Derivation and Validation of a Model to Predict Clinically Significant Portal Hypertension Using Transient Elastography and FIB-4.

Background: Liver biopsy and hepatic venous pressure gradient (HVPG), the gold standard for assessing advanced fibrosis (AF) and clinically significant portal hypertension (CSPH), are invasive, costly, and time-consuming.

Goal: We investigated if the combination of fibrosis index based on 4 factors (FIB-4) and liver stiffness measure (LSM) can identify AF and more importantly, CSPH.

Patients And Methods: Patients with chronic liver disease referred for transjugular liver biopsy were analyzed retrospectively.

Radial Artery Access Complications: Prevention, Diagnosis and Management.

The transradial approach for cardiac catheterization, coronary angiography, and percutaneous intervention is associated with a lower risk of access site-related complications compared to the transfemoral approach. However, with increasing utilization of transradial access for not only coronary procedures but also peripheral vascular procedures, healthcare personnel are more likely to encounter radial access site complications, which can be associated with morbidity and mortality. There is significant heterogeneity in the reporting of incidence, manifestations, and management of radial access site complications, at least partly due to vague presentation and under-diagnosis.

Vitamin D: Dosing, levels, form, and route of administration: Does one approach fit all?

The 4 International Conference on Controversies in Vitamin D was held as a virtual meeting in September, 2020, gathering together leading international scientific and medical experts in vitamin D. Since vitamin D has a crucial role in skeletal and extra-skeletal systems, the aim of the Conference was to discuss improved management of vitamin D dosing, therapeutic levels and form or route of administration in the general population and in different clinical conditions. A tailored approach, based on the specific mechanisms underlying vitamin D deficiency in different diseases that were discussed, was recommended.

25-Hydroxycholesterol 3-Sulfate Recovers Acetaminophen Induced Acute Liver Injury via Stabilizing Mitochondria in Mouse Models.

Acetaminophen (APAP) overdose is one of the most frequent causes of acute liver failure (ALF). N-acetylcysteine (NAC) is currently being used as part of the standard care in the clinic but its usage has been limited in severe cases, in which liver transplantation becomes the only treatment option. Therefore, there still is a need for a specific and effective therapy for APAP induced ALF.

Bile Acid Receptors and the Gut-Liver Axis in Nonalcoholic Fatty Liver Disease.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been significantly increased due to the global epidemic of obesity. The disease progression from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is closely linked to inflammation, insulin resistance, and dysbiosis. Although extensive efforts have been aimed at elucidating the pathological mechanisms of NAFLD disease progression, current understanding remains incomplete, and no effective therapy is available.

Anticholinergic Medication Burden in Parkinson's Disease Outpatients.

Background: Individuals with Parkinson's disease (PD) may be especially vulnerable to future cognitive decline from anticholinergic medications.

Objective: To characterize anticholinergic medication burden, determine the co-occurrence of anticholinergic and cholinesterase inhibitors, and to assess the correlations among anticholinergic burden scales in PD outpatients.

Methods: We studied 670 PD outpatients enrolled in a clinic registry between 2012 and 2020.

The Implications of Power Mobility on Body Weight in a Veteran Population.

Background: The prevalence of obesity is increasing in the United States. A common concern among health care providers is that prescribing a power mobility device (PMD) may decrease physical activity and lead to obesity and increasing morbidity. This study analyzes the effect of PMD prescriptions over a 2-year period on body mass index (BMI) and body weight in a population of veterans both as a whole and in BMI/age subgroups.

Axonal injury following mild traumatic brain injury is exacerbated by repetitive insult and is linked to the delayed attenuation of NeuN expression without concomitant neuronal death in the mouse.

Mild traumatic brain injury (mTBI) affects brain structure and function and can lead to persistent abnormalities. Repetitive mTBI exacerbates the acute phase response to injury. Nonetheless, its long-term implications remain poorly understood, particularly in the context of traumatic axonal injury (TAI), a player in TBI morbidity via axonal disconnection, synaptic loss and retrograde neuronal perturbation.

