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Background: Clinical trials and registry studies are essential for advancing research and developing novel treatments. However, these studies rely on manual entry of thousands of variables for each patient. Repurposing real-world data can significantly simplify the data collection, reduce transcription errors, and make the data entry process more efficient, consistent, and cost-effective., Methods: We developed an open-source computational pipeline to collect laboratory and medication information from the electronic health record (EHR) data and populate case report forms. The pipeline was developed and validated with data from two independent pediatric hospitals in the US as part of the Long-terM OUtcomes after Multisystem Inflammatory Syndrome In Children (MUSIC) study. Our pipeline allowed the completion of two of the most time-consuming forms. We compared automatically extracted results with manually entered values in one hospital and applied the pipeline to a second hospital, where the output served as the primary data source for case report forms., Findings: We extracted and populated 51,845 laboratory and 4913 medication values for 159 patients in two hospitals participating in a prospective pediatric study. We evaluated pipeline performance against data for 104 patients manually entered by clinicians in one of the hospitals. The highest concordance was found during patient hospitalization, with 91.59% of the automatically extracted laboratory and medication values corresponding with the manually entered values. In addition to the successfully populated values, we identified an additional 13,396 laboratory and 567 medication values of interest for the study., Interpretation: The automatic data entry of laboratory and medication values during admission is feasible and has a high concordance with the manually entered data. By implementing this proof of concept, we demonstrate the quality of automatic data extraction and highlight the potential of secondary use of EHR data to advance medical science by improving data entry efficiency and expediting clinical research., Funding: NIH Grant 1OT3HL147154-01, U24HL135691, UG1HL135685., Competing Interests: Declaration of interests The authors declare no competing interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The canonical K ir 6.2/SUR2A ventricular K ATP channel is highly ATP-sensitive and remains closed under normal physiological conditions. These channels activate only when prolonged metabolic compromise causes significant ATP depletion and then shortens the action potential to reduce contractile activity. Pharmacological activation of K ATP channels is cardioprotective, but physiologically, it is difficult to understand how these channels protect the heart if they only open under extreme metabolic stress. The presence of a second K ATP channel population could help explain this. Here, we characterise the biophysical and pharmacological behaviours of a constitutively active K ir 6.1-containing K ATP channel in ventricular cardiomyocytes., Experimental Approach: Patch-clamp recordings from rat ventricular myocytes in combination with well-defined pharmacological modulators was used to characterise these newly identified K + channels. Action potential recording, calcium (Fluo-4) fluorescence measurements and video edge detection of contractile function were used to assess functional consequences of channel modulation., Key Results: Our data show a ventricular K + conductance whose biophysical characteristics and response to pharmacological modulation were consistent with K ir 6.1-containing channels. These K ir 6.1-containing channels lack the ATP-sensitivity of the canonical channels and are constitutively active., Conclusion and Implications: We conclude there are two functionally distinct populations of ventricular K ATP channels: constitutively active K ir 6.1-containing channels that play an important role in fine-tuning the action potential and K ir 6.2/SUR2A channels that activate with prolonged ischaemia to impart late-stage protection against catastrophic ATP depletion. Further research is required to determine whether K ir 6.1 is an overlooked target in Comprehensive in vitro Proarrhythmia Assay (CiPA) cardiac safety screens., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Introduction: The implant-supported prosthetic treatment strategy is commonly chosen in modern dentistry to address tooth loss caused by a variety of conditions or dental defects. To achieve healthy and natural-looking results in implant dentistry, it is essential to replicate the peri-implant soft tissue. The gingival tissue that surrounds implants is quite accurately replicated by gingival masks. They facilitate more accurate prosthesis restoration design, enhance periodontal health, and promote oral cleanliness. Furthermore, gingival masks allow for the accurate observation of superstructure seating on implant analogs, which is essential for creating superstructures that fit perfectly., Aim and Objective:  To evaluate the change in tear strength and tensile strength of three different gingival mask materials (esthetic mask auto mix, Gi-Mask and Gingifast Rigid) available in the market at various time intervals., Materials and Methods: Total of 540 specimens were fabricated with 180 samples of each group. Changes in tensile strength and tear strength of three different gingival mask materials (esthetic mask auto mix, Gi-Mask and Gingifast Rigid) at intervals of one day, three days, and seven days were measured by a universal testing machine. Statistical analysis was done using one-way ANOVA and Tukey Post Hoc test. We also performed correlation and regression analyses on tear and tensile strength., Results: The null hypothesis, which is supported by these data, claims that there is no discernible variation in the tear strength and tensile strength of three distinct materials across various time intervals. Thus, the null hypothesis was rejected, and it was concluded that there was a significant change in the tear strength and tensile strength of these gingival mask materials at different time intervals. Esthetic mask auto mix has a high tear strength compared to Gi-Mask and gingifast rigid. Gi-Mask has the least tear strength among all three. Tensile strength decreases as time increases, but the Esthetic mask auto mix has high strength compared to Gi-Mask and gingifast rigid., Conclusion: Selecting the right material for gingival masks is essential, taking into account the clinical scenario and the articulation time. Time influences gingival mask materials' tear strength and tensile strength, which impacts their performance and durability. Esthetic mask auto mix has a high tear and tensile strength compared to Gi-Mask and gingifast rigid., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Raval et al.)

