Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones.

The majority of approved therapies for many diseases are developed to target their underlying pathophysiology. Understanding disease pathophysiology has thus proven vital to the successful development of clinically useful medications. Stroke is generally accepted as the leading cause of adult disability globally and ischemic stroke accounts for the most common form of the two main stroke types. Despite its health and socioeconomic burden, there is still minimal availability of effective pharmacological therapies for its treatment. In this review, we take an in-depth look at the etiology and pathophysiology of ischemic stroke, including molecular and cellular changes. This is followed by a highlight of drugs, cellular therapies, and complementary medicines that are approved or undergoing clinical trials for the treatment and management of ischemic stroke. We also identify unexplored potential targets in stroke pathogenesis that can be exploited to increase the pool of effective anti-stroke and neuroprotective agents through de novo drug development and drug repurposing.

A management framework for sudden water pollution: A systematic review output.

Numerous sudden water pollution (SWP) incidents have occurred frequently in recent years, constituting a potential risk to human, socio-economic, and ecological health. This paper systematically reviews the current literature, with the view to establishing a management framework for SWP incidents. Only 39 of the 327 downloaded articles were selected, and the ROSES protocol was utilized in this review. The results indicated industries, mining sites, and sewage treatment plants as key SWP contributors through accidental leakages, traffic accidents, illegal discharge, natural disasters, and terrorist attacks. These processes also presented five consequences, including the contamination of drinking water sources, disruption of drinking water supply, ecological damage, loss of human life, and agricultural water pollution. Meanwhile, five mitigation strategies included reservoir operation, real-time monitoring, early warning, and chemical and biological treatments. Although an advancement in mitigation strategies against SWP was observed in this review, previous studies reported only a few prevention strategies. Considering that this review provided an SWP-based management framework and a hydrodynamic model selection guideline, which provide a foundation for implementing proactive measures against the SWP. These guidelines and the SWP-based management framework require practical field trials for future studies. PRACTITIONER POINTS: Sudden water pollution increases with industrial growth but decrease with awareness. Human and ecosystem health and social economy are the endpoint receptacles. Mitigation strategies include reservoir dispatch, early warning, and treatments. DPSIR model forms the basis for proving proactive measures against sudden pollution. This review provides a guideline for the selection hydrodynamic models application.

Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review.

BACKGROUND: The advent of the hepatitis B vaccine has achieved tremendous success in eradicating and reducing the burden of hepatitis B infection, which is the main culprit for hepatocellular carcinoma-one of the most fatal malignancies globally. Response to the vaccine is achieved in about 90-95% of healthy individuals and up to only 50% in immunocompromised patients. This review aimed to provide an overview of hepatitis B vaccine non-response, the mechanisms involved, B cell amnesia, and strategies to overcome it. METHODS: Databases, including Google Scholar, PubMed, Scopus, Cochrane, and ClinicalTrials.org, were used to search and retrieve articles using keywords on hepatitis B vaccine non-response and B cell amnesia. The PRISMA guideline was followed in identifying studies, screening, selection, and reporting of findings. RESULTS: A total of 133 studies on hepatitis B vaccine non-response, mechanisms, and prevention/management strategies were included in the review after screening and final selection. Factors responsible for hepatitis B vaccine non-response were found to include genetic, immunological factors, and B cell amnesia in healthy individuals. The genetic factors were sex, HLA haplotypes, and genetic polymorphisms in immune response markers (cytokines). Non-response was common in conditions of immunodeficiency, such as renal failure, haemodialysis, celiac disease, inflammatory bowel disease, hepatitis C co-infection, and latent hepatitis B infection. Others included diabetes mellitus and HIV infection. The mechanisms involved were impaired immune response by suppression of response (T helper cells) or induced suppression of response (through regulatory B and T cells). DISCUSSION: A comprehensive and careful understanding of the patient factors and the nature of the vaccine contributes to developing effective preventive measures. These include revaccination or booster dose, vaccine administration through the intradermal route, and the use of adjuvants in the vaccine.

Distal tibial trabecular morphometry in a Sprague Dawley rat model of fetal alcohol syndrome: a micro focus X-ray computed tomography case-control study.

Introduction: intrauterine alcohol exposure has adverse health effects on the offspring, which may result in fetal Alcohol Spectrum Disorders (FASD). The neurological and craniofacial aspects have been well studied; however, long bones have received limited attention despite the short stature reported in FASD children. Methods: time-mated (n=13) pregnant Sprague Dawley dams were assigned to either the ethanol (n=5), saline control (n=5) or untreated group (n=3) which received no treatment. The ethanol and saline control dams were treated with 0.015ml/g of 25.2% ethanol or 0.9% saline, respectively. Treatment was for the first 19 days of gestation. Two pups from each dam were used and terminated at 21 days of age. Paired tibiae were harvested. Each bone was scanned using a Nikon XTH 225L 3D-µCT to investigate trabeculae morphometry. Results: the ethanol group had less bone to total volume (BT/TV), thinnest trabeculae (TbTh) which were less spaced (TbSp) compared to the controls. However, number of trabecular (TbN) remained unaffected in all three groups. Tibial length was similar in all three groups; however, the distal metaphysis volume was smallest in the ethanol group. Logistic regression showed that the distal medullary canal area and trabecular separation were the main parameters affected the most in gestational alcohol. The negative correlation of trabecular thickness and spacing in the ethanol group may be a contributor to bone weakness. Conclusion: gestational alcohol exposure affects bone internal morphology in addition to the bone size. Overall, this study supports the findings of clinical observation of small stature in FAS children.