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Abstract Inhibiting angiotensin-converting enzyme 1 (ACE1) is a key strategy for managing hypertension as it prevents the formation of angiotensin II, a potent vasoconstrictor. Given the adverse effects associated with synthetic inhibitors, there is an increasing focus on exploring natural bioactive peptides as potential ACE1 inhibitors. Hemopressins (Hp) are peptides derived from hemoglobin. The present study investigated the ACE1 inhibitory activity of two Hp variants, Hp bearing phenylalaine (Hp-F) and Hp bearing leucine (Hp-L), using a combination of in vitro and in silico methodologies. In enzyme inhibition assays, Hp-L variants exhibited better inhibition when compared to Hp-F variants. Furthermore, in molecular docking and molecular dynamics simulations, Hp-L variants displayed favorable binding characteristics, in terms of binding energy and interactions, supporting their potential to be effective ACE1 inhibitors. The peptides were observed to interact with key residues involved in binding widely used ACE1 inhibitors. Notably, peptide RVD-Hp-L (RVDPVNFKLLSH) showed the lowest IC50 value, higher binding affinity and sustained interactions while binding to the catalytic site of ACE1. Finally, the substitution of phenylalanine with leucine in hemopressins significantly enhances their binding affinity and inhibitory potency.

Abstract Background Colombia, which hosts over 3 million of the Venezuelan diaspora, is lauded for its progressive approach to social integration, including providing migrants access to its universal health coverage system. However, barriers to healthcare persist for both migrant and host populations, with poorly understood disparities in healthcare-seeking behaviors and associated costs. This is the first study to link healthcare-seeking behaviors with costs for Venezuelan migrants in Colombia, encompassing costs of missing work or usual activities due to healthcare events. Methods We use self-reported survey data from Venezuelan migrants and Colombians living in Colombia (September-November 2020) to compare healthcare-seeking behaviors and cost variables by nationality using two-sampled t-tests or Chi-square tests (X 2 ). The International Classification of Diseases was used to compare reported household illnesses for both populations. Average health service direct costs were estimated using the Colombian Government’s Suficiencia database and self-reported out-of-pocket (OOP) payments for laboratory and pharmacy services. Indirect costs were calculated by multiplying self-reported days of missed work or usual activities with estimated income levels, derived by matching characteristics using the Gran Enquesta Integrada de Hogares database. We calculate economic burdens for both populations, combining self-reported healthcare-seeking behaviors and estimated healthcare service unit costs across six healthcare-seeking behavior categories. Results Despite similar disease profiles, Venezuelan migrants are 21.3% more likely to forego formal care than Colombians, with 746.3% more Venezuelans reporting lack of health insurance as their primary reason. Venezuelan women and uninsured report the greatest difficulties in accessing health services, with accessing medications becoming more difficult for Venezuelan women during the COVID-19 pandemic. Colombians cost the health system more per treated illness event (US$40) than Venezuelans (US$26) in our sample, over a thirty-day period. Venezuelans incur higher costs for emergency department visits (123.5% more) and laboratory/ pharmacy OOP payments (24.7% more). Conclusions While Colombians and Venezuelans share similar disease burdens, significant differences exist in access, cost, and health-seeking behaviors. Increasing Venezuelan health insurance enrollment and tackling accessibility barriers are crucial for ensuring healthcare equity and effectively integrating the migrant population. Findings suggest that improving migrant access to primary healthcare would produce savings in Colombian healthcare expenditures.

Abstract H-bonded liquid crystals (HBLCs) are newly synthesized with PyBF viz., (4-pyridyl)-benzylidene-4′-fluoro aniline as the proton acceptor which is non-mesogenic and alkyloxy benzoic acids viz., nOBAs (n = 3, 12) as the mesogenic proton donors. The H-bond formed is confirmed by FTIR spectroscopy. Polarizing Optical Microscopy confirmed the H-bonded compound’s mesomorphic textures, and the thermal analysis is carried out using a Differential Scanning Calorimeter. The influence of fluorine atom on mesomorphic stability is studied. The nonlinear optical properties of the H-bonded compound is studied using DFT theoretical approach. This work supports the SDG-9 of the United Nations. Graphical abstract

Introduction: During the Epithelial-mesenchymal Transition (EMT) process, cells undergo a transformation in which they lose their epithelial characteristics and acquire mesenchymal traits. This phenomenon was observed during the metastatic stage of neoplastic disorders, such as cervical cancer. Certain indicators are present during EMT. Aim: To evaluate the role of EMT in utero-cervical carcinoma by analysing the expressions of E-cadherin and vimentin in histopathologically confirmed cases. Materials and Methods: This retrospective cross-sectional study was conducted over a period of two years, from January 1, 2013, to December 31, 2014, at the Department of Pathology in a tertiary care centre and referral hospital. A total of 50 histopathologically confirmed cases of utero-cervical Squamous Cell Carcinoma (SCC) were included in this study. These case were analysed focusing on variables such as age, age at marriage, parity, family history, and hormonal intake. Tumour stages and grades were assessed alongside E-cadherin and vimentin expressions using Immunohistochemistry (IHC). Results were statistically analysed, and the database was created in MS Excel (Version 2007) and analysed using IBM Statistical Package for the Social Sciences (SPSS) Statistics software version 20.0, with significance set at p

Getting around in modern cities has become a daily puzzle for both residents and travelers. As cities increasingly evolve into complex hubs of innovation and development, the demand for efficient transportation solutions has never been higher. In the multifaceted field of urban transportation, cost-effective and efficient mobility remains a high priority. This paper looks at how cities are planning better ways for people to travel and move within the growing scope of multimodal transportation, a paradigm shift beyond traditional single-mode transit systems. Our approach to improving urban transport revolves around a few key principles: integration, innovation, and collaboration. Integration means bringing together different modes of transportation – like buses, trains, bikes, and even new technologies like ride-sharing services to make it easier for people to switch between them. This transformative approach not only aims to reduce congestion and reduce environmental footprints but also prioritizes user experience while ensuring a harmonious blend of convenience, sustainability, and accessibility. We use new technology and ideas to ensure that travel is easy, quick, and good for the environment. Looking at new trends and examples from around the world, this overview shows how cities are shaping a better future for everyone's daily commute. In this paper, we use Lingo software to solve a numerical example related to multi-modal transportation, demonstrating practical solutions for real-world implementation. Through innovation, we can find creative solutions to urban transportation challenges. Additionally, public transportation enhancements, such as the introduction of synchronized bus routes and electric vehicle charging stations, underline the commitment to sustainability and inclusivity. In the dynamic urban transportation landscape, cities will revolutionize our approach to providing cost-effective and efficient mobility solutions.

