The University of Texas Medical Branch (UTMB) is a public academic health science center in Galveston, Texas. It is part of the University of Texas System. UTMB includes the oldest medical school in Texas, and has about 11,000 employees. In February 2019, it received an endowment of $560 million.Established in 1891 as the University of Texas Medical Department, UTMB has grown from one building, 23 students and 13 faculty members to more than 70 buildings, more than 2,500 students and more than 1,000 faculty. It has four schools, three institutes for advanced study, a comprehensive medical library, four on-site hospitals (including an affiliated Shriners Hospital for Children), a network of clinics that provide primary and specialized medical care and numerous research facilities. UTMB's primary missions are health sciences education, medical research (it is home to the Galveston National Laboratory) and health care services. Its emergency department at John Sealy Hospital is certified as a Level I Trauma Center and serves as the lead trauma facility for a nine-county region in Southeast Texas; it is one of only three Level I Trauma centers serving all ages in Southeast Texas.In fiscal year 2012, UTMB received 20 percent of its $1.5 billion budget from the State of Texas to help support its teaching mission, hospital operation and Level 1 Trauma Center; UTMB generates the rest of its budget through its research endeavors, clinical services and philanthropy. It provides a significant amount of charity care (almost $96 million in 2012), and treats complex cases such as transplants and burns.In 2003 UTMB received funding to construct a $150 million Galveston National Biocontainment Laboratory on its campus, one of the few non-military facilities of this level. It houses several Biosafety Level 4 research laboratories, where studies on highly infectious materials can be carried out safely. It has schools of medicine, nursing, allied health professions, and a graduate school of biomedical sciences, as well as an institute for medical humanities. UTMB also has a major contract with the Texas Department of Corrections to provide medical care to inmates at all TDC sites in the eastern portion of Texas. UTMB also has similar contracts with local governments needing inmate medical care.
Introduction: Despite growing interest in the nature and impact of cognitive disengagement syndrome (CDS), few studies have examined environmental factors associated with CDS such as the possible role of trauma exposure. The current study used a community sample of young adolescents and a multi-informant, multi-method design to examine the association between type of trauma exposure and symptoms of CDS and attention-deficit/hyperactivity disorder (ADHD). Methods: Youth ages 10—12 (N = 341, 52.7
Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia and is associated with a markedly increased risk of thromboembolic stroke, primarily originating from the left atrial appendage (LAA). Percutaneous left atrial appendage occlusion (LAAO) is an established alternative for stroke prevention in patients with contraindications to long-term oral anticoagulation. Transesophageal echocardiography (TEE) has traditionally guided LAAO, but intracardiac echocardiography (ICE) is increasingly adopted to facilitate conscious sedation and operator-controlled imaging. Comparative real-world safety and effectiveness data between ICE and TEE remain limited. We conducted a retrospective, multicenter cohort study using the TriNetX Research Network, comprising 112 healthcare organizations. Adult patients with atrial fibrillation who underwent percutaneous LAAO guided exclusively by ICE or TEE were identified. The primary endpoint was 30-day all-cause mortality. Secondary endpoints included pericardial effusion, stroke/cerebrovascular accident (CVA), major bleeding, acute kidney injury (AKI), device-related complications, and all-cause hospitalization or emergency department encounters, assessed at 30 and 365 days. Propensity score matching (1:1) was performed using demographics, comorbidities, medications, prior procedures, and laboratory values. Risk ratios, absolute risk differences, Kaplan-Meier analyses, and multivariable Cox proportional hazards models were used to compare outcomes. Among 10,629 eligible patients, 3,930 underwent ICE-guided LAAO and 6,699 underwent TEE-guided LAAO. After propensity score matching, 3,442 patients remained in each cohort with well-balanced baseline characteristics. At 30 days, all-cause mortality was numerically lower with ICE than TEE (0.4
The pathological misfolding and aggregation of the microtubule associated protein tau (MAPT), a full length Tau2N4R with 441aa, is considered the principal disease relevant constituent in tauopathies including Alzheimer's disease (AD) with an imbalanced ratio in 3R/4R isoforms. The exact cellular fluid composition, properties, and changes that coincide with tau misfolding, seed formation, and propagation events remain obscure. The proteostasis network, along with the associated osmolytes, is responsible for maintaining the presence of tau in its native structure or dealing with misfolding. In this study, for the first time, the roles of natural brain osmolytes are being investigated for their potential effects on regulating the conformational stability of the tau monomer (tauM) and its propensity to aggregate or disaggregate. Herein, the effects of physiological osmolytes myo-inositol, taurine, trimethyl amine oxide (TMAO), betaine, sorbitol, glycerophosphocholine (GPC), and citrulline on tau's aggregation state were investigated. The overall results indicate the ability of sorbitol and GPC to maintain the monomeric form and prevent aggregation of tau, whereas myo-inositol, taurine, TMAO, betaine, and citrulline promote tau aggregation to different degrees, as revealed by protein morphology in atomic force microscopy images. Biochemical and biophysical methods also revealed that tau proteins adopt different conformations under the influence of these osmolytes. TauM in the presence of all osmolytes expressed no toxicity when tested by a lactate dehydrogenase assay. Investigating the conformational stability of tau in the presence of osmolytes may provide a better understanding of the complex nature of tau aggregation in AD and the protective and/or chaotropic nature of osmolytes.
