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Spinal epidural hematoma is a rare disease and is most commonly idiopathic. Other common causes are vascular malformations, coagulopathy, hypertension, surgery, and trauma. Epidural vascular hamartoma associated with hemorrhage is a less known entity. We report an unusual case of epidural vascular hamartoma associated with hemorrhage resulting in back pain and neurological deficits. A distinctive feature of this case was waxing and waning signs and symptoms with evidence of radiological resolution of the lesion in the phase of remission. [ABSTRACT FROM AUTHOR]

Mycobacterium avium subspecies paratuberculosis (MAP) infection leads to chronic, persistent granulomatous enteritis, causing prolonged diarrhoea and emaciation. The disease is managed using medications such as antibiotics, live vaccines, mycobacteriophage therapies and other treatments; however, a notable proportion of affected animals do not show improvement with this approach. We hypothesise that immunoinhibitory receptors TIM-3 (T cell immunoglobulin mucin protein-3) and PD-1 (Programmed death receptor 1) may be upregulated on Peripheral blood mononuclear cells (PBMCs) of MAP-seropositive bovines, potentially contributing to immune exhaustion. Samples (blood and faeces) were collected from 32 diarrhoeic bovines suspected of MAP infection; eight apparently healthy buffaloes from the dairy farm at Hisar, Haryana and from 14 cows (suffering from chronic diarrhoea, weakness and emaciation) housed in stray cattle shed. MAP infection was estimated using indigenous ELISA (i-ELISA), faecal IS900 PCR, culture and acid-fast staining. TIM-3 and PD-1 gene expression on PBMCs were determined using qRT-PCR. TIM3 expression was relatively higher (~400-fold, 330-fold, 112-fold, 65-fold and 16-fold) in 5 chronically diarrhoeic PBMCs samples (MAP-seropositive), and higher PD-1 expression (around ~7-fold, 1.75-fold, 2.5-fold, 7.6-fold) was recorded in 4 diarrhoeic MAP-seropositive animals, compared to apparently healthy and other MAP-seronegative diarrhoeic animals. High co-expression of TIM-3 and PD-1 levels was also recorded in chronically diarrhoeic, emaciated stray cattle. Understanding immune responses in field conditions might aid in the therapeutic management of paratuberculosis. [ABSTRACT FROM AUTHOR]

The benefits of Blood Flow Restriction Therapy (BFRT) have gained attention in recent times. This review aimed to evaluate the immediate (up to 24 hours), intermediate (up to 6 weeks), and long term (6–10 weeks) effects of BFRT plus exercises (EX) compared to EX only on athletic performance (sprint and jump performance), muscle strength, and hypertrophy in athletes and physically active population. A literature search was conducted to select randomized controlled trials across four electronic databases from inception till April 2021. The search yielded twenty-seven studies in total. Based on eligibility criteria, twenty-one studies were analyzed. No differences were found between both groups for immediate (standardized mean difference [SMD] −0.02, 95% confidence interval [CI] −0.31, 0.27) and long-term effects (SMD −0.30, 95%CI −0.90, 0.30) on sprint performance. For jump performance, no significant effect was observed immediately (SMD −0.02 (95% CI −1.06, 1.02) and long term (SMD −0.40 (95% CI −1.46, 0.67). Similarly, muscle torque at intermediate (SMD 0.90 (95% CI −1.01, 2.81) and long term (SMD −0.54 (95% CI −1.19, 0.12), muscle strength at intermediate (SMD 1.12 (95% CI 0.20, 2.04), and long term (SMD −0.07 (95% CI −0.56, 0.42) also showed non-significant effects. Muscle hypertrophy at intermediate (SMD 0.16 (95% CI −0.31, 0.63) and long term (SMD −0.20 (95% CI −0.90, 0.50) were not statistically significant. There was no significant difference observed in BFRT plus EX group compared to the EX-group on athletic performance, muscle strength, and muscle hypertrophy. [ABSTRACT FROM AUTHOR]