Abstract Pemphigus represents a spectrum of autoimmune‐mediated blistering diseases associated with high morbidity, mortality and reduced quality of life (QoL). Despite an increase in pemphigus clinical trials, the varied instrument measurements of disease severity and QoL outcomes make comparisons between studies challenging. This study aimed to evaluate trends in the use of disease severity and QoL outcome measurements in pemphigus clinical trials. A review of pemphigus clinical trials was conducted using the PubMed, Embase, Cochrane Reviews and ClinicalTrials.gov databases up until September 2023. Only pemphigus randomized clinical trials that assessed at least one disease severity and/or QoL outcome were included. Overall, 53 clinical trials were eligible for this review. All clinical trials evaluated a disease severity outcome, with the Pemphigus Disease Area Index being the most used validated questionnaire (28.3% of trials) and more popular after 2015 (47.8% of trials since). The autoimmune bullous skin disorder intensity score (7.6%) and visual analogue measurements (7.6%) have fallen out of favour. Most studies now include lab parameters (56.5% of trials after 2015), with anti‐desmoglein 1 and 3 antibody levels (30.2%), immunoglobulins (IgG and/or IgM and IgA) (11.3%), and anti‐drug antibody levels (7.6%) being frequently evaluated. A small portion of trials evaluated QoL (26.5% of studies), with the autoimmune bullous quality of life being the most common (15.1%), however QoL utilization as an outcome measure has been increasing since 2015 (61.1% of trials since). Standardising the use of validated outcome measurements allows for better data interpretation, comparability and clinical application of results.

Abstract Background Monkeypox (Mpox) is an important human pathogen without etiological treatment. A viral-host interactome study may advance our understanding of molecular pathogenesis and lead to the discovery of suitable therapeutic targets. Methods GEO Expression datasets characterizing mRNA profile changes in different host responses to poxviruses were analyzed for shared pathway identification, and then, the Protein–protein interaction (PPI) maps were built. The viral gene expression datasets of Monkeypox virus (MPXV) and Vaccinia virus (VACV) were used to identify the significant viral genes and further investigated for their binding to the library of targeting molecules. Results Infection with MPXV interferes with various cellular pathways, including interleukin and MAPK signaling. While most host differentially expressed genes (DEGs) are predominantly downregulated upon infection, marked enrichments in histone modifiers and immune-related genes were observed. PPI analysis revealed a set of novel virus-specific protein interactions for the genes in the above functional clusters. The viral DEGs exhibited variable expression patterns in three studied cell types: primary human monocytes, primary human fibroblast, and HeLa, resulting in 118 commonly deregulated proteins. Poxvirus proteins C6R derived protein K7 and K7R of MPXV and VACV were prioritized as targets for potential therapeutic interventions based on their histone-regulating and immunosuppressive properties. In the computational docking and Molecular Dynamics (MD) experiments, these proteins were shown to bind the candidate small molecule S3I-201, which was further prioritized for lead development. Results MPXV circumvents cellular antiviral defenses by engaging histone modification and immune evasion strategies. C6R-derived protein K7 binding candidate molecule S3I-201 is a priority promising candidate for treating Mpox.

Amphicrine carcinoma, in which endocrine and epithelial cell constituents are present within the same cell, is very rare. It is different from adenocarcinoma and Mixed Neuroendocrine-Non neuroendocrine neoplasms (MiNEN). In the current World Health Organisation (WHO) classification of gastrointestinal tumours, the only mention of an amphicrine tumour is in the form of Goblet Cell Adenocarcinoma (GCA) in the appendix, which has both neuroendocrine and non neuroendocrine characteristics in the same cell. Authors hereby report the case of a 63-year-old female who presented with complaints of abdominal pain of a six-month duration. Endoscopy showed a polypoidal lesion in the duodenum. Distal radical gastrectomy was done. Microscopy of the lesion showed atypical signet-ring-like cells and goblet-like mucinous cells with fine granular chromatin. On immunohistochemistry, the tumour cells were positive for CK7, synaptophysin, and chromogranin. The cells showed Periodic Acid-Schiff stain (PAS) positive, diastase-resistant material in the cytoplasm. These cells also showed mucicarmine positivity. Considering the biphenotypic nature of tumour cells, the diagnosis of amphicrine carcinoma was given. Amphicrine carcinomas have unique features in histopathology, immunohistochemistry, special stains, and genetic profile.

Abstract Polatuzumab vedotin is a CD79b‐directed antibody–drug conjugate that targets B cells and delivers the cytotoxic payload monomethyl auristatin E (MMAE). The phase III POLARIX study (NCT03274492) evaluated polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R‐CHP) as first‐line treatment of diffuse large B‐cell lymphoma (DLBCL). To examine dosing decisions for this regimen, population pharmacokinetic (popPK) analysis, using a previously developed popPK model, and exposure–response (ER) analysis, were performed. The popPK analysis showed no clinically meaningful relationship between cycle 6 (C6) antibody‐conjugated (acMMAE)/unconjugated MMAE area under the concentration–time curve (AUC) or maximum concentration, and weight, sex, ethnicity, region, mild or moderate renal impairment, mild hepatic impairment, or other patient and disease characteristics. In the ER analysis, C6 acMMAE AUC was significantly associated with longer progression‐free and event‐free survival (both p = 0.01). An increase of

Abstract The recent article by Harit et al. in Human Genomics reported a novel association of the C allele of rs479200 in the human EGLN1 gene with severe COVID-19 in Indian patients. The gene in context is an oxygen-sensor gene whose T allele has been reported to contribute to the inability to cope with hypoxia due to increased expression of the EGLN1 gene and therefore persons with TT genotype of EGLN1 rs479200 are more susceptible to severe manifestations of hypoxia. In contrast to this dogma, Harit et al. showed that the C allele is associated with the worsening of COVID-19 hypoxia without suggesting or even discussing the scientific plausibility of the association. The article also suffers from certain epidemiological, statistical, and mathematical issues that need to be critically elaborated and discussed. In this context, the findings of Harit et al. may be re-evaluated.

Background Recent trials have confirmed the effectiveness of promising dengue control technologies – two vaccines and Wolbachia. These would generally be applied at the municipal level. To help local officials decide which, if any, control strategy to implement, they need affordable, timely, and accurate data on dengue burden. Building on our previous work in Mexico, Indonesia, and Thailand, we developed a streamlined prospective method to estimate dengue burden at the municipal level quickly, accurately, and efficiently. Methods The method entails enrolling and repeatedly interviewing 100 patients with laboratory-confirmed dengue. They will be selected after screening and testing about 1,000 patients with clinical dengue. The method will capture both acute and chronic effects relating to disease, economic burden, and psychological impacts (presenteeism). The total time requirements are 1.5 years, comprised of 0.25 years for planning and approvals, 1 year for data collection (a full dengue cycle), and 0 .25 years for data cleaning and analysis. A collaboration with municipal and academic colleagues in the city of Semarang, Central Java, Indonesia shows how the method could be readily applied in Indonesia’s eighth largest city (population 1.8 million). Conclusions Many surveillance studies gather only information on numbers of cases. This proposed method will provide a comprehensive picture of the dengue burden to the health system, payers, and households at the local level.

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Key Clinical Message Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure associated with pregnancy without any other known cause. With a prognosis that can vary from the complete recovery of left ventricular function to maternal mortality as well as recurrence with subsequent pregnancies, early diagnosis and treatment of PPCM is important in management. Bromocriptine treatment is beneficial effects on LVEF and mortality in women with severe acute PPCM in addition to standard heart failure therapy. However, further study is required to establish its effect in PPCM. Abstract Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure associated with pregnancy without any other known cause. Most of the clinical presentation is similar to symptoms of advanced pregnancy making the diagnosis difficult. Reported are three patients who developed dyspnea, orthopnea, and dry cough during the first week of puerperium. On examination, bilateral lower limb edema and bilateral basal lung crepitation were present in all patients. Chest radiograph showed pulmonary edema in cases two and three, and pleural effusion in case one. All patients had reduced left ventricular ejection fraction and raised N‐terminal pro‐b‐type natriuretic peptide (NT‐proBNP) levels. Case two developed PPCM in the background of left pyelonephritis. Case three was complicated by acute kidney injury. All patients were managed with bromocriptine, diuretics, beta‐blockers, ACE inhibitors, and fluid restriction. Hence, PPCM though rare should be considered as a differential in women presenting with features of heart failure in later months of pregnancy or within 5 months of delivery.

