methods remains challenging. The existence of different haplotypes and genotypes within a species can significantly influence various aspects of its biology, including host preference, reproductive capacity, resistance to pesticides, and vector competence for plant viruses. Understanding the genetic diversity and population structure of cryptic species within T. tabaci will not only aid in the development of more effective control strategies tailored to specific genetic variants but also in monitoring population dynamics, tracking invasive species, and implementing quarantine measures to prevent the spread of economically damaging thrips biotypes. Methods This study aims to explore intraspecies genetic diversity and molecular evolutionary relationships of the mitochondrial cytochrome oxidase gene subunit I (mtCOI) in T. tabaci populations from India. To capture diversity within the Indian T. tabaci populations, amplicon sequencing was performed for the thrips mtCOI gene from eight diverse localities in India. A total of 48 sequences retrieved for the mtCOI gene from the NCBI Nucleotide database were analysed. Results Multiple insertions and deletions were detected at various genomic positions across the populations from different localities, with the highest variation observed in the 300–400 genome position range. Molecular diversity analyses identified 30 haplotypes within the population, with certain subpopulations exhibiting higher gene flow. Analysis of single nucleotide polymorphism patterns within the mtCOI gene across diverse Indian locales revealed significant intrapopulation genetic heterogeneity and its potential repercussions on gene functionality. Elevated F statistics (Fst) values in the northern–western subpopulations suggested high genetic variability, particularly evident in haplotype networks originating mainly from the northern region, notably Delhi. While most populations displayed stable and ancient evolutionary histories, thrips populations from northern, western, and north-eastern regions indicated rapid growth.

The Nipah virus (NiV) belongs to the Henipavirus genus is a serious public health concern causing numerous outbreaks with higher fatality rate. Unfortunately, there is no effective medication available for NiV. To investigate possible inhibitors of NiV infection, we used in silico techniques to discover treatment candidates in this work. As there are not any approved treatments for NiV infection, the NiV-enveloped attachment glycoprotein was set as target for our study, which is responsible for binding to and entering host cells. Our in silico drug design approach included molecular docking, post-docking molecular mechanism generalised born surface area (MM-GBSA), absorption, distribution, metabolism, excretion/toxicity (ADME/T), and molecular dynamics (MD) simulations. We retrieved 418 phytochemicals associated with the neem plant ( Azadirachta indica ) from the IMPPAT database, and molecular docking was used to ascertain the compounds’ binding strength. The top 3 phytochemicals with binding affinities of −7.118, –7.074, and −6.894 kcal/mol for CIDs 5280343, 9064, and 5280863, respectively, were selected for additional study based on molecular docking. The post-docking MM-GBSA of those 3 compounds was −47.56, –47.3, and −43.15 kcal/mol, respectively. As evidence of their efficacy and safety, all the chosen drugs had favorable toxicological and pharmacokinetic (Pk) qualities. We also performed MD simulations to confirm the stability of the ligand-protein complex structures and determine whether the selected compounds are stable at the protein binding site. All 3 phytochemicals, Quercetin (CID: 5280343), Cianidanol (CID: 9064), and Kaempferol (CID: 5280863), appeared to have outstanding binding stability to the target protein than control ribavirin, according to the molecular docking, MM-GBSA, and MD simulation outcomes. Overall, this work offers a viable approach to developing novel medications for treating NiV infection.

Abstract Earth went through at least two periods of global glaciation (i.e., “Snowball Earth” states) during the Neoproterozoic, the shortest of which (the Marinoan) may not have lasted sufficiently long for its termination to be explained by the gradual volcanic build‐up of greenhouse gases in the atmosphere. Large asteroid impacts and supervolcanic eruptions have been suggested as stochastic geological events that could cause a sudden end to global glaciation via a runaway melting process. Here, we employ an energy balance climate model to simulate the evolution of Snowball Earth's surface temperature after such events. We find that even a large impactor (diameters of d ∼ 100 km) and the supervolcanic Toba eruption (74 Kyr ago), are insufficient to terminate a Snowball state unless background CO2 has already been driven to high levels by long‐term outgassing. We suggest, according to our modeling framework, that Earth's Snowball states would have been resilient to termination by stochastic events.

Purpose: To examine the potential anti-inflammatory activity of the methanolic extract of Ziziphus mauritiana (MEZM) in inflammatory bowel disease conditions. Materials and Methods: A total of 36 adult male Albino Wistar rats were divided into six groups. The first group (normal control) was administered with normal saline, and the second group (disease control) was administered with 4% acetic acid via the rectal route. The third group (sulfasalazine group) received the standard treatment of 100 mg/kg sulfasalazine, while three test groups were administered with 100, 200, and 300 mg/kg of MEZM. On the 14th day, a macroscopic examination was conducted to assess colonic inflammation, ulceration, and levels of cytokines including interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin13 (IL-13), and tumour necrosis factorα (TNFα), which were estimated to investigate the inflammatory response. Result: The cytokine levels increased significantly in the disease control group compared to the normal control group with P value

The foraminiferal environmental DNA (eDNA) metabarcoding based on high-throughput sequencing (HTS) is a powerful tool to unravel the hidden genetic diversity and environmental lineages. Results from the eDNA approach provided valuable insight into an unplumbed diversity of soft-bodied monothalamous foraminifers [1]. Micropaleontologists overlooked monothalamids due to their soft organic and/or finely agglutinated test, which often gets destroyed during routine morphological investigations [2]. On the other hand, some foraminifera taxonomists or studies included monothalamids (soft-shelled species) in ecological and diversity investigations ranging from deep-sea locations to coastal marine habitats [1,3,4]. Here, we document our metabarcoding analysis of foraminiferal diversity and abundance from the mining-affected estuaries of the Indian state of Goa. High-throughput sequencing using the Illumina platform indicated the overwhelming abundance of monothalamous foraminifers in the studied estuarine sediments. For the first time, such detailed data of the foraminiferal diversity utilizing sedimentary environmental DNA (eDNA) methods was carried out in India. The raw sequence data used for analysis is available in NCBI under the Sequence Read Archive (SRA) with the BioProjects and SRA accession number: PRJNA1040471. The presented data may be used as baseline information for eDNA-based biomonitoring and biodiversity assessment surveys from Indian marine habitats across time and space.

