CSF proteins of inflammation, proteolysis and lipid transport define preclinical AD and progression to AD dementia in cognitively unimpaired individuals.

This preclinical AD CSF proteome study identified a panel of 12-CSF markers detecting amyloid positivity and clinical progression to AD with high accuracy; some of these CSF proteins related to immune function, neurotrophic processes, energy metabolism and endolysosomal functioning (e.g., ITGB2, CLEC5A, IGFBP-1, CST3) changed before amyloid positivity is established.

Hypoxia and TNF-alpha modulate extracellular vesicle release from human induced pluripotent stem cell-derived cardiomyocytes.

Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the heart under homeostatic and pathological conditions, such as myocardial infarction (MI). However, the basic mechanisms driving cardiomyocyte-derived EV (CM-EV) production following stress are poorly understood. In this study, we generated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that express NanoLuc-tetraspanin reporters.

Short-term Frailty Index Fluctuations in Older Adults: Noise or Signal?

Background: Reversible short-term fluctuations in the frailty index (FI) are often thought of as representing only noise or error. Here, we assess (i) the size and source of short-term FI fluctuations, (ii) variation across sociodemographic characteristics, (iii) association with chronic diseases, (iv) correlation with age, frailty level, frailty change, and mortality, and (v) whether fluctuations reflect discrete health transitions.

Methods: Nationwide, biweekly longitudinal data from 426 community-dwelling older adults (70+) were collected in the FRequent health Assessment In Later life (FRAIL70+) study using a measurement burst design (5 122 repeated observations, median of 13 repeated observations per person).

Quantitative flow ratio versus fractional flow reserve for coronary revascularisation guidance (FAVOR III Europe): a multicentre, randomised, non-inferiority trial.

Background: Fractional flow reserve (FFR) or non-hyperaemic pressure ratios are recommended to assess functional relevance of intermediate coronary stenosis. Both diagnostic methods require the placement of a pressure wire in the coronary artery during invasive coronary angiography. Quantitative flow ratio (QFR) is an angiography-based computational method for the estimation of FFR that does not require the use of pressure wires.

Prospectively predicting violent and aggressive incidents in prison practice with the Risk Screener Violence (RS-V): Results from a multisite prison study.

Preventing in-prison violence and maintaining a safe environment is an important goal within prison settings. Screening for violence risk may provide a valuable addition to reach this goal. Within the Dutch prison system, the Risk Screener Violence (RS-V) has become an important new element in overall risk management.

Sexual education and development after early childhood sexual abuse: A qualitative study of experiences of parents and children.

Background: In the Amsterdam Sexual Abuse Case (ASAC), infants and toddlers experienced childhood sexual abuse (CSA). The perpetrator was convicted, and psychosocial care was offered to children and families. A research project was established to investigate the impact of CSA at an early age, with this study specifically focusing on sexual education and development.

The effectiveness of Problem Management Plus at 1-year follow-up for Syrian refugees in a high-income setting.

Aims: Problem Management Plus (PM+) has been effective in reducing mental health problems among refugees at three-month follow-up, but there is a lack of research on its long-term effectiveness. This study examined the effectiveness of PM+ in reducing symptoms of common mental disorders at 12-month follow-up among Syrian refugees in the Netherlands.

Methods: This single-blind, parallel, controlled trial randomised 206 adult Syrians who screened positive for psychological distress and impaired functioning to either PM+ in addition to care as usual (PM+/CAU) or CAU alone.

Diagnosis of myelodysplastic syndromes: the classic and the novel.

The Myelodysplastic syndromes (MDS) are a heterogenous group of clonal bone marrow (BM) stem cell myeloid neoplasms, characterized by bone marrow (BM) dysplasia, macrocytic anemia or cytopenia with a tendency for leukemic transformation. The suspicion of MDS is raised by a typical but not specific clinical picture and routine labs, but the gold standard for MDS diagnosis is still BM examination with the presence of uni-or multi-lineage dysplasia and blast percentage, together with exclusion of other reasons. Cytogenetics is also a part of the diagnostic process.

