The impact of common and rare genetic variants on bradyarrhythmia development.

To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively.

Integrating genetic subtypes with PET scan monitoring to predict outcome in diffuse large B-cell lymphoma.

Next Generation Sequencing-based subtyping and interim- and end of treatment positron emission tomography (i/eot-PET) monitoring have high potential for upfront and on-treatment risk assessment of diffuse large B-cell lymphoma patients. We performed Dana Farber Cancer Institute (DFCI) and LymphGen genetic subtyping for the HOVON84 (n = 208, EudraCT-2006-005174-42) and PETAL (n = 204, EudraCT-2006-001641-33) trials retrospectively combined with DFCI genetic data (n = 304). For all R-CHOP treated patients (n = 592), C5/MCD- and C2/A53-subtypes show significantly worse outcome independent of the international prognostic index.

Clinical benefit of chronic non-invasive ventilation in severe stable COPD: a matter of persistent hypercapnia improvement.

Purpose: In patients with chronic obstructive pulmonary disease (COPD) treated with chronic non-invasive ventilation (NIV), the relation between improvements in nocturnal transcutaneous partial pressure of CO (PtcCO) and daytime arterial partial pressure of CO (PaCO) remains uncertain. Also, to what extent improvements in nocturnal PtcCO result in better health-related quality of life (HRQL), exercise capacity, lung function and survival has not been investigated.

Patients And Methods: Patients with COPD who were initiated on chronic NIV were prospectively followed for 6 months.

In vivo comparison of resin infiltration outcomes under different light conditions: A randomized controlled clinical trial.

Objective: Success of resin infiltration for the masking of MIH-lesions remains difficult to predict, prompting suggestions to adjust the treatment protocol. This exploratory in vivo study aims to evaluate whether monitoring the resin infiltration process using transmitted light, compared to ambient light, enables a better estimation of when the infiltration process is completed, and to assess how the treatment success, i.e.

Tirzepatide Associated With Reduced Albuminuria in Participants With Type 2 Diabetes: Pooled Post Hoc Analysis From the Randomized Active- and Placebo-Controlled SURPASS-1-5 Clinical Trials.

Objective: Tirzepatide, a long-acting, glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, reduced urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) decline in people with type 2 diabetes and high cardiovascular risk in the SURPASS-4 trial. To examine the generalizability of these findings, we assessed change from baseline in UACR for tirzepatide (5, 10, and 15 mg) compared with active and placebo treatment in a broad population from the SURPASS-1-5 trials.

Research Design And Methods: This post hoc analysis examined data from the overall pooled SURPASS-1-5 population and subgroups defined by baseline UACR ≥30 mg/g.

Systolic Blood Pressure and Pulse Pressure in Heart Failure: Pooled Participant-Level Analysis of 4 Trials.

Background: Hypertension is common in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), and current guidelines recommend treating systolic blood pressure (SBP) to a target <130 mm Hg. However, data supporting treatment to this target are limited. Additionally, pulse pressure (PP), a marker of aortic stiffness, has been associated with increased risk of cardiovascular events, but its prognostic impact in HFpEF has not been extensively studied.

[Genomic Characterization of SARS-CoV-2 Isolates Obtained from Antalya, Türkiye].

As the number of coronavirus diseases-2019 (COVID-19) cases have decreased and measures have started to be implemented at an individual level rather than in the form of social restrictions, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) still maintains its importance and has already taken its place in the spectrum of agents investigated in multiplex molecular test panels for respiratory tract infections in routine diagnostic use. In this study, we aimed to present mutation analysis and clade distribution of whole genome sequences from randomly selected samples that tested positive with SARS-CoV-2 specific real-time reverse transcription polymerase chain reaction (rRT-PCR) test at different periods of the pandemic in our laboratory with a commercial easy-to-use kit designed for next-generation sequencing systems. A total of 84 nasopharyngeal/oropharyngeal swab samples of COVID-19 suspected patients which were sent for routine diagnosis to the medical microbiology laboratory and detected as SARSCoV-2 RNA positive with rRT-PCR were randomly selected from different periods for sequence analysis.

Gene expression profiling in PBMCs for acute rejection in lung transplant recipients reveals myeloid responses.

The acute rejection (AR) diagnosis depends on transbronchial biopsy, which is semi-invasive and not easily performed Our study used the Nanostring gene expression technology on PBMCs obtained from lung transplant recipients (LTRs) to search for biomarkers. We identified distinct differential gene profiles between patients with stable status (STA) and AR. Subsequently, we independently evaluated monocyte compositions in PBMCs using flow cytometry and assessed the levels of 7 chemokines in serum using Luminex.