Abstract A study to determine the impact of cyclosporine (Neoral), an inhibitor of P‐gp, on the pharmacokinetics of pralsetinib (trade name GAVRETO®) was conducted in 15 healthy adult volunteers. A single 200 mg dose of pralsetinib was administered orally alone and in combination with cyclosporine with a 9‐day washout between treatments. Co‐administration with cyclosporine resulted in a clinically relevant increase in pralsetinib maximum plasma concentration (Cmax) and area under the plasma concentration–time curve extrapolated to infinity (AUC0–∞) with associated geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of 148% (109, 201) and 181% (136, 241), respectively. These findings provide insight into concomitant dosing of pralsetinib with inhibitors of P‐gp given the increases in pralsetinib exposure observed when administered with cyclosporine. Based on these results, co‐administration of pralsetinib with P‐gp inhibitors is not recommended. In the event that co‐administration cannot be avoided, it is recommended that the dose of pralsetinib be reduced.

Abstract Objectives To describe findings from an otolaryngology‐specific needs assessment tool in Zimbabwe. Methods Surveys were developed and shared with Low‐Middle Income Country (LMIC) hosting institutions in Zimbabwe and to High‐Income Country surgical trip participants (HIC). Respondents were otolaryngologists identified online and through professional networks who had participated in a surgical trip. Results The most common procedures Zimbabwe otolaryngologists reported treating were adenotonsillectomy (85.7%), chronic rhinosinusitis (71.4%), chronic otitis (57.1%), and head and neck tumor intervention (57.1%). The most common untreatable conditions that host physicians wanted to treat were skull base surgery (71.4%), flap reconstructions (57.1%), and laryngotracheal reconstruction (57.1%). The largest discrepancy between host desires and visiting team offerings were flap reconstruction (57.1%), nasal bone deformities (37.1%), and laryngotracheal reconstruction (17.1%). Perceptions of short‐term surgical trips (STST) were recorded for host and visiting teams, and important differences between the public and private sectors of care in Zimbabwe were also identified. Conclusion The surveys utilized in this study served as a bidirectional needs assessment of the requirements and care goals of host institutions and visiting teams in Zimbabwe. Differences between public and private sectors of care, particularly regarding infrastructure, resources, and surgical goals, were revealed, and the results can be utilized as part of efforts to maximize efforts within global surgical partnerships. Level of Evidence VI.

OBJECTIVES:. To evaluate the relationship between early IV fluid volume and hospital outcomes, including death in-hospital or discharge to hospice, in septic patients with and without heart failure (HF). DESIGN:. A retrospective cohort study using logistic regression with restricted cubic splines to assess for nonlinear relationships between fluid volume and outcomes, stratified by HF status and adjusted for propensity to receive a given fluid volume in the first 6 hours. An ICU subgroup analysis was performed. Secondary outcomes of vasopressor use, mechanical ventilation, and length of stay in survivors were assessed. SETTING:. An urban university-based hospital. PATIENTS:. A total of 9613 adult patients were admitted from the emergency department from 2012 to 2021 that met electronic health record-based Sepsis-3 criteria. Preexisting HF diagnosis was identified by the International Classification of Diseases codes. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. There were 1449 admissions from patients with HF. The relationship between fluid volume and death or discharge to hospice was nonlinear in patients without HF, and approximately linear in patients with HF. Receiving 0–15 mL/kg in the first 6 hours was associated with lower likelihood of death or discharge to hospice compared with 30–45 mL/kg (odds ratio = 0.61; 95% CI, 0.41–0.90; p = 0.01) in HF patients, but no significant difference for non-HF patients. A similar pattern was identified in ICU admissions and some secondary outcomes. Volumes larger than 15–30 mL/kg for non-HF patients and 30–45 mL/kg for ICU-admitted non-HF patients were not associated with improved outcomes. CONCLUSIONS:. Early fluid resuscitation showed distinct patterns of potential harm and benefit between patients with and without HF who met Sepsis-3 criteria. Restricted cubic splines analysis highlighted the importance of considering nonlinear fluid outcomes relationships and identified potential points of diminishing returns (15–30 mL/kg across all patients without HF and 30–45 mL/kg when admitted to the ICU). Receiving less than 15 mL/kg was associated with better outcomes in HF patients, suggesting small volumes may be appropriate in select patients. Future studies may benefit from investigating nonlinear fluid–outcome associations and a focus on other conditions like HF.

Abstract Objective Recent clinical guidelines for sepsis management emphasize immediate antibiotic initiation for suspected septic shock. Though hypotension is a high‐risk marker of sepsis severity, prior studies have not considered the precise timing of hypotension in relation to antibiotic initiation and how clinical characteristics and outcomes may differ. Our objective was to evaluate antibiotic initiation in relation to hypotension to characterize differences in sepsis presentation and outcomes in patients with suspected septic shock. Methods Adults presenting to the emergency department (ED) June 2012–December 2018 diagnosed with sepsis (Sepsis‐III electronic health record [EHR] criteria) and hypotension (non‐resolving for ≥30 min, systolic blood pressure 60 min after (“late”) treatment. Results Among 2219 patients, 55% received early treatment, 13% immediate, and 32% late. The late subgroup often presented to the ED with hypotension (median 0 min) but received antibiotics a median of 191 min post‐ED presentation. Clinical characteristics notable for this subgroup included higher prevalence of heart failure and liver disease (p

Summary: Familial Mediterranean fever (FMF) is a periodic fever syndrome caused by variation in MEFV. FMF is known for IL-1β dysregulation, but the innate immune landscape of this disease has not been comprehensively described. Therefore, we studied circulating inflammatory proteins, and the function of monocytes and (albeit less extensively) neutrophils in treated FMF patients in remission. We found that monocyte IL-1β and IL-6 production was enhanced upon stimulation, in concordance with alterations in the plasma inflammatory proteome. We did not observe changes in neutrophil functional assays. Subtle differences in chromatin accessibility and transcriptomics in our small patient cohort further argued for monocyte dysregulation. Together, these observations suggest that the MEFV-mutation-mediated primary immune dysregulation in monocytes leads to chronic inflammation that is subsequently associated with counterregulatory epigenetic/transcriptional changes reminiscent of tolerance. These data increase our understanding of the innate immune changes in FMF, aiding future management of chronic inflammation in these patients.

