The antihyperglycemic potential of pyrazolobenzothiazine 1, 1-dioxide novel derivative in mice using integrated molecular pharmacological approach.

Diabetes Mellitus is a metabolic disease characterized by elevated blood sugar levels caused by inadequate insulin production, which subsequently leads to hyperglycemia. This study was aimed to investigate the antidiabetic potential of pyrazolobenzothiazine derivatives in silico, in vitro, and in vivo. Molecular docking of pyrazolobenzothiazine derivatives was performed against α-glucosidase and α-amylase and compounds were selected based on docking score, bonding interactions and low root mean square deviation (RMSD). Enzyme inhibition assay against α-glucosidase and α-amylase was performed in vitro using p-nitrophenyl-α-D-glucopyranoside (PNPG) and starch substrate. Synthetic compound pyrazolobenzothiazine (S1) exhibited minimal conformational changes during the 100 ns MD simulation run. S1 also revealed effective IC50 values for α-glucosidase (3.91 µM) and α-amylase (8.89 µM) and an enzyme kinetic study showed low ki (- 0.186 µM, - 1.267 µM) and ki' (- 0.691 µM, - 1.78 µM) values with the competitive type of inhibition for both enzymes α-glucosidase and α-amylase, respectively. Moreover, studies were conducted to check the effect of the synthetic compound in a mouse model. A low necrosis rate was observed in the liver, kidney, and pancreas through histology analysis performed on mice. Compound S1 also exhibited a good biochemical profile with lower sugar level (110-115 mg/dL), increased insulin level (25-30 µM/L), and low level of cholesterol (85 mg/dL) and creatinine (0.6 mg/dL) in blood. The treated mice group also exhibited a low % of glycated haemoglobin (3%). This study concludes that S1 is a new antidiabetic-agent that helps lower blood glucose levels and minimizes the complications associated with type-II diabetes.

Shining insights: Deciphering the biogenic synthesis of Ajuga bracteosa-mediated gold nanoparticles with advanced microscopy techniques.

In this study, gold nanoparticles (AuNPs) were bioreduced from Ajuga bracteosa, a medicinal herb known for its therapeutic properties against various diseases. Different fractions of the plant extract were used, including the methanolic fraction (ABMF), the n-hexane fraction (ABHF), the chloroform fraction (ABCF), and the aqueous extract for AuNPs synthesis. The characterization of AuNPs was performed using UV-Vis spectrophotometry, FT-IR, XRD, EDX, and TEM. UV-Vis spectroscopy confirmed the formation of AuNPs, with peaks observed at 555 nm. FT-IR analysis indicated strong capping of phytochemicals on the surface of AuNPs, which was supported by higher total phenolic contents (TPC) and total flavonoid contents (TFC) in AuNPs. XRD results showed high crystallinity and a smaller size distribution of AuNPs. TEM analysis revealed the spherical shape of AuNPs, with an average size of 29 ± 10 nm. The biologically synthesized AuNPs exhibited superior antibacterial, antioxidant, and cytotoxic activities compared to the plant extract fractions. The presence of active biomolecules in A. bracteosa, such as neoclerodan flavonol glycosides, diterpenoids, phytoecdysone, and iridoid glycosides, contributed to the enhanced biological activities of AuNPs. Overall, this research highlights the potential of A. bracteosa-derived AuNPs for various biomedical applications due to their remarkable therapeutic properties and effective capping by phytochemicals. RESEARCH HIGHLIGHTS: This research underscores the growing significance of herbal medicine in contemporary healthcare by exploring the therapeutic potential of Ajuga bracteosa and gold nanoparticles (AuNPs). The study highlights the notable efficacy of A. bracteosa leaf extracts and AuNPs in treating bacterial infections, demonstrating their bactericidal effects on a range of strains. The anti-inflammatory properties of plant extracts and nanoparticles are evidenced through paw edema method suggesting their applicability in managing inflammatory conditions. These findings position A. bracteosa and AuNPs as potential candidates for alternative and effective approaches to modern medication.

Stroke characteristics and outcomes in urban Tanzania: Data from the Prospective Lake Zone Stroke Registry.

