Nicotine levels in flavoured hookah (waterpipe) tobacco products: discrepancies between labelled and measured levels.

Background: Hookah tobacco smoking is prevalent among youth and young adults. While health warning labels play a critical role in communicating the health risks of tobacco product use to consumers, compliance with US Federal Regulation's nicotine warning requirements on hookah tobacco packaging is low. Some labelling suggests that consumers are exposed to 'only 0.

Late-onset diseases and patient education: additional considerations for polygenic risk score regulation.

In a recent article, Haining outline several ethical and regulatory considerations for polygenic risk scores (PRSs), which may expand current embryonic screening to include polygenic diseases and non-disease traits. I argue in this response that the authors overlook a few crucial issues that nations should address. For adult-onset diseases, regulations must not only account for predictive accuracy of PRSs but also establish the precise circumstances that warrant testing-such as a disease's severity and the average age at which symptoms manifest.

Efficacy, safety, and target engagement of dazukibart, an IFNβ specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

Background: Dermatomyositis is a chronic autoimmune disease with distinctive cutaneous eruptions and muscle weakness, and the pathophysiology is characterised by type I interferon (IFN) dysregulation. This study aims to assess the efficacy, safety, and target engagement of dazukibart, a potent, selective, humanised IgG1 neutralising monoclonal antibody directed against IFNβ, in adults with moderate-to-severe dermatomyositis.

Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial was conducted at 25 university-based hospitals and outpatient sites in Germany, Hungary, Poland, Spain, and the USA.

Induced pluripotent stem-cell-derived CD19-directed chimeric antigen receptor natural killer cells in B-cell lymphoma: a phase 1, first-in-human trial.

Background: FT596 is an induced pluripotent stem-cell (iPSC)-derived chimeric antigen receptor (CAR) natural killer (NK) cell therapy with three antitumour modalities: a CD19 CAR; a high-affinity, non-cleavable CD16 Fc receptor; and interleukin-15-interleukin-15 receptor fusion. In this study, we aimed to determine the recommended phase 2 dose (RP2D) and evaluate the safety and tolerability of FT596 as monotherapy and in combination with rituximab. We also aimed to evaluate the antitumour activity and characterise the pharmacokinetics of FT596 as monotherapy and in combination with rituximab.

Depression and dementia: interrogating the causality of the relationship.

Background: Depression is often cited as a major modifiable risk factor for dementia, though the relative contributions of a true causal relationship, reverse causality and confounding factors remain unclear. This study applied a subset of the Bradford Hill criteria for causation to depression and dementia including strength of effect, specificity, temporality, biological gradient and coherence.

Methods: A total of 491 557 participants in UK Biobank aged between 40 and 69 at enrolment and followed up for a mean duration of 12.

'Sneaky' uninflamed oesophageal candidiasis: morphological clues and comparison with candidiasis associated with inflammation.

Aims: esophagitis is usually readily identified on routine H&E-stained sections as the infection typically presents with prominent acute inflammation as a clue to search for organisms. However, in some cases, inflammation is absent, and detection of organisms relies on the observation of zones exhibiting parakeratosis with a delicate 'flaky' appearance. Our study aimed to establish a correlation between the histomorphology of oesophageal candidiasis and an associated clinical profile.

GWAS of CRP response to statins further supports the role of APOE in Statin Response: a GIST consortium study.

Statins are first-line treatments in the primary and secondary prevention of cardiovascular disease. Clinical studies show statins act independently of lipid-lowering mechanisms to decrease C-reactive protein (CRP), an inflammation marker. We aim to elucidate genetic loci associated with CRP statin response.

The first five years of implementing Missouri's medication first approach to opioid use disorder treatment: Plateaus, regressions, and underbellies of progress.

Introduction: Missouri's Medication First ("MedFirst") approach promotes same-day and long-term low-threshold access to medications for opioid use disorder (MOUD). Since 2017, Missouri's SAMHSA-funded State Targeted and State Opioid Response (STR/SOR) grants have supported MedFirst services (both medical and psychosocial) for uninsured individuals with opioid use disorder at state-contracted treatment programs. Though MedFirst demonstrated early success, results - with attention to possible racial disparities - must be revisited after five years of implementation.

Gut microbiome dysbiosis is not associated with portal vein thrombosis in patients with end-stage liver disease: a cross-sectional study.

Background: Portal vein thrombosis (PVT) is a common complication in patients with end-stage liver disease (ESLD). The portal vein in ESLD patients is proposedly an inflammatory vascular bed due to translocation of endotoxins and cytokines from the gut. We hypothesized that a pro-inflammatory gut microbiome and elevated trimethylamine N-oxide (TMAO), a driver of thrombosis, may contribute to PVT development.

Accurate evaluation of factor VIII activity of efanesoctocog alfa in the presence of emicizumab.

Background: Efanesoctocog is a B-domain-deleted, Fc-fusion FVIII linked to the D'D3 domain of VWF and two XTEN polypeptides, designed for an ultra-extended half-life for prophylaxis in hemophilia A, but also aiding in managing acute bleeding or surgery in patients on long-term emicizumab. However, no current laboratory method accurately measures FVIII levels in the presence of emicizumab. We hypothesized that the chromogenic (CSA) FVIII assay, specifically calibrated for efanesoctocog using bovine coagulation factors, could provide an accurate assessment of efanesoctocog activity.

Systematic Analysis of the Design, Methodology and Patient Population Characteristics of the Pediatric Direct Oral Anticoagulant (DOAC) Trials of Venous Thromboembolism Treatment.