Abstract This ethnic sensitivity analysis used data from the phase III POLARIX study (NCT03274492) to assess polatuzumab vedotin pharmacokinetics (PKs) in Asian versus non‐Asian patients with previously untreated diffuse large B‐cell lymphoma and examined the appropriateness of extrapolating global study findings to Asian patients. PK and population PK (PopPK) analyses assessed polatuzumab vedotin analyte exposures by ethnicity (Asian [n = 84] vs. non‐Asian [n = 345] patients) and region (patients enrolled from Asia [n = 80] vs. outside Asia [n = 349]). In patients from Asia versus outside Asia, observed mean antibody‐conjugated monomethyl auristatin E (acMMAE) concentrations were comparable (1.2% lower at cycle [C]1 postdose, 4.4% higher at C4 predose; and 6.8% lower at C4 postdose in patients from Asia). Observed mean unconjugated MMAE was lower in patients from Asia by 6.5% (C1 postdose), 20.0% (C4 predose), and 15.3% (C4 postdose). In the PopPK analysis, C6 area under the curve and peak plasma concentrations were also comparable for acMMAE (6.3% and 3.0% lower in Asian vs. non‐Asian patients, respectively) and lower for unconjugated MMAE by 19.1% and 16.7%, respectively. By region, C6 mean acMMAE concentrations were similar, and C6 mean unconjugated MMAE concentrations were lower, in patients enrolled from Asia versus outside Asia, by 3.9%–7.0% and 17.3%–19.7%, respectively. In conclusion, polatuzumab vedotin PKs were similar between Asian and non‐Asian patients by ethnicity and region, suggesting PKs are not sensitive to Asian ethnicity and dose adjustments are not required in Asian patients to maintain efficacy and safety.

Introduction: The transitional stage of a person’s physical and psychological development, known as school age, is strongly related to adolescence. An individual’s oral health significantly impacts their general health and happiness. Oral health is a crucial component of overall well-being and can affect one’s level of self-esteem. Even common dental conditions like dental trauma and untreated caries can have an impact on an individual’s selfesteem, which in turn can affect their quality of life. Aim: To explore the dental problems and self-esteem of schoolage children. Materials and Methods: A cross-sectional study was conducted in selected schools of Mangaluru, Karnataka, India. A total of 86 school children aged between 10 and 15 years were included using a non probability purposive sampling technique. The study duration was eight months, from February 2021 to September 2021. A self-structured rating scale was employed to assess self-esteem, and a self-structured checklist was used to assess dental issues. Survey participants who scored higher than four on the checklist were invited to complete a selfesteem evaluation scale to gain further insights into their dental concerns. Data analysis was performed using the Statistical Package for Social Sciences (SPSS) version 23.0, applying descriptive and inferential statistics to evaluate the collected data. The relationship and association between the concepts were examined using Karl Pearson’s correlation coefficient and the Chi-square test. Results: According to the study’s findings, 75 (87.2%) school children had moderate self-esteem, while 11 (12.8%) had high self-esteem regarding dental issues. The majority of school children, 52 (60.5%), had moderate dental problems, while 23 (26.7%) had severe dental problems, and 11 (12.8%) had very severe dental problems. The results of the study also revealed a significant relationship between school-aged children’s dental issues and their sense of self-worth. The calculated p-values indicate that there was no significant association between selfesteem and demographic data. However, there was a significant association between dental problems and other demographic variables, such as family income per month. Conclusion: Based on the present study’s findings, schoolaged children experienced mild dental issues, and there was a substantial link between these issues and students’ self-esteem. Additionally, the study showed that there was no significant association between self-esteem and demographic data. However, a significant association was found between dental problems and various demographic variables, such as family income per month. Therefore, it is argued that each person’s self-esteem in relation to dental issues may differ.

Abstract Infections and vaccines can induce enhanced long-term responses in innate immune cells, establishing an innate immunological memory termed trained immunity. Here, we show that monocytes with a trained immunity phenotype, due to exposure to the Bacillus Calmette-Guérin (BCG) vaccine, are characterized by an increased biosynthesis of different lipid mediators (LM) derived from long-chain polyunsaturated fatty acids (PUFA). Pharmacological and genetic approaches show that long-chain PUFA synthesis and lipoxygenase-derived LM are essential for the BCG-induced trained immunity responses of human monocytes. Furthermore, products of 12-lipoxygenase activity increase in monocytes of healthy individuals after BCG vaccination. Grasping the underscoring lipid metabolic pathways contributes to our understanding of trained immunity and may help to identify therapeutic tools and targets for the modulation of innate immune responses.

The identification of gas leakages is a significant factor to be taken into consideration in various industries such as coal mines, chemical industries, etc., as well as in residential applications. In order to reduce damage to the environment as well as human lives, early detection and gas type identification are necessary. The main focus of this paper is multimodal gas data that were obtained simultaneously by using multiple sensors for gas detection and a thermal imaging camera. As the reliability and sensitivity of low-cost sensors are less, they are not suitable for gas detection over long distances. In order to overcome the drawbacks of relying just on sensors to identify gases, a thermal camera capable of detecting temperature changes is also used in the collection of the current multimodal dataset The multimodal dataset comprises 6400 samples, including smoke, perfume, a combination of both, and neutral environments. In this paper, convolutional neural networks (CNNs) are trained on thermal image data, utilizing variants such as bidirectional long–short-term memory (Bi-LSTM), dense LSTM, and a fusion of both datasets to effectively classify comma separated value (CSV) data from gas sensors. The dataset can be used as a valuable source for research scholars and system developers to improvise their artificial intelligence (AI) models used for gas leakage detection. Furthermore, in order to ensure the privacy of the client’s data, this paper explores the implementation of federated learning for privacy-protected gas leakage classification, demonstrating comparable accuracy to traditional deep learning approaches.

A line-field confocal optical coherence tomography (LC-OCT) combines confocal microscopy and optical coherence tomography into a single, rapid, easy-to-use device. This meta-analysis was performed to determine the reliability of LC-OCT for diagnosing malignant skin tumors. PubMed, EMBASE, Web of Science databases, and the Cochrane Library were searched for research studies in the English language from inception till December 2023. To assess quality and the risk of bias, the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used. The sensitivity and specificity of each study were calculated. The bivariate summary sensitivity and specificity were calculated using the linear mixed model. Five studies with 904 reported per lesion analyses in our study; the specificity and sensitivity ranged from 67% to 97% and 72% to 92%, respectively. The pooled specificity and sensitivity were 91% (95% CI: 76–97%) and 86.9% (95% CI: 81.8–90.8%), respectively. The summary sensitivity and specificity from the bivariate approach are 86.9% (95% CI: 81.8–90.8%) and 91.1% (95% CI: 76.7–97.0%), respectively. The area under the curve is 0.914. LC-OCT shows great sensitivity and specificity in diagnosing malignant skin tumors. However, due to the limited number of studies included in our meta-analysis, it is premature to elucidate the true potential of LC-OCT.

Background: Public perception regarding the disease and concerns regarding safety and reliability of the new COVID 19 vaccine is the determining factor for acceptance of the vaccine. Objectives: To assess the risk perception of the health science students towards COVID 19 and COVID 19 vaccination. Methodology: A total of 701 health science students from Kasturba Medical College, Mangalore and Manipal College of Dental Sciences, Mangalore were included in this cross-sectional study. Institutional Ethics Committee permission was obtained prior to the commencement of the study. Risk perception towards COVID 19 and COVID 19 vaccination was assessed using Health belief model questionnaire. Data was analysed using IBM SPSS for windows version 25.0, Armonk, New York, 25.0. Results: Among the total participants, a higher proportion (57.6%) of the participants had a strong belief that COVID 19 can cause serious infection and 75.1% had strong belief that COVID 19 vaccine could provide protection against infection. Majority, 62% of the participants had received the 1st dose of vaccine, however, 37.6% had hesitancy. Conclusion: A lower percentage of the study participants had hesitancy towards COVID 19 vaccine. Major reasons for hesitancy were fear of side effects, history of allergic reactions, concern about safety and efficacy of the vaccine.