BACKGROUND: Stroke is a second leading cause of death globally, with an estimated one in four adults suffering a stroke in their lifetime. We aimed to describe the clinical characteristics, quality of care, and outcomes in adults with stroke in urban Northwestern Tanzania. METHODS: We analyzed de-identified data from a prospective stroke registry from Bugando Medical Centre in Mwanza, the second largest city in Tanzania, between March 2020 and October 2022. This registry included all adults ⩾18 years admitted to our hospital who met the World Health Organization clinical definition of stroke. Information collected included demographics, risk factors, stroke severity using the National Institutes of Health Stroke Scale, brain imaging, indicators for quality of care, discharge modified Rankin Scale, and in-hospital mortality. We examined independent factors associated with mortality using logistic regression. RESULTS: The cohort included 566 adults, of which 52% (294) were female with a mean age of 65 ± 15 years. The majority had a first-ever stroke 88% (498). Premorbid hypertension was present in 86% (488) but only 41% (200) were taking antihypertensive medications before hospital admission; 6% (32) had HIV infection. Ischemic strokes accounted for 66% (371) but only 6% (22) arriving within 4.5 h of symptom onset. In-hospital mortality was 29% (127). Independent factors associated with mortality were severe stroke (adjusted odds ratio (aOR) = 1.81, 95% confidence interval (CI) = 1.47-2.24, p < 0.001), moderate to severe stroke (aOR = 1.49, 95% CI = 1.22-1.84, p < 0.001), moderate stroke (aOR = 1.80, 95% CI = 1.52-2.14, p < 0.001), leukocytosis (aOR = 1.19, 95% CI = 1.03-1.38, p = 0.022), lack of health insurance coverage (aOR = 1.15, 95% CI = 1.02-1.29, p = 0.025), and not receiving any form of venous thromboembolism prophylaxis (aOR = 1.18, 95% CI = 1.02-1.37, p = 0.027). CONCLUSION: We report a stroke cohort with poor in-hospital outcomes in urban Northwestern Tanzania. Early diagnosis and treatment of hypertension could prevent stroke in this region. More work is needed to raise awareness about stroke symptoms and to ensure that people with stroke receive guidelines-directed therapy.

The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.

Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

Posterior circulation cerebral infarction: A review of clinical, imaging features, management, and outcomes.

Objective: This narrative review discusses posterior circulation cerebral infarcts (PCCI) and provides an update given recent randomized trials in the management of basilar artery occlusion (BAO). We examine clinical characteristics, imaging protocols, management updates, and outcomes of PCCI. Methods: The following databases were searched: MEDLINE, Scopus, Google Scholar, and Web of Science for articles on PCCI. We included randomized trials and observational studies in humans. We also reviewed relevant references from the literature identified. Results: PCCI and BAO is associated with high morbidity and mortality. Early assessment and accurate diagnosis of PCCI remains a clinical challenge. Neuroimaging advances have improved early detection, but barriers remain due to costs and availability. Recent randomized trials provide new insights for BAO patients and support the efficacy of endovascular thrombectomy. Discussion: PCCI requires specific diagnostic and management that is distinct from anterior circulation stroke. While further studies are needed in varied populations and in the subset of BAO patients presenting with milder deficits, growing randomized data support the treatment of BAO patients with endovascular thrombectomy.

