Small-molecule-induced ERBB4 activation to treat heart failure.

Heart failure is a common and deadly disease requiring new treatments. The neuregulin-1/ERBB4 pathway offers cardioprotective benefits, but using recombinant neuregulin-1 as therapy has limitations due to the need for intravenous delivery and lack of receptor specificity. We hypothesize that small-molecule activation of ERBB4 could protect against heart damage and fibrosis.

Cyclophosphamide is not associated with clinically relevant late pulmonary dysfunction in Dutch survivors of childhood cancer - The DCCSS-LATER 2 PULM sub-study.

Background: Treatment for childhood cancer may increase the risk of long-term pulmonary complications and dysfunction. Pulmonary surveillance is recommended after established pulmonary toxic exposures, including bleomycin, busulfan, carmustine (BCNU), lomustine (CCNU), radiotherapy to a field exposing the lungs, and pulmonary surgery. However, the role of cyclophosphamide as a pulmonary toxic agent is debated.

Prevalence and determinants of metabolic syndrome in 2338 childhood cancer survivors: A Dutch Childhood Cancer Survivor LATER 2 study.

Background: Because the occurrence of metabolic syndrome (MetS) might contribute to childhood cancer survivor's excess risk of cardiovascular disease, the authors assessed the prevalence and determinants of MetS in the Dutch Childhood Cancer Survivor Study (DCCSS-LATER2) cohort.

Methods: In total, 2338 adult childhood cancer survivors (CCS) were cross-sectionally assessed for the prevalence of MetS, using the Lifelines cohort (N = 132,226 adults without a history of cancer) as references. The prevalence of MetS was clinically assessed using existing classifications, as well as an alternative method using dual-energy x-ray absorptiometry fat% instead of waist circumference to define abdominal adiposity.

Dried blood spot LC-MS/MS quantification of voclosporin in renal transplant recipients using volumetric dried blood spot sampling.

Voclosporin is a potent immunosuppressive agent currently approved for treating active lupus nephritis. Based on its potential antiviral activity, it has also been investigated as immunosuppressive agent in an investigator-initiated study in SARS-CoV2 positive kidney transplant recipients. As with many immunosuppressive agents, optimizing dosing regimens to achieve therapeutic efficacy while minimizing toxicity remains a critical challenge in clinical practice.

Monitoring and modulating cardiac bioelectricity: from Einthoven to end-user.

In 2024, we celebrate the 100th anniversary of Willem Einthoven receiving the Nobel Prize for his discovery of the mechanism of the electrocardiogram (ECG). Building on Einthoven's legacy, electrocardiography allows the monitoring of cardiac bioelectricity through solutions to the so-called forward and inverse problems. These solutions link local cardiac electrical signals with the morphology of the ECG, offering a reversible connection between the heart's electrical activity and its representation on the body surface.

Gender-affirming medical treatment for adolescents: a critical reflection on "effective" treatment outcomes.

Background: The scrutiny surrounding gender-affirming medical treatment (GAMT) for youth has increased, particularly concerning the limited evidence on long-term treatment outcomes. The Standards of Care 8 by the World Professional Association for Transgender Health addresses this by outlining research evidence suggesting "effective" outcomes of GAMT for adolescents. However, claims concerning what are considered "effective" outcomes of GAMT for adolescents remain implicit, requiring further reflection.

Cost-Effective and Sustainable Drug Use in Hospitals: A Systematic and Practice-Based Approach.

Background And Objective: Rising healthcare costs challenge the financial sustainability of healthcare systems. Interventional pharmacoeconomics has emerged as a vital discipline to improve the cost-effective and sustainable use of drugs in clinical practice. However, current efforts are often fragmented, highlighting the need for an integrated hospital-wide approach.

Long-term risk and characteristics of cerebrovascular events after upper body radiotherapy among childhood cancer survivors in the DCCSS-LATER cohort.

Cerebrovascular events (CVEs) are serious late adverse events among childhood cancer survivors. We estimated the incidence and risk factors of symptomatic CVEs and described the clinical characteristics among childhood cancer survivors after upper body radiotherapy. The Dutch Childhood Cancer Survivor Study LATER cohort study includes 5-year childhood cancer survivors diagnosed View Article and Find Full Text PDF

The economic impact of purulent vaginal discharge in dairy herds within a single lactation.