Musculoskeletal Pain in Adolescents Engaged in Impact and Nonimpact Sports-ABCD Growth Study.

Purpose: This study aimed to identify, through a 28-week follow-up, the association between pain and engagement in different sports among adolescents.

Methods: In total, 63 adolescents reported the occurrence of pain, which was tracked weekly. Participants were categorized into 2 groups based on their sports participation: "swimming group" and "other sports group.

Targeting a key FAK-tor: the therapeutic potential of combining focal adhesion kinase (FAK) inhibitors and chemotherapy for chemoresistant non-small cell lung cancer.

Introduction: NSCLC is the leading cause of cancer-related deaths globally, with a low survival rate primarily due to NSCLC frequently becoming chemoresistant. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase involved in pathways regulating multiple processes in the cell, including survival, migration, and the TME, that contribute to both tumor progression and drug resistance. Recently, FAK inhibitors (FAKi) have shown promising potential for the treatment of NSCLC.

Periodic health evaluation in Para athletes: a position statement based on expert consensus.

Para athletes present a broad range of sports-related injuries and illnesses, frequently encountering barriers when accessing healthcare services. The periodic health evaluation (PHE) is a valuable tool for continuously monitoring athletes' health, screening for health conditions, assisting in the surveillance of health problems by establishing baseline information and identifying barriers to athlete's performance. This position statement aims to guide sports healthcare providers in the PHE for Para athletes across key impairment categories: intellectual, musculoskeletal, neurological and vision.

The Effect of 6 weeks Physical Activity on Cognitive Control and Trait Impulsivity in Multi-problem Young Adults: First Findings of an RCT-study.

This study aimed to report the effect of a 6-week light-active versus moderate-active physical activity intervention embedded in a multimodal day treatment program on selected measures of cognitive control (i.e., response inhibition, error processing, and cognitive interference) and trait impulsivity.

Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry.

Background: Adjuvant anti-PD-1 therapy improves relapse free survival in stage III melanoma, but also leads to immune-related adverse events (irAEs). Older patients are of particular interest due to comorbidities and frailty, which may impact their ability to tolerate irAEs and benefit from anti-PD-1 therapy. This study aimed to explore associations between clinical parameters and the occurrence of grade ≥ 3 irAEs and recurrence-free survival (RFS) in older patients with radically resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy.

Midostaurin added to 10-day decitabine, for patients unfit for intensive chemotherapy with AML and higher risk MDS, irrespective of FLT3 mutational status, does not improve outcome.

The treatment of older patients with acute myeloid leukemia (AML) considered unfit for receiving intensive chemotherapy is challenging. Based on the hypothesis that addition of the broad tyrosine kinase inhibitor (TKI) midostaurin could improve the response to hypomethylating agents, irrespective of FLT3 gene mutational status, we conducted a randomized phase II multicenter study to assess the tolerability and efficacy of the addition of midostaurin to a 10-day schedule of decitabine in unfit (i.e.

The temporal sequence and reciprocal relationships of frailty, social isolation and loneliness in older adults across 21 years.

Background: It is unclear whether social isolation and loneliness may precede frailty status or whether frailty may precipitate social isolation and loneliness. We investigated the reciprocal and temporal sequence of social isolation, loneliness, and frailty among older adults across 21 years.

Methods: We used seven waves of the Longitudinal Aging Study Amsterdam from 2302 Dutch older adults (M = 72.

Gene-environmental influence of space and microgravity on red blood cells with sickle cell disease.

A fundamental question in human biology and for hematological disease is how do complex gene-environment interactions lead to individual disease outcome? This is no less the case for sickle cell disease (SCD), a monogenic disorder of Mendelian inheritance, both clinical course, severity, and treatment response, is variable amongst affected individuals. New insight and discovery often lie between the intersection of seemingly disparate disciplines. Recently, opportunities for space medicine have flourished and have offered a new paradigm for study.

Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial.

Background: Deep grey matter pathology is a key driver of disability worsening in people with multiple sclerosis. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique which quantifies local magnetic susceptibility from variations in phase produced by changes in the local magnetic field. In the deep grey matter, susceptibility has previously been validated against tissue iron concentration.