Outcomes of Patients with Gastrointestinal Stromal Tumors in the Past Decade.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms of the gastrointestinal tract (GIT) that represent approximately 1 to 2 percent of primary gastrointestinal (GI) cancers. Owing to their rarity, very little is known about their overall epidemiology, and the prognostic factors of their pathology. The current study aimed to evaluate the independent determinants of mortality in patients diagnosed with GISTs over the past decade. METHODS: Our study comprised 2374 patients diagnosed with GISTs from 2000 to 2017 from the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed the baseline characteristics, and overall mortality (OM), as well as the cancer-specific mortality (CSM) of GISTs. Variables with a p value < 0.01 in the univariate Cox regression were incorporated into the multivariate Cox model, to determine the independent prognostic factors. RESULTS: Multivariate Cox proportional hazard regression analyses of factors affecting the all-cause mortality and GIST-related mortality among US patients between 2010 and 2017 revealed a higher overall mortality in non-Hispanic Black patients (HR = 1.516, 95% CI 1.172-1.961, p = 0.002), patients aged 80+ (HR = 9.783, 95% CI 4.185-22.868, p = 0), followed by those aged 60-79 (HR = 3.408, 95% CI 1.488-7.807, p = 0.004); male patients (HR = 1.795, 95% CI 1.461-2.206, p < 0.001); patients with advanced disease with distant metastasis (HR = 3.865, 95% CI 2.977-5.019, p < 0.001), followed by cases with regional involvement via both direct extension and lymph node involvement (HR = 3.853, 95% CI 1.551-9.57, p = 0.004); and widowed patients (HR = 1.975, 95% CI 1.494-2.61, p < 0.001), followed by single patients (HR = 1.53, 95% CI 1.154-2.028, p = 0.003). The highest CSM was observed in the same groups, except widowed patients and patients aged 60-79. The highest CSM was also observed among patients that underwent chemotherapy (HR = 1.687, 95% CI 1.19-2.392, p = 0.003). CONCLUSION: In this updated study on the outcomes of patients with GISTs, we found that non-Hispanic Black patients, male patients, and patients older than 60 years have a higher mortality with GISTs. Furthermore, patients who have received chemotherapy have a higher GIST-specific mortality, and married patients have a lower mortality. However, we do not know to what extent these independent prognostic factors interact with each other to influence mortality. This study paves the way for future studies addressing these interactions. The results of this study may help treating clinicians to identify patient populations associated with a dismal prognosis, as those may require closer follow-up and more intensive therapy; furthermore, with married patients having a better survival rate, we hope to encourage clinicians to involve family members of the affected patients early in the disease course, as the social support might impact the prognosis.

The Role of p90 Ribosomal S6 Kinase (RSK) in Tyrosine Kinase Inhibitor (TKI)-Induced Cardiotoxicity.

Targeted therapy, such as tyrosine kinase inhibitors (TKIs), has been approved to manage various cancer types. However, TKI-induced cardiotoxicity is a limiting factor for their use. This issue has raised the need for investigating potential cardioprotective techniques to be combined with TKIs. Ribosomal S6-kinases (RSKs) are a downstream effector of the mitogen-activated-protein-kinase (MAPK) pathway; specific RSK isoforms, such as RSK1 and RSK2, have been expressed in cancer cells, in which they increase tumour proliferation. Selective targeting of those isoforms would result in tumour suppression. Moreover, activation of RSKs expressed in the heart has resulted in cardiac hypertrophy and arrhythmia; thus, inhibiting RSKs would result in cardio-protection. This review article presents an overview of the usefulness of RSK inhibitors that can be novel agents to be assessed in future research for their effect in reducing cancer proliferation, as well as protecting the heart from cardiotoxicity induced by TKIs.

Phytochemical-Mediated Biosynthesis of Silver Nanoparticles from Strobilanthes glutinosus: Exploring Biological Applications.

The application of green synthesis for silver nanoparticles in nanomedicine has experienced significant growth. Strobilanthes glutinosus, a plant primarily located in the Himalayas, remains largely unexplored. Considering the biomedical value of S. glutinosus, phytochemicals from this plant were used for the biosynthesis of silver nanoparticles. Silver nanoparticles were synthesized from aqueous extract of root and leaves of Strobilanthes glutinosus. The synthesized silver nanoparticles were characterized using UV-Vis spectrophotometry, Fourier-transform infrared spectroscopy, transmission electron microscopy, and X-ray diffraction. Total phenolic and flavonoid contents of plants were determined and compared with nanoparticles. The biomedical efficacy of plant extracts and silver nanoparticles was assessed using antioxidant and antibacterial assays. The UV-Vis spectra of leaf- and root-extract-mediated AgNPs showed characteristic peaks at 428 nm and 429 nm, respectively. TEM images revealed the polycrystalline and spherical shapes of leaf- and root-extract-mediated AgNPs with size ranges of 15-60 nm and 20-52 nm, respectively. FTIR findings shown the involvement of phytochemicals of root and leaf extracts in the reduction of silver ions into silver nanoparticles. The crystalline face-centered cubic structure of nanoparticles is depicted by the XRD spectra of leaf and root AgNPs. The plant has an ample amount of total phenolic content (TPC) and total flavonoid content (TFC), which enhance the scavenging activity of plant samples and their respective AgNPs. Leaf and root AgNPs have also shown good antibacterial activity, which may enhance the medicinal value of AgNPs.

Age- and Sex-Specific Trends in Medical Complications After Acute Ischemic Stroke in the United States.

