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Background Defensins are key effector molecules of innate immunity that can contribute towards the diagnosis and monitoring of chronic obstructive pulmonary disease (COPD). The present study was conducted to investigate the role of alpha-defensins in patients with COPD by quantifying serum and sputum samples. Methods A total of 180 patients were enrolled and divided into four groups, and sputum and serum values of alpha-defensins were assessed. The sensitivity, specificity, and accuracy of sputum alpha-defensin as a diagnostic biomarker were evaluated to assess its utility in diagnosing COPD. Results The mean value of sputum alpha-defensins was found to be statistically significant amongst the four groups (P < 0.001). The highest levels were found in subjects with AECOPD (385.76 ± 116.62 ng/mL). Sputum alpha-defensins were found to be negatively correlated with FEV 1 values (rho = −0.31, P < 0.001). Conclusion Sputum alpha-defensins can be used as a potential marker for predicting acute exacerbation of COPD. In addition, they could serve as an indicator of disease severity in COPD patients.

Abstract Context Children with human immunodeficiency virus (HIV) infection frequently present with opportunistic infections of the lung that may be associated with high mortality rate. There is no study, to the best of our knowledge, correlating specific radiographic patterns of chest infections with CD4 levels of immunity in HIV-infected children of Indian subcontinent (where prevalence of respiratory tuberculosis is very high). Aims To study the radiological patterns of chest infections in HIV-infected children, and to correlate these radiological findings with CD4 cell count and final diagnosis. Methods Forty-five HIV-infected children (1–18 years of age) with suspected chest infections were included in the study. The baseline and the most recent CD4 counts were recorded for each patient. Chest X-ray (CXR) was obtained in all the patients, and multi-detector computed tomography (MDCT) chest was done in 27 patients having clinical suspicion of infection with normal or equivocal findings on CXR. Chest radiographs and MDCT chest were analyzed for different radiological patterns of chest infections. Imaging findings were correlated with CD4 count range for disease spectrum. The final etiopathological diagnosis was achieved in combination with clinico-radiological findings, laboratory data, cytohistopathology and follow-up imaging. Results Out of 45 children confirmed to be HIV-infected, 27 (60%) had bacterial infection, 14 (31.11%) had tuberculosis, and four (8.89%) had fungal infection. Consolidation on CXR/CT strongly suggested bacterial etiology (P

Conventional agriculture heavily relies on chemical compounds, adversely impacting health and ecosystem. Ensuring sustainable soil health necessitates the intelligent delivery of components to crop plants without any losses. Nanomaterials hold significant potential for enhancing agrochemical efficiency (50%), crop production (10–20%), and soil health. The nanomaterial improve different soil properties and its mechanism in soil and plant compartments, remains poorly understood. This review addresses critical questions regarding role of NMs in improving soil health, its mechanism and effects in the environment. Highlighting knowledge gaps, the article outlines essential areas for future research to ensure sustainable applications of nanotechnology in agriculture.

The present study aimed to investigate the effects of various mulching strategies on the growth and yield of peach crops, as well as on soil hydrothermal regimes, weed infestation, and microbial properties. A field experiment was conducted, implementing various organic residue mulches including locally available grass and pine needle mulch, as well as inorganic mulches such as black and transparent mulch, control treatment comprising blanket recommendation. Results indicated that plots with black polythene mulch showed the highest fruit productivity, fruit yield, fruit length and diameter. Furthermore, black mulch and mulch mat treatments demonstrated complete weed control efficiency. Weed species Anagalis arvensis showed the highest maximum frequency, density, relative frequency, and relative density, while Biden pilosa had the highest abundance and relative abundance. The study also found that the impact of grass and pine mulch was of interest, as it helped regulate soil hydrothermal regimes and significantly enhanced total viable count, microbial activity, and microbial biomass carbon. In conclusion, these findings emphasize the potential of mulching techniques to improve peach crop yield and soil health.

Introduction: Lung cancer carries the highest cancer-related mortality rates worldwide. Despite all recent advances, the mortality from lung cancer is still rising. A better understanding of the risk factors may help us predict responses to chemotherapy for better management. Aim: To evaluate predictors of response to chemotherapy in advanced Non-Small Cell Lung Cancer (NSCLC) patients. Materials and Methods: This was a prospective cohort study conducted in the Department of Pulmonary Medicine at Government Medical College and Hospital, Chandigarh, India. A total of 60 confirmed cases of advanced (stage IIIB and IV) NSCLC patients were enrolled consecutively for a duration of two years. Baseline clinical parameters, routine blood tests, spirometry, exercise capacity using the 6 Minute Walk Test Distance (6MWTD), and Computed Tomography (CT)-based tumour size were recorded. Certain pre-defined patient, disease, and therapy-related factors (age, gender, dyspnoea, baseline blood tests, tumour size, histology, etc.) were evaluated for their possible role as predictors of treatment response in advanced NSCLC patients. A positive response was defined if the response to chemotherapy was Complete Response (CR) or Partial Response (PR), and a negative response if the response was Progressive Disease (PD) or Stable Disease (SD) as per revised RECIST (Response evaluation criteria in solid tumors) 1.1 criteria. Variables between the two groups were compared using the Mann-Whitney U test and Chi-square test. To find out the factors that may predict response to treatment, univariate and multivariate logistic regression analysis were used. Results: Out of a total of 60 confirmed cases of NSCLC patients, only 40 patients were able to complete the four cycles of chemotherapy. The mean age of the patients was 58.5±9.6 years. There were a total of 35 males (87.5%) and five females (12.5%) in the study. Out of 40 patients, 27 (67.5%) had squamous cell carcinoma and 13 (32.5%) had adenocarcinoma. On univariate analysis, Neutrophil-Lymphocyte Ratio (NLR) had a statistically significant association with tumour response (p3.81) NLR (p=0.002) were found as independent predictors of poor response to chemotherapy. Conclusion: Pre-treatment high NLR and advanced age are significant factors for a poor response to chemotherapy treatment in advanced NSCLC patients.

Background: Women and racialized minorities continue to be underrepresented in cardiovascular (CV) trial outcomes data, despite comprising a significant global burden of CV disease. This study evaluated the impact of trial characteristics on the temporal enrollment of women and racialized minorities in prominent CV trials published in the period 1986-2023. Methods: MEDLINE was searched for CV trials published in The Lancet, the Journal of the American Medical Association, and the New England Journal of Medicine. Participant and investigator demographics, types of interventions, clinical indications, and funding sources were compared according to the enrollment of women or racialized minorities. Results: From 799 studies, including 4,071,921 patients, the enrollment of women and racialized minorities significantly increased from 1986 to 2023 (both P ≤ 0.001). Although the enrollment of women varied by trial indication, comprising 25.0% of coronary artery disease, 35.2% of noncoronary and/or vascular disease, 13.8% of heart failure, 17.0% of arrhythmia, and 28.7% of other CV trials (P ≤ 0.001), it did not differ by peer-reviewed vs industry funding. First authors who were women were more likely than first authors who were men to enroll significantly more women (P = 0.01). Conclusions: Active efforts to increase diverse enrollment, along with improved reporting, including of sex and race, in future CV trials may increase the generalizability of their findings and applicability to global populations. RÉsumÉ: Contexte: Les femmes et les groupes racisés demeurent sous-représentés dans les données de résultats d’essais cliniques sur les maladies cardiovasculaires (CV) malgré l’important fardeau global associé à ces maladies. Cette étude visait à évaluer l’effet des caractéristiques des essais sur la sélection temporelle des femmes et des membres de groupes racisés dans les essais portant principalement sur les maladies CV durant la période de 1986 à 2023. Méthodologie: La base de données MEDLINE a été consultée à la recherche d’essais sur les maladies CV publiés dans The Lancet, Journal of the American Medical Association et New England Journal of Medicine. Les données démographiques des participants et des chercheurs, les types d’interventions, les indications cliniques et les sources de financement ont été comparés en fonction de la sélection des femmes ou des membres de groupes racisés. Résultats: Dans 799 études cumulant 4 071 921 patients, la sélection des femmes et des membres de groupes racisés a augmenté significativement entre 1986 et 2023 (p ≤ 0,001 dans les deux cas). Bien que la sélection des femmes variait en fonction des indications des essais, soit 25,0 % dans les essais portant sur les coronaropathies, 35,2 % pour les maladies non coronariennes et/ou vasculaires, 13,8 % pour l’insuffisance cardiaque, 17,0 % pour l’arythmie et 28,7 % pour d’autres maladies CV (p ≤ 0,001), elle ne différait pas selon que les études étaient révisées par des pairs ou qu’elles étaient financées par l’industrie. Lorsqu’une femme était l’autrice principale, le nombre de femmes sélectionnées était susceptible d’être plus élevé que lorsque l’auteur principal était un homme (p = 0,01). Conclusions: Des efforts actifs pour diversifier davantage la sélection des participants et mieux rendre compte des différences, notamment en ce qui concerne le sexe et la race, pourraient élargir la portée des conclusions des futurs essais sur les maladies CV et leur application à l’ensemble de la population.