Few studies examining the patient outcomes of concurrent neurological manifestations during acute COVID-19 leveraged multinational cohorts of adults and children or distinguished between central and peripheral nervous system (CNS vs. PNS) involvement. Using a federated multinational network in which local clinicians and informatics experts curated the electronic health records data, we evaluated the risk of prolonged hospitalization and mortality in hospitalized COVID-19 patients from 21 healthcare systems across 7 countries. For adults, we used a federated learning approach whereby we ran Cox proportional hazard models locally at each healthcare system and performed a meta-analysis on the aggregated results to estimate the overall risk of adverse outcomes across our geographically diverse populations. For children, we reported descriptive statistics separately due to their low frequency of neurological involvement and poor outcomes. Among the 106,229 hospitalized COVID-19 patients (104,031 patients ≥18 years; 2,198 patients <18 years, January 2020-October 2021), 15,101 (14%) had at least one CNS diagnosis, while 2,788 (3%) had at least one PNS diagnosis. After controlling for demographics and pre-existing conditions, adults with CNS involvement had longer hospital stay (11 versus 6 days) and greater risk of (Hazard Ratio = 1.78) and faster time to death (12 versus 24 days) than patients with no neurological condition (NNC) during acute COVID-19 hospitalization. Adults with PNS involvement also had longer hospital stay but lower risk of mortality than the NNC group. Although children had a low frequency of neurological involvement during COVID-19 hospitalization, a substantially higher proportion of children with CNS involvement died compared to those with NNC (6% vs 1%). Overall, patients with concurrent CNS manifestation during acute COVID-19 hospitalization faced greater risks for adverse clinical outcomes than patients without any neurological diagnosis. Our global informatics framework using a federated approach (versus a centralized data collection approach) has utility for clinical discovery beyond COVID-19., Competing Interests: All authors report no competing interests or conflicts of interest. JGK reports a consulting relationship with the i2b2-tranSMART Foundation through Invocate, Inc. RB reports being a shareholder of Biomeris s.r.l. and Engenome s.r.l. DAH reports entitled to royalties from the University of Michigan for licensing of the EMERSE "synonyms". AM’s work is being funded by the Federal Ministry of Education and Research (BMBF) in Germany in the framework of the MIRACUM Consortium. AM reports being a shareholder of Biomeris s.r.l. BM reports being co-founder and equity owner from DESKI. DLM has received research support from the National Institutes of Health, Department of Veteran Affairs, and the University of Pittsburgh/Pittsburgh Health Data Alliance outside of this work. PA reports consulting for CCHMC and BCH. NG is a co-founder and equity owner of Datavisyn. ZX has served as a Consultant for Genentech/Roche. The institution of ZX has received research support from the National Institute of Health, the National Multiple Sclerosis Society, Food and Drug Administration, the Pittsburgh Foundation, the PNC Charitable Trust, the Ethel Vincent Trust, and Genentech / Roche., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Thyroid dysfunction is a widespread and complex issue in the field of endocrine disorders. It has a significant impact on multiple physiological systems, particularly on the heart. This review explores the complex interaction between thyroid dysfunction and cardiac dynamics, examining the detailed network of molecular, cellular, and systemic changes that underlie the close connection between these two physiological areas. Thyroid dysfunction, which includes both hyperthyroidism and hypothyroidism, is a common endocrine condition that affects millions of people worldwide. The thyroid hormones thyroxine and triiodothyronine regulate various metabolic activities essential for maintaining cellular balance. Disruptions in thyroid function result in widespread consequences, affecting the cardiovascular system. Thyroid hormones directly impact cardiac muscle cells, controlling their ability to contract, their electrical properties, and their reaction to hypertrophy. Thyroid dysfunction goes beyond the level of individual cells and involves complex interactions among vascular dynamics, neurohormonal control, and endothelial function. These factors all contribute to the development of cardiovascular illness. The impact of thyroid dysfunction on cardiac structure, function, and outcomes is not limited to a one-way pattern. Instead, it involves a dynamic two-way interaction. The manifestations of this condition can vary from minor changes in the electrical activity of the heart to more obvious structural abnormalities, such as an increase in the size of the heart muscle and a decrease in its ability to relax during the filling phase. Furthermore, the correlation between thyroid dysfunction and adverse cardiovascular outcomes, such as heart failure and arrhythmias, highlights the clinical importance of this connection. This review provides a complete overview of the relationship between thyroid dysfunction and cardiac dynamics by analyzing a wide range of research from clinical, molecular, and epidemiological perspectives. This study seeks to enhance our comprehension of the comprehensive effects of thyroid dysfunction on the anatomy and function of the heart by explaining the complex molecular mechanisms and systemic consequences. The goal is to establish a basis for informed clinical treatment and future research efforts., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Olanrewaju et al.)

Topic modeling aims to discover latent themes in collections of text documents. It has various applications across fields such as sociology, opinion analysis, and media studies. In such areas, it is essential to have easily interpretable, diverse, and coherent topics. An efficient topic modeling technique should accurately identify flat and hierarchical topics, especially useful in disciplines where topics can be logically arranged into a tree format. In this paper, we propose Community Topic, a novel algorithm that exploits word co-occurrence networks to mine communities and produces topics. We also evaluate the proposed approach using several metrics and compare it with usual baselines, confirming its good performances. Community Topic enables quick identification of flat topics and topic hierarchy, facilitating the on-demand exploration of sub- and super-topics. It also obtains good results on datasets in different languages., (© The Author(s) 2024.)