BACKGROUND AND OBJECTIVES: To test the hypothesis that the age and sex-specific prevalence of infectious (pneumonia, sepsis, and urinary tract infection [UTI]) and noninfectious (deep venous thrombosis [DVT], pulmonary embolism [PE], acute renal failure [ARF], acute myocardial infarction [AMI], and gastrointestinal bleeding [GIB]) complications increased after acute ischemic stroke (AIS) hospitalization in the United States from 2007 to 2019. METHODS: We conducted a serial cross-sectional study using the 2007-2019 National Inpatient Sample. Primary AIS admissions in adults (aged 18 years or older) with and without complications were identified using International Classification of Diseases codes. We quantified the age/sex-specific prevalence of complications and used negative binomial regression models to evaluate trends over time. RESULTS: Of 5,751,601 weighted admissions, 51.4% were women. 25.1% had at least 1 complication. UTI (11.8%), ARF (10.1%), pneumonia (3.2%), and AMI (2.5%) were the most common complications, while sepsis (1.7%), GIB (1.1%), DVT (1.2%), and PE (0.5%) were the least prevalent. Marked disparity in complication risk existed by age/sex (UTI: men 18-39 years 2.1%; women 80 years or older 22.5%). Prevalence of UTI (12.9%-9.7%) and pneumonia (3.8%-2.7%) declined, but that of ARF increased by ≈3-fold (4.8%-14%) over the period 2007-2019 (all p < 0.001). AMI (1.9%-3.1%), DVT (1.0%-1.4%), and PE (0.3%-0.8%) prevalence also increased (p < 0.001), but that of sepsis and GIB remained unchanged over time. After multivariable adjustment, risk of all complications increased with increasing NIH Stroke Scale (pneumonia: prevalence rate ratio [PRR] 1.03, 95% CI 1.03-1.04, for each unit increase), but IV thrombolysis was associated with a reduced risk of all complications (pneumonia: PRR 0.80, 85% CI 0.73-0.88; AMI: PRR 0.85, 95% CI 0.78-0.92; and DVT PRR 0.87, 95% CI 0.78-0.98). Mechanical thrombectomy was associated with a reduced risk of UTI, sepsis, and ARF, but DVT and PE were more prevalent in MT hospitalizations compared with those without. All complications except UTI were associated with an increased risk of in-hospital mortality (sepsis: PRR 1.97, 95% CI 1.78-2.19). DISCUSSION: Infectious complications declined, but noninfectious complications increased after AIS admissions in the United States in the last decade. Utilization of IV thrombolysis is associated with a reduced risk of all complications.

Basilar artery occlusion: A review of clinicoradiologic features, treatment selection, and endovascular techniques.

Basilar artery occlusion (BAO) is an infrequent but often fatal subtype of stroke. Predicting outcomes and selecting patients for endovascular therapy (EVT) remains challenging. Advances in neuroimaging and the development of prognostic scoring systems have augmented clinical decision-making over time. Recent randomized trials, BEST (Basilar Artery Occlusion Endovascular Intervention vs. Standard Medical Treatment), BASICS (Basilar Artery International Cooperation Study), BAOCHE (Basilar Artery Occlusion CHinese Endovascular Trial) and ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion), compared EVT and medical management for patients with BAO. These trials yielded mixed results. The former two suggested unclear benefit while the latter two supported a benefit of EVT. While all had limitations, most providers agree caution should be exercised when excluding patients from EVT who may stand to benefit. Further studies are therefore needed to determine the effectiveness, safety, selection criteria, and optimal technical approach for EVT among patients with BAO. Hyperacute-phase advanced imaging can offer several benefits to aid decision making. It is reasonable to exclude patients with low National Institutes of Health Stroke Scale (NIHSS), large imaging-proven cores, and evidence of perforator occlusion by branch atheromatous disease. Herein, we review the clinical presentation, imaging work-up, treatments, and clinical outcomes for BAO, while highlighting knowledge gaps in treatment selection and technique.

Bisphenol A is a carcinogen that induces lipid accumulation, peroxisome proliferator­activated receptor­Î³ expression and liver disease.