Long-term trends in educational inequalities in alcohol-attributable mortality, and their impact on trends in educational inequalities in life expectancy.

Background: Previous studies on socio-economic inequalities in mortality have documented a substantial contribution of alcohol-attributable mortality (AAM) to these inequalities. However, little is known about the extent to which AAM has contributed to time trends in socio-economic inequalities in mortality.

Objective: To study long-term trends in educational inequalities in AAM and assessed their impact on trends in educational inequalities in life expectancy in three European countries.

Why some coalitions benefit from historical myths more than others.

Behavioural ecologies in themselves can create variation in fitness interdependencies among individuals, and hence modulate the functionality of invoking historical myths. We develop this possibility for the case where coalitions form to attack and exploit enemies, or to defend and protect against hostile out-groups. We propose that invoking historical myths are functional and observed especially when groups aggressively expand.

Primary sclerosing cholangitis in children with inflammatory bowel disease: An ESPGHAN position paper from the Hepatology Committee and the IBD Porto group.

Objective: We aimed to provide an evidence-supported approach to diagnose, monitor, and treat children with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC).

Methods: The core group formulated seven PICO-structured clinical questions. A systematic literature search from inception to December 2022 was conducted by a medical librarian using MEDLINE and EMBASE.

Seasonality in mortality and its impact on life expectancy levels and trends across Europe.

Background: Seasonal fluctuations in mortality affect annual life expectancy at birth (e). Nevertheless, evidence on the impact of seasonal mortality on longevity is very limited and mainly restricted to assessing season-specific mortality levels due to shocks (e.g.

The argumentative role of patient companions in (shared) decision-making.

Objective: This study aims to examine the type of involvement of patient companions in the argumentative exchanges in consultations and explore when their contributions should be taken into account in shared decision-making (SDM).

Methods: A qualitative analysis was carried out using transcribed medical consultations (N = 10) between health professionals (doctors at a regional Dutch hospital), adult patients and informal patient companions. Insights from argumentation theory were used to develop an inventory of twelve theoretically distinct discussion situations involving patient companions, distinguishing possible discussion roles, disagreement types and coalition formations.

The Screening Visual Complaints questionnaire-acquired brain injury: Development and evaluation of psychometric properties in a community sample.

Purpose: Visual complaints are a common consequence of acquired brain injury (ABI). Yet, they may be overlooked in clinical practice. The present study aims to develop a screening instrument for assessing visual complaints in individuals with ABI and evaluate its psychometrics properties in a community sample.

Nano-Armed Limosilactobacillus reuteri for Enhanced Photo-Immunotherapy and Microbiota Tryptophan Metabolism against Colorectal Cancer.

Despite being a groundbreaking approach to treating colorectal cancer (CRC), the efficacy of immunotherapy is significantly compromised by the immunosuppressive tumor microenvironment and dysbiotic intestinal microbiota. Here, leveraging the superior carrying capacity and innate immunity-stimulating property of living bacteria, a nanomedicine-engineered bacterium, LR-S-CD/CpG@LNP, with optical responsiveness, immune-stimulating activity, and the ability to regulate microbiota metabolome is developed. Immunoadjuvant (CpG) and carbon dot (CD) co-loaded plant lipid nanoparticles (CD/CpG@LNPs) are constructed and conjugated to the surface of Limosilactobacillus reuteri (LR) via reactive oxygen species (ROS)-responsive linkers.

Real-World Evidence of the Prevalence of Driver Mutations in Anorectal Melanoma.

Introduction: Anorectal melanoma is a rare neoplasm with an aggressive behavior and poor prognosis. Recently, recurrent gene mutations related to anorectal melanoma have been identified in a small series of cases, and this holds promise for targeted therapies, analogous to cutaneous melanoma. The purpose of this study was to analyze testing rates and prevalence of mutations in anorectal melanoma in the Dutch population.

Membrane-embedded CdaA is required for efficient synthesis of second messenger cyclic di-AMP.

Cyclic di-adenylate monophosphate (cyclic di-AMP) is an important second messenger in microorganisms. Cyclic di-AMP regulates bacterial cell volume and turgor via control of potassium and compatible solute transport but is also involved in many other processes, including the activation of the metazoan innate immune response to bacterial infections. We compare the activity of full-length membrane-embedded CdaA, the enzyme that synthesizes cyclic di-AMP, with the water-soluble catalytic domain CdaA-DAC.