Despite its importance, formal education in healthcare training programs on sex- and gender-specific cardiovascular disease (CVD) risk factors, symptoms, treatment, and outcomes is lacking. We completed rapid reviews of the academic and grey literature to describe the current state of women-specific CVD education in medical, nursing, and other healthcare education programs. Second, we analyzed results from a Canada-wide survey of healthcare professional education programs to identify gaps in curricula related to sex- and gender-specific training in CVD. Our academic review yielded only 15 peer-reviewed publications, and our online search only 20 healthcare education programs, that note that they specifically address women, or sex and gender, and CVD in their curricula. Across both searches, the majority of training and education programs were from the USA, varied greatly in length, delivery mode, and content covered, and lacked consistency in evaluation. Of surveys sent to 213 Canadian universities and other entry-to-practice programs, 80 complete responses (37.6%) were received. A total of 47 respondents (59%) reported that their programs included women-specific CVD content. Among those programs without content specific to CVD in women, 69.0% stated that its inclusion would add “quite a bit” or “a great deal” of value to the program. This study highlights the emerging focus on and substantial gaps in women-specific CVD training and education across healthcare education programs. All medical, nursing, and healthcare training programs are implored to incorporate sex- and gender-based CVD content into their regular curricula as part of a consolidated effort to minimize gaps in cardiovascular care. Résumé: Malgré la prévalence des maladies cardiovasculaires (CV), les programmes d’enseignement en santé accordent peu d’attention aux facteurs de risque, aux symptômes, aux traitements et aux issues selon le sexe ou le genre. Premièrement, nous avons fait une revue rapide de la littérature universitaire et la littérature grise pour faire état de la formation sur les maladies CV spécifiques aux femmes dans les programmes d’enseignement en médecine, en soins infirmiers et autres domaines de la santé. Deuxièmement, nous avons analysé les résultats d’une enquête menée à l’échelle du Canada sur des programmes de formation professionnelle pour cerner les lacunes dans les programmes au chapitre de la formation sur les maladies CV en fonction du sexe et du genre. Notre analyse de la littérature universitaire a permis de relever seulement 15 publications révisées par des pairs à ce sujet, et notre recherche en ligne a mis au jour seulement 20 programmes d’enseignement qui comportent un volet portant spécifiquement sur les femmes, ou bien le sexe et le genre, et les maladies CV. Ces deux enquêtes ont révélé que la majorité des programmes de formation et d’enseignement étaient aux États-Unis et qu’ils présentaient une grande diversité sur le plan de la durée, du mode d’enseignement et du contenu abordé. De plus, les méthodes d’évaluation n’étaient pas uniformes. Parmi les sondages envoyés à 213 universités et programmes d’admission à la pratique au Canada, 80 réponses complètes (37,6 %) ont été reçues. Quarante-sept des établissements qui ont répondu (59 %) ont signalé que leurs programmes comprenaient du contenu portant sur les maladies CV spécifiques aux femmes. Parmi les établissements dont les programmes ne comportaient aucun contenu spécifique aux femmes, 69,0 % ont indiqué qu’une telle inclusion ajouterait « beaucoup » ou « énormément » de valeur au programme. Cette étude met en lumière l’attention nouvelle accordée à la formation et à l’enseignement sur les maladies CV spécifiques aux femmes ainsi que les lacunes substantielles observées à cet égard dans les programmes d’enseignement en santé. Les programmes de formation en médecine, en soins infirmiers et en santé sont vivement invités à intégrer du contenu spécifique au sexe et au genre pour ce qui est des maladies CV dans un effort concerté visant à réduire les lacunes dans les soins cardiovasculaires.

Despite significant progress in medical research and public health efforts, gaps in knowledge of women’s heart health remain across epidemiology, presentation, management, outcomes, education, research, and publications. Historically, heart disease was viewed primarily as a condition in men and male individuals, leading to limited understanding of the unique risks and symptoms that women experience. These knowledge gaps are particularly problematic because globally heart disease is the leading cause of death for women. Until recently, sex and gender have not been addressed in cardiovascular research, including in preclinical and clinical research. Recruitment was often limited to male participants and individuals identifying as men, and data analysis according to sex or gender was not conducted, leading to a lack of data on how treatments and interventions might affect female patients and individuals who identify as women differently. This lack of data has led to suboptimal treatment and limitations in our understanding of the underlying mechanisms of heart disease in women, and is directly related to limited awareness and knowledge gaps in professional training and public education. Women are often unaware of their risk factors for heart disease or symptoms they might experience, leading to delays in diagnosis and treatments. Additionally, health care providers might not receive adequate training to diagnose and treat heart disease in women, leading to misdiagnosis or undertreatment. Addressing these knowledge gaps requires a multipronged approach, including education and policy change, built on evidence-based research. In this chapter we review the current state of existing cardiovascular research in Canada with a specific focus on women. Résumé: En dépit des avancées importantes de la recherche médicale et des efforts en santé publique, il reste des lacunes dans les connaissances sur la santé cardiaque des femmes sur les plans de l’épidémiologie, du tableau clinique, de la prise en charge, des résultats, de l’éducation, de la recherche et des publications. Du point de vue historique, la cardiopathie a d’abord été perçue comme une maladie qui touchait les hommes et les individus de sexe masculin. De ce fait, la compréhension des risques particuliers et des symptômes qu’éprouvent les femmes est limitée. Ces lacunes dans les connaissances posent particulièrement problème puisqu’à l’échelle mondiale la cardiopathie est la cause principale de décès chez les femmes. Jusqu’à récemment, la recherche en cardiologie, notamment la recherche préclinique et clinique, ne portait pas sur le sexe et le genre. Le recrutement souvent limité aux participants masculins et aux individus dont l’identité de genre correspond au sexe masculin et l’absence d’analyses de données en fonction du sexe ou du genre ont eu pour conséquence un manque de données sur la façon dont les traitements et les interventions nuisent aux patientes féminines et aux individus dont l’identité de genre correspond au sexe féminin, et ce, de façon différente. Cette absence de données a mené à un traitement sous-optimal et à des limites de notre compréhension des mécanismes sous-jacents de la cardiopathie chez les femmes, et est directement reliée à nos connaissances limitées, et à nos lacunes en formation professionnelle et en éducation du public. Le fait que les femmes ne connaissent souvent pas leurs facteurs de risque de maladies du cœur ou les symptômes qu’elles peuvent éprouver entraîne des retards de diagnostic et de traitements. De plus, le fait que les prestataires de soins de santé ne reçoivent pas la formation adéquate pour poser le diagnostic et traiter la cardiopathie chez les femmes les mène à poser un mauvais diagnostic ou à ne pas traiter suffisamment. Pour pallier ces lacunes de connaissances, il faut une approche à plusieurs volets, qui porte notamment sur l’éducation et les changements dans les politiques, et qui repose sur la recherche fondée sur des données probantes. Dans ce chapitre, nous passons en revue l’état actuel de la recherche existante sur les maladies cardiovasculaires au Canada, plus particulièrement chez les femmes.

