Healthcare resource utilization and costs of using Cariprazine as the first versus subsequent adjunctive therapy for major depressive disorder.

Aim: Inadequate response to antidepressant therapy (ADT) is common in major depressive disorder (MDD); atypical antipsychotic (AA) adjunctive therapy may be effective for these patients. This study aimed to compare healthcare resource utilization (HRU) and costs between patients initiating the AA cariprazine as their first adjunctive therapy vs those initiating cariprazine subsequently.

Methods: The Merative MarketScan® Commercial Database (January 1, 2015, to June 30, 2021) was used to identify US adults with MDD and ≥1 pharmacy claim for cariprazine adjunctive to ADT in 2018 or after.

Phase I trial of ATR inhibitor elimusertib with FOLFIRI in advanced or metastatic gastrointestinal malignancies (ETCTN 10406).

Background: ATR is an apical DDR kinase activated at damaged replication forks. Elimusertib is an oral ATR inhibitor and potentiates irinotecan in human colorectal cancer models.

Methods: To establish dose and tolerability of elimusertib with FOLFIRI, a Bayesian Optimal Interval trial design was pursued.

Healthy Aging and the Gut Microbiome in People With and Without HIV.

Background: Aging-related comorbidities are more common in people with human immunodeficiency virus (HIV) compared to people without HIV. The gut microbiome may play a role in healthy aging; however, this relationship remains unexplored in the context of HIV.

Methods: 16S rRNA gene sequencing was conducted on stool from 1409 women (69% with HIV; 2304 samples) and 990 men (54% with HIV; 1008 samples) in the MACS/WIHS Combined Cohort Study.

Impact of the WHO safe childbirth checklist on birth attendant behavior and maternal-newborn outcomes: A systematic review and meta-analysis.

Background: The intrapartum period is critical for reducing maternal and perinatal morbidity and mortality. The WHO's Safe Childbirth Checklist (SCC) was designed as a reminder of the most critical, evidence-based practices (EBPs) to improve quality care and reduce preventable complications and deaths.

Objective: To assess the impact of SCC on birth attendant behavior and maternal and newborn health outcomes.

Cripto-1 acts as a molecular bridge linking nodal to ALK4 via distinct structural domains.

The TGF-β family ligand Nodal is an essential regulator of embryonic development, orchestrating key processes such as germ layer specification and body axis formation through activation of SMAD2/3-mediated signaling. Significantly, this activation requires the co-receptor Cripto-1. However, despite their essential roles in embryogenesis, the molecular mechanism through which Cripto-1 enables Nodal to activate the SMAD2/3 pathway has remained elusive.

Chemical and temporal manipulation of early steps in protein assembly tunes the structure and intermolecular interactions of protein-based materials.

The Drosophila intrinsically disordered protein Ultrabithorax (Ubx) undergoes a series of phase transitions, beginning with noncovalent interactions between apparently randomly organized monomers, and evolving over time to form increasingly ordered coacervates. This assembly process ends when specific dityrosine covalent bonds lock the monomers in place, forming macroscale materials. Inspired by this hierarchical, multistep assembly process, we analyzed the impact of protein concentration, assembly time, and subphase composition on the early, noncovalent stages of Ubx assembly, which are extremely sensitive to their environment.

The Feasibility of Omega-3 Supplementation Compared to Placebo in the Management of Long COVID Symptoms Among Healthcare Workers: A Randomized Controlled Trial.

Background:  COVID-19 is known to cause significant multisystem inflammatory responses, leading to symptoms beyond the acute phase of illness. These "long COVID" symptoms affect quality of life and interfere with daily activities. This pilot study looks at the feasibility, tolerability, and safety of omega-3 (docosahexaenoic acid+eicosapentaenoic acid, EPA) among healthcare workers with long COVID symptoms in New Jersey.

Genotype-function-phenotype correlations for SCN1A variants identified by clinical genetic testing.

Objective: Interpretation of clinical genetic testing, which identifies a potential genetic etiology in 25% of children with epilepsy, is limited by variants of uncertain significance. Understanding functional consequences of variants can help distinguish pathogenic from benign alleles. We combined automated patch clamp recording with neurophysiological simulations to discern genotype-function-phenotype correlations in a real-world cohort of children with SCN1A-associated epilepsy.

Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches.

Central nervous system (CNS) injuries, such as ischemic stroke (IS), intracerebral hemorrhage (ICH) and traumatic brain injury (TBI), are a significant global burden. The complex pathophysiology of CNS injury is comprised of primary and secondary injury. Inflammatory secondary injury is incited by damage-associated molecular patterns (DAMPs) which signal a variety of resident CNS cells and infiltrating immune cells.

Psychotropic Polypharmacy in Dementia: A Retrospective Analysis for People with Neuropsychiatric Symptoms Referred to an Australian Dementia Support Service.

Background And Objectives: Despite their limited benefits and serious adverse effects, psychotropics remain frequently prescribed for neuropsychiatric symptoms (NPS) of dementia. Psychotropic polypharmacy, the use of two or more concomitant psychotropic medications, is therefore not recommended for people with dementia. The objectives of this study were to investigate the prevalence of psychotropic polypharmacy in Australians living with dementia whose caregivers sought external NPS support from Dementia Support Australia (DSA; the national provider of NPS support) and the association of psychotropic polypharmacy with their demographics and NPS characteristics.

Quantifying glucose uptake at the single cell level with confocal microscopy reveals significant variability within and across individuals.

Measurement of glycated hemoglobin (HbA1c) in human red blood cells plays a critical role in the diagnosis and treatment of diabetes mellitus. However, recent studies have suggested large variation in the relationship between average glucose levels and HbA1c, creating the need to understand glucose variability at the cellular level. Here, we devised a fluorescence-based method to quantitatively observe GLUT1-mediated intracellular glucose analog tracer uptake in individual RBCs utilizing microfluidics and confocal microscopy.

OGG1 and MUTYH repair activities promote telomeric 8-oxoguanine induced senescence in human fibroblasts.

Telomeres are hypersensitive to the formation of the common oxidative lesion 8-oxoguanine (8oxoG), which impacts telomere stability and function. OGG1 and MUTYH glycosylases initiate base excision repair (BER) to remove 8oxoG or prevent mutation. Here, we show OGG1 loss or inhibition, or MUTYH loss, partially rescues telomeric 8oxoG-induced premature senescence and associated proinflammatory responses, while loss of both glycosylases causes a near complete rescue in human fibroblasts.

Retrospective Evaluation of Novel Synthetic Opioids and Xylazine Chronic Intake by Post-Mortem Hair Testing.

Fentanyl and its derivatives (nonpharmaceutical fentanyl, NPFs) represent the largest group among synthetic opioids. Fentanyl-related deaths and fatalities from tampering with pharmaceutical products have been reported. Furthermore, in the United States, adulterants such as xylazine and other substances, including the nitazenes class of opioids, have been found in an increasing number of unintentional overdose deaths, drug seizures, and reports of use by recreational drug users.

Origins of T-cell-mediated autoimmunity in acquired aplastic anaemia.

Acquired aplastic anaemia (AA) is an autoimmune bone marrow failure disease resulting from a cytotoxic T-cell-mediated attack on haematopoietic stem and progenitor cells (HSPCs). Despite significant progress in understanding the T-cell repertoire alterations in AA, identifying specific pathogenic T cells in AA patients has remained elusive, primarily due to the unknown antigenic targets of the autoimmune attack. In this review, we will synthesize findings from several decades of research to critically evaluate the current knowledge on T-cell repertoires in AA.

Impact of Atrial Fibrillation Diagnosis-to-Ablation Time on 24-Month Efficacy and Safety Outcomes in the Cryo Global Registry.

Background And Aims: Early rhythm-control therapy in atrial fibrillation (AF) results in higher freedom from atrial arrhythmia (AA) recurrence and improved cardiovascular outcomes. The optimal timing of Cryoballoon ablation (CBA) is unknown.

Methods: We evaluated AA recurrence and procedure-related complications of early vs.

Clinical outcomes among COVID-19 patients initiated on molnupiravir in Denmark - A national registry study.

Background: Molnupiravir (MOV) is an orally bioavailable ribonucleoside with antiviral activity against all tested SARS-CoV-2 variants. We describe the demographic, clinical, and treatment characteristics of non-hospitalized Danish patients treated with MOV and their clinical outcomes following MOV initiation.