In spite of recent advances made in understanding its progression, cancer is still a leading cause of death across the nations. Molecular pathophysiology of these cancer cells largely differs depending on cancer types and even within the same tumor. Pathological mineralization/calcification is seen in various tissues including breast, prostate, and lung cancer. Osteoblast-like cells derived after trans-differentiation of mesenchymal cells usually drive calcium deposition in various tissues. This study aims to explore the presence of osteoblast-like potential in lung cancer cells and its prevention. ALP assay, ALP staining, nodule formation, RT-PCR, RT-qPCR, and western blot analysis experiments were carried out in lung cancer A549 cells to achieve said objective. Expressions of various osteoblast markers (e.g., ALP, OPN, RUNX2, and Osterix) along with osteoinducer genes (BMP-2 and BMP-4) were observed in A549 cells. Moreover, ALP activity and ability leading to nodule formation revealed the presence of osteoblast-like potential in lung cancer cells. Here, BMP-2 treatment increased expressions of osteoblast transcription factors such as RUNX2 and Osterix, enhanced ALP activity, and augmented calcification in this cell line. It was also observed that antidiabetic metformin inhibited BMP-2 mediated increase in osteoblast-like potential and calcification in these cancer cells. The current study noted that metformin blocked BMP-2 mediated increase in epithelial to mesenchymal transition (EMT) in A549 cells. The above findings for the first time unravel that A549 cells possess osteoblast-like potential which drives lung cancer calcification. Metformin might prevent BMP-2 induced osteoblast-like phenotype of the lung cancer cells with concomitant inhibition of EMT to inhibit lung cancer tissue calcification., (© 2023 Wiley Periodicals LLC.)

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras., Methods: We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites., Findings: Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES -1.18 years [95% CI -2.05, -0.32]), had fewer respiratory symptoms (RD -0.15 [95% CI -0.33, -0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD -0.35 [95% CI -0.64, -0.07]), lower lymphocyte count (ES -0.16 × 10 9 /uL [95% CI -0.30, -0.01]), lower C-reactive protein (ES -28.5 mg/L [95% CI -46.3, -10.7]), and lower troponin (ES -0.14 ng/mL [95% CI -0.26, -0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES -1.6 years [95% CI -2.5, -0.8]), had less frequent SIRS (RD -0.18 [95% CI -0.30, -0.05]), lower lymphocyte count (ES -0.39 × 10 9 /uL [95% CI -0.52, -0.25]), lower troponin (ES -0.16 ng/mL [95% CI -0.30, -0.01]) and less frequently received anticoagulation therapy (RD -0.19 [95% CI -0.37, -0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (-1.3 days [95% CI -2.3, -0.4])., Interpretation: Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time., Funding: None., Competing Interests: The authors have no conflicts of interests to declare related to the content of this manuscript. JNW has research grant funding from National Heart, Lung, and Blood Institute (NHLBI), the Department of Defense, the Centres for Disease Control (CDC), and Pfizer; has been a consultant for Pfizer; chaired the Independent Events Adjudication Committees for Novartis, Pfizer, and Bristol-Myer-Squibb; and received honoraria from Daiichi Sankyo for service on the Steering Committee of the ENNOBLE-ATE Trial and from UpToDate. GSO has research grant funding from the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), and from the National Cancer Institute (NCI). DAH has research grant funding from the National Center for Advancing Translational Sciences (NCATS). TGG has research grant funding from the Institute of Health Carlos III, the European Regional Development Fund (ERDF), the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), and National Cancer Institute (NCI). KFK has research grant funding from the National Institute of Child Health and Human Development (NIHCD). SEM has research grant funding from the National Center for Advancing Translational Sciences (NCATS). AD has research grant funding from Pfizer. DMT has research grant funding from NIH. AMS has research grant funding from the National Heart, Lung, and Blood Institute (NHLBI) and from the National Center for Advancing Translational Sciences (NCATS). GV has internal research funding from the Centre Hospitalier Universitaire de Bordeaux. ZX has research grant funding from the National Institute of Neurological Disorders and Stroke (NINDS). None of these funding sources had any role in supporting the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. All the other authors have no conflicts of interests to declare., (© 2023 The Authors.)

Objective: To explore the efficacy of ultrasonography as an additional diagnostic tool in superficial odontogenic fascial space infections of maxillofacial region and modifying the treatment plan when needed., Materials and Methods: Forty patients with superficial fascial space infections underwent a detailed clinical, plain radiological and ultrasonographic examination. Based on the ultrasonographic findings, final diagnosis was made and compared with clinical findings. Patients diagnosed with cellulitis were given medical line of treatment, and those with abscess were subjected to incision and drainage along with standard general supportive care and removal of etiologic agent., Results: In this study, out of 40 patients (male = 22, female = 18), clinical diagnosis of cellulitis was made in 26 cases (65%) and abscess in 14 (35.0%). On USG examination, cellulitis was present in 21 cases (52.5%), while abscess in 19 (47.5%). Final diagnosis of cellulitis was made in 13 (59.1%) males and 12(66.7%) females, while abscess was confirmed in 9 (40.9%) male and 6 (33.3%) female patients. The results showed that sensitivity of the clinical examination alone was 64% with 33% specificity, and for USG, sensitivity was 84% with specificity of 100%., Conclusion: The adjuvant role of ultrasonography in the diagnosis and timely management of superficial fascial space infections is promising owing to its accessibility, relative safety, repeatability and cost-effectiveness., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Association of Oral and Maxillofacial Surgeons of India 2021.)