This final chapter of the Canadian Women’s Heart Health Alliance “ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women” presents ATLAS highlights from the perspective of current status, challenges, and opportunities in cardiovascular care for women. We conclude with 12 specific recommendations for actionable next steps to further the existing progress that has been made in addressing these knowledge gaps by tackling the remaining outstanding disparities in women’s cardiovascular care, with the goal to improve outcomes for women in Canada. Résumé: Dans ce chapitre final de l’ATLAS sur l’épidémiologie, le diagnostic et la prise en charge de la maladie cardiovasculaire chez les femmes de l’Alliance canadienne de santé cardiaque pour les femmes, nous présentons les points saillants de l’ATLAS au sujet de l’état actuel des soins cardiovasculaires offerts aux femmes, ainsi que des défis et des occasions dans ce domaine. Nous concluons par 12 recommandations concrètes sur les prochaines étapes à entreprendre pour donner suite aux progrès déjà réalisés afin de combler les lacunes dans les connaissances, en s’attaquant aux disparités qui subsistent dans les soins cardiovasculaires prodigués aux femmes, dans le but d’améliorer les résultats de santé des femmes au Canada.

Cardiovascular disease (CVD) is the leading cause of death in women worldwide, and of premature death in women in Canada. Despite improvements in cardiovascular care over the past 15-20 years, acute coronary syndrome (ACS) and CVD mortality continue to increase among women in Canada. Chest pain is a common symptom leading to emergency department visits for both men and women. However, women with ACS experience worse outcomes. compared with those of men, due to misdiagnosis or lack of diagnosis resulting in delayed care and underuse of guideline-directed medical therapies. CVD mortality rates are highest in Indigenous and racialized women and those with a disproportionately high number of adverse social determinants of health. CVD remains underrecognized, underdiagnosed, undertreated, and underresearched in women. Moreover, a lack of awareness of unique symptoms, clinical presentations, and sex-and-gender specific CVD risk factors, by healthcare professionals, leads to outcome disparities. In response to this knowledge gap, in acute recognition and management of chest-pain syndromes in women, the Canadian Women’s Heart Health Alliance performed a needs assessment and review of CVD risk factors and ACS pathophysiology, through a sex and gender lens, and then developed a unique chest-pain assessment protocol utilizing modified dynamic programming algorithmic methodology. The resulting algorithmic protocol is presented. The output is intended as a quick reference algorithm that could be posted in emergency departments and other acute-care settings. Next steps include protocol implementation evaluation and impact assessment on CVD outcomes in women. Résumé: Les maladies cardiovasculaires (MCV) sont la principale cause de décès chez les femmes dans le monde et de décès prématuré chez les femmes au Canada. Malgré les progrès réalisés dans le domaine des soins cardiovasculaires au cours des 15 à 20 dernières années, les taux de syndrome coronarien aigu (SCA) et de mortalité due aux MCV continuent d’augmenter chez les femmes au Canada. La douleur thoracique est un symptôme fréquent qui pousse les hommes et les femmes à se rendre aux urgences. Toutefois, les femmes atteintes d’un SCA présentent de moins bons résultats cliniques que les hommes, en raison d’erreurs de diagnostic ou d’une absence de diagnostic causant des retards dans les soins prodigués et une sous-utilisation des traitements médicaux préconisés dans les lignes directrices. Les taux de mortalité liée aux MCV sont les plus élevés chez les femmes autochtones et les femmes racialisées ainsi que chez celles qui présentent un nombre particulièrement élevé de déterminants sociaux de la santé défavorables. Les MCV continuent d’être sous-estimées, sous-diagnostiquées et sous-traitées chez les femmes et ne sont pas suffisamment étudiées dans cette population. De plus, la méconnaissance par les professionnels de la santé des symptômes, des tableaux cliniques et des facteurs de risque de MCV selon le sexe et le genre entraînent des disparités dans les résultats cliniques. Pour combler ces lacunes dans les connaissances en matière de reconnaissance et de prise en charge des symptômes de douleur thoracique chez les femmes, l’Alliance canadienne de la santé cardiaque des femmes a réalisé une évaluation des besoins et un examen des facteurs de risque de MCV et de la physiopathologie du SCA en tenant compte des particularités liées au sexe et au genre, et a ensuite élaboré un protocole unique d’évaluation de la douleur thoracique faisant appel à une méthodologie algorithmique par programmation dynamique modifiée. Nous présentons le protocole algorithmique qui en est issu. Ce résultat se veut un algorithme de référence rapide pouvant être diffusé dans les services d’urgences et les autres services de soins de courte durée. Les prochaines étapes de notre travail seront d’évaluer la mise en œuvre du protocole et son incidence sur les issues cardiovasculaires chez les femmes.

Abstract Background The advent of immune checkpoint inhibitors (ICIs) represented a significant breakthrough in cancer therapy. Recently, the combined use of atezolizumab and bevacizumab was approved as first‐line treatment for unresectable hepatocellular carcinoma (HCC). Exposure to a novel and diverse spectrum of immune‐related adverse events (irAEs) has increased with the growing utilization of ICIs, however, a comprehensive understanding surrounding newer agents is still lacking. The incidence of kidney toxicities is rare but rising, often underreported due to the lack of confirmatory biopsies. Here, we present a rare case of biopsy‐proven acute interstitial nephritis (AIN) following atezolizumab‐bevacizumab treatment of advanced unresectable HCC. Case An 84‐year‐old male with T4N0M0 hepatocellular carcinoma was admitted after cycle 5 of atezolizumab due to decreased urine output and dysuria with a serum creatine of 4.7 mg/dL compared to a baseline of 1.3 mg/dL. To confirm the diagnosis of possible intrinsic renal injury, an ultrasound‐guided non‐focal biopsy of the left kidney was performed, revealing AIN. Potential exacerbatory medications, such as proton‐pump inhibitors, were discontinued. The patient was discharged on oral steroids with improvement in serum creatinine. Before completing the steroid taper, the patient developed pneumocystis pneumonia and eventually transitioned to hospice care. Conclusion This case highlights the valuable role renal biopsy can play in accurately capturing irAEs and guiding appropriate management in the setting of ICI‐induced AKI. It also exemplifies important considerations for steroid treatment of irAEs in the setting of comorbidities, such as diabetes.

The study was conducted on apparently healthy caprine lungs to evaluate the efficacy of different plastination techniques by gross biometrical and morphological analysis of the formalin fixed and plastinated specimens. The gross biometrical analysis was made on all the formalin fixed lungs and after that the samples were divided as Group I and Group II with 6 animals in each group. In method I, after proper fixation, the specimens were dehydrated in three changes of acetone (two weeks each), then impregnated in two changes of glycerol for 15 days each and cured in muslin cloth containing corn starch. In method II, modified plastination solution was used as impregnation solution. The plastinates prepared by method I were soft to touch, odorless, the elasticity and colour of lung tissue was near normal, whereas the lungs plastinated by method II were hard to touch and their color turned to whitish grey. The biometric data showed that the shrinkage in weight of lungs was 47.99% in method I and 85.46% in method II. The shrinkage in length of apex to base of right lung was 14.36% and that of left lung was 16.18% by method I. In method II, the length from apex to base was reduced to be 35.84% and 34.83 in right and left lungs, respectively. It was concluded from present study that the plastinated glycerine specimens (Method I) showed lesser deviations from their near natural state as compared to the plastinates prepared by Indigenous method (Method II). The shrinkage was more evident in plastinates prepared Indigenous method (Method II) than by glycerine method (Method I). So, it is recommended that glycerine method of plastination should be preferred to any other method of plastination.

Lead (Pb) is known to cause neurological changes, but antioxidants, chelators, and anti-inflammatory agents mitigates Pb toxicity. Previously, we reported antioxidant and anti-inflammatory effects of 3-hydroxy-3′,4′,5′-trimethoxyflavone (HTMF) derived from Ocimum basilicum L. leaves. This research investigates the neuroprotective properties of HTMF against Pb induced neurotoxicity in rats. Rats were orally administered lead acetate (100 mg/kg) daily for 30 days to induce neurotoxicity, then treated with HTMF (5 and 10 mg/kg) 30 min after Pb exposure. Cognitive and motor functions and brain biochemical parameters were determined to understand HTMF’s mechanism of action. Pb exposure impaired cognition and motor skills, elevated Pb levels, TBARS, TNF-α, IL-6 and MAO A & B, and reduced GSH levels in the brain. HTMF treatment significantly improved memory, motor deficits, and metabolic abnormalities induced by Pb, attributed to its chelating, antioxidative, anti-inflammatory, and monoaminergic modulating properties, suggesting its potential as a therapeutic agent for metal-induced brain injuries.