Method: Among all adults (>18 years) who received MOV between 16 December 2021 and 30 April 2022 in an outpatient setting in Denmark, we summarized their demographic and clinical characteristics at baseline and post-MOV outcomes using descriptive statistics.

Return to Sport After Distal Biceps Tendon Repair: A Systematic Review.

Background: Ruptures of the distal biceps tendon (DBT) can affect the range of motion and strength of the elbow, raising concerns for patients seeking to restore normal function and engage in their regular activities, particularly returning to previous levels of sport participation.

Purpose: To characterize and assess the rate and timing of return to sport (RTS) after DBT repair.

Study Design: Systematic review; Level of evidence, 4.

Machine Learning-Based Prediction of Binge Drinking among Adults in the United State: Analysis of the 2022 Health Information National Trends Survey.

Little is known about the association of social media and belief in alcohol and cancer with binge drinking. This study aimed to perform feature selection and develop machine learning (ML) tools to predict occurrence of binge drinking among adults in the United State. A total of 5,886 adults including 1,252 who ever experienced with binge drinking were selected from the 2022 Health Information National Trends Survey (HINTS 6).

What Matters Most for Long-Acting Antiretroviral Therapy? A Best-Worst Scaling Discrete Choice Experiment.

Introduction: Florida remains a high-incidence, high-prevalence setting for HIV. Long-acting (LA) antiretroviral therapies (ART) could improve HIV-related outcomes and reduce transmission. This study identifies preferred LA ART characteristics and classes of preference among people with HIV (PWH) in Florida.

Genetic context modulates aging and degeneration in the murine retina.

Background: Age is the principal risk factor for neurodegeneration in both the retina and brain. The retina and brain share many biological properties; thus, insights into retinal aging and degeneration may shed light onto similar processes in the brain. Genetic makeup strongly influences susceptibility to age-related retinal disease.

Cinnamaldehyde impacts key cellular signaling pathways for induction of programmed cell death in high-grade and low-grade human glioma cells.

Objective: Primary tumors of the brain and a large percent of malignant brain tumors are gliomas. Gliomas comprise high-grade gliomas like glioblastoma multiforme (GBMs), many of which have mutation in the tumor suppressor p53 gene and low-grade gliomas (LGGs). LGGs can progress to GBMs due to various factors.

Mapping the effectiveness and risks of GLP-1 receptor agonists.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are increasingly being used to treat diabetes and obesity. However, their effectiveness and risks have not yet been systematically evaluated in a comprehensive set of possible health outcomes. Here, we used the US Department of Veterans Affairs databases to build a cohort of people with diabetes who initiated GLP-1RA (n = 215,970) and compared them to those who initiated sulfonylureas (n = 159,465), dipeptidyl peptidase 4 (DPP4) inhibitors (n = 117,989) or sodium-glucose cotransporter-2 (SGLT2) inhibitors (n = 258,614), a control group composed of an equal proportion of individuals initiating sulfonylureas, DPP4 inhibitors and SGLT2 inhibitors (n = 536,068), and a control group of 1,203,097 individuals who continued use of non-GLP-1RA antihyperglycemics (usual care).

Pharmacogenetic associations of GATA4 and KCNQ1 with ibrutinib cardiovascular toxicity.

Ibrutinib treatment is often complicated by cardiovascular side effects (CVSEs). The objective of this retrospective pharmacogenetic study is to replicate a previously reported association of 'high-risk' patients, who are homozygous carriers of at least two of GATA4 rs804280 AA, KCNQ1 rs163182 GG, and KCNQ1 rs2237895 AA, with increased risk of hypertension or atrial fibrillation, and explore associations for other pharmacogenes (e.g.

Associations Among Emotion Regulation, COVID Stress, Alcohol Use, and Intimate Partner Aggression Among College Students During the COVID-19 Pandemic.

Purpose: Intimate partner aggression (IPA) increased after the onset of the COVID-19 pandemic. Following the Vulnerability-Stress-Adaptation (VSA) model, the current study examined associations among emotion regulation (ER) difficulties (an enduring vulnerability), COVID stress (a current stressor), alcohol use (a maladaptive coping strategy), and physical, psychological, and cyber IPA perpetration during the first eight months of the pandemic.

Method: Participants were 215 college students in current relationships from three universities across the US.