A Review of Implementation Concepts and Strategies Surrounding Traumatic Brain Injury Clinical Care Guidelines.

Despite considerable efforts to advance the science surrounding traumatic brain injury (TBI), formal efforts supporting the current and future implementation of scientific findings within clinical practice and healthcare policy are limited. While many and varied guidelines inform the clinical management of TBI across the spectrum, clinicians and healthcare systems are not broadly adopting, implementing, and/or adhering to them. As part of the Brain Trauma Blueprint TBI State of the Science, an expert workgroup was assembled to guide this review article, which describes: (1) possible etiologies of inadequate adoption and implementation; (2) enablers to successful implementation strategies; and (3) strategies to mitigate the barriers to adoption and implementation of future research.

Cardiac Effects of Phosphodiesterase-5 Inhibitors: Efficacy and Safety.

The coexistence of cardiovascular disease and erectile dysfunction is widespread, possibly owing to underlying endothelial dysfunction in both diseases. Millions of patients with cardiovascular disease are prescribed phosphodiesterase-5 (PDE5) inhibitors for the management of erectile dysfunction. Although the role of PDE5 inhibitors in erectile dysfunction therapy is well established, their effects on the cardiovascular system are unclear.

Evaluating the Bioenergetics Health Index Ratio in Leigh Syndrome Fibroblasts to Understand Disease Severity.

Several pediatric mitochondrial disorders, including Leigh syndrome (LS), impact mitochondrial (mt) genetics, development, and metabolism, leading to complex pathologies and energy failure. The extent to which pathogenic mtDNA variants regulate disease severity in LS is currently not well understood. To better understand this relationship, we computed a glycolytic bioenergetics health index (BHI) for measuring mitochondrial dysfunction in LS patient fibroblast cells harboring varying percentages of pathogenic mutant mtDNA (, ) exhibiting deficiency in complex V or complex I (, ).

Is Sleep Disordered Breathing Confounding Rehabilitation Outcomes in Spinal Cord Injury Research?

The purpose of this article is to highlight the importance of considering sleep-disordered breathing (SDB) as a potential confounder to rehabilitation research interventions in spinal cord injury (SCI). SDB is highly prevalent in SCI, with increased prevalence in individuals with higher and more severe lesions, and the criterion standard treatment with continuous positive airway pressure remains problematic. Despite its high prevalence, SDB is often untested and untreated in individuals with SCI.

Severe Vitamin B12 Deficiency Mimicking Microangiopathic Hemolytic Anemia.

Most individuals with vitamin B12 deficiency present with anemia, fatigue, and neurologic disturbances such as paresthesia and loss of sensory function if chronic. However, in severe states, it may manifest as hemolytic anemia, thrombocytopenia, schistocytosis, elevated lactate dehydrogenase, and low reticulocyte production. This phenomenon is known as pseudo-thrombotic microangiopathy (TMA), and is most commonly due to pernicious anemia.

Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer's disease-like neuroinflammation and cognitive impairment.

Background: Human genetic association studies point to immune response and lipid metabolism, in addition to amyloid-beta (Aβ) and tau, as major pathways in Alzheimer's disease (AD) etiology. Accumulating evidence suggests that chronic neuroinflammation, mainly mediated by microglia and astrocytes, plays a causative role in neurodegeneration in AD. Our group and others have reported early and dramatic losses of brain sulfatide in AD cases and animal models that are mediated by ApoE in an isoform-dependent manner and accelerated by Aβ accumulation.

Impulsivity and Medical Care Utilization in Veterans Treated for Substance Use Disorder.

Impulsivity has been defined by acting rashly during positive mood states (positive urgency; PU) or negative mood states (negative urgency; NU) and by excessive de-valuation of deferred rewards. These behaviors reflect a "live in the now" mentality that is not only characteristic of many individuals with severe substance use disorder (SUD) but also impedes medical treatment compliance and could result in repeated hospitalizations or other poor health outcomes. We sought preliminary evidence that impulsivity may relate to adverse health outcomes in the veteran population.