Currently, there are no guidelines or consensus recommendations on the antithrombotic management of peripheral artery disease (PAD) from an Indian perspective. In this article, we have summarized clinical practice recommendations on antithrombotic management of (i) asymptomatic chronic PAD (cPAD), (ii) symptomatic cPAD (intermittent claudication [IC] and chronic limb-threatening ischemia [CLTI]), and (iii) after revascularization (endovascular and surgical). An electronic search of the PubMed database was undertaken to identify relevant articles. Various combinations of keywords such as PAD, chronic peripheral arterial disease, asymptomatic chronic peripheral arterial disease, symptomatic chronic peripheral arterial disease, dual antiplatelet therapy, single antiplatelet therapy, dual pathway inhibition, antithrombotic, revascularization, endovascular, and surgical were used. Randomized controlled trials, case reports, practice guidelines, systematic literature reviews, and meta-analyses were screened and assessed. A roundtable meeting of experts (n = 13) was conducted to arrive at clinical practice recommendations. Experts made their decisions based on the evidence and guideline recommendations. In patients with asymptomatic cPAD and significant peripheral artery stenosis (PAS), long-term single antiplatelet therapy may be considered at the discretion of the clinician. There is no clear evidence in favor of long-term dual antiplatelet therapy in symptomatic cPAD. Experts agreed that low-dose rivaroxaban plus aspirin should be considered in patients with asymptomatic cPAD with >50% PAS and conditions such as diabetes and polyvascular disease. This combination was also suggested in patients with IC, CLTI, postendovascular (stent based/nonstent), and surgical revascularization to reduce cardiovascular and limb ischemic risk, including major amputation in the absence of high bleeding risk or other contraindications.

Tracheal agenesis is a rare and life-threatening airway malformation, and currently, there is no curative treatment available. The described case involves a preterm male newborn at 30 weeks of gestational age who could not be intubated during resuscitation, despite multiple attempts. However, the baby could be ventilated after oesophageal intubation. Tracheal stenosis/atresia was suspected, and airway evaluation was performed using a thin, flexible fiberoptic bronchoscope. No tracheal opening could be identified, and upon introducing the bronchoscope into the oesophagus, a triluminal opening was found, through which the scope could not be further navigated. To further delineate the anatomy, a Contrast-enhanced Computed Tomography (CECT) thorax was performed, revealing the absence of a tracheal lumen and the communication of both bronchi at the carina with the oesophagus. Unfortunately, the baby succumbed to the illness after three days. Tracheal agenesis is an anatomical malformation that typically presents as respiratory distress and the absence of an audible cry at birth. Attempts to establish a definite airway are unsuccessful, which may result in early neonatal death. Oesophageal intubation may temporarily establish ventilation until palliative surgery is performed.

Introduction: Considering the pathophysiology of nasal obstruction, changes in certain parameters such as Peripheral Blood Eosinophil Count (PBEC), bedside pulmonary function test, Peak Expiratory Flow Rate (PEFR), and Electrocardiography (ECG) may have some correlation with postoperative pulmonary complications such as upper airway obstruction, loss of pharyngeal muscle tone, and postobstructive pulmonary oedema. Aim: To observe and analyse the changes in PBEC, bedside pulmonary function test, PEFR, and ECG in patients undergoing Functional Endoscopic Sinus Surgery (FESS). Materials and Methods: A prospective cohort study was conducted at Bharati Hospital, Pune, Maharashtra, India over a two-year duration from December 2020 to October 2022. A total of 50 patients aged above 18 years undergoing FESS surgery were included in the study. The statistical analysis was performed using the Chi-square test and student’s t-test. After thorough preoperative evaluation, the aforementioned predictors were recorded. General anaesthesia management for FESS surgery was done according to the standard protocol. Vigilant intraoperative monitoring of vital parameters including peak airway pressure and plateau pressure was performed. After shifting the patients to the recovery room, they were observed for: 1) Hypoxia; 2) Hypercarbia; 3) Laryngospasm; 4) Bronchospasm; and 5) Pulmonary oedema. Results: A total of 50 patients aged between 18 years and 65 years with the mean age was 41.7±15.4 years were included in the study, with 32 males and 18 females. Only 24% of the study population showed postoperative hypoxia, while the rest of the complications were not observed in any patient. Changes in eosinophil count, PEFR, and ECG did not have any correlation with postoperative hypoxia and were statistically insignificant. Bedside pulmonary function tests, including the Sabrasez breath-holding test and the Sabrasez single breath count test, showed changes in 30% and 76% of patients, respectively. Forced Expiratory test change was seen in 72% of patients. Among these, 19.4% showed hypoxia. Out of the 12 cases showing postoperative hypoxia, seven had a disease duration of less than six months. Conclusion: The Sabrasez breath-holding test and Sabrasez single breath count are good predictors for postoperative hypoxia in patients undergoing FESS surgery. Shorter duration of nasal obstruction also showed postoperative hypoxia.

Respiratory symptoms are ubiquitous in children and, even though they may be the harbinger of poor long-term outcomes, are often trivialised. Adverse exposures pre-conception, antenatally and in early childhood have lifetime impacts on respiratory health. For the most part, lung function tracks from the pre-school years at least into late middle age, and airflow obstruction is associated not merely with poor respiratory outcomes but also early all-cause morbidity and mortality. Much would be preventable if social determinants of adverse outcomes were to be addressed. This review presents the perspectives of paediatricians from many different contexts, both high and low income, including Europe, the Americas, Australasia, India, Africa and China. It should be noted that there are islands of poverty within even the highest income settings and, conversely, opulent areas in even the most deprived countries. The heaviest burden of any adverse effects falls on those of the lowest socioeconomic status. Themes include passive exposure to tobacco smoke and indoor and outdoor pollution, across the entire developmental course, and lack of access even to simple affordable medications, let alone the new biologicals. Commonly, disease outcomes are worse in resource-poor areas. Both within and between countries there are avoidable gross disparities in outcomes. Climate change is also bearing down hardest on the poorest children. This review highlights the need for vigorous advocacy for children to improve lifelong health. It also highlights that there are ongoing culturally sensitive interventions to address social determinants of disease which are already benefiting children.

Renal cell carcinoma (RCC), particularly the clear cell subtype (ccRCC), poses a significant global health concern due to its increasing prevalence and resistance to conventional therapies. Early detection of ccRCC remains challenging, resulting in poor patient survival rates. In this study, we employed a bioinformatic approach to identify potential prognostic biomarkers for kidney renal clear cell carcinoma (KIRC). By analyzing RNA sequencing data from the TCGA-KIRC project, differentially expressed genes (DEGs) associated with ccRCC were identified. Pathway analysis utilizing the Qiagen Ingenuity Pathway Analysis (IPA) tool elucidated key pathways and genes involved in ccRCC dysregulation. Prognostic value assessment was conducted through survival analysis, including Cox univariate proportional hazards (PH) modeling and Kaplan–Meier plotting. This analysis unveiled several promising biomarkers, such as MMP9, PIK3R6, IFNG, and PGF, exhibiting significant associations with overall survival and relapse-free survival in ccRCC patients. Cox multivariate PH analysis, considering gene expression and age at diagnosis, further confirmed the prognostic potential of MMP9, IFNG, and PGF genes. These findings enhance our understanding of ccRCC and provide valuable insights into potential prognostic biomarkers that can aid healthcare professionals in risk stratification and treatment decision-making. The study also establishes a foundation for future research, validation, and clinical translation of the identified prognostic biomarkers, paving the way for personalized approaches in the management of KIRC.