The dissimilar welding of Inconel 718 (IN-718) alloy and AISI 410 martensitic stainless steel (MSS-410) is crucial in advanced gas turbines, and ultra-supercritical power plants to meet the demands of different operating conditions and lower the cost. However, the dissimilar fusion welding of IN-718/MSS-410 is challenging due to the differences in thermal expansion coefficient, physical and mechanical properties of base metals. In this study, the solid-state vacuum diffusion bonding (VDB) technology is employed to develop the dissimilar IN-718/MSS-410 joints. The aim of this study is to find the optimal combination of VDB parameters such as diffusion bonding pressure-DBP (MPa), diffusion bonding temperature-DBT (°C) and diffusion bonding time-DBt (min) for enhancing the strength of IN-718/MSS-410 joints. The response surface methodology (RSM) was integrated for designing the experimental matrix. The strength performance of VDB joints was evaluated by conducting the lap shear strength (LSS) and bonding strength (BS) tests. The mathematical LSS and BS predicting models were established using regression analysis and verified employing the variance analysis. The microstructural features were analyzed using optical and scanning electron microscopy (SEM). The X-ray diffractometer (XRD) was employed to identify the phases evolution in the joint interface. The experimental results revealed that the IN-718/MSS-410 joints diffusion bonded using the DBP of 14 MPa, DBT of 960 °C and DBt of 90 min exhibited the greater LSS of 280 MPa and BS of 373 MPa. The prediction models accurately predicted the LSS and BS of IN-718/MSS-410 joints within 2 % error at 95 % confidence. It is primarily concerned with developing the optimal bonding width with the fewest possible embrittlement implications and better joining interface coalescence. According to variance analysis, the DBt was the most significant parameter influencing the LSS and BS of joints followed by the DBP and DBT.

Background: Antibiotics are frequently utilized in livestock, particularly poultry, for therapy and growth promotion, resulting in antimicrobial resistance. Multidrug-resistant bacteria are frequent in poultry samples from India. The purpose of this study was to better understand main antibiotic consumption patterns in poultry value chains, as well as antibiotic knowledge and practices among the stakeholders. Methods: A cross-sectional survey was conducted in Assam and Karnataka, India. The poultry farmers were interviewed on antibiotic usage, antibiotic knowledge, feeding practices, and preventive measures on the farm. Poultry farmers reported their veterinarians, and we also interviewed them on knowledge and practices related to antimicrobial use in poultry and antimicrobial resistance. Item response theory (IRT) was used to assess the association between the answers and demographic factors. Results: This survey interviewed 62 poultry farmers and 11 veterinarians. Small poultry farms with fewer than 4000 birds were owned by 51.6% of farmers. Most poultry farmers had heard about antibiotics, and 62.9% thought they cured all diseases. If one chicken is sick, 72.6% said others should be given antibiotics to prevent the disease. All veterinarians utilized tetracyclines, aminoglycosides, and cephalexin on the poultry farms. Over half (54.5%) stated antibiotics prevent diseases, and 72.7% said they treat and prevent diseases. Some (45.5%) said antibiotics boost growth. IRT analysis showed that 8 questions assessed a knowledge scale well. Univariable analysis showed that Assam farmers and women were likely to have have more knowledge. Conclusion: The poultry farmers were mostly unaware of the relation between antibiotic use and antimicrobial resistance. Despite being aware, the veterinarians agreed with use antibiotics as a prophylactic measure. It is vital that these stakeholders understand the repercussions of such widespread antibiotic use. In order to increase knowledge, frequent trainings and antimicrobial stewardship programmes with effective communication and incentives for behaviour change should be conducted.

The service life and durability of the prestressed concrete (PC) structures mainly depend on the corrosion resistance of the prestressing strands, wires, or tendons. Once corrosion occurs in the strands, identifying the location and quantifying the phases of corrosion is a very challenging task. Thus, this paper presents a novel way to monitor the corrosion process and identify the deterioration in a PC beam using an embedded piezo sensor (EPS) based on the electro-mechanical impedance (EMI) technique. The accelerated corrosion tests were conducted on a PC beam in which EPS was attached to the prestressing wire inside the beam to monitor the changes in the EMI signature during the corrosion progression. In addition, statistical damage indices such as root mean square deviation is identified to quantify the damage due to corrosion. Further, this study identifies the deterioration in mechanical changes such as stiffness, mass, and damping by extracting the equivalent structural parameters from the raw EMI signatures. Based on qualitative and quantitative results, it is found that the EPS effectively senses the changes at different time intervals during the corrosion process and identifies the damage of corrosion. Also, the equivalent stiffness parameter identified from raw EMI signatures is realistically measuring the material deterioration under corrosion and identifying the corrosion phases. Hence, it is concluded that the EMI technique based on EPS in structural health monitoring of PC beam can accurately assess the deterioration under the effect of corrosion.