Hyperglycaemia at the time of myocardial infarction has an adverse effect on prognosis irrespective of a prior diagnosis of diabetes, suggesting glucose is the damaging factor. In ex vivo models of ischaemia, we demonstrated that deleterious effects of acutely elevated glucose are PKCα/β-dependent, and providing PKCα/β are inhibited, elevated glucose confers cardioprotection. Short pre-treatments with high glucose were used to investigate time-dependent glucose cardiotoxicity, with PKCα/β inhibition investigated as a potential mechanism to reverse the toxicity. Freshly isolated non-diabetic rat cardiomyocytes were exposed to elevated glucose to investigate the time-dependence toxic effects. High glucose challenge for >7.5 min was cardiotoxic, proarrhythmic and lead to contractile failure, whilst cardiomyocytes exposed to metabolic inhibition following 5-min high glucose, displayed a time-dependent protection lasting ∼15 min. This protection was further enhanced with PKCα/β inhibition. Cardioprotection was measured as a delay in contractile failure and K ATP channel activation, improved contractile and Ca 2+ transient recovery and increased cell survival. Finally, the effects of pre-ischaemic treatment with high glucose in a whole-heart coronary ligation protocol, where protection was evident with PKCα/β inhibition. Selective PKCα/β inhibition enhances protection suggesting glycaemic control with PKC inhibition as a potential cardioprotective therapeutics in myocardial infarction and elective cardiac surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Brennan, Esposito, Abdelaziz, Martin, Makwana, Sims, Squire, Sharma, Chadwick and Rainbow.)

Background and objective Pleural effusion develops when there is disequilibrium between pleural fluid formation and absorption. Light's criteria are currently used to differentiate transudative from exudative effusion. If the pleural effusion is exudative, it requires extensive diagnostic workup to identify the local cause of the effusion. Pleural fluid cell count and differentials, glucose level, adenosine deaminase (ADA), fluid GeneXpert for Mycobacterium tuberculosis (MTb), fluid culture, and cytology are currently used for further evaluation of exudative pleural effusions. However, the sensitivity and specificity of the above tests are not dependable. The pleural fluid C-reactive protein (CRP) is likely to reflect serum CRP levels because the CRP in the pleural fluid may be caused by increased diffusion from the blood due to inflamed capillary leakage. In this study, we aimed to examine the role of pleural fluid CRP levels in the differential diagnosis of exudative effusion. Materials and methods Based on Light's criteria, this study included 100 patients with exudative pleural effusion. Serum CRP and pleural fluid CRP were assessed with the CRP-Turbilatex-quantitative turbidometric immunoassay method based on the principle of an agglutination reaction. Receiver operating characteristic (ROC) curves were generated by plotting sensitivity against 1-specificity, and the area under the curve (AUC) with a 95% confidence interval (CI) was calculated. After data collection, statistical analysis was performed using SPSS Statistics v28.0 (IBM, Armonk, NY). Results Our study showed a significant difference in pleural fluid CRP levels (p<0.001). Pleural fluid CRP was significantly higher in the empyema and parapneumonic groups compared to tuberculous and malignant effusions. The optimal cut-off value of CRP ≥47.4 mg/dl yielded 87.5% sensitivity and 92.5% specificity in differentiating parapneumonic effusion from tuberculous effusion. Pleural fluid CRP proved to be an excellent marker for distinguishing parapneumonic effusion from malignancy (cut-off value ≥49.2 mg/dl, 75% sensitivity, and 85.7% specificity) and parapneumonic plus empyema from tuberculous effusion plus malignant effusion (cut-off value ≥47.4 mg/dl, 84.6% sensitivity, and 90.8% specificity). Conclusion Pleural fluid CRP levels can be used as an additional tool in the differential diagnosis of exudative effusion. It significantly differentiates parapneumonic effusion and empyema from tuberculous and malignant effusions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Makwana et al.)

Introduction Although chronic obstructive pulmonary disease (COPD) is preventable and treatable, it is a major public health problem. The mortality risks are higher in patients with exacerbations. Magnesium (Mg) is crucial in numerous physiological processes, including membrane stabilization. However, incomplete information is available regarding the effect of magnesium on the frequency of acute exacerbation of COPD. Objectives To determine the serum magnesium level in COPD patients and its correlation with acute exacerbation of COPD. Materials and methods This cross-sectional study included 100 patients diagnosed with acute exacerbation of COPD. The serum magnesium level was measured in all patients with acute exacerbation of COPD at admission. Serum Mg level <1.7 mg/dl was considered hypomagnesemia. The correlation between serum magnesium level and duration of hospital stay and patient outcome was studied.  Results In the present study, hypomagnesemia was reported in 57% of patients with acute exacerbation of COPD. The duration of hospital stay (more than seven days) among hypomagnesemia (80.7%) patients was significantly higher than that of the normomagnesemia patients (55.8%). Mortality in patients with hypomagnesemia was higher than in patients with normomagnesemia, although not statistically significant. Conclusion Hypomagnesaemia is a common finding in acute exacerbation of COPD. The level of magnesium found is related to the length of hospital stay, but it is not related to mortality among patients with acute exacerbation of COPD. Further studies with larger sample sizes and extended follow-up periods are required to validate the results., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Makwana et al.)

Simvastatin is an established anti-hyperlipidemic drug and few studies have indicated its role in the mitigation of oxidative stress. However, a systematic study considering molecular binding/interaction of simvastatin with anti-oxidant enzymes followed by confirmational in vitro and in vivo studies have never been done. We investigated the molecular binding of simvastatin with multiple anti-oxidant enzymes and assessed their levels after the treatment of simvastatin in vitro and in vivo . This study is the first to show the molecular binding of simvastatin to catalase through molecular docking analysis. Moreover, the anti-oxidative properties of simvastatin have not been studied in Lipopolysaccharide (LPS) induced oxidative stress in HepG2 cells. We found that simvastatin effectively attenuated oxidative stress in LPS induced HepG2 cells and high-fat diet (HFD) fed hyperlipidemic rats by increasing the levels of antioxidant enzymes. The activity of catalase and superoxide dismutase (SOD) both increased significantly in oxidatively stressed HepG2 cells after the treatment with simvastatin (10 ​μM, 24 ​h). In addition to this, he original cell morphology of oxidatively stressed cells was restored by simvastatin, and an increase in antioxidant enzymes, catalase (0.08 U/cells to 0.12 U/cells), and SOD (0.57 U/cells to 0.74 U/cells) was also noted in HepG2 cells. Furthermore, a significant increase in the antioxidant enzymes such as Catalase, SOD, and reduced glutathione (GSH) was noted after simvastatin treatment in the HFD model. Moreover, we also observed degradation of by-products of lipid peroxidation thiobarbituric acid reactive substances (TBARs), nitric oxide (NO), and protein carbonyl levels. This indicates that simvastatin enhances anti-oxidant enzyme activities and can be repurposed for the treatment of oxidative stress in liver diseases in humans after extensive clinical trials., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V.)