Introduction: The pediatric direct oral anticoagulation (DOAC) trials provide an opportunity to evaluate and characterize challenges in their design and execution to inform future antithrombotic trials.

Objective: To perform a systematic review of pediatric DOAC trials for the treatment of venous thromboembolism to critically appraise their methodology and understand the feasibility and challenges.

Methods: Systematic search of MEDLINE, EMBASE, the Cochrane Library and ClinicalTrials.

Preclinical and in silico studies of 3-benzothioyl-1-(3-hydroxy-3-phenyl-3-propyl)-1-methylthiourea: a promising agent for depression and anxiety.

The study investigated the anxiolytic, antidepressant, sedative/hypnotic and in silico molecular docking properties of the synthetic ephedrine-based derivative of thiourea, 3-benzothioyl-1-(3-hydroxy-3-phenyl-3-propyl)-1-methylthiourea. Safety profile of the compound at various doses was determined in an acute toxicity test. Results showed significant anti-anxiety effects of the compound in all mice studies.

Transcriptomic Analysis of Effects of Developmental PCB Exposure in the Hypothalamus of Female Rats.

This study investigated the consequences of perinatal exposure to Aroclor 1221 (A1221), a weakly estrogenic polychlorinated biphenyl (PCB) mixture and known endocrine-disrupting chemical (EDC), in female rats. Previous work has shown behavioral and physiological effects of A1221, and the current study extended this work to comprehensive transcriptomic profiling of two hypothalamic regions involved in the control of reproduction: the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). Female Sprague-Dawley rats were fed a cookie treated with a small volume of A1221 (1 mg/kg) or vehicle (3% DMSO in sesame oil) during pregnancy from gestational days 8-18 and after birth from postnatal (P) days 1-21, exposing the offspring via placental and lactational transfer.

An update on Botulinum Toxin Treatment of Painful Diabetic Neuropathy, Post-traumatic Painful Neuropathy/Neuralgia, Post- herpetic neuralgia and Occipital Neuralgia.

The literature in botulinum toxin treatment for painful diabetic neuropathy (PDN), post traumatic neuralgia (PTN), postherpetic neuralgia (PHN) and occipital neuralgia (ON) was reviewed up to Oct 1st 2024. Using the efficacy criteria set forth by the Assessment and Guideline subcommittee of the American Academy of Neurology, the current levels of efficacy for these conditions could be designated as followings: PDN: B (probably effective, two class II study), PTN: A (effective, two class I studies); PHN: A (effective, two class I studies), ON: (undetermined due to lack of blinded investigations). Due to the small number of patients in these studies, proof of efficacy requires conduction of controlled and blinded studies in large cohorts of patients with longer follow ups.

Use of continuous glucose monitoring and point-of-care glucose testing in hospitalized patients with diabetes mellitus in non-intensive care unit settings: A systematic review and meta-analysis of randomized controlled trials.

The benefits of using continuous glucose monitoring (CGM) in hospitalized patients with diabetes remain uncertain. Point-of-care (POC) glucose testing is the standard of care in this setting. We compared the effect of adding CGM to POC testing versus POC testing alone on glycemic outcomes in this population.

Transcatheter versus Surgical Aortic Valve Replacement in Patients Younger than 65 Years in the US.

Objective: To characterize trends and outcomes of aortic valve replacement in patients <65 with aortic stenosis between 2013 and 2021.

Methods: This retrospective analysis included 9,557 patients who underwent biological aortic valve replacement in California, New York, and New Jersey from 2013 through 2021. Patients were stratified by approach: transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR).

Lower limb strength differentiates between fallers and non-fallers with multiple sclerosis.

Objective: To determine whether hip flexion (HF), extension (HE), abduction (HA), knee flexion (KF) and extension (KE), and ankle plantarflexion (APF) and dorsiflexion (ADF) Maximum Voluntary Contraction (MVC) differentiates between non-fall and fall history in persons with MS (PwMS) after accounting for age, gender, fatigue, disability, and disease duration.

Design: Secondary analysis of a cross-sectional study.

Setting: Community-based comprehensive MS Center PARTICIPANTS: 172 persons with MS who completed a one-time visit INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: Lower limb (LL) MVC was measured for each muscle group as isometric peak torque (Newton-meter: Nm) of both limbs (Strongest: S; Weakest: W) using a Biodex Dynamometer and normalized by body weight (Nm/kg).

Improving outcomes for care partners of individuals with traumatic brain injury: Results for a mHealth randomized control trial of the CareQOL app.

Objective: To test the efficacy of a randomized control trial low-touch mobile health intervention designed to promote care partner self-awareness and self-care.

Design: This randomized controlled trial (RCT) included a baseline assessment of self-report surveys of health-related quality of life (HRQOL), care partner-specific outcomes, and the functional/mental status of the person with TBI, as well as a 6-month home monitoring period that included three daily questions about HRQOL, monthly assessments of 12 HRQOL domains, and the use of a Fitbit® to continuously monitor physical activity and sleep. HRQOL surveys were repeated at 3- and 6-months post-home monitoring.

Optimized mammalian expression system for the ubiquitin E3 ligase E6AP/UBE3A.

E6AP/UBE3A is the founding member of the HECT (Homologous to the E6-AP Carboxyl Terminus) ubiquitin E3 ligase family, which add ubiquitin post-translationally to protein substrates. E6AP has been structurally defined in complex with human papillomavirus (HPV) oncoprotein E6 and its gain-of-function substrate tumor suppressor p53; however, there is currently no report of E6AP being expressed and purified from mammalian cells, as studies to date have isolated E6AP from E. coli or insect cells.