Meta-Analysis of Noncompartmental Pharmacokinetic Parameters to Evaluate the Impact of CYP2C19 and CYP2C9 Genetic Polymorphisms on Abrocitinib Exposure.

Abrocitinib is a selective Janus kinase 1 inhibitor approved for the treatment of atopic dermatitis. It is metabolized primarily by cytochrome P450 (CYP) 2C19 (approximately 53%) and CYP2C9 (approximately 30%), which form 2 active metabolites. The pharmacologic activity of abrocitinib is attributable to the unbound exposures of abrocitinib and those metabolites with active moiety area under the plasma concentration-time curve (AUC) considered the best measure of the total pharmacological effect.

Iterative Design, Feasibility, and Preliminary Efficacy Testing for the Development of a Cooperative Card Game Intervention to Reduce Loneliness and Foster Social Connection.

To present the design, development, and pilot testing of , an empirically derived cooperative card game intervention to reduce loneliness and enhance connection. Theory and empirical evidence from domains such as self-disclosure, interpersonal closeness, and serious games informed the design of this game. Iterative design was used to develop the intervention, followed by feasibility and preliminary efficacy pilot testing.

Association between skeletal muscle mitochondrial dysfunction and insulin resistance in patients with rheumatoid arthritis: a case-control study.

Background: Insulin resistance affects a substantial proportion of patients with rheumatoid arthritis (RA). Skeletal muscle mitochondrial dysfunction results in the accumulation of lipid intermediates that interfere with insulin signaling. We therefore sought to determine if lower oxidative phosphorylation and muscle mitochondrial content are associated with insulin resistance in patients with RA.

Effects of a virtual voice-based coach delivering problem-solving treatment on emotional distress and brain function: a pilot RCT in depression and anxiety.

Consumer-based voice assistants have the ability to deliver evidence-based treatment, but their therapeutic potential is largely unknown. In a pilot trial of a virtual voice-based coach, Lumen, delivering problem-solving treatment, adults with mild-to-moderate depression and/or anxiety were randomized to the Lumen intervention (n = 42) or waitlist control (n = 21). The main outcomes included changes in neural measures of emotional reactivity and cognitive control, and Hospital Anxiety and Depression Scale [HADS] symptom scores over 16 weeks.

The Type I Interferon Signature Reflects Multiple Phenotypic and Activity Measures in Dermatomyositis.

Objective: The type 1 interferon (IFN) pathway is up-regulated in dermatomyositis (DM). We sought to define how organ-specific disease activity as well as autoantibodies and other clinical factors are independently associated with systemic type I IFN activity in adult patients with DM.

Methods: RNA sequencing was performed on 355 whole blood samples collected from 202 well-phenotyped DM patients followed up during the course of their clinical care.

Within-person associations of optimistic and pessimistic expectations with momentary stress, affect, and ambulatory blood pressure.

Background And Objectives: Although dispositional optimism and pessimism have been prospectively associated with health outcomes, little is known about how these associations manifest in everyday life. This study examined how short-term optimistic and pessimistic expectations were associated with psychological and physiological stress processes.

Methods: A diverse sample of adults (= 300) completed a 2-day/1-night ecological momentary assessment and ambulatory blood pressure (ABP) protocol at ∼45-minute intervals.

Immunological Insights into Cigarette Smoking-Induced Cardiovascular Disease Risk.

Smoking is one of the most prominent addictions of the modern world, and one of the leading preventable causes of death worldwide. Although the number of tobacco smokers is believed to be at a historic low, electronic cigarette use has been on a dramatic rise over the past decades. Used as a replacement for cigarette smoking, electronic cigarettes were thought to reduce the negative effects of burning tobacco.

Design and Formative Evaluation of a Virtual Voice-Based Coach for Problem-solving Treatment: Observational Study.

Background: Artificial intelligence has provided new opportunities for human interactions with technology for the practice of medicine. Among the recent artificial intelligence innovations, personal voice assistants have been broadly adopted. This highlights their potential for health care-related applications such as behavioral counseling to promote healthy lifestyle habits and emotional well-being.

Computing Components of Everyday Stress Responses: Exploring Conceptual Challenges and New Opportunities.

Repeated assessments in everyday life enables collecting ecologically valid data on dynamic, within-persons processes. These methods have widespread utility and application and have been extensively used for the study of stressors and stress responses. Enhanced conceptual sophistication of characterizing intraindividual stress responses in everyday life would help advance the field.

Vaccine Attitudes and COVID-19 Vaccine Intention Among Parents of Children With Kidney Disease or Primary Hypertension.

Rationale & Objective: Children with kidney disease and primary hypertension may be more vulnerable to COVID-19. We examined COVID-19 vaccine hesitancy among parents of children with chronic kidney disease or hypertension.

Study Design: Sequential explanatory mixed-methods design; survey followed by in-depth interviews.

Neutrophil Migratory Patterns: Implications for Cardiovascular Disease.

The body's inflammatory response involves a series of processes that are necessary for the immune system to mitigate threats from invading pathogens. Leukocyte migration is a crucial process in both homeostatic and inflammatory states. The mechanisms involved in immune cell recruitment to the site of inflammation are numerous and require several cascades and cues of activation.

Modeling SARS-CoV-2: Comparative Pathology in Rhesus Macaque and Golden Syrian Hamster Models.

Coronavirus disease 2019 (COVID-19) in humans has a wide range of presentations, ranging from asymptomatic or mild symptoms to severe illness. Suitable animal models mimicking varying degrees of clinical disease manifestations could expedite development of therapeutics and vaccines for COVID-19. Here we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulted in subclinical disease in rhesus macaques with mild pneumonia and clinical disease in Syrian hamsters with severe pneumonia.