Endometriosis is a debilitating gynecologic disorder that affects ∼10% of women of reproductive age. Endometriosis is characterized by growth of endometriosis lesions within the abdominal cavity, generally thought to arise from retrograde menstruation of shed endometrial tissue. While the pathophysiology underlying peritoneal endometriosis lesion formation is still unclear, the interaction between invading endometrial tissue and the peritoneal mesothelial lining is an essential step in lesion formation. In this study, we assessed proteomic differences between eutopic endometrial stromal cells (ESCs) from women with and without endometriosis in response to peritoneal mesothelial cell (PMC) exposure, using single-cell cytometry by time-of-flight (CyTOF). Co-cultured primary eutopic ESCs from women with and without endometriosis with an established PMC line were subjected to immunostaining with a panel of Maxpar CyTOF metal-conjugated antibodies (n = 28) targeting cell junction and mesenchymal markers, which are involved in cell-cell adhesions and epithelial-mesenchymal transition. Exposure of the ESCs to PMCs resulted in a drastic shift in cellular expression profiles in ESCs derived from endometriosis, whereas little effect by PMCs was observed in ESCs from non-endometriosis subjects. The transcription factor SNAI1 was consistently repressed by PMC interactions. ESCs from endometriosis patients are unique in that they respond to PMCs by undergoing changes in adhesive properties and mesenchymal characteristics that would facilitate lesion formation., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Tobacco use is one of the main causes of periodontitis. E-cigarette are gaining in popularity, and studies are needed to better understand the impact of e-cigarettes on oral health. Objective: To perform a longitudinal study to evaluate the adverse effects of e-cigarettes on periodontal health. Methods: Naïve E-cigarette users, cigarette smokers, and non-smokers were recruited using newspaper and social media. Age, gender, and ethnicity, were recorded. Participants were scheduled for two visits 6 months apart. At each visit, we collected data on the frequency and magnitude of e-cigarette and cigarette use, and alcohol consumption. Carbon monoxide (CO) levels, cotinine levels, salivary flow rate, periodontal probing depth (PD), bleeding on probing (BoP), and clinical attachment loss (CAL) were also determined at both baseline and follow-up visits and compared between groups with two-way repeated measures ANOVA. Periodontal diagnosis and other categorical variables were compared between groups with the chi-square statistic and logistic regression. Results: We screened 159 subjects and recruited 119 subjects. One-hundred-one subjects (31 cigarette smokers, 32 e-cigarette smokers, and 38 non-smokers) completed every assessment in both visits. The retention and compliance rate of subjects was 84.9%. The use of social media and craigslist was significant in recruiting e-cigarette subjects. Ethnicity and race differed between groups, as did average age in the male subjects. Carbon monoxide and salivary cotinine levels were highest among cigarette smokers. Bleeding on probing and average PDs similarly increased over time in all three groups, but CAL uniquely increased in e-cigarette smokers. Rates of severe periodontal disease were higher in cigarette smokers and e-cigarette users than non-smokers, but interpretation is confounded by the older age of the cigarette smokers. Conclusion: Among the recruited participants, CAL after 6 months was significantly worse only in the e-cigarette smokers. This study design and protocol will assist in future larger studies on e-cigarette and oral health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xu, Aboseria, Janal, Pushalkar, Bederoff, Vasconcelos, Sapru, Paul, Queiroz, Makwana, Solarewicz, Guo, Aguallo, Gomez, Shelly, Aphinyanaphongs, Gordon, Corby, Kamer, Li and Saxena.)

Background and Aims: Modern psychiatry brings tremendous value to the treatment of mental illness, however, at times is inadequate in providing holistic care within a patient's broader cultural framework. Traditional healing and modern psychiatry together offer a comprehensive, patient-centred approach to treatment, which encompass a patient's spiritual and religious beliefs. In this context, "Dava-Dua" intervention-combination of psychiatric medicine and faith healing-is implemented by the Government of Gujarat at Mira Data Dargah in Mehsana District. The study assesses intervention outcomes, understand implementation challenges and patients' perspectives on the treatment., Methods: Using a multi-method research approach, case records from July 2008 to March 2018 were retrieved for secondary analysis of patients' profile and outcomes; 26 patients from three groups: Dava, Dua and Dava-Dua; and 6 mental health service providers were interviewed to assess perspectives of patients and service providers on mental health, implementation barriers and facilitators., Results: Despite some implementation challenges, the findings indicate that collaboration of modern psychiatry medicine and faith-based treatment practices certainly benefit patients with otherwise limited access to mental health care thereby protects human rights of patients., Conclusion: Dava-Dua model compliments existing primary healthcare services. It provides an access to modern medicine without compromising patients' religious and spiritual practices. It has the potential to scale-up and replicate where faith-healing is the prime treatment modality to cure mental illness provided implementation challenges are proactively addressed., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Family Medicine and Primary Care.)