In this study, we demonstrated the antiviral efficacy of hesperetin against multiple poxviruses, including buffalopox virus (BPXV), vaccinia virus (VACV), and lumpy skin disease virus (LSDV). The time‐of‐addition and virus step‐specific assays indicated that hesperetin reduces the levels of viral DNA, mRNA, and proteins in the target cells. Further, by immunoprecipitation (IP) of the viral RNA from BPXV‐infected Vero cells and a cell‐free RNA‐IP assay, we demonstrated that hesperetin‐induced reduction in BPXV protein synthesis is also consistent with diminished interaction between eukaryotic translation initiation factor eIF4E and the 5′ cap of viral mRNA. Molecular docking and MD simulation studies were also consistent with the binding of hesperetin to the cap‐binding pocket of eIF4E, adopting a conformation similar to m7GTP binding. Furthermore, in a BPXV egg infection model, hesperetin was shown to suppress the development of pock lesions on the chorioallantoic membrane and associated mortality in the chicken embryos. Most importantly, long‐term culture of BPXV in the presence of hesperetin did not induce the generation of drug‐resistant viral mutants. In conclusion, we, for the first time, demonstrated the antiviral activity of hesperetin against multiple poxviruses, besides providing some insights into its potential mechanisms of action. [ABSTRACT FROM AUTHOR]

Aim: Urine as a biofluid has been rarely used as a diagnostic fluid in oral diseases. The article aims to systematically review the utility of human urinary carcinogen metabolites as an approach for obtaining important information about tobacco and cancer. Materials and Methods: The following article reviews the use of urine and its metabolites as biomarkers in various lesions of the oral cavity including oral squamous cell carcinoma and as a screening method in evaluating tobacco and its components. A bibliographic comprehensive search was carried out in the main databases: PUBMED, SciELO, Google Scholar, VHL, and LILACS for articles that were published from 1985 to 2020. The inclusion criteria were "urinary metabolites," "oral cancer/HNSCC," "body fluids," "tobacco," and "metabolomics." A total of 55 articles were collected which included laboratory studies, systematic reviews, and literature of urinary metabolites in tobacco users. Results: Most of the studies carried out show accurate results with high sensitivity of urinary metabolite biomarkers in individuals with tobacco-based habits and lesions caused by them. Conclusion: The review indicates that urinary metabolite analysis demonstrates its applicability for the diagnosis and prognosis of disease. Urine is a remarkable and useful biofluid for routine testing and provides an excellent resource for the discovery of novel biomarkers, with an advantage over tissue biopsy samples due to the ease and less invasive nature of collection. [ABSTRACT FROM AUTHOR]