Peripheral arterial disease (PAD) affects 12 % of adult population and is increasing globally and in India. Peripheral arterial disease when associated with atherosclerosis in two or more other arterial beds such as coronary artery disease (CAD), mesenteric/renal artery and cerebrovascular disease (CVD), is known as polyvascular disease. The Reduction of Atherothrombosis for Continued Health (REACH) registry reported that 1 out of 6 patients had multi-vascular bed involvement. Progression of PAD to critical limb ischaemia (CLI) is seen in 1 % of affected patients per year, but patients who progress to CLI may have a 10- to 15-fold increased risk of cardiovascular death.The 2019 ECS/EAS guidelines for the management of dyslipidaemias have suggested that for primary or secondary prevention in very high risk, patients should follow a therapeutic regimen that achieves >50 % LDL-C reduction from baseline and an LDL-C goal of

The present study aimed to characterize the atresia of antral follicles of buffalo. Two types of atresia, cystic and obliterative, were observed in the buffalo ovary. The cystic atresia was characterized by complete degeneration of the granulosa cells with the antrum filled with fluid. In obliterative atresia, the granulosa cells degenerated, and the surrounding theca cells started invaginating into the antrum. The ingrowth of these connective tissues filled the antrum. The histological picture of tertiary follicles showed that the atresia occurred in successive stages. The atretic changes observed were pyknosis of granulosa cells, the creation of small spaces between the cells, and the loosening of the cumulus oophorus cells. Two patterns were observed based on the start of atresia, i.e. antral atresia and basal atresia. At places, call-exner bodies were observed in the granulosa cell layer. The collagen fiber-containing basal lamina started separating from the theca layer at locations and later became hypertrophied in the cystic atresia type. In contrast, in the obliterative atresia, the collagen fibers were seen as abundant in growth towards the lumen and later, it filled the whole antral cavity. Disruptions of reticular fibers as stained with Gridley’s stain were observed in the cystic type of atresia, and ingrowth of reticular fibers in the antrum and formation of corpus atreticum were contributed by reticular fibers also.

Psychological co-morbidities are common in chronic obstructive pulmonary disease (COPD) but remain overlooked. Psychosocial interventions are deemed to promote mental health and optimize management. This study aimed to determine the role of detailed psychological evaluation and treatment in the comprehensive management of COPD. COPD patients after screening with the general health questionnaire-12 (GHQ-12) for psychological co-morbidity were divided into three groups (26 patients each): i) group A [GHQ-12 score3, in addition, received management by a psychiatrist and counseling by a pulmonologist, respectively). At baseline and 8 weeks of follow-up, all participants were evaluated for respiratory [forced expiratory volume in the first second (FEV1), six-minute walk distance (6-MWD), St. George's respiratory questionnaire (SGRQ), modified medical research council (mMRC) dyspnea scale], and psychological [GHQ-12, patient distress thermometer (PDT), coping strategy checklist (CSCL), World Health Organization-quality of life-brief (WHOQOL-Bref-26), and depression anxiety stress scales (DASS)] parameters. Psychological distress (GHQ-12>3) decreased significantly at follow-up, with 11.5% and 53.8% of patients having psychological distress in groups B and C, respectively, versus baseline (p

Abstract Background The filamentous fungus Rasamsonia emersonii has immense potential to produce biorefinery relevant thermostable cellulase and hemicellulase enzymes using lignocellulosic biomass. Previously in our lab, a hyper-cellulase producing strain of R. emersonii was developed through classical breeding and system biology approaches. ACE1, a pivotal transcription factor in fungi, plays a crucial role in negatively regulating the expression of cellulase genes. In order to identify the role of ACE1 in cellulase production and to further improve the lignocellulolytic enzyme production in R. emersonii, CRISPR/Cas9 mediated disruption of ACE1 gene was employed. Results A gene-edited ∆ACE1 strain (GN11) was created, that showed 21.97, 20.70 and 24.63, 9.42, 18.12%, improved endoglucanase, cellobiohydrolase (CBHI), β-glucosidase, FPase, and xylanase, activities, respectively, as compared to parental strain M36. The transcriptional profiling showed that the expression of global regulator (XlnR) and different CAZymes genes including endoglucanases, cellobiohydrolase, β-xylosidase, xylanase, β-glucosidase and lytic polysaccharide mono-oxygenases (LPMOs) were significantly enhanced, suggesting critical roles of ACE1 in negatively regulating the expression of various key genes associated with cellulase production in R. emersonii. Whereas, the disruption of ACE1 significantly down-regulated the expression of CreA repressor gene as also evidenced by 2-deoxyglucose (2-DG) resistance phenotype exhibited by edited strain GN11 as well as appreciably higher constitutive production of cellulases in the presence of glucose and mixture of glucose and disaccharide (MGDs) both in batch and flask fed batch mode of culturing. Furthermore, ∆ACE1 strains were evaluated for the hydrolysis of biorefinery relevant steam/acid pretreated unwashed rice straw slurry (Praj Industries Ltd; 15% substrate loading rate) and were found to be significantly superior when compared to the benchmark enzymes produced by parent strain M36 and Cellic Ctec3. Conclusions Current work uncovers the crucial role of ACE1 in regulating the expression of the various cellulase genes and carbon catabolite repression mechanism in R. emersonii. This study represents the first successful report of utilizing CRISPR/Cas9 genome editing technology to disrupt the ACE1 gene in the thermophlic fungus R. emersonii. The improved methodologies presented in this work might be applied to other commercially important fungal strains for which genetic manipulation tools are limited.

Abstract Rome IV bowel disorders of gut brain interaction (DGBI) and non-alcoholic fatty liver disease (NAFLD) are highly prevalent entities with overlapping pathophysiology and risk factors. We aimed to evaluate the prevalence and burden of Rome IV irritable bowel syndrome (IBS) in patients with NAFLD. Patients diagnosed with NAFLD were recruited from a specialist liver clinic. All participants completed assessments to determine liver fibrosis severity, including liver stiffness measurement (LSM), completed the Rome IV diagnostic questionnaire for bowel disorders of gut brain interaction, the IBS symptom severity score (IBS-SSS), and the EQ-5D-5L to measure of quality-of-life (QoL). 142 patients with NAFLD (71 (50%) female, mean age 53.5 (SD ± 14.9), BMI 35.2 (SD ± 8.1) kg/M2) were recruited. 79 (55.6%) patients met criteria for a Rome IV bowel DGBI, including 50 patients (35.2%) who met the criteria for IBS (mean IBS-SSS 277.2 (SD ± 131.5)). There was no difference in liver fibrosis scores between those with and without Rome IV IBS (FIB-4 scores p = 0.14, LSM p = 0.68). Patients with NAFLD and Rome IV IBS had significantly worse QoL scores (EQ-VAS p = 0.005 and EQ-5D-5L index p = 0.0007), impairment of usual activities of daily living (p = 0.012) and were more likely to report anxiety or depression (p = 0.038). Rome IV bowel DGBI such as IBS are highly prevalent in patients with NAFLD attending liver clinics and are associated with impaired QoL and psychosocial distress.

Objectives. This study aimed to report clinical outcomes of patients with vaginal melanoma (VaM) or vulvar melanoma (VuM) who were treated with immune checkpoint inhibitors (ICI) and discuss the development of immune-related adverse events (irAE). Materials and Methods. This is a retrospective case series of patients diagnosed with VaM or VuM between July 2011 and September 2022 at the University of Virginia, Emily Couric Clinical Cancer Center. Patient demographics, disease characteristics, treatment outcomes, and adverse events were abstracted. The primary outcome was incidence of irAE. Results. Eight patients were included in this study, four with VaM and four with VuM. Most (n = 6) had local or regional disease at first presentation, and 25% (n = 2) presented with distant metastasis. All patients received a CTLA-4 inhibitor and 75% (n = 6) received PD-1 inhibitor alone or in combination with a CTLA-4 inhibitor. Most (75%, n = 6) patients experienced irAE. Of those who had irAE, 83% (n = 5) required therapy interruption or discontinuation. Most (66%, n = 4) underwent ICI rechallenge of which 75% (n = 3) experienced subsequent irAE. Of all patients in the series, 75% of patients (n = 6) had partial or complete response to ICI. Conclusion. This series is the first to detail incidence of irAEs and ICI rechallenges in vulvovaginal melanoma. Our findings indicate that while ICIs are effective, their use is associated with significant irAE development. Rechallenge of ICI after irAE is feasible but associated with risk of recurrent/new irAE. Further studies are needed to better quantify this risk.