Introduction: Aragvadhadi Taila (ART) is one of the herbomineral formulations mentioned in Chakradatta indicated in Shwitra (vitiligo). Modification of Taila form into gel form reduces the risk of contamination in view of arsenical contents ( Manahshila , Haratala ) assures precise dose administration at desired site (by avoiding spreading). The gel is a comparatively acceptable dosage form than that of medicated oil., Aim: The aim of the study is to evaluate the comparative efficacy of Aragvadhadi formulation in Taila (ART: Aragvadhadi Taila ) and gel (ARG: Aragvadhadi gel) dosage forms with the internal administration of Rasayana Churna in the management of Shwitra ., Materials and Methods: The study was a randomized open labeled, involving 66 patients of Shwitra that were randomly divided into two groups. Patients registered in group A ( n = 34) were treated with local applications of ART and group B ( n = 32) with ARG for 2 months. Rasayana Churna (3 g), along with the equal quantity of honey and Ghrita was given twice a day after the meal in both groups. Wilcoxon signed-rank test was applied to evaluate the effect of therapy in the individual group for subjective criteria like vitiligo area scoring index score, size and number of patches, Rukshata (dryness), Saparidaha (burning sensation), Bahalatva (thickening), Kandu (itching) while the comparison of results between the groups for the same by applying Coefficient of Variation (CV)., Results: Group B showed better and consistent results in all signs and symptoms except Rukshata, Saparidaha in terms of Coefficient of Variation. In both the groups, statistically highly significant improvement was found in signs and symptoms of Shwitra such as Saparidaha, Kandu , size of patches and number of patches; however, the difference between the groups was statistically insignificant., Conclusion: Both the forms (ART, ARG) of Aragvadhadi formulation along with Rasayana Churna were found as a safe and effective treatment in vitiligo with significant pigment regeneration capacity as topical use for application over 2 months., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 AYU (An International Quarterly Journal of Research in Ayurveda).)

Background: Psoralea corylifolia Linn. ( P . Corylifolia L.), frequently familiar as Bakuchi in Samskrit, is an endangered and medicinally important plant. Its medicinal usage is reported in Indian pharmaceutical codex, the Chinese, British and the American Pharmacopoeia, and in different traditional systems of medicines such as Ayurveda, Unani and Siddha. However, no scientifically pharmacognosy study has been reported on leaf, root, and stem part of P . Corylifolia L. Classics emphasized the use of leaf, root and stem of P . Corylifolia L. for on the management of dental carries, diarrhea , dysentery, etc., in the form of local application as well as internal administration., Aim: The aim of this study was to evaluate comparative pharmacognosy, phytochemical studies, and physicochemical analysis of leaf, root and stem of P . Corylifolia L., Materials and Methods: Studies of leaf, root, stem, and their powder for phytochemical tests, histochemical tests, psoralen chemical test, and physicochemical analysis were performed by standard methods., Result: All the different parts of the plant exhibit oleoresin and other cellular contents, i.e., vessels fibers, lignified pitted vessels, etc., in pharmacognosy studies. In phytochemical study; observations indicate that coumarins, steroids, and flavonoids are present in leaf, stem, and root samples. Basified alcoholic extracts of powders of all test samples showed yellowish color of fluorescence at 366 nm whereas none of the samples showed any color at 254 nm during chemical test of psoralen., Conclusion: Pharmacognostical study on leaf, root and stem of Bakuchi ( P. corylifolia L.) contributed Certain pharmacognostical parameters i.e; oleoresin, vascular bundles, parenchyma cells with rhomboidal crystals, pericyclic fibres etc parameters that will be applicable for authentication and identification of the parts of drug. There is a need to focus on the preliminary throughput phytochemical screening of plants for their probable use in therapeutics. As no published evidences are developed on comparative pharmacognosy and preliminary physicochemical analysis of leaf, root and stem of P. corylifolia L. plant, the results documented in the present study may be used as a standard in subsequent studies. These observations can be of use for further research studies., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 AYU (An International Quarterly Journal of Research in Ayurveda).)

Introduction: Foremost, Rasamanikya is described in Rasendra Chintamani by Acharya Dhundhuknath. It is a formulation that is prepared from the arsenical drug, i.e., orpiment ( Haratala ). Haratala is classified under Uparasa Varga in Rasa classics and is also included under Schedule E1 in D and C act 1940. In classics, there are so many media mentioned for purification process ( Shodhana ) of orpiment. In the present study, Kushmanda Swarasa (juice of Benincasa hispida [Thunb.] Cogn) and Churnodaka (lime water) are adopted as the purification media for orpiment., Aim: The aim of this study was to standardize the pharmaceutical procedure of Rasamanikya and develop a comparative analytical profile of both the formulation, i.e., Rasamanikya prepared by Kushmanda Swarasa and Churnodaka Shodhita Haratala ., Materials and Methods: The study was carried out in two stages as follows: Shodhana of Haratala and preparation of Rasamanikya by Kupipakwa method. Both the samples of Rasamanikya were analyzed for organoleptic and physicochemical parameters. The samples of final products were also analyzed through sophisticated analytical parameters, i.e., X-ray diffraction (XRD), Inductively coupled plasma-atomic emission spectroscopy (ICP-AES), CHNS and O, Field emission gun-scanning electron microscopy (FEG-SEM), Fourier transform infrared spectroscopy (FTIR) and Thermo-gravimetric analysis (TGA)., Results: Average 2 h duration was required for the preparation of Rasamanikya formulation from 600 g of purified orpiment. In XRD analysis, both samples have different diffraction patterns. In ICP-AES analysis, both samples have the same percentage of arsenic. More percentage loss was noted in the TGA of Rasamanikya prepared with Churnodaka Shodhita Haratala than that of Kushmanda Swarasa Shodhita Haratala ., Conclusion: Rasamanikya prepared by two different media of Shodhita Haratala did not found to have a substantial difference in pharmaceutical procedure. However, there was a considerable difference in the analytical study. Kupipakwa procedure can be used for large-scale preparation., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 AYU (An International Quarterly Journal of Research in Ayurveda).)

