Evaluation of Blood-Based Plasma Biomarkers as Potential Markers of Amyloid Burden in Preclinical Alzheimer's Disease.

Background: Participant eligibility for the A4 Study was determined by amyloid PET imaging. Given the disadvantages of amyloid PET imaging in accessibility and cost, blood-based biomarkers may serve as a sufficient biomarker and more cost-effective screening tool for patient enrollment into preclinical AD trials.

Objective: To determine if a blood-based screening test can adequately identify amyloid burden in participants screened into a preclinical AD trial.

Cardiovascular Outcome Trials in Type 2 Diabetes: What Do They Mean for Clinical Practice?

Cardiovascular disease is the leading cause of morbidity and mortality in people with diabetes, and deaths from heart disease are two to four times higher among adults with type 2 diabetes. Trials such as the U.K.

Pulse wave velocity and central aortic pressure in systolic blood pressure intervention trial participants.

Unlabelled: Arterial stiffness, typically assessed as the aortic pulse wave velocity (PWV), and central blood pressure levels may be indicators of cardiovascular disease (CVD) risk. This ancillary study to the Systolic Blood Pressure Intervention Trial (SPRINT) obtained baseline assessments (at randomization) of PWV and central systolic blood pressure (C-SBP) to: 1) characterize these vascular measurements in the SPRINT cohort, and 2) test the hypotheses that PWV and C-SBP are associated with glucose homeostasis and markers of chronic kidney disease (CKD). The SphygmoCor® CPV device was used to assess carotid-femoral PWV and its pulse wave analysis study protocol was used to obtain C-SBP.

A gene co-expression module implicating the mitochondrial electron transport chain is associated with long-term response to lithium treatment in bipolar affective disorder.

Lithium is the first-line treatment for bipolar affective disorder (BPAD) but two-thirds of patients respond only partially or not at all. The reasons for this high variability in lithium response are not well understood. Transcriptome-wide profiling, which tests the interface between genes and the environment, represents a viable means of exploring the molecular mechanisms underlying lithium response variability.

Effect of HIV-1 low-level viraemia during antiretroviral therapy on treatment outcomes in WHO-guided South African treatment programmes: a multicentre cohort study.

Background: Antiretroviral therapy (ART) that enables suppression of HIV replication has been successfully rolled out at large scale to HIV-positive patients in low-income and middle-income countries. WHO guidelines for these regions define failure of ART with a lenient threshold of viraemia (HIV RNA viral load ≥1000 copies per mL). We investigated the occurrence of detectable viraemia during ART below this threshold and its effect on treatment outcomes in a large South African cohort.

Pyroptosis by caspase11/4-gasdermin-D pathway in alcoholic hepatitis in mice and patients.

Unlabelled: Alcoholic hepatitis (AH) continues to be a disease with high mortality and no efficacious medical treatment. Although severe AH is presented as acute on chronic liver failure, what underlies this transition from chronic alcoholic steatohepatitis (ASH) to AH is largely unknown. To address this question, unbiased RNA sequencing and proteomic analyses were performed on livers of the recently developed AH mouse model, which exhibits the shift to AH from chronic ASH upon weekly alcohol binge, and these results are compared to gene expression profiling data from AH patients.

A Rare Case of Exclusively Oncocytic Mucoepidermoid Carcinoma with MAML2 Translocation.

Mucoepidermoid carcinoma is the most common malignant tumor of the salivary gland. The oncocytic variant of mucoepidermoid carcinoma (OMEC) is rare and a small subset shows exclusive oncocytic morphology. Here we report an OMEC case of the parotid gland in a 74-year-old woman with exclusive oncocytes and rare mucocytes.

Multicentre safety of adding Focal Impulse and Rotor Modulation (FIRM) to conventional ablation for atrial fibrillation.

Aims: Focal Impulse and Rotor Modulation (FIRM) uses 64-electrode basket catheters to identify atrial fibrillation (AF)-sustaining sites for ablation, with promising results in many studies. Accordingly, new basket designs are being tested by several groups. We set out to determine the procedural safety of adding basket mapping and map-guided ablation to conventional pulmonary vein isolation (PVI).

p16INK4A expression is frequently increased in periorbital and ocular squamous lesions.

Background: p16 expression is a well established biomarker of cervical dysplasia and carcinoma arising from high risk human papilloma virus infection. Increased p16 expression is also seen in squamous neoplasms arising at other sites, including head, neck, and oropharyngeal tract. Squamous lesions are also frequently encountered at ocular surface and peri-orbital skin sites, but the prevalence of increased p16 expression in these lesions has been poorly studied.

Mechanisms Underlying AF: Triggers, Rotors, Other?

There is ongoing debate regarding the precise mechanisms underlying atrial fibrillation (AF). An improved understanding of these mechanisms is urgently needed to improve interventional strategies to suppress and eliminate AF, since the success of current strategies is suboptimal. At present, guidelines for AF ablation focus on pulmonary vein (PV) isolation for the prevention of arrhythmia.

Post-mortem timing of skeletal muscle biochemical and mechanical degradation.

Fresh cadaveric human tissue is a valuable resource that is used to address important clinical questions. However, it is unknown how post-mortem time impacts skeletal muscle mechanical and biochemical properties. We simulated morgue conditions in rabbits and tested the passive mechanical properties of muscle bundles, and the degradation of myosin heavy chain, collagen, and titin at specific intervals up to 7 days post-mortem.

Reductions in systolic blood pressure with liraglutide in patients with type 2 diabetes: insights from a patient-level pooled analysis of six randomized clinical trials.

Aims: To quantify the effect of liraglutide on systolic blood pressure (SBP) and pulse in patients with type 2 diabetes (T2D), and assess the influence of covariates on observed SBP reductions.

Methods: A patient-level pooled analysis of six phase 3, randomized trials was conducted.

Results: The analysis included 2792 randomized patients.

C-reactive protein and pain sensitivity: findings from female twins.

Background: Systemic inflammation and pain sensitivity may contribute to the development and maintenance of chronic pain conditions.

Purpose: We examined the relationship between systemic inflammation as measured by C-reactive protein (CRP) and cold pain sensitivity in 198 female twins from the University of Washington Twin Registry. We also explored the potential role of familial factors in this relationship.

Adenylate cyclase 6 determines cAMP formation and aquaporin-2 phosphorylation and trafficking in inner medulla.

Arginine vasopressin (AVP) enhances water reabsorption in the renal collecting duct by vasopressin V₂ receptor (V₂R)-mediated activation of adenylyl cyclase (AC), cAMP-promoted phosphorylation of aquaporin-2 (AQP2), and increased abundance of AQP2 on the apical membrane. Multiple isoforms of adenylate cyclase exist, and the roles of individual AC isoforms in water homeostasis are not well understood. Here, we found that levels of AC6 mRNA, the most highly expressed AC isoform in the inner medulla, inversely correlate with fluid intake.