Theoretical and empirical analysis of the middle-income trap. To test the validity to be able to fix a middle-income band to classify a country in the middle-income trap.

Abstract Background Immune checkpoint inhibitors have revolutionized therapy of advanced and metastatic cancers. However, a significant proportion of patients do not respond to immune checkpoint inhibitors or develop resistance. Therefore, novel therapies or combinations of therapies that may act synergistically are needed. It has been suggested that induction of trained immunity may increase the response to immune checkpoint inhibitor therapy, through reprogramming myeloid cells toward an antitumor phenotype. On the other hand, activation of the immune system also carries the risk of potentially sustaining tumorgenicity and increasing immune- related toxicity. Case presentation We report the case of a 37-year-old Dutch male suffering from gastric neuroendocrine carcinoma with liver metastases and high risk for an unfavorable outcome, who was treated with a combination of programmed cell death protein 1 inhibitor nivolumab and the trained immunity-inducer Bacillus Calmette–Guérin vaccine as a salvage therapy. Three doses of BCG vaccine were administered at 3-month intervals, in conjunction with the immune checkpoint inhibitor regimen. At a certain point, radiation therapy was added to the treatment regimen. During the combination of these therapies, the patient developed immune-mediated colitis, which necessitated discontinuation of all treatments. Bacillus Calmette–Guérin vaccination induced a trained immune response with elevated monocyte-derived interleukin-6 and interleukin-1β production capacity. From the first vaccination with Bacillus Calmette–Guérin until 3 months after the last vaccination with Bacillus Calmette–Guérin, the patient displayed only mild progression of the primary tumor and no progression of the metastases. Conclusion In this study, we show the feasibility to combine checkpoint inhibitor therapy with inducers of trained immunity in a patient with an aggressive neuroendocrine tumor. Autoimmune side effects are common under programmed cell death protein 1 inhibitor therapy, which was considered the most likely cause of colitis, although an additive effect of Bacillus Calmette–Guérin vaccination or radiotherapy cannot be excluded. The patient displayed only mild progression during the combination therapy, but larger studies are warranted to fully explore the potential benefit of trained immunity inducers as an adjuvant to immune checkpoint inhibitor therapy.

Abstract Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in infants, the immunocompromised, and the elderly. RSV infects the airway epithelium via the apical membrane and almost exclusively sheds progeny virions back into the airway mucus (AM), making RSV difficult to target by systemically administered therapies. An inhalable “muco‐trapping” variant of motavizumab (Mota‐MT), a potent neutralizing mAb against RSV F is engineered. Mota‐MT traps RSV in AM via polyvalent Fc‐mucin bonds, reducing the fraction of fast‐moving RSV particles in both fresh pediatric and adult AM by ≈20–30‐fold in a Fc‐glycan dependent manner, and facilitates clearance from the airways of mice within minutes. Intranasal dosing of Mota‐MT eliminated viral load in cotton rats within 2 days. Daily nebulized delivery of Mota‐MT to RSV‐infected neonatal lambs, beginning 3 days after infection when viral load is at its maximum, led to a 10 000‐fold and 100 000‐fold reduction in viral load in bronchoalveolar lavage and lung tissues relative to placebo control, respectively. Mota‐MT‐treated lambs exhibited reduced bronchiolitis, neutrophil infiltration, and airway remodeling than lambs receiving placebo or intramuscular palivizumab. The findings underscore inhaled delivery of muco‐trapping mAbs as a promising strategy for the treatment of RSV and other acute respiratory infections.

Introduction: Traditional medicine has traditionally appreciated the use of Podophyllum peltatum, a large herbaceous species with origins in eastern United States and southern Canada. This swiftly growing plant has recently sparked new interest due to its many uses. A true treasure of phytochemicals can be found there. This comprehensive review delves into the medicinal potential of Podophyllum peltatum, commonly known as mayapple, a rhizomatous perennial plant. Also, Dysosma pleianthum (bajiaolian), a species of May apple, is a traditional Chinese herbal medicine rich in podophyllotoxin. Mayapple has a long history of traditional use by indigenous peoples, and it has garnered significant attention from pharmacologists and medical researchers for its potential in treating various ailments, including cancer and viral infections. Methodology: The online databases including Google Scholar, and PubMed, were searched using different keywords: P. peltatum, antimicrobial activity, traditional uses, and antitumor activity. A total of 124 relevant papers out of 365 including the search terms were selected from the year 2000 to 2022.The purpose of this review was therefore to summarise the previously reported traditional uses and toxicity of the chosen plant species. Results: The results of our analysis showed that mayapple contains lignans with anti-cancer properties, leading to the development of FDA-approved cancer drugs such as etoposide. This review provided insights into the plant's morphology, taxonomy, traditional uses, agriculture, pharmacological investigation, chemical constituents, and analytical analysis. Conclusion: Podophyllum peltatum is a useful medicinal plant but the highlighted toxicological aspects of mayapple, emphasize the need for caution in its use due to its potential for systemic toxicity when consumed in excessive doses.

Background: Ziziphus mauritiana (Rhamnaceae), also known as Ziziphus jujuba Mill is used in traditional Chinese medicine to treat pain, vertigo, amnesia, and sleeplessness. The objective of this research was to examine the anxiolytic properties of the ethanolic extract of Ziziphus mauritiana (EEZM) in several behavioral paradigms using Swiss albino mice as experimental subjects. Methodology: after an oral acute toxicity investigation, adult mice were administered EEZM at doses of 200 and 400 mg/kg, orally, and/or diazepam at a dose of 5 mg/kg, intraperitoneally. Subsequently, the mice were exposed to several behavioral assessments. The open-field test included recording the number of square fields crossed while in the light/dark test, the time spent in the light area was calculated and in the Elevated Plus Maze test, the time spent in both the open and closed arms, as well as the number of entries into the open arm were calculated. Furthermore, a comprehensive examination of phytochemicals was conducted. Results: The anti-anxiety efficacy of the ethanol extract of Z. mauritiana was shown to be statistically significant (p

This study was conducted to test the suitability of using nine types of millets namely finger millet, pearl millet, white and yellow sorghum, little millet, barnyard millet, proso millet, kodo millet, and browntop millet in seven popular Indian meal preparations based on sensory characteristics and nutrient value. The popular Indian meal preparations tested were boiled grain, dosa, idli, bisi belle bath, pulao, puttu, and pongal. In total, 53 variations in meal preparations were developed using the millets and seven polished white rice-based meal preparations were developed as control. The main findings indicated that meal preparation crafted from various millets garnered overall sensory scores closely resembling to those derived from polished white rice. Notably, little millet exhibited high scores in pongal and dosa, and achieved elevated overall sensory scores compared to meal preparation from polished white rice. Bisi belle bath made of barnyard millet scored higher in overall sensory score than polished white rice. Moreover, there was significant association between some types of millets’ overall sensory characteristics (p