In this research endeavor, we sought to enhance the efficacy of bamboo fibers through modification with the surfactant cetyltrimethylammonium bromide (CTAB) for the purpose of removing Reactive Blue 235 from effluent. Our investigation encompassed a comprehensive exploration of the impact of crucial parameters, namely, adsorbent dosage (0.25 g–1.25 g), contact time (10–80 min), pH (2–12), initial dye concentration (20–100 mg/L), and temperature (298 K, 308 K, and 318 K) on the dynamics of dye removal. The optimum dye removal efficiency of 94% for Reactive Blue 235 was obtained at an adsorbent dosage of 0.5 g/50 ml of dye solution, initial dye concentration of 40 mg/L, pH of 6, and contact time of 40 min. The experimental framework included the anticipation of data aligned with various isothermal and kinetic models, facilitating a nuanced understanding of the adsorption process. Our findings unveiled that the kinetics of adsorption adhered to a second-order model, while the Langmuir isotherm model aptly described the adsorption behavior. Particularly noteworthy was the monolayer’s adsorption capacity, quantified at an impressive 7.39 mg·g−1 at a temperature of 318 K. The value of Freundlich’s constant, KF, increases with an increase in temperature indicating the endothermic nature of adsorption. The magnitude of E obtained from Dubinin–Radushkevich isotherm varying from 3.92 to 4.66 kJ/mol on increasing temperature from 298 K to 318 K suggests that adsorption of RB235 on BAT is a physisorption (value of E is between 1 and 8 kJ/mol). Delving into the thermodynamic aspects of the process, we calculated ΔH and ΔS to be 54.88 kJ/mol and 184.54 J/mol/K, respectively. The consistently negative values of ΔG (between −0.183 kJ/mol and −3.884 kJ/mol) at all temperatures underscored the feasibility, spontaneity, and entropy-driven nature of the adsorption of RB235 on CTAB-treated bamboo fiber (BAT). What sets our study apart is the deliberate utilization of bamboo fibers sourced from local waste streams, embodying a commitment to sustainable practices. Beyond its effectiveness in effluent treatment, our approach aligns with eco-friendly principles by repurposing indigenous waste materials, contributing to a more sustainable and environmentally responsible future.

In this paper, the Parseval K-g-frames are constructed from a given K-g-frame by scaling the elements of the K-g-frame with the help of diagonal operators, and these frames are named scalable K-g-frames. Also, we prove some properties of scalable K-g-frames and construct new scalable K-g-frames from a given K-g-frame. The necessary and sufficient conditions for a K-g-frame to be scalable are given. Further, equivalent conditions for the scalability of K-g-frames and the K-frames induced by K-g-frames are obtained. Finally, it is shown that the direct sum of two scalable K-g-frames is again a scalable K-g-frame for some suitable bounded linear operator K.

Liquid-liquid phase separation plays a crucial role in cellular physiology, as it leads to the formation of membrane-less organelles in response to various internal stimuli, contributing to various cellular functions. However, the influence of exogenous stimuli on this process in the context of disease intervention remains unexplored. In this current investigation, we explore the impact of doxorubicin on the abnormal self-assembly of p53 using a combination of biophysical and imaging techniques. Additionally, we shed light on the potential mechanisms behind chemoresistance in cancer cells carrying mutant p53.Our findings reveal that doxorubicin co-localizes with both wild-type p53 (WTp53) and its mutant variants. Our in vitro experiments indicate that doxorubicin interacts with the N-terminal-deleted form of WTp53 (WTp53ΔNterm), inducing liquid-liquid phase separation, ultimately leading to protein aggregation. Notably, the p53 variants at the R273 position exhibit a propensity for phase separation even in the absence of doxorubicin, highlighting the destabilizing effects of point mutations at this position.The strong interaction between doxorubicin and p53 variants, along with its localization within the protein condensates, provides a potential explanation for the development of chemotherapy resistance. Collectively, our cellular and in vitro studies emphasize the role of exogenous agents in driving phase separation-mediated p53 aggregation.

Gross and ultrasonographic studies were conducted on the mammary gland of goat (n=18 for each study) during pre-pubertal, lactating and non-lactating stages. Mammary gland was located into the inguinal region and divided into two halves by mammary groove which was prominent during lactation stage. Each halve had separate glandular body and conical teat divisible into tip, mid and base regions. The mammary gland contained numerous lactiferous ducts which opened into the gland sinus that continued distally as teat sinus and teat canal. The gland sinus and teat sinus were separated from each other by annular folds, which were more prominent in lactating animals. At the junction of teat sinus and teat canal, small mucosal elevation was observed as Furstenberg’s rosette. Teat wall was lined by skin, teat internal mucosal layer and teat sinus from outside to inside. Ultrasonographic observations showed that the lactating mammary gland contained an echogenic structure of variable size indicating gland sinus, lactiferous ducts, blood vessels, glandular parenchyma, while the homogenous echogenic component depicting more connective tissue stroma in non-lactating and pre-pubertal goat. The teat wall was made up of innermost hyperechogenic layer (teat mucosa), middle hypoechogenic (fibromuscular) layer and mild hyperechogenic teat skin. Teat sinus was anechogenic, however teat canal was demarcated by hyperechogenic streak. Biometrical and ultrasonographic observations were recorded on teat canal length, maximum diameter of teat, maximum teat wall thickness. Present study showed that there was no significant difference in biometric and ultrasonographic measurements of goat teat. Therefore, it may be concluded that the gross and ultrasonographic observations may be used to diagnose any abnormality in the udder during clinical examination.

Objective: Despite demonstrating improvements in cardiovascular disease, kidney disease, and survival outcomes, guideline-directed antihyperglycemic medications such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like-peptide-1 receptor agonists (GLP1-RA), are underutilized. Many obstacles constrain their use including lack of systematic provider and patient education, concern for medication side effects, and patient affordability. Methods: We designed a multimodality, systems-based approach to address these challenges with the goal of increasing medication utilization across the largest healthcare system in New York State. This multispecialty collaborative included provider and patient education, an electronic health record-enabled platform to identify eligible patients, and access to pharmacists for medication guidance and addressing insurance coverage barriers. Surveys were administered following grand rounds lectures and knowledge-based questionnaires were given before and after case-based sessions for housestaff, with results analyzed using a two-sided Student's t-test. Rates of first prescriptions of SGLT2i/GLP1-RA in combined and individual analyses were compared between the pre- and post-education periods (6 months prior to 3/31/2021 and 6 months post 8/19/2021), and the change in prescriptions per 100 eligible-visits was assessed using the incidence density approach. Results: Among grand rounds participants, 69.3% of respondents said they would make changes to their clinical practice. Knowledge increased by 14.7% (p-value

On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a pandemic. According to the findings of various studies conducted around the world, the serological response varies greatly among different populations, with the determinants of variable response still unknown, including the role of disease severity, which is thought to have a definite correlation. The purpose of this study was to assess serial SARS-CoV-2 IgG antibody response in COVID-19 patients and correlate it with disease severity. It was a longitudinal observational study in which 45 patients (age >18 yrs), were enrolled who had recovered from COVID-19 and were reporting to the post-COVID Care OPD Clinic. Patients who had been on long-term immunosuppressive therapy prior to SARS-CoV-2 infection were not eligible. All patients had not been immunized against SARS-CoV-2 and had no history of contact with recent COVID-19 cases. The patients underwent serial blood tests to determine serum IgG titers specific for SARS-CoV-2 at 30, 60, and 90 days after being diagnosed with COVID-19. Chemiluminescence was used to perform a semi-quantitative evaluation of the SARS-CoV-2 IgG antibody. At 30 days after confirmed SARS-CoV-2 infection, 98.78% had detectable serum IgG levels, and sero-reversion (loss of previously detectable antibodies) occurred in 2.5% at 60 days and 90 days. Serum IgG was found to peak at 30 days out of the three time points of measurement (30, 60, and 90 days from diagnosis). Serum IgG levels at 90 days were significantly lower than those at 30 days (p