The trend of e-cigarette use among teens is ever increasing. Here we show the dysbiotic oral microbial ecology in e-cigarette users influencing the local host immune environment compared with non-smoker controls and cigarette smokers. Using 16S rRNA high-throughput sequencing, we evaluated 119 human participants, 40 in each of the three cohorts, and found significantly altered beta-diversity in e-cigarette users (p = 0.006) when compared with never smokers or tobacco cigarette smokers. The abundance of Porphyromonas and Veillonella (p = 0.008) was higher among vapers. Interleukin (IL)-6 and IL-1β were highly elevated in e-cigarette users when compared with non-users. Epithelial cell-exposed e-cigarette aerosols were more susceptible for infection. In vitro infection model of premalignant Leuk-1 and malignant cell lines exposed to e-cigarette aerosol and challenged by Porphyromonas gingivalis and Fusobacterium nucleatum resulted in elevated inflammatory response. Our findings for the first time demonstrate that e-cigarette users are more prone to infection., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Psychosocial rehabilitation is the process that facilitates opportunities for persons with chronic mental illness to reach their optimal level of independent functioning in society and for improving their quality of life. However, such psychosocial rehabilitation centers are limited in India., Aims: The present study assesses psychosocial rehabilitation centers (of urban day-care and rural residential rehabilitation center) operated by Ashadeep Charitable Foundation, a civil service organization and its effect on health outcomes of patients living with chronic mental illness., Materials and Methods: Records of 170 cases were retrieved for secondary analysis of demographic information, diagnosis, duration of stay, and health outcomes., Results: Rehabilitation activities included yoga, light physical exercises, group discussion, training for daily living skills, social skills, life skills, vocational training, individual, and family counseling. In addition, extensive outreach activities, mental health camps were also integral part of the rehabilitation activities. Patients who have accessed rehabilitation services were diagnosed with schizophrenia, psychosis, bipolar disorder, depression, and intellectual disability. The average duration of rehabilitation of patients (other than persons with intellectual disability) was ranged from three to four months. Out of those rehabilitated, 69% of them were successfully re-integrated with the family., Conclusion: Combination of pharmacological and psychosocial interventions are effective for re-integrate patients with mental illness to the family. This model of community-based rehabilitation has potential for scale-up., Competing Interests: There are no conflicts of interest., (Copyright: © Journal of Family Medicine and Primary Care.)

Key Points: Acute hyperglycaemia at the time of a heart attack worsens the outcome for the patient. Acute hyperglycaemia is not limited to diabetic patients and can be due to a stress response in non-diabetics. This study suggests that the damaging cardiac effects of hyperglycaemia can be reversed by selective PKC inhibition. If PKCα/β isoforms are inhibited, then high glucose itself becomes protective against ischaemic damage. Selective PKC inhibition may therefore be a useful therapeutic tool to limit the damage that can occur during a heart attack by stress-induced hyperglycaemia., Abstract: Hyperglycaemia has a powerful association with adverse prognosis for patients with acute coronary syndromes (ACS). Previous work shows that high glucose prevents ischaemic preconditioning and causes electrical and mechanical disruption via protein kinase C α/β (PKCα/β) activation. The present study aimed to: (i) determine whether the adverse clinical association of hyperglycaemia in ACS can be replicated in preclinical cellular models of ACS and (ii) determine the importance of PKCα/β activation to the deleterious effect of glucose. Freshly isolated rat, guinea pig or rabbit cardiomyocytes were exposed to simulated ischaemia after incubation in the presence of normal (5 mm) or high (20 mm) glucose in the absence or presence of small molecule or tat-peptide-linked PKCαβ inhibitors. In each of the four conditions, the following hallmarks of cardioprotection were recorded using electrophysiology or fluorescence imaging: cardiomyocyte contraction and survival, action potential stability and time to failure, intracellular calcium and ATP, mitochondrial depolarization, ischaemia-sensitive leak current, and time to K ir 6.2 opening. High glucose alone resulted in decreased cardiomyocyte contraction and survival; however, it also imparted cardioprotection in the presence of PKCα/β inhibitors. This cardioprotective phenotype displayed improvements in all of the measured parameters and decreased myocardium damage during whole heart coronary ligation experiments. High glucose is deleterious to cellular and whole-heart models of simulated ischaemia, in keeping with the clinical association of hyperglycaemia with an adverse outcome in ACS. PKCαβ inhibition revealed high glucose to show a cardioprotective phenotype in this setting. The results of the present study suggest the potential for the therapeutic application of PKCαβ inhibition in ACS associated with hyperglycaemia., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

Objectives: The study aims to understand the process and factors influencing the implementation of structured oral examination (SOE) for undergraduate medical students; in comparison with conventional oral examination (COE) in pharmacology., Methods: In a randomized, parallel group study, 123 students of pharmacology were divided into two groups, SOE (n = 63) and COE (n = 60). Students of each group were subdivided into two, and four examiners took viva voce individually. Three sets of questionnaires from autonomic nervous system were prepared, each having 15 items with increasing difficulty levels and were validated by subject experts and pretested. Ten minutes were allotted for each student for each viva. Feedback of students and faculty about the novel method was obtained., Results: SOE yielded significantly lower marks as compared to COE. There were significant inter-examiner variations in marks awarded in SOE and COE. Other factors influencing implementation were difficulty in structuring viva, rigid time limits, lack of flexibility in knowledge content, monotony, and fatigue. The students perceived this format not different from COE but felt that it required in-depth preparation of topic. Faculty opined that SOE led to less drift from main topic and provided uniform coverage of topics in given time., Conclusion: Conducting SOE is a resource-intensive exercise. Despite structuring, inter-examiner variability was not completely eliminated. The students' performance was depended on factors related to examiners such as teaching experience, vernacular language used, and lack of training. Orientation and training of examiners in assessment strategies is necessary. Standardization of questionnaire is necessary before the implementation of SOE for summative assessment.