Abstract Alectinib, approved as 150 mg capsules for the treatment of adults with advanced ALK‐positive non‐small cell lung cancer, is being assessed in children with ALK‐positive solid and central nervous system tumors. An ad hoc pediatric‐friendly suspension of alectinib, prepared from capsule contents, is under investigation as an alternative formulation for children who cannot swallow capsules. This randomized, crossover, relative bioavailability, and food effect study evaluated alectinib administered as an oral suspension versus capsule formulation following conventional venipuncture and capillary microsampling. A total of 28 healthy adult subjects received a 600 mg single dose of alectinib in two groups: fasted (n = 14) and mixed fed (n = 14; seven receiving high‐fat meal and seven receiving low‐fat meal). Combined alectinib + M4 (active metabolite) exposure was higher for suspension versus capsule, with geometric mean ratio (GMR) of 2.6 for area under the concentration–time curve extrapolated to infinity (AUC0‐∞) and 3.0 for maximum observed concentration (Cmax) under fasted conditions, and 1.7 for both parameters for mixed fed. The suspension showed increased alectinib + M4 AUC0‐∞ following a high‐fat meal versus fasted conditions (GMR 1.7 [90% confidence interval 1.4–2.2]). Alectinib AUC0‐∞ and Cmax measured in venous and capillary samples were generally similar for the suspension and capsule. Single oral doses of 600 mg alectinib suspension and capsule were well tolerated, with no safety concerns. Based on these findings, the oral suspension of alectinib appears suitable for use in pediatric studies after appropriate dose adjustment relative to the capsule.

Abstract Background The COVID-19 pandemic in parallel with concerns about bias in grading resulted in many medical schools adopting pass/fail clinical grading and relying solely on narrative assessments. However, narratives often contain bias and lack specificity. The purpose of this project was to develop asynchronous faculty development to rapidly educate/re-educate > 2000 clinical faculty spread across geographic sites and clinical disciplines on components of a well-written narrative and methods to minimize bias in the assessment of students. Methods We describe creation, implementation, and pilot data outcomes for an asynchronous faculty development curriculum created by a committee of volunteer learners and faculty. After reviewing the literature on the presence and impact of bias in clinical rotations and ways to mitigate bias in written narrative assessments, the committee developed a web-based curriculum using multimedia learning theory and principles of adult learning. Just-in-time supplemental materials accompanied the curriculum. The Dean added completion of the module by 90% of clinical faculty to the department chairperson’s annual education metric. Module completion was tracked in a learning management system, including time spent in the module and the answer to a single text entry question about intended changes in behavior. Thematic analysis of the text entry question with grounded theory and inductive processing was used to define themes of how faculty anticipate future teaching and assessment as a result of this curricula. Outcomes Between January 1, 2021, and December 1, 2021, 2166 individuals completed the online module; 1820 spent between 5 and 90 min on the module, with a median time of 17 min and an average time of 20.2 min. 15/16 clinical departments achieved completion by 90% or more faculty. Major themes included: changing the wording of future narratives, changing content in future narratives, and focusing on efforts to change how faculty teach and lead teams, including efforts to minimize bias. Conclusions We developed a faculty development curriculum on mitigating bias in written narratives with high rates of faculty participation. Inclusion of this module as part of the chair’s education performance metric likely impacted participation. Nevertheless, time spent in the module suggests that faculty engaged with the material. Other institutions could easily adapt this curriculum with provided materials.

SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naïve Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the one-year follow-up. We assessed determinants of systemic anti-S1 and anti-N immunoglobulin type G (IgG) responses using trial data. Participants were randomised to BCG or placebo vaccination, reported daily symptoms, SARS-CoV-2 test results, and COVID-19 vaccinations, and donated blood for SARS-CoV-2 serology at two time points. In the 970 participants, anti-S1 geometric mean antibody concentrations (GMCs) were much higher than anti-N GMCs. Anti-S1 GMCs significantly increased with increasing number of immune events (SARS-CoV-2 infection or COVID-19 vaccination): 104.7 international units (IU)/mL, 955.0 IU/mL, and 2290.9 IU/mL for one, two, and three immune events, respectively (p < 0.001). In adjusted multivariable linear regression models, anti-S1 and anti-N log10 concentrations were significantly associated with infection severity, and anti-S1 log10 concentration with COVID-19 vaccine type/dose. In univariable models, anti-N log10 concentration was also significantly associated with acute infection duration, and severity and duration of individual symptoms. Antibody concentrations were not associated with long COVID or long-term loss of smell/taste.

Background: The incidence of PCOS among females is increasing. Awareness among women about PCOS can help in early diagnosis and prevention by making lifestyle modifications. Lifestyle modifications not only help in prevention of disease but also in managing the symptoms and complications. Objectives: 1. To find out the perception regarding PCOS among students of different courses. 2. To assess the knowledge about PCOS among students Methodology: A cross-sectional study on Undergraduate medical, dental and allied health sciences students enrolled in KMC, Mangalore and MCODS, Mangalore Results: 12.6% of the students had a family history of PCOS. 85% of the students have heard about PCOS. Out of the people who have heard about PCOS 20% have been diagnosed with it. Out of the people who have heard about PCOS, most of the students knew that PCOS is associated with irregular periods, infertility, mood swings and hormonal disturbances. Conclusion: Awareness about PCOS is maximum among MBBS students followed by AHS and then BDS students.

Pralsetinib is a kinase inhibitor indicated for the treatment of metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer. Pralsetinib is primarily eliminated by the liver and hence hepatic impairment (HI) is likely alter its pharmacokinetics (PK). Mild HI has been shown to have minimal impact on the PK of pralsetinib. This hepatic impairment study aimed to determine the pralsetinib PK, safety and tolerability in subjects with moderate and severe HI, as defined by the Child–Pugh and National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) classification systems, in comparison to subjects with normal hepatic function. Based on the Child–Pugh classification, subjects with moderate and severe HI had similar systemic exposure (area under the plasma concentration time curve from time 0 to infinity [AUC0–∞]) to pralsetinib, with AUC0–∞ geometric mean ratios (GMR) of 1.12 and 0.858, respectively, compared to subjects with normal hepatic function. Results based on the NCI-ODWG classification criteria were comparable; the AUC0–∞ GMR were 1.22 and 0.858, respectively, for subjects with moderate and severe HI per NCI-ODWG versus those with normal hepatic function. These results suggested that moderate and severe hepatic impairment did not have a meaningful impact on the exposure to pralsetinib, thus not warranting a dose adjustment in this population.

Holliday Junction (HJ) is an important intermediate in homologous recombination and is involved in DNA break repair. It is a highly dynamic structure and transitions between two stacked isomers through an intermediate open conformer. However, the insight into the effect of environmental confinement on HJ conformation population is incomplete. The understanding would be an important bridge between studies generally carried out in aqueous buffers and confined environments, as found in vivo. By employing fluorescence-based techniques we investigated the effect of confinement on HJ conformation using reverse micelle encapsulation as a model for confined space. We observed that inside the confinement of reverse micelle, HJ prefers to adopt stacked conformation. Most strikingly, even at lower divalent cation concentrations, the preference for stacked conformation is prevalent over an open conformation. The conformational heterogeneity also reduces with increasing degree of confinement. Our finding suggests that such confinement-induced changes in the conformer population might influence the interaction and activity of the HJ-recognizing proteins in the cellular environment.

