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.

Inhibition of diacylglycerol lipase α induced blood-brain barrier breach in female Sprague-Dawley rats.

The endocannabinoid system's significance in maintaining blood-brain barrier (BBB) integrity under physiological and pathological conditions is suggested by several reports, but the underlying molecular mechanisms are not well understood. In this paper, we investigated the effects of depletion of 2-arachidonoylglycerol (2-AG), one of the main endocannabinoids in the central nervous system, on BBB integrity using pharmacological tools. Female Sprague-Dawley rats were injected with the diacylglycerol lipase α (DAGLα) inhibitor LEI-106 (40 mg/kg, i.

PET imaging of Mn labeled DOTATATE and DOTAJR11.

Manganese-52 is gaining interest as an isotope for PET imaging due to its desirable decay and chemical properties for radiopharmaceutical development. Somatostatin receptor 2 (SSTR2) is significantly overexpressed by neuroendocrine tumors (NETs) and is an important target for nuclear imaging and therapy. As an agonist, [Ga]Ga-DOTATATE has demonstrated significant internalization upon interaction with receptor ligands, whereas [Ga]Ga-DOTA-JR11(as an antagonist) exhibits limited internalization but better pharmacokinetics and increased tumor uptake.

Quantification and prediction of human fetal (-)-Δ-tetrahydrocannabinol/(±)-11-OH-Δ-tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicity.

Prenatal cannabis use is associated with neurodevelopmental deficits, likely due to exposure to the psychoactive cannabinoid, (-)-Δ-tetrahydrocannabinol, and its active metabolite, (±)-11-OH-Δ-tetrahydrocannabinol. To determine causality, preclinical studies mimicking human fetal cannabinoid exposure must be conducted. Here we show cannabinoid concentrations across gestation in maternal plasma and paired fetal tissues in trimester 1 and 2 and maternal plasma and fetal umbilical venous plasma in trimester 3.

Dihydropyrimidine enzyme activity and its effect on chemotherapy toxicity: importance of genetic testing.

Purpose: Patients with partial or complete DPD deficiency have decreased capacity to degrade fluorouracil and are at risk of developing toxicity, which can be even life-threatening.

Case: A 43-year-old man with moderately differentiated rectal adenocarcinoma on capecitabine presented to the emergency department with complaints of nausea, vomiting, diarrhea, weakness, and lower abdominal pain for several days. Laboratory findings include grade 4 neutropenia (ANC 10) and thrombocytopenia (platelets 36,000).

Ritlecitinib, a JAK3 /TEC inhibitor, modulates the markers of celiac autoimmunity in alopecia areata and vitiligo patients.

Background: Celiac disease (CeD) has shown an association with autoimmune disorders including vitiligo and alopecia areata (AA). Ritlecitinib, a JAK3 and TEC kinase family inhibitor, has been approved for treatment of patients with AA and is in late-stage development for vitiligo. Ritlecitinib inhibits cytotoxic T cells, NK cells, and B cells which play a role in the pathogenesis of CeD.

Daily associations between sleep and alcohol use among veterans: Acute and cumulative effects.

Background And Aims: Military veterans demonstrate high rates of heavy drinking and insomnia, but few if any studies have tested real-world, daily associations between sleep and alcohol use within this population. Moreover, although daily diary and experimental studies among civilians have found negative associations between alcohol use and sleep, these patterns change with consecutive days of drinking and may differ for those with insomnia. This study measured (a) acute and cumulative day-level associations between sleep and alcohol use among heavy-drinking US veterans and (b) the extent to which insomnia moderates these associations.

Head-to-Head Comparison Between Phosphatidylethanol Versus Indirect Alcohol Biomarkers for Diagnosis of MetALD Versus MASLD: A Prospective Study.

Background: The current subclassification of steatotic liver disease (SLD) relies on validated questionnaires, such as Alcohol Use Disorders Identification Test (AUDIT) and Lifetime Drinking History (LDH), which, while useful, are impractical and lack precision for their use in routine clinical practice. Phosphatidylethanol (PEth) is a quantitative, objective alcohol biomarker with high sensitivity and specificity.

Aims: To assess the diagnostic accuracy of PEth for differentiating metabolic dysfunction and alcohol-associated liver disease (MetALD) from metabolic dysfunction-associated steatotic liver disease (MASLD) in a large, population-based, prospective, multiethnic cohort of individuals with overweight or obesity.

Descriptive analysis of interpreter service mode costs & usage in Northwestern Wisconsin pre and peri COVID-19.

Background: Interpreter service mode (in person, audio, or video) can impact patient experiences and engagement in the healthcare system, but clinics must balance quality with costs and volume to deliver services. Videoconferencing and telephone services provide lower cost options, effective where on site interpreters are scarce, or patients with limited English proficiency (LEP) and/or interpreters are unable to visit healthcare centers. The COVID 19 pandemic generated these conditions in Northwest Wisconsin (NWWI).

Safety and Efficacy of Deutetrabenazine at High versus Lower Daily Dosages in the ARC-HD Study to Treat Chorea in Huntington Disease.

Background: Huntington disease (HD) is a progressive neurodegenerative disease that causes psychiatric and neurological symptoms, including involuntary and irregular muscle movements (chorea). Chorea can disrupt activities of daily living, pose safety issues, and may lead to social withdrawal. The vesicular monoamine transporter 2 inhibitors tetrabenazine, deutetrabenazine, and valbenazine are approved treatments that can reduce chorea.

Association between herpes simplex virus infection and Alzheimer's disease biomarkers: analysis within the MAPT trial.

In vitro and animal studies have suggested that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits, hyperphosphorylation of tau, and/or neuronal loss. Here, we studied the association between HSV-1 and Alzheimer's disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan.

Alterations in newborn metabolite patterns with preterm birth and diabetes in pregnancy.

Background: This study examines the influence of prematurity and diabetes (DM) in pregnancy on metabolite patterns at birth, and associations with adiposity development in a prospective cohort.

Methods: Term and preterm (30-36 weeks gestational age [GA]) infants were enrolled and body composition assessments completed through discharge. Targeted metabolomics was used to assess metabolites in cord or infant blood in the first 2 days.

Inflammatory biomarkers profiles and cognition among older adults.

Inflammation plays a major role in cognitive aging. Most studies on peripheral inflammation and cognitive aging focused on selected major inflammatory biomarkers. However, inflammatory markers are regulated and influenced by each other, and it is therefore important to consider a more comprehensive panel of markers to better capture diverse immune pathways and characterize the overall inflammatory profile of individuals.