Bisphenol (BP) A is an exogenous endocrine disruptor that mimics hormones closely associated with health complications, e.g., obesity and cancers. The present study aimed to evaluate the effects of BPA on human liver cells and tissue. The peroxisome proliferator-activated receptor (PPAR)-γ expression profile across tumour samples and paired normal tissue was first analysed using GEPIA. Subsequently, BPA-treated liver THLE-2 cell viability was evaluated using an MTT assay. Clusterin, PPARα and PPARγ gene expression in BPA-treated THLE-2 cells was assessed using GEPIA before validating the gene expression using real-time PCR and analysing overall survival using TCGA data in GEPIA. Cytoplasmic lipid accumulation was examined in BPA-treated THLE-2 cells using Oil Red O staining, and liver tissue was examined using haematoxylin and eosin staining. Finally, cytochrome P450 (CYP) gene expression was assessed in BPA-treated THLE-2 cells using real-time PCR. PPARγ is likely the primary nuclear receptor protein involved in lipid accumulation in THLE-2 cells following BPA treatment and is associated with liver disease. THLE-2 cells exposed to BPA showed a decrease in viability and lipid accumulation after 48 h treatment. Higher PPARγ gene expression was significantly associated with survival of patients with liver cancer, with an average survival time of <80 months. Haematoxylin and eosin-stained sections showed notable disruption of the liver architecture in tissue exposed to BPA. Downregulated CYP1A1 and CYP1B1 gene expression implied that BPA-treated THLE-2 cells decreased capacity for carcinogen metabolism, while upregulated CYP2S1 gene expression exerted minimal cytotoxicity. The present study revealed that BPA served as a carcinogen, enhanced tumorigenesis susceptibility and may induce other types of liver disease.

Hydrogel patch with pretreated stem cells accelerates wound closure in diabetic rats.

Delay in wound healing is a diabetes mellites resulting disorder causing persistent microbial infections, pain, and poor quality of life. This disorder is treated by several strategies using natural biomaterials, growth factors and stem cells molded into various scaffolds which possess the potential to accelerate the closure of impaired diabetic wounds. In this study, we developed a hydrogel patch using chitosan (CS) and polyethylene glycol (PEG) with laden bone marrow-derived mesenchymal stem cells (BMSCs) that were pretreated with fibroblast growth factor 21 (FGF21). The developed hydrogel patches were characterized by scanning electron microscopy and fourier transform infrared (FTIR) spectroscopy. After studying the swelling behavior, growth factor (FGF21) was used to modulate BMSC in the hyperglycemic environment. Later, FGF21 treated BMSC were embedded in CS/PEG hydrogel patch and their wound closure effect was assessed in diabetic rats. The results showed that CS/PEG hydrogel patches have good biocompatibility and possess efficient BMSC recruiting properties. The application of CS/PEG hydrogel patches accelerated wound closure in diabetic rats as compared to the control groups. However, the use of FGF21 pretreated BMSCs laded CS/PEG hydrogel patches further increased the therapeutic efficacy of wound closure in diabetic rats. This study demonstrated that the application of a hydrogel patch of CS/PEG with FGF21 pretreated BMSCs improves diabetic wound healing, but further studies are needed on larger animals before the use of these dressings in clinical trials.

A comprehensive review of COVID-19 detection techniques: From laboratory systems to wearable devices.

Screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among symptomatic and asymptomatic patients offers unique opportunities for curtailing the transmission of novel coronavirus disease 2019, commonly known as COVID-19. Molecular diagnostic techniques, namely reverse transcription loop-mediated isothermal amplification (RT-LAMP), reverse transcription-polymerase chain reaction (RT-PCR), and immunoassays, have been frequently used to identify COVID-19 infection. Although these techniques are robust and accurate, mass testing of potentially infected individuals has shown difficulty due to the resources, manpower, and costs it entails. Moreover, as these techniques are typically used to test symptomatic patients, healthcare systems have failed to screen asymptomatic patients, whereas the spread of COVID-19 by these asymptomatic individuals has turned into a crucial problem. Besides, respiratory infections or cardiovascular conditions generally demonstrate changes in physiological parameters, namely body temperature, blood pressure, and breathing rate, which signifies the onset of diseases. Such vitals monitoring systems have shown promising results employing artificial intelligence (AI). Therefore, the potential use of wearable devices for monitoring asymptomatic COVID-19 individuals has recently been explored. This work summarizes the efforts that have been made in the domains from laboratory-based testing to asymptomatic patient monitoring via wearable systems.