Human life and health have interacted reciprocally with the surrounding environment and animal fauna for ages. This relationship is evident in developing nations, where human life depends more on the animal population for food, transportation, clothing, draft power, and fuel sources, among others. This inseparable link is a potent source of public health issues, especially in outbreaks of zoonotic diseases transmitted from animals to humans. Zoonotic diseases are referred to as diseases that are naturally transmitted between vertebrate animals and humans. Among the globally emerging diseases in the last decade, 75% are of animal origin, most of which are life-threatening. Since most of them are caused by potent new pathogens capable of long-distance transmission, the impact is widespread and has serious public health and economic consequences. Various other factors also contribute to the transmission, spread, and outbreak of zoonotic diseases, among which industrialization-led globalization followed by ecological disruption and climate change play a critical role. In this regard, all the possible strategies, including advances in rapid and confirmatory disease diagnosis and surveillance/monitoring, immunization/vaccination, therapeutic approaches, appropriate prevention and control measures to be adapted, and awareness programs, need to be adopted collaboratively among different health sectors in medical, veterinary, and concerned departments to implement the necessary interventions for the effective restriction, minimization, and timely control of zoonotic threats. The present review focuses on the current scenario of zoonotic diseases and their counteracting approaches to safeguard their health impact on humans., Competing Interests: Conflict of Interest The authors report that they have no known financial conflicts of interest., (Copyright © 2024 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition induced by platelet-activating IgG antibodies that recognize PF4/heparin complexes. Diagnosis of HIT relies on enzyme immunologic assays (EIAs) and functional assays [serotonin release assay (SRA)]. Our institution uses a latex immunoturbidimetric assay (LIA), which has shown a positive-predictive value (PPV) of 55.6%, and a negative-predictive value (NPV) of 99.7%. The low PPV of EIAs/LIAs, in combination with the clinical delay in obtaining results of a SRA, commonly leads to a false-positive diagnosis of HIT and inappropriate treatment. We performed a single-institution retrospective study at a large tertiary center to assess patient management decisions and economic costs following a false-positive HIT (LIA) test. This study found an 89.5% incidence of false-positive HIT (LIA) tests. 97.4% of patients underwent anticoagulation changes. 69.6% of patients were switched to argatroban. Of patients with a false-positive HIT immunoassay (LIA), 42 (40.7%) patients were on a prophylactic dose of anticoagulation at the time of HIT (LIA) positivity, of which 22 (52.4%) were switched to full anticoagulation with either argatroban or fondaparinux. Of the 22 patients switched to full anticoagulation, 15 (68%) had low-probability 4T scores. Seven (8.8%) of patients had bleeding events after HIT (LIA) positivity. All seven patients were switched to argatroban from a full-dose heparin anticoagulation. Five of the seven patients were considered major bleeds. Utilization of argatroban incurred substantial costs, estimated at approximately $73 000 for false-positive HIT cases. False-positive HIT (LIA) tests contribute to unwarranted anticoagulation changes, increased bleeding risks, and substantial healthcare costs. Incorporating the 4T score into diagnostic algorithms may help mitigate these risks by guiding appropriate clinical decisions. Future research should focus on refining diagnostic approaches and standardizing management strategies to improve patient outcomes and cost-effectiveness in HIT diagnosis and management., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The human U1 snRNA is encoded by a multigene family consisting of transcribed variants and defective pseudogenes. Many variant U1 (vU1) snRNAs have been demonstrated to not only be transcribed but also processed by the addition of a trimethylated guanosine cap, packaged into snRNPs, and assembled into spliceosomes; however, their capacity to facilitate pre-mRNA splicing has, so far, not been tested. A recent systematic analysis of the human snRNA genes identified 178 U1 snRNA genes that are present in the genome as either tandem arrays or single genes on multiple chromosomes. Of these, 15 were found to be expressed in human tissues and cell lines, although at significantly low levels from their endogenous loci, <0.001% of the canonical U1 snRNA. In this study, we found that placing the variants in the context of the regulatory elements of the RNU1-1 gene improves the expression of many variants to levels comparable to the canonical U1 snRNA. Application of a previously established HeLa cell-based minigene reporter assay to examine the capacity of the vU1 snRNAs to support pre-mRNA splicing revealed that even though the exogenously expressed variant snRNAs were enriched in the nucleus, only a few had a measurable effect on splicing., (© 2024 Wong et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Background: Type 2 diabetes mellitus constitutes approximately 90% of all reported forms of diabetes mellitus. Insulin resistance characterizes this manifestation of diabetes. The prevalence of this condition is commonly observed in patients aged 45 and above; however, there is an emerging pattern of younger cohorts receiving diagnoses primarily attributed to lifestyle-related variables, including obesity, sedentary behavior, and poor dietary choices. The enzyme SGLT2 exerts a negative regulatory effect on insulin signaling pathways, resulting in the development of insulin resistance and subsequent elevation of blood glucose levels. The maintenance of glucose homeostasis relies on the proper functioning of insulin signaling pathways, while disruptions in insulin signaling can contribute to the development of type 2 diabetes., Objective: Our study aimed to identify novel SGLT2 inhibitors by high-throughput virtual Screening., Methods: We screened the May bridge Hit Discover database to identify potent hits followed by druglikeness, synthetic accessibility, PAINS alert, toxicity estimation, ADME assessment, and consensus molecular docking., Results: The screening process led to the identification of three molecules that demonstrated significant binding affinity, favorable drug-like properties, effective ADME, and minimal toxicity., Conclusion: The identified molecules could manage T2DM effectively by inhibiting SGLT2, providing a promising avenue for future therapeutic strategies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)