Abstract Background and Aims Dengue is endemic in Thailand and imposes a high burden on the health system and society. We conducted a prospective cohort study in Umphang District, Tak Province, Thailand, to investigate the share of dengue cases with long symptoms and their duration. Here we present the results of the enrollment process during the COVID‐19 pandemic with implications and challenges for research and policy. Methods In a prospective cohort study conducted in Umphang District, Thailand, we examined the prevalence of persistent symptoms in dengue cases. Clinically diagnosed cases were offered free laboratory testing, We enrolled ambulatory dengue patients regardless of age who were confirmed through a highly sensitive laboratory strategy (positive NS1 and/or IgM), agreed to follow‐up visits, and gave informed consent. We used multivariate logistic regressions to assess the probability of clinical dengue being laboratory confirmed. To determine the factors associated with study enrollment, we analyzed the relationship of patient characteristics and month of screening to the likelihood of participation. To identify underrepresented groups, we compared the enrolled cohort to external data sources. Results The 150 clinical cases ranged from 1 to 85 years old. Most clinical cases (78%) were confirmed by a positive laboratory test, but only 19% of those confirmed enrolled in the cohort study. Women, who were half as likely to enroll as men, were underrepresented in the cohort. Conclusions The Thai physicians' clinical diagnoses at this rural district hospital had good agreement with laboratory diagnoses. By identifying underrepresented groups and disparities, future studies can ensure the creation of statistically representative cohorts to maximize their scientific value. This involves recruiting and retaining underrepresented groups in health research, such as women in this study. Promising strategies for meaningful inclusion include multi‐site enrollment, offering in‐home or virtual services, and providing in‐kind benefits like childcare for underrepresented groups.

Key Clinical Message Reconceptualising acute Musculoskeletal (MSK) injuries with both stress‐ and tissue‐ based factors is required to consider prior influences of mental health disorders on acute persistent MSK pain presentations. This report describes repeated emergency presentations of an individual with acute persistent MSK pain in their twenties living with mental health. Their mental health diagnoses included depression, mood disorders, and anorexia nervosa. This person also had mental health related inpatient admissions that were not captured under the retrospective record review for a large district hospital emergency department using the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) classification system. This case report attempts to demonstrate that improving the understanding of preexisting vulnerabilities and mental health diagnoses may assist with informing healthcare design to develop specialised care pathways for acute injury presentations within triage settings.

The proper functioning of the immune system depends on an appropriate balance between pro-inflammation and anti-inflammation. When the balance is disrupted and the system is excessively biased towards inflammation, immune responses cannot return within the normal range, which favors the onset of diseases of autoimmune or inflammatory nature. In this scenario, it is fundamental to find new compounds that can help restore this balance and contribute to the normal functioning of the immune system in humans. Here, we show the properties of a fungal compound with a strong safety profile in humans, AM3, as an immunomodulatory molecule to decrease excessive cytokine production in human cells. Our results present that AM3 treatment of human peripheral blood mononuclear cells and monocytes decreased their pro-inflammatory cytokine secretion following the challenge with bacterial lipopolysaccharide. Additionally, AM3 skewed the differentiation profile of human monocytes to macrophages towards a non-inflammatory phenotype without inducing tolerance, meaning these cells kept their capacity to respond to different stimuli. These effects were similar in young and elderly individuals. Thus, the fungal compound, AM3 may help reduce excessive immune activation in inflammatory conditions and keep the immune responses within a normal homeostatic range, regardless of the age of the individual.

Abstract Hemorphins, short bioactive peptides produced by enzymatic cleavage of β-hemoglobin, exhibit antihypertensive properties by inhibiting angiotensin-1 converting enzyme (ACE1). ACE1 is a key player in the renin–angiotensin system (RAS) and regulates blood pressure. ACE1 and its homolog, ACE2, which exhibit opposing activities in the RAS, share considerable similarity in their catalytic domains. The primary objective of this study was to identify and contrast the molecular mechanisms underlying the interaction of hemorphins of camels and that of other mammals with the two ACE homologs. In silico docking and molecular dynamics simulations were performed for ACE1 and ACE2, along with in vitro confirmatory assays for ACE1. The C-domain of ACE1, primarily involved in regulating blood pressure, was used along with the N-terminal peptidase domain of ACE2. The findings revealed conserved hemorphin interactions with equivalent regions of the two ACE homologs and differential residue-level interactions reflecting the substrate preferences of ACE1 and ACE2 considering their opposing functions. Therefore, conserved residue-level associations and implications of poorly conserved regions between the two ACE receptors may potentially guide the discovery of selective domain-specific inhibitors. The findings of this study can provide a basis for the treatment of related disorders in the future.

In the current smart tech world, there is an immense need of automating tasks and processes to avoid human intervention, save time and energy. Nowadays, mobile phones have become one of the essential things for human beings either to call someone, connect to the internet, while driving people need mobile phones to receive or make a call, use google maps to know the routes and many more. Normally in cars, mobile holders are placed on the dashboard to hold the mobile and the orientation of the phone needs to be changed according to the driver's convenience manually, but the driver may distract from driving while trying to access mobile phone which may lead to accidents. To solve this problem, an auto adjustable mobile holder is designed in such a way that it rotates according to the movement of the driver and also it can even alert the driver when he feels drowsiness. Image Processing is used to detect the movement of the driver which is then processed using LabVIEW software and NI myRIO hardware. NI Vision development module is used to perform face recognition and servo motors are used to rotate the holder in the required position. Simulation results show that the proposed system has achieved maximum accuracy in detecting faces, drowsiness and finding the position coordinates.

Introduction: A border zone infarct (BI) is defined as an infarction that is localized to watersheds or border zones in the brain. BI is further classified into cortical border zone infarct (CBZ) and internal border zone infarct (IBZ). This study was conducted to explore the clinical and radiological characteristics of BI. Materials and Method: The study was conducted on eligible 400 acute ischemic stroke patients out of which 52 BI patients (diagnosed by the radiologist on DWI MRI images), patients >18 yrs of age were selected and divided into two groups of IBZ and CBZ infarct patients. The degree of intracranial and extracranial stenosis and characteristics on clinical presentation were assessed. The data were collected and analyzed using SPSS version 20.0 software at significance level p-value 0.05). Conclusion: Association of BI with events causing hypotension or hypovolemia is well-established in our study, association of BI with large vessel atherosclerosis is common, and its contribution to CBZ and IBZ seems to be equal.