COVID-19 Vaccine Hesitancy among Health Professional Students: Cross-Sectional Data from the First Wave of the HOLISTIC Cohort Study.

Vaccine hesitancy has been observed around the world, but there is a paucity of data among a broad range of U.S. health professional students. The goal of this report is to present findings about COVID-19 vaccine hesitancy among a cross-section of U.S. health professional students and determine if hesitancy varies by demographic characteristics, health science college, and other factors. A cross-sectional analysis of HOLISTIC Cohort Study participants enrolled from April 14 2021 to May 5 2021 at seven health sciences colleges in the University of Illinois Chicago was used. Exploratory and confirmatory factor analysis were used to evaluate vaccine hesitancy items and identify domains. Among 555 health professional students, three domains (perceived benefit, trustworthiness, and risk) contribute to vaccine hesitancy. Significant differences were observed in the domains among students of different races as well as vaccination history. Compared to students in the College of Medicine, students in the Colleges of Applied Health Science (OR 0.43; CI [0.19-0.96]), Pharmacy (OR 0.38; CI [0.17-0.87]), Nursing (OR 0.35; CI [0.16-0.78]), and Social Work (OR 0.30; CI [0.11-0.78]) reported lower perceived benefit. Compared to students in the College of Medicine, students in the College of Applied Health Sciences (OR 0.39; CI [0.17-0.94]), Dentistry (OR 0.27; CI [0.10-0.76]), Nursing (OR 0.38; CI [0.16-0.94]), and Social work (OR 0.31; CI [0.11-0.86]) reported more trustworthiness and more concerns about risk (OR 2.80; CI [1.15-6.81] for College of Applied Health Sciences, OR 9.12; CI [2.80-29.75] for Dentistry, OR 3.77; CI [1.47-9.65] for Nursing, OR 3.14; CI [1.02-9.67] for Social Work). Our findings suggest the need for a tailored vaccination strategy among different subgroups of health professional students.

Valproate Teratogenicity: A Moving Target.

Within several years after receiving U.S. Food and Drug Administration (FDA) approval in the late 1970s, valproate was shown to increase the risk for major congenital malformations and learning disabilities in the offspring of women who used the drug during pregnancy. Nonetheless, its use in pregnant women has persisted for more than four decades, recently resulting in numerous lawsuits and, in countries other than the United States, criminal indictments of the manufacturers of valproate. The use of valproate in pregnancy persisted and extended beyond its original indication for the treatment of epilepsy. Several recent studies indicate that the drug is more often prescribed to treat pregnant women with bipolar depression and migraine than for seizure control. Especially concerning is the absence of valproate from the list of more than 60 drugs for which the FDA has implemented Risk Evaluation and Mitigation Strategies to prevent or limit untoward consequences associated with specific drugs. Until this step is taken, avoidance of the teratogenic effects of valproate will rely on the vigilance of those caring for women and people with the potential to get pregnant.

Ischemic Stroke at a Tertiary Academic Hospital in Tanzania: A Prospective Cohort Study With a Focus on Presumed Large Vessel Occlusion.

Background: Large vessel ischemic strokes account for more than one-third of all strokes associated with substantial morbidity and mortality without early intervention. The incidence of large vessel occlusion (LVO) is not known in sub-Saharan Africa (SSA). Definitive vessel imaging is not routinely available in resource-limited settings. Aims: We aimed to investigate the burden and outcomes of presumed LVO among patients with ischemic stroke admitted to a large tertiary academic hospital in Tanzania. Methods: This cohort study recruited all consenting first-ever ischemic stroke participants admitted at a tertiary hospital in Tanzania. Demographic data were recorded, and participants were followed up to 1 year using the modified Rankin Scale (mRS). A diagnosis of presumed LVO was made by a diagnostic neuroradiologist and interventional neurologist based on contiguous ischemic changes in a pattern consistent with proximal LVO on a non-contrast computed tomography head. We examined factors associated with presumed LVO using logistic regression analysis. Inter-observer Kappa was calculated. Results: We enrolled 158 first-ever ischemic strokes over 8 months with a mean age of 59.7 years. Presumed LVO accounted for 39.2% [95% confidence interval (CI) 31.6-47.3%] and an overall meantime from the onset of stroke symptoms to hospital arrival was 1.74 days. Participants with presumed LVO were more likely to involve the middle cerebral artery (MCA) territory (70.9%), p < 0.0001. Independent factors on multivariate analysis associated with presumed LVO were hypertension [adjusted odds ratio (aOR) 5.74 (95% CI: 1.74-18.9)] and increased waist-hip ratio [aOR 7.20 (95% CI: 1.83-28.2)]. One-year mortality in presumed LVO was 80% when compared with 73.1% in participants without presumed LVO. The Cohen's Kappa inter-observer reliability between the diagnostic neuroradiologist and interventional neurologist was 0.847. Conclusion: There is a high burden of presumed LVO associated with high rates of 1-year morbidity and mortality at a tertiary academic hospital in Tanzania. Efforts are needed to confirm these findings with definitive vessel imaging, promoting cost-effective preventive strategies to reduce the burden of non-communicable diseases (NCDs), and a call for adopting endovascular therapies to reduce morbidity and mortality.