The ultimate goal of this study was developing antimicrobial food-contact materials based on natural phenolic compounds using nanotechnological approaches. Among the methyl-β-cyclodextrin-encapsulated phenolics tested, curcumin showed by far the highest activity toward Escherichia coli with a minimum inhibitory concentration of 0.4 mM. Curcumin was enclosed in liposome-type polydiacetylene/phosholipid nanovesicles supplemented with N-hydroxysuccinimide and glucose. The fluorescence spectrum of the nanovesicles suggested that curcumin was located in their bilayer region. Free-suspended nanovesicles tended to bind to the bacterial surface and demonstrated bactericidal activity toward Gram-negative (E. coli) and vegetative cells of Gram-positive (Bacillus cereus) bacteria reducing their counts from 5 log CFU mL(-1) to an undetectable level within 8 h. The nanovesicles were covalently bound to silanized glass. Incubation of E. coli and B. cereus with nanovesicle-coated glass resulted in a 2.5 log reduction in their counts. After optimization this approach can be used for controlling microbial growth, cross-contamination, and biofilm formation on food-contacting surfaces.

Purpose: To explore the relationship between degree of rurality and glucose (hemoglobin A1c), blood pressure (BP), and lipid (LDL) control among patients with diabetes., Methods: Descriptive study; 1,649 patients in 205 rural practices in the United States. Patients' residence ZIP codes defined degree of rurality (Rural-Urban Commuting Areas codes). Outcomes were measures of acceptable control (A1c < = 9%, BP < 140/90 mmHg, LDL < 130 mg/dL) and optimal control (A1c < 7%, BP < 130/80 mmHg, LDL < 100 mg/dL). Statistical significance was set at P < .008 (Bonferroni's correction)., Findings: Although the proportion of patients with reasonable A1c control worsened by increasing degree of rurality, the differences were not statistically significant (urban 90%, large rural 88%, small rural 85%, isolated rural 83%; P = .10); mean A1c values also increased by degree of rurality, although not statistically significant (urban 7.2 [SD 1.6], large rural 7.3 [SD 1.7], small rural 7.5 [SD 1.8], isolated rural 7.5 [SD 1.9]; P = .16). We observed no differences between degree of rural and reasonable BP or LDL control (P = .42, P = .23, respectively) or optimal A1c or BP control (P = .52, P = .65, respectively). Optimal and mean LDL values worsened as rurality increased (P = .08, P = .029, respectively)., Conclusions: In patients with diabetes who seek care in the rural Southern United States, we observed no relationship between degree of rurality of patients' residence and traditional measures of quality of care. Further examination of the trends and explanatory factors for relative worsening of metabolic control by increasing degree of rurality is warranted., (© 2012 National Rural Health Association.)

The aim of this investigation was to develop fast dissolving tablet of cinnarizine. A combination of super disintegrants, i.e., sodium starch glycolate (SSG) and crosscarmellose sodium (CCS) were used along with camphor as a subliming material. An optimized concentration of camphor was added to aid the porosity of the tablet. A 3(2) full factorial design was applied to investigate the combined effect of two formulation variables: Amount of SSG and CCS. Infrared (IR) spectroscopy was performed to identify the physicochemical interaction between drug and polymer. IR spectroscopy showed that there is no interaction of drug with polymer. In the present study, direct compression was used to prepare the tablets. The powder mixtures were compressed into tablet using flat face multi punch tablet machine. Camphor was sublimed from the tablet by exposing the tablet to vacuum drier at 60°C for 12 hours. All the formulations were evaluated for their characteristics such as average weight, hardness, wetting time, friability, content uniformity, dispersion time (DT), and dissolution rate. An optimized tablet formulation (F 9) was found to have good hardness of 3.30 ± 0.10 kg/cm(2), wetting time of 42.33 ± 4.04 seconds, DT of 34.67 ± 1.53 seconds, and cumulative drug release of not less than 99% in 16 minutes.

Parenteral administration of pharmaceutical products is one of the most popular methods used to produce quick onset of action and also 100% bioavailability. Main problem occurs with the parenteral drug delivery is lack of convenience, affordability, accuracy, sterility, safety etc. Such drawbacks with this delivery system makes it less preferable. Hence, all the disadvantages of these systems can be easily overcome by use of prefilled syringes. The objective of this review article is to provide information regarding prefilled syringes; it's method of preparation, direction to use, advantages, its future scope, and development.

Aim: To determine whether there was any regional variation in the prevalence of azoospermia, oligozoospermia and mean sperm counts in male partners of infertile couples from different parts of India., Methods: Data on 16,714 semen samples analyzed over the past five years from six different laboratories located in five cities of India were collated and evaluated., Results: There was a regional variation in the prevalence of azoospermia. The prevalence of azoospermia was extremely high in Kurnool and Jodhpur (38.3% and 37.4%, respectively). There was also a regional variation in the prevalence of oligozoospermia (51%) in Kurnool. There was no significant difference in the mean sperm counts in normospermic men., Conclusion: There is a regional variation in the prevalence of azoospermia and oligozoospermia in the male partners of infertile couples from different regions of India. The prevalence of azoospermia in Kurnool and Jodhpur is higher than any other worldwide reported literature. Further studies need to be carried out to determine the cause of this.