Background & aims: Cystic Fibrosis related liver disease (CFLD) is the 3rd largest cause of death in Cystic Fibrosis (CF). As advances in pulmonary therapies have increased life-expectancy, CFLD has become more prevalent. Current guidelines may underdiagnose liver fibrosis, particularly in its early stages. Newer modalities for the assessment of fibrosis may provide a more accurate assessment. FibroScan is validated in assessing fibrosis for several aetiologies including alcohol and fatty liver, the CFLD cohort have an entirely different phenotype so the cut off values are not transferrable. We appraised fibrosis assessment tools to improve diagnosis of CFLD. Methods: A prospective cohort (n = 114) of patients from the Manchester Adult Cystic Fibrosis Centre, UK were identified at annual assessment. Demographic data including co-morbidity, CFTR genotyping, biochemistry and imaging were used alongside current guidelines to group into CFLD and CF without evidence of liver disease. All patients underwent liver stiffness measurement (LSM) and assessment of serum-based fibrosis biomarker panels. A new diagnostic criterion was created and validated in a second, independent cohort. Results: 12 of 114 patient classified as CFLD according to the European Cystic Fibrosis Society best practice guidelines. No specific risk factors for development of CFLD were identified. Liver enzymes were elevated in patients with CFLD. Serum biomarker panels did not improve diagnostic criteria. LSM accurately predicted CFLD. A new diagnostic criterion was proposed and validated in a separate cohort, accurately predicating CFLD in 10 of 32 patients (31 %). Conclusion: We present a cohort of patients with CF assessed for the presence of liver fibrosis using blood biomarkers and LSM based platforms. We propose a new, simplified diagnostic criteria, capable of accurately predicting liver disease in patients with CF.Clinical trials number: NCT04277819

Summary: Myofibroblasts are responsible for scarring during fibrosis. The scar propagates mechanical signals inducing a radical transformation in myofibroblast cell state and increasing profibrotic phenotype. Here, we show mechanical stress from progressive scarring induces nuclear softening and de-repression of heterochromatin. The parallel loss of H3K9Me3 enables a permissive state for distinct chromatin accessibility and profibrotic gene regulation. Integrating chromatin accessibility profiles with RNA expression provides insight into the transcription network underlying the switch in profibrotic myofibroblast states, emphasizing mechanoadaptive regulation of PAK1 as key drivers. Through genetic manipulation in liver and lung fibrosis, loss of PAK1-dependent signaling impairs the mechanoadaptive response in vitro and dramatically improves fibrosis in vivo. Moreover, we provide human validation for mechanisms underpinning PAK1-mediated mechanotransduction in liver and lung fibrosis. Collectively, these observations provide insight into the nuclear mechanics driving the profibrotic chromatin landscape in fibrosis, highlighting actomyosin-dependent mechanisms as potential therapeutic targets in fibrosis.

Inflammation is a distinguished clinical manifestation of COVID-19 and type 2 diabetes mellitus (T2DM), often associated with inflammatory dysfunctions, insulin resistance, metabolic dysregulation, and other complications. The present study aims to test the hypothesis that serum concentrations of PAR-1 levels differ between COVID-19 diabetic patients (T2DM) and non-diabetic COVID-19 patients and determine their association with different biochemical parameters and inflammatory biomarkers. T2DM patients with COVID-19 (n = 50) with glycated hemoglobin (HbA1c) levels of (9.23 ± 1.66) and non-diabetic COVID-19 patients (n = 50) with HbA1c levels (4.39 ± 0.57) were recruited in this study. The serum PAR-1 levels (ELISA method) were determined in both groups and correlated with parameters such as age, BMI, inflammatory markers including CRP, interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), D-dimer, homocysteine, and N-terminal pro–B-type natriuretic peptide (NT-proBNP). Demographic variables such as BMI (29.21 ± 3.52 vs. controls 21.30 ± 2.11) and HbA1c (9.23 ± 1.66 vs. controls 4.39 ± 0.57) were found to be statistically elevated in COVID-19 T2DM patients compared to non-diabetic COVID-19 patients. The concentrations of several inflammatory biomarkers and PAR-1 were remarkably increased in the COVID-19 T2DM group when compared with the non-diabetic COVID-19 group. The univariate analysis revealed that increased serum PAR-1 estimations were positively correlated with enhanced HbA1c, BMI, inflammatory cytokines, D-dimer, homocysteine, and NT-proBNP. The findings in the current study suggest that increased levels of serum PAR-1 in the bloodstream could potentially serve as an independent biomarker of inflammation in COVID-19 patients with T2DM.

Frequent imaging manifestations of pulmonary tuberculosis are airspace or interstitial nodules with or without tree-in-bud nodules, consolidation, cavitation, ground glass opacity, miliary nodules, lymphadenopathy and pleural effusion. It is unusual to encounter cystic changes in patients with pulmonary tuberculosis, and these findings should be differentiated from other cystic lung diseases. This case series describes five cases of cystic lung disease in children with tuberculosis (TB) with illustrative chest radiography and CT findings. Contribution: The manuscript highlights the need to consider tuberculosis as a possible cause of acquired cystic lung disease in appropriate clinical settings, particularly in endemic regions.

Introduction and Objective: The reported incidence of COVID-related acute limb ischemia (CRALI) ranged from 3.7% to 9.6% in the literature. We report on consolidated data of patients with CRALI from 21 centers across India, which spanned the first two waves of COVID-the period of May 2020 to June 2021. Materials and Methods: Study design: Multicenter study from May 2022 to June 2021. Retrospective analysis of prospectively collected data was done. Inclusion criteria: All patients who presented with signs and symptoms of acute limb ischemia or acute on chronic limb ischemia and who also tested positive for COVID through rapid antigen test or real time polymerase chain reaction. Results: Data for 268 patients from 21 centers across India was available for analysis. 71% were males and 85% were >45 years of age. Majority of patients (n = 191) presented with acute symptoms. Best medical management with antiplatelets and anticoagulants was the only treatment in 34% of patients. Open embolectomy was attempted in 42%, endovascular procedures in 8% and amputation as primary procedure in 14.5%. Higher grades of ischemia were associated with significantly poorer limb salvage, amputation and mortality in the immediate and 14 days follow up (P < 0.001). At 14 days 173 limbs were salvaged (64.5%). Eighty patients underwent amputations (29.8%); 26 of the 80 (32%) were minor amputations (trans-metatarsal and less), so the major amputation rate was 20.1%. Maximum number of deaths were in the group that had undergone medical management (23%), while the least number of deaths were seen in the patients that had undergone some form of intervention, open surgical (2%) or endovascular procedure (4%). Looking at 14-day outcomes, the numbers of deaths in the patients managed with medical methods increased to 30%, open surgical to 7% and endovascular procedures to 8%. Conclusion: CRALI presented both as a primary presentation or developed later during the disease. Early surgical and endovascular interventions in these patients can help in achieving decent limb salvage rates.

Introduction: COVID-19, is a highly contagious disease caused by Novel Corona Virus SARS-Cov-2. After initial infection, most patients recover completely, but in some patients, symptoms may persist for variable duration. This study was planned to evaluate different persistent symptoms of long COVID among the people of Northern India, who had asymptomatic or mild disease during active infection stage. Methods: A cross sectional study was done in Chandigarh, India, during August 2021 to June 2022. A total of 647 recovered COVID-19 patients, who had suffered of COVID almost ≥3 months back were included in the study. A self-designed questionnaire was developed for the survey. Participants were followed up till 3 months. Results: Out of 647 subjects enrolled, 27.5% had some post-COVID symptoms. Among symptomatic, 55.1% were males and 44.9% were females. Post-COVID headache was significantly more common in females. Sleep disturbances and history of pain and pressure that spreads to arms were significantly more common among non-smokers. Sleep disturbances and change of appetite were significantly more common among non-alcohol users. Chest discomfort and change of appetite were found to be significantly more common among non-hypertensive subjects. Symptoms of chest discomfort, sleep disturbances, anxiety, feeling of sadness on daily basis and forgetfulness was significantly more common among subjects without underlying heart disease, while weakness among patients with underlying lung disease. Poor concentration was found to be significantly more common among patients without underlying lung disease and that in the age group 26-50 years, followed by 51-75 years and 76-100 years. Conclusion: This study attempted to assess the prevalence of post COVID complications among the asymptomatic and mild COVID patients. From the clinical point of view, physicians should be aware of the symptoms, signs, and biomarkers present in patients previously affected by COVID-19 to promptly assess, identify and halt long COVID-19 progression, minimize the risk of chronic effects and to re-establish pre-COVID-19 health.

Subcutaneous emphysema and pneumomediastinum are uncommon complications seen in COVID −19 patients that tend to worsen their prognosis. Being a new disease, management of this new complication of this disease is not well defined in the literature. We present a case series of six patients of probable/confirmed COVID who developed pneumomediastinum at varied time intervals from the onset of symptoms. Timely recognition and management led to recovery in all of them. Management done in this case series may help in providing data to formulate treatment guidelines for this potentially fatal disease.