BACKGROUND:The use of balloon guide catheter (BGC) has been associated with better reperfusion and clinical outcomes in mechanical thrombectomy (MT) for large vessel occlusion stroke. However, the impact of BGC on angiographic and clinical outcomes in patients with distal medium vessel occlusion (DMVO) strokes undergoing MT has not been extensively investigated. METHODS:This is a retrospective analysis of a prospectively collected database from 14 comprehensive stroke centers in the United States and Europe. Patients with anterior circulation DMVO due to middle cerebral artery (MCA) M3/M4 or anterior cerebral artery (ACA) A1/A2-3 were included. The cohort was divided into BGC and non-BGC groups. Multivariable logistic regression and inverse probability of treatment weighting (IPTW) were used for comparison. The primary outcome was first pass effect (FPE) defined as modified treatment in cerebral infarction (mTICI) grade 2C/3 after single device pass. RESULTS:Among 199 patients who were eligible for analysis, 81 (40.7%) were female. The median age was 69 (60-81) years, and National Institutes of Health Stroke Scale score was 13 (7-18). The BGC group (n=73) had higher rates of FPE (53.4% vs 13.7%; IPTW aOR 5.63, 95%CI (2.43 to 13.10), P<0.001) compared with the non-BGC group (n=126). The BGC group had higher rates of modified Rankin Scale (mRS) 0-1 (42.9% vs 27.1%; IPTW aOR 2.78, 95% CI (1.10 to 7.07), P=0.031), mRS 0-2 (60.3% vs 41.5%; IPTW aOR 4.31, 95% CI (1.66 to 11.19), P=0.003), and lower rates of mortality at 90-days (12.7% vs 25.4%; IPTW aOR 0.32, 95% CI (0.11 to 0.98), P=0.047) compared with the non-BGC group. The rates of successful reperfusion at the end of the procedure and symptomatic intracerebral hemorrhage were comparable between both groups. CONCLUSION:The present study suggests that the use of BGC in DMVO undergoing MT may be associated with improved angiographic and clinical outcomes with no safety concerns. Prospective studies are warranted.
There are no approved treatments for Lassa fever, which is estimated to cause 100,000 to 300,000 infections and 5,000 deaths annually in West Africa1,2. Recently, it was shown that 4'-fluorouridine (also known as EIDD-2749), an orally available ribonucleoside analogue, protected guinea pigs from lethal challenge with the lineage IV prototype Josiah strain of Lassa virus when treatment was delayed beyond the onset of clinical signs of disease3. Here we assessed the therapeutic efficacy of 4'-fluorouridine in an African green monkey model of Lassa fever using the contemporary and apparently more pathogenic lineage VII Togo strain of Lassa virus. Daily treatment with 4'-fluorouridine beginning 6 days after Lassa virus infection, when the monkeys were viraemic and clinically ill, resulted in rapid and complete clearance of infectious virus in 4 out of 5 monkeys, and all treated monkeys survived to the pre-determined study end-point. Targeted transcriptomics showed that cellular responses and control of cytokinaemia contributed to the development of immunity. Our findings support the further development of 4'-fluorouridine both as a post-exposure prophylaxis to control outbreaks and as a therapeutic agent to treat symptomatic patients.