Background: In women, menopause constitutes the end of a fertile life as a result of ovarian aging. It is characterized by a significant decrease in estrogen concentration along with the change in the body weight, altered distribution of adipose tissue, less energy expenditure as well as modification in insulin secretion, and insulin sensitivity resulting in the development of type 2 diabetes mellitus (T2DM). The low circulating concentration of sex hormone-binding globulin (SHBG) contributes to the increased risk of type 2 diabetes in postmenopausal women. Methods: The present study was conducted at Justice K. S. Hegde Charitable Hospital, Deralakatte, Mangaluru. This case–control study was performed on 400 postmenopausal women with and without T2DM, aged 45–65 years, recruited based on the eligibility criteria. Five milliliters of fasting blood were collected, centrifuged, and stored at −80°C until analysis. Genomic DNA was isolated from the whole blood using a standard protocol. DNA was amplified using the polymerase chain reaction. Amplified products were sequenced using the Sanger sequencing method. Statistical analyses were performed using the SPSS software version 26. Results: Based on the SHBG single-nucleotide polymorphisms (SNP) rs1799941, the circulating levels of SHBG showed a significant difference between the genotype. Conclusions: The major allele of rs1799941 has shown reduced the levels of circulating SHBG with an increased risk of T2DM. Hyperglycemia along its association with endogenous hormone and SNP in the SHBG gene may contribute to the diabetic risk in the postmenopausal women.

Abstract Ipatasertib, an AKT inhibitor, in combination with prednisone and abiraterone, is under evaluation for the treatment of metastatic castration‐resistant prostate cancer (mCRPC). Hyperglycemia is an on‐target effect of ipatasertib. An open‐label, single‐arm, single‐sequence, signal‐seeking study (n = 25 mCRPC patients) was conducted to evaluate the glucose changes across four different treatment periods: ipatasertib alone, ipatasertib‐prednisone combination, ipatasertib‐prednisone‐abiraterone combination (morning dose), and ipatasertib‐prednisone‐abiraterone combination (evening dose). Continuous glucose monitoring (CGM) was used in this study to compare the dynamic glucose changes across the different treatment periods. Four key parameters: average glucose, peak glucose and % time in range (70–180 and >180 mg/dl) were evaluated for this comparison. Ipatasertib‐prednisone‐abiraterone combination when administered in the morning after an overnight fast significantly increased average glucose, peak glucose and % time in range >180 mg/dl compared to ipatasertib monotherapy. Ipatasertib, when co‐administered with abiraterone, increased ipatasertib and M1 (G‐037720) metabolite exposures by approximately 1.5‐ and 2.2‐fold, respectively. Exposure–response analysis results show that increased exposures of ipatasertib in combination with abiraterone are associated with increased glucose levels. When ipatasertib‐prednisone‐abiraterone combination was administered as an evening dose compared to a morning dose, lowered peak glucose and improved % time in range was observed. The results from this study suggest that dosing ipatasertib after an evening meal followed by overnight fasting can be an effective strategy for managing increased glucose levels.

Introduction: Ziziphus jujube (ZJ) or Chinese date or Indian ber is one of the extensively studied medicinal plants as it is a rich source of phytochemicals and thus may encourage a healthy diet. It is a medium-sized native plant of the Rhamnaceae family and is one of the earliest fruits with the greatest significance in Chinese medicine. Traditional Chinese Medicine (TCM) practitioners have used it for treating hysteria in female patients along with fatigue, anorexia, and diarrhea in cases of spleen deficiency syndrome. Ziziphus jujube (Z. jujube) is traditionally used by the locals to treat dandruff, arthritis, chronic constipation, acne, antibacterial, and cardiac diseases. Jujube includes a variety of components, including flavonoids, triterpenic acids, amino acids, cerebrosides, mineral components, phenolic acids, and polysaccharides. Methodology: The online databases including Google Scholar, Scopus, PubMed, and Web of Science, were searched using different keywords: Z. jujube, antimicrobial activity, traditional uses, and antitumor activity. The purpose of this review was therefore to summarise the previously reported phytopharmacological status of the chosen plant species. Results: The results of our analysis revealed that Ziziphus jujube contains a variety of biologically active compounds including, flavonoids, terpenoids, etc. In addition, previous research has demonstrated that plant extracts and isolated principles of ZJ also possess significant pharmacological activity including anti-tumor, anti-inflammatory, antioxidant, anti-melanogenic and others. Discussion: Jujube has a good potential for generating therapeutics and supplements for prophylaxis as well as treatment against cancer, inflammation, and iron/vitamin deficiencies, according to the below-mentioned human and animal studies. Also, clinical research has shown that jujube is a safe and efficient herb for human intake and thus should be included in dietary intakes and as active constituents in pharmaceutical formulations. Conclusion: Jujubes are an invaluable source of bioactive chemicals that can be incorporated into food for humans and show promise for the treatment of mild and life-threatening medical disorders. This review will encourage other scientists to continue their research on the selected plant species, especially in the areas of toxicity and bioactivity.

Summary: Defects in intestinal epithelial tight junctions (TJs) allow paracellular permeation of noxious luminal antigens and are important pathogenic factors in inflammatory bowel disease (IBD). We show that alpha-tocopherylquinone (TQ), a quinone-structured oxidation product of vitamin E, consistently enhances the intestinal TJ barrier by increasing barrier-forming claudin-3 (CLDN3) and reducing channel-forming CLDN2 in Caco-2 cell monolayers (in vitro), mouse models (in vivo), and surgically resected human colons (ex vivo). TQ reduces colonic permeability and ameliorates colitis symptoms in multiple colitis models. TQ, bifunctionally, activates both aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. Genetic deletion studies reveal that TQ-induced AhR activation transcriptionally increases CLDN3 via xenobiotic response element (XRE) in the CLDN3 promoter. Conversely, TQ suppresses CLDN2 expression via Nrf2-mediated STAT3 inhibition. TQ offers a naturally occurring, non-toxic intervention for enhancement of the intestinal TJ barrier and adjunct therapeutics to treat intestinal inflammation.

Mostly produced as a by-product of zinc (Zn) mining, cadmium (Cd) is used in solar photovoltaic cells, battery storage, alloys, pigments, plating, and in nuclear reactors. However, it is also a regulated toxic substance with a long history of environmental and health impacts. As the mining of both Zn and Cd will need to increase to support the global energy transition, the status of Cd as either a resource or a pollutant has major implications for global supply chains and environmental management. Here, we present a new global, site-specific database and analysis of Cd resources in Zn-bearing mineral deposits and mines. Our database, which exceeds past Cd studies in scope, transparency and replicability is made available in full to support future assessments of Cd and Zn resources, mine production and associated risks. It includes 927 sites subject to detailed geological data compilation and analysis. Collectively, these sites suggest a new global resource estimate of 3.3 Mt Cd (95% confidence interval: 2.7–6.1 Mt). A preliminary geospatial analysis of sites in our database and mine toxicity indicators was also conducted. It shows that: As ∼27% of Cd resources are in countries that do not refine it, our study highlights the need for further research exploring global Cd trade flows and associated emissions. Heavy metal pollution in mining and metal production regions is an ongoing challenge, and our global dataset refines our understanding of its magnitude and distribution.

Abstract Duodenal varices (DVs) are ectopic gastrointestinal varices (ECVs) associated with portal hypertension (PH). We present the case of an 82‐year‐old woman who presented with symptomatic anemia secondary to DV hemorrhage diagnosed on oesophagogastroduodenoscopy. This lesion was treated with endoscopic adrenaline injection and clip application. The patient re‐presented on multiple occasions with bleeding recurrence localized to the duodenum, which was managed with intramuscular octreotide and oral beta‐blockade resulting in sustained remission of bleeding. This case highlights a rare cause of upper gastrointestinal hemorrhage and highlights the value of somatostatin analogues for conservative treatment of DVs.