Treatment of latent pulmonary tuberculosis (TB) in the household contacts of TB has been included in the National Tuberculosis Elimination Program (NTEP) to achieve the target of TB elimination of Govt of India by 2025. However, there are no clear estimates of the prevalence of latent TB among the contacts that could suggest the impact of this intervention. The study was conducted to find the prevalence of and factors predicting latent TB among household contacts of pulmonary TB. All microbiological confirmed pulmonary TB patients registered between January 2020 to July 2021 and their household contacts were enrolled. All contacts underwent Mantoux testing to find the prevalence of latent TB. All symptomatic patients also underwent CXR and sputum examination to diagnose active pulmonary TB. Thereafter different demographic and clinical factors were evaluated to find predictors of latent TB using logistic regression model. A total of 118 pulmonary TB cases and their 330 household contacts were enrolled. The prevalence of latent TB and active TB among the contacts was found to be 26.36% and 3.03% respectively. The female gender of index TB cases was independently associated with a high proportion of latent TB cases in the family. (aOR-2.32; 95%CI-1.07-5.05; p=0.03). Neither the higher sputum smear positivity nor the severity of chest radiograph of index TB cases had any association with the number of contacts being diagnosed as latent TB or active TB. The results showed a significant prevalence of latent TB among household contacts with pulmonary TB. The severity of the disease in the index patient had no association with the prevalence of latent TB.

Abstract Preclinical pharmacokinetic (PK) studies in animal models during the formulation development phase give preliminary evidence and near clear picture of the PK behavior of drug and/or its dosage forms before clinical studies on humans and help in the tailoring of the dosage form according to the expected and requisite clinical behavior. The present work reports a first of its kind preclinical PK study on extended-release (ER) solid oral dosage forms of venlafaxine (VEN) in New Zealand White rabbits. The VEN is a highly prescribed and one of the safest and most effective therapeutic agents used in the treatment of different types of depression disorders worldwide. The multiple-reaction monitoring (MRM) LC–MS/MS method developed for this purpose demonstrated enough reliability in simultaneously quantitating VEN and its equipotent metabolite O-desmethylvenlafaxine (ODV) in rabbit plasma. The method described uses solid-phase extraction for sample preparation followed by an ultrafast LC–MS/MS analysis. The chromatographic separation was achieved isocratically with a predominantly polar mobile phase by employing RPLC. The triple quadrupole LC/MS/MS system operated in MRM mode used an ESI probe as an ion source in positive polarity. The validation results are within the permissible limits of US FDA recommendations and acceptance criteria for bioanalytical method validation.

Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, pose a significant global health challenge, emphasizing the need for novel neuroprotective agents. Basil (Ocimum spp.) has been recognized for its therapeutic potential, and numerous studies have reported neuroprotective effects. In this manuscript, we present a computational protocol to extricate the underlying mechanism of action of basil compounds in neuroprotective effects. Molecular docking-based investigation of the chemical interactions between selected bioactive compounds from basil and key neuroprotective targets, including AChE, GSK3β, γ-secretase, and sirtuin2. Our results demonstrate that basil compound myricerone caffeoyl ester possesses a high affinity of −10.01 and −8.85 kcal/mol against GSK3β and γ-secretase, respectively, indicating their potential in modulating various neurobiological processes. Additionally, molecular dynamics simulations were performed to explore the protein–ligand complexes’ stability and to analyze the bound basil compounds’ dynamic behavior. This comprehensive computational investigation enlightens the putative mechanistic basis for the neuroprotective effects of basil compounds, providing a rationale for their therapeutic use in neurodegenerative disorders after further experimental validation.

Alzheimer’s disease (AD) is caused by plaque agglomeration and entanglement in several areas of the neural cells, which leads to apoptosis. The main etiology of AD is senile dementia, which is linked to amyloid-beta (Aβ) deregulation and tau perivascular pathogeny. Hyperphosphorylated tau has a propensity for microtubules, which elevate the instability and tau-protein congregates, leading to accumulation of neurofibrillary tangles (NFTs). Tau hyperphosphorylation is susceptible to GSK-3, which has led to an emerging hypothesis regarding the pathogenesis of AD. Accordingly, attempts have been made to conduct investigations and achieve further advancements on new analogues capable of inhibiting the GSK-3 protein, which are currently in the clinical trials. In this analysis, we have evaluated certain GSK-3 inhibitor variants utilising scaffolding and framework devised techniques with pharmacological characteristics, accompanied by computational screenings (pharmacokinetics and docking). The structure-based designed analogues interacted effectively with the active amino acids of GSK-3β target protein. The in silico pharmacokinetic studies revealed their drug-like properties. The analogues with best interactions and binding scores will be considered in the future to completely demonstrate their potential relevance as viable GSK-3 inhibitors.

Aim: The study aims to test the hypothesis that concentrations of adropin and afamin differ between patients in various stages of chronic kidney disease when compared with healthy controls. The study also investigates the association of the biomarkers (adropin and afamin) with CKD-MBD and traditional cardiovascular risk parameters in CKD patients. Methodology: The cross-sectional study includes the subjects divided into four groups comprising the control group (healthy volunteers = 50), CKD stages 1–2 patients (n = 50), CKD stages 3–4 patients (n = 50), CKD stage 5 patients (n = 50). Serum concentrations of adropin and afamin were determined using ELISA. Clinical variables (renal, lipid, and CKD-MBD parameters) were correlated to adropin and afamin concentrations. Results: Afamin concentration was found to be higher in group IV, followed by groups III and II when compared to the control group, i.e., (83.243 ± 1.46, 64.233 ± 0.99, and 28.948 ± 0.72 vs. 14.476 ± 0.5) mg/L (p < 0.001), and adropin concentration was found to be lower in group IV as compared to groups III, II, and I (200.342 ± 8.37 vs. 284.682 ± 9.89 vs. 413.208 ± 12.32 vs. 706.542 ± 11.32) pg/mL (p < 0.001), respectively. Pearson correlation analysis showed that afamin was positively correlated with traditional cardiovascular risk biomarkers, while adropin showed a negative correlation. Conclusions: Adropin and afamin may potentially serve as futuristic predictors for the deterioration of renal function and may be involved in the pathological mechanisms of CKD and its associated complications such as CKD-MBD and high lipid levels.

No drug on the market, as a single entity, participates in different pathways involved in the pathology of Alzheimer’s disease. The current study is aimed at the exploration of multifunctional chalcone derivatives which can act on multiple targets involved in Alzheimer’s disease. A series of novel aminoethyl-substituted chalcones have been developed using in silico approaches (scaffold morphing, molecular docking, and ADME) and reported synthetic methods. The synthesized analogs were characterized and evaluated biologically using different in vitro assays against AChE, AGEs, and radical formation. Among all compounds, compound PS-10 was found to have potent AChE inhibitory activity (IC50 = 15.3 nM), even more than the standard drug (IC50 = 15.68 nM). Further, the in vivo evaluation of PS-10 against STZ-induced dementia in rats showed memory improvement (Morris Water Maze test) in rats. Also, PS-10 inhibited STZ-induced brain AChE activity and oxidative stress, further strengthening the observed in vitro effects. Further, the molecular dynamic simulation studies displayed the stability of the PS-10 and AChE complex. The novel aminoethyl-substituted chalcones might be considered potential multifunctional anti-Alzheimer’s molecules.

Alzheimer’s disease (AD) is the prime cause of 65–80% of dementia cases and is caused by plaque and tangle deposition in the brain neurons leading to brain cell degeneration. β-secretase (BACE-1) is a key enzyme responsible for depositing extracellular plaques made of β-amyloid protein. Therefore, efforts are being applied to develop novel BACE-1 enzyme inhibitors to halt plaque build-up. In our study, we analyzed some Elenbecestat analogues (a BACE-1 inhibitor currently in clinical trials) using a structure-based drug design and scaffold morphing approach to achieve a superior therapeutic profile, followed by in silico studies, including molecular docking and pharmacokinetics methodologies. Among all the designed compounds, SB306 and SB12 showed good interactions with the catalytic dyad motifs (Asp228 and Asp32) of the BACE-1 enzyme with drug-likeliness properties and a high degree of thermodynamic stability confirmed by the molecular dynamic and stability of the simulated system indicating the inhibitory nature of the SB306 and SB12 on BACE 1.