Adverse Effects of Bisphenol A on the Liver and Its Underlying Mechanisms: Evidence from In Vivo and In Vitro Studies.

BPA is a known endocrine-disrupting agent that is capable of binding to the estrogen receptor and has exhibited adverse effects in many laboratory animal and in vitro studies. Moreover, it also been shown to have estrogenic, antiandrogenic, inflammatory, and oxidative properties. The widespread presence of BPA in the environment presents a considerable threat to humans. BPA has been shown to be leached into the human ecosystem, where it is commonly found in food products consumed by humans. Although the concentration is relatively low, its prolonged consumption may cause a variety of deleterious health effects. The liver is an important organ for metabolizing and detoxifying toxic metabolites to protect organisms from potentially toxic chemical insults. BPA that is ingested will be eliminated by the liver. However, it has also induced hepatoxicity and injury via various mechanisms. To find research demonstrating the effects of BPA on kidney, a number of databases, including Google Scholar, MEDLINE, PubMed, and the Directory of Open Access Journals, were searched. Thus, this review summarizes the research on the relationship between BPA and its effects on the liver-derived from animals and cellular studies. The underlying mechanism of liver injury caused by BPA is also elucidated.

Health professional students at the University of Illinois Chicago (HOLISTIC) Cohort Study: A protocol.

OBJECTIVES: The objectives of the HOLISTIC Cohort Study are to establish a prospective cohort study covering a period of three years that characterizes the health of students within and across health professional education programs at the University of Illinois Chicago (UIC) during the coronavirus disease 2019 (COVID-19) pandemic, implement an interprofessional student research team, and generate a meaningful dataset that is used to inform initiatives that improve student health. This report describes the protocol of the HOLISTIC Cohort Study, including survey development, recruitment strategy, and data management and analysis. METHODS: An interprofessional student research team has been organized with the goal of providing continuous assessment of study design and implementation across the seven health science colleges (applied health sciences, dentistry, medicine, nursing, pharmacy, public health, and social work) at the University of Illinois Chicago in Chicago, IL. To be eligible to participate in the HOLISTIC Cohort Study, students are required to be 1) age 18 years or older; 2) enrolled full- or part-time in one or more of UIC's seven health science colleges; and 3) enrolled in a program that prepares its graduates to enter a healthcare profession. The study protocol includes a series of three recruitment waves (Spring 2021 [April 14, 2021, to May 5, 2021; completed], Spring 2022, Spring 2023). In the first recruitment wave, eligible students were sent an invitation via electronic mail (e-mail) to complete an online survey. The online survey was based on the U.S. Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System 2019 survey and the 2014 World Health Organization Report of the Strategic Advisory Group of Experts Working Group Vaccine Hesitancy Scale. Electronic informed consent and study data are collected and managed using Research Electronic Data Capture (REDCap) tools. This study utilizes convenience sampling from all seven health science colleges at UIC with a target recruitment total of 2,000 participants. DISCUSSION AND FUTURE DIRECTIONS: A total of 555 students across all seven health science colleges (10.8% of 5,118 students who were invited; 27.6% of target sample size) enrolled in the cohort during the first recruitment wave. The pilot data establishes the feasibility of the study during the COVID-19 pandemic. Adaptations to overcome barriers to study implementation, including the use of remote, rather than in-person, study meetings, staff training, and participant recruitment are discussed. For the second and third waves of recruitment, the student research team will seek institutional review board (IRB) approval to implement additional enrollment strategies that are tailored to each health science college, such as online newsletters, virtual townhalls, flyers on bulletin boards near classrooms tailored to each health science college.