Selective Isolation of Liver-Derived Extracellular Vesicles Redefines Performance of miRNA Biomarkers for Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Definitive diagnosis of the progressive form, non-alcoholic steatohepatitis (NASH), requires liver biopsy, which is highly invasive and unsuited to early disease or tracking changes. Inadequate performance of current minimally invasive tools is a critical barrier to managing NAFLD burden.

In-Depth Site-Specific O-Glycosylation Analysis of Glycoproteins and Endogenous Peptides in Cerebrospinal Fluid (CSF) from Healthy Individuals, Mild Cognitive Impairment (MCI), and Alzheimer's Disease (AD) Patients.

Site-specific O-glycoproteome mapping in complex biological systems provides a molecular basis for understanding the structure-function relationships of glycoproteins and their roles in physiological and pathological processes. Previous O-glycoproteome analysis in cerebrospinal fluid (CSF) focused on sialylated glycoforms, while missing information on other glycosylation types. In order to achieve an unbiased O-glycosylation profile, we developed an integrated strategy combining universal boronic acid enrichment, high-pH fractionation, and electron-transfer and higher-energy collision dissociation (EThcD) for enhanced intact O-glycopeptide analysis.

Retention of the NLRP3 Inflammasome-Primed Neutrophils in the Bone Marrow Is Essential for Myocardial Infarction-Induced Granulopoiesis.

Background: Acute myocardial infarction (MI) results in overzealous production and infiltration of neutrophils to the ischemic heart. This is mediated in part by granulopoiesis induced by the S100A8/A9-NLRP3-IL-1β signaling axis in injury-exposed neutrophils. Despite the transcriptional upregulation of the NLRP3 (Nod Like Receptor Family Pyrin Domain-Containing 3) inflammasome and associated signaling components in neutrophils, the serum levels of IL-1β (interleukin-1β), the effector molecule in granulopoiesis, were not affected by MI, suggesting that IL-1β is not released systemically.

Neutrophils in cardiovascular disease: warmongers, peacemakers, or both?

Neutrophils, the most abundant of all leucocytes and the first cells to arrive at the sites of sterile inflammation/injury act as a double-edged sword. On one hand, they inflict a significant collateral damage to the tissues and on the other hand, they help facilitate wound healing by a number of mechanisms. Recent studies have drastically changed the perception of neutrophils from being simple one-dimensional cells with an unrestrained mode of action to a cell type that display maturity and complex behaviour.

Role of Extracellular Vesicle-Derived Biomarkers in Drug Metabolism and Disposition.

Extracellular vesicles (EVs) are small, nonreplicating, lipid-encapsulated particles that contain a myriad of protein and nucleic acid cargo derived from their tissue of origin. The potential role of EV-derived biomarkers to the study of drug metabolism and disposition (DMD) has gained attention in recent years. The key trait that makes EVs an attractive biomarker source is their capacity to provide comparable insights to solid organ biopsy through an appreciably less invasive collection procedure.

Intra-individual Associations of Perceived Stress, Affective Valence, and Affective Arousal with Momentary Cortisol in a Sample of Working Adults.

Background: Research pairing ecological momentary assessment (EMA) methodology and ambulatory cortisol during daily life is still rare, as is careful testing of the within-person associations between stress, affect, and cortisol. Using a circumplex approach, we considered both valence and arousal components of affect.

Purpose: To examine the within-person covariation of momentary cortisol with momentary perceived stress, affective valence, and affective arousal in everyday life.

Oxidative Stress in Neutrophils: Implications for Diabetic Cardiovascular Complications.

Neutrophil behavior and function are altered by hyperglycemia associated with diabetes. Aberrant activation by hyperglycemia causes neutrophils to respond with increased production of reactive oxidative species (ROS). Excess ROS, a signature of primed neutrophils, can intracellularly induce neutrophils to undergo NETosis, flooding surrounding tissues with ROS and damage-associated molecular patterns such as S100 calcium binding proteins (S100A8/A9).

Evaluation of the Association of Polymorphisms With Palbociclib-Induced Neutropenia: Pharmacogenetic Analysis of PALOMA-2/-3.

Background: The most frequently reported treatment-related adverse event in clinical trials with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib is neutropenia. Allelic variants in ABCB1 and ERCC1 might be associated with early occurrence (i.e.

In-depth Site-specific Analysis of N-glycoproteome in Human Cerebrospinal Fluid and Glycosylation Landscape Changes in Alzheimer's Disease.

As the body fluid that directly interchanges with the extracellular fluid of the central nervous system (CNS), cerebrospinal fluid (CSF) serves as a rich source for CNS-related disease biomarker discovery. Extensive proteome profiling has been conducted for CSF, but studies aimed at unraveling site-specific CSF N-glycoproteome are lacking. Initial efforts into site-specific N-glycoproteomics study in CSF yield limited coverage, hindering further experimental design of glycosylation-based disease biomarker discovery in CSF.

Exploring the Use of Serum-Derived Small Extracellular Vesicles as Liquid Biopsy to Study the Induction of Hepatic Cytochromes P450 and Organic Anion Transporting Polypeptides.

Liver-derived small extracellular vesicles (sEVs), prepared from small sets of banked serum samples using a novel two-step protocol, were deployed as liquid biopsy to study the induction of cytochromes P450 (CYP3A4, CYP3A5, and CYP2D6) and organic anion transporting polypeptides (OATP1B1 and OATP1B3) during pregnancy (nonpregnant (T0), first, second, and third (T3) trimester women; N = 3 each) and after administration of rifampicin (RIF) to healthy male subjects. Proteomic analysis revealed induction (mean fold-increase, 90% confidence interval) of sEV CYP3A4 after RIF 300 mg × 7 days (3.5, 95% CI = 2.