Extracellular proteolytic activation of Pseudomonas aeruginosa aminopeptidase (PaAP) and insight into the role of its non-catalytic N-terminal domain.

Pseudomonas aeruginosa secretes several endopeptidases, including elastase, alkaline proteinase (Apr), a lysine-specific endopeptidase (LysC), and an aminopeptidase (PaAP), all of which are important virulence factors. Activation of the endopeptidases requires removal of an inhibitory N-terminal propeptide. Activation of pro-PaAP, in contrast, requires C-terminal processing.

Eccentric hypertrophy in an animal model of mid- and long-term premature ventricular contraction-induced cardiomyopathy.

Background: Tachycardia and heart rate irregularity are proposed triggers of premature ventricular contraction-induced cardiomyopathy (PVC-cardiomyopathy). Bigeminal premature atrial and ventricular contractions (PACs and PVCs) increase heart rate and result in rhythm irregularities but differ in their effects on ventricular synchrony. Comparing chronic bigeminal PACs with PVCs would provide insights into mechanisms of PVC-cardiomyopathy.

Pre-Clinical Activity of Amino-Alcohol Dimeric Naphthoquinones as Potential Therapeutics for Acute Myeloid Leukemia.

Background: The clinical outcomes of patients with Acute Myeloid Leukemia (AML) remain unsatisfactory. Therefore the development of more efficacious and better-tolerated therapy for AML is critical. We have previously reported anti-leukemic activity of synthetic halohydroxyl dimeric naphthoquinones (BiQ) and aziridinyl BiQ.

Novel oral anticoagulants in the treatment of radial artery occlusion.

Transradial access of the vascular system for coronary angiography and percutaneous coronary intervention has become the primary approach in several cardiac catheterization laboratories across the world. The paradigm shift from transfemoral access has been driven by improved outcomes in patients undergoing these cardiac procedures by transradial access. Radial artery occlusion is the most common vascular complication of transradial coronary procedures.

Synopsis of the 2020 U.S. VA/DoD Clinical Practice Guideline for the Management of Adult Overweight and Obesity.

Introduction: In May of 2020, the U.S. Veterans Health Administration (VHA) and Department of Defense (DoD) approved a new joint clinical practice guideline for assessing and managing patients who have overweight and obesity.

Clinical and translational insights on premature ventricular contractions and PVC-induced cardiomyopathy.

The medical community's understanding of the consequences of premature ventricular contractions (PVCs) and PVC-induced cardiomyopathy has been derived mostly from observational and large population-based studies. Due to the difficulty of predicting the development of PVC-cardiomyopathy, the acute and chronic cardiac effects of PVCs and the mechanism of PVC-cardiomyopathy have been derived from pre-clinical studies with large animal models. Recently, these studies have described myocardial substrates that could potentially increase morbidity and mortality in patients with frequent PVCs and PVC-cardiomyopathy.

Atherogenic Dyslipidemia After Liver Transplantation: Mechanisms and Clinical Implications.

Cardiovascular disease (CVD), particularly atherosclerosis-associated CVD, is a major cause of long-term mortality after liver transplantation (LT). The liver is central in lipid homeostasis, and changes associated with insulin resistance, weight gain, adipose tissue inflammation, and development of nonalcoholic fatty liver disease (NAFLD) after LT promote atherogenesis. These factors synergistically alter lipid homeostasis, thereby leading to the production of proatherogenic lipoproteins, which contribute to the heighted risk of CVD-associated events observed in LT recipients.

Bladder wall micromotion measured by non-invasive ultrasound: initial results in women with and without overactive bladder.

Objective: Rhythmic contractions of the bladder wall during filling result from the synchronization of bladder wall micromotion and are often observed in the urodynamic tracings of individuals with urinary overactive bladder (OAB). This study's objective was to develop a novel, non-invasive method to measure bladder wall micromotion and to conduct an initial study to test the hypothesis that elevated micromotion is associated with OAB.

Methods: This prospective study enrolled women with OAB and asymptomatic volunteers as measured by the ICIQ-OAB survey.