PCovNet: A presymptomatic COVID-19 detection framework using deep learning model using wearables data.

While the advanced diagnostic tools and healthcare management protocols have been struggling to contain the COVID-19 pandemic, the spread of the contagious viral pathogen before the symptom onset acted as the Achilles' heel. Although reverse transcription-polymerase chain reaction (RT-PCR) has been widely used for COVID-19 diagnosis, they are hardly administered before any visible symptom, which provokes rapid transmission. This study proposes PCovNet, a Long Short-term Memory Variational Autoencoder (LSTM-VAE)-based anomaly detection framework, to detect COVID-19 infection in the presymptomatic stage from the Resting Heart Rate (RHR) derived from the wearable devices, i.e., smartwatch or fitness tracker. The framework was trained and evaluated in two configurations on a publicly available wearable device dataset consisting of 25 COVID-positive individuals in the span of four months including their COVID-19 infection phase. The first configuration of the framework detected RHR abnormality with average Precision, Recall, and F-beta scores of 0.946, 0.234, and 0.918, respectively. However, the second configuration detected aberrant RHR in 100% of the subjects (25 out of 25) during the infectious period. Moreover, 80% of the subjects (20 out of 25) were detected during the presymptomatic stage. These findings prove the feasibility of using wearable devices with such a deep learning framework as a secondary diagnosis tool to circumvent the presymptomatic COVID-19 detection problem.

A pilot and feasibility study of a randomized clinical trial testing a self-compassion intervention aimed to increase physical activity behaviour among people with prediabetes.

BACKGROUND: Seventy-five per cent of individuals with prediabetes will eventually be diagnosed with type 2 diabetes. Physical activity is a cornerstone in reducing type 2 diabetes risk but can be a challenging behaviour to adopt for those living with prediabetes. Individuals with prediabetes experience difficult emotions associated with being at risk for a chronic disease, which can undermine self-regulation. Self-compassion enhances self-regulation because it mitigates difficult emotions and promotes adaptive coping. We performed a pilot randomized controlled trial to determine the feasibility and acceptability of a self-compassion informed intervention to increase physical activity for persons with prediabetes. METHODS: This explanatory mixed methods study tested the feasibility and acceptability of a two-arm, randomized, single-blind, actively controlled, 6-week online intervention. Using a 1:1 allocation ratio, participants (identified as people with prediabetes, low physical activity, and low self-compassion) were randomized to a self-compassion (Mage = 60.22 years) or control condition (Mage = 56.13 years). All participants received behaviour change education (e.g. SMART goals, action-coping planning) and either other health knowledge (control condition: e.g. sleep, benefits of water) or self-compassion training (intervention condition: practising mindfulness, writing a letter to themselves offering the same support that they would offer to a friend). The primary outcome was to determine the feasibility and acceptability of the trial. To be considered feasible, our outcomes needed to meet or surpass our pre-determined criteria (e.g. time for group formation: 14-20 participants per month). Feasibility was assessed by examining the recruitment rates, retention, adherence, fidelity, and capacity. Semi-structured interviews were conducted with participants to determine trial acceptability. As a secondary purpose, we examined the means on key study variables (secondary and exploratory variables; see Table 1) at all planned time points (baseline, intervention-end, 6- and 12-week follow-up) to identify if they are suitable to include in the efficacy trial (see Additional Table 3). RESULTS: Eighteen participants were screened and randomized to one of two conditions. Retention, instructor fidelity, safety, capacity, adherence to most of the study aspects, and acceptability by participants and facilitators all met the criteria for feasibility. Recruitment rate, process time, and adherence to home practice were below our criteria, and we offer ways to address these shortcomings for the efficacy trial. CONCLUSION: The results from this study suggest that it should be feasible to deliver our intervention while highlighting the alterations to components that may be altered when delivering the efficacy trial. We outline our changes which should improve and enhance the feasibility and acceptability of our planned intervention. Funding for this study was from the Canadian Institutes of Health Research (CIHR). TRIAL REGISTRATION: ClinicalTrials.gov, NCT04402710 . Registered on 09 April 2020.