The goal of this study was to calculate the cost of purulent vaginal discharge (PVD) in dairy cows. The data set included 11,051 cows from 16 dairy herds located in 4 regions of the US. Purulent vaginal discharge was characterized as a mucopurulent, purulent, or reddish-brownish vaginal discharge collected at 28 ± 7 d in milk.

Sedative effects of intramuscular alfaxalone-methadone-midazolam versus ketamine-methadone-midazolam in cats.

Objective: To assess depth and quality of sedation and the ability to place an intravenous catheter in cats after intramuscular (IM) injection with alfaxalone-methadone-midazolam (AMM) or ketamine-methadone-midazolam (KMM).

Study Design: Blinded randomized clinical trial.

Animals: A group of 46 healthy Domestic Short Hair cats.

Limited evidence of infection with other tick-borne pathogens in patients tested for Lyme neuroborreliosis in the Netherlands.

Ixodes ricinus is the main vector of the causative agents of Lyme neuroborreliosis. This tick species can also transmit tick-borne encephalitis virus (TBEV), spotted fever group (SFG) Rickettsia and Borrelia miyamotoi to humans. These tick-borne pathogens are present in Dutch ticks and have also been associated with human neurological infections, but well characterized disease cases are seldom reported.

Targeted reproductive management for lactating Holstein cows: Economic return.

Targeted reproductive management (TRM), employing automated monitoring devices (AMD), is as an alternative to the blanket adoption of ovulation synchronization protocols (OvSP) for first postpartum artificial insemination (AI) and a means of reducing the use of OvSP for re-AI of non-pregnant cows. We hypothesized that a TRM that relies heavily on AI of cows on AMD-detected estrus increases improves reproductive performance and economic return. Early-postpartum estrus characteristics of multiparous (n = 941) cows were evaluated at 40 and 41 DIM (Herds 1and 2, respectively) and early-postpartum estrus characteristics of primiparous (n = 539) cows were evaluated at 54 and 55 DIM (Herds 1 and 2, respectively).

Precision Dosing of Intravenous Tocilizumab: Development of Pharmacokinetic Model-Derived Tapering Strategies for Patients With Rheumatoid Arthritis.

Background: Tocilizumab targets the interleukin-6 receptor, and dosing is complex owing to its nonlinear clearance related to target binding. Therefore, tapering tocilizumab requires a different approach than that of tumor necrosis factor inhibitors (TNFi). This study aimed to identify these differences and enable personalized treatment of rheumatoid arthritis (RA) beyond TNFi therapy.

Timing of puberty suppression in transgender adolescents and sexual functioning after vaginoplasty.

Background: Sexual function in transgender adolescents after puberty suppression has been a topic of recent clinical and scientific questions.

Aim: This study aimed to explore the long-term effects of early treatment with puberty suppression on sexual functioning of transfeminine individuals after vaginoplasty.

Methods: This retrospective cohort study included 37 transfeminine individuals treated with a gonadotropin-releasing hormone agonist (puberty suppression), estrogen, and vaginoplasty (penile inversion technique or intestinal vaginoplasty) at the Center of Expertise on Gender Dysphoria in Amsterdam, the Netherlands, between 2000 and 2016.

Treatment Preference Archetypes in Eosinophilic Esophagitis and Their Implications for Therapy.

Introduction: Little is known about how patients make decisions about and prioritize therapies and disease management in eosinophilic esophagitis (EoE). We aimed to systematically identify and characterize patient perspectives and attitudes that influence decision making for EoE management.

Methods: To understand the diverse attitudes and values of patients with EoE, we designed a study using the Q-method.

Game-Based eHealth Interventions for the Reduction of Fatigue in People With Chronic Diseases: Systematic Review and Meta-Analysis.

Background: Fatigue is a common and debilitating side effect of chronic diseases, significantly impacting patients' quality of life. While physical exercise and psychological treatments have been shown to reduce fatigue, patients often struggle with adherence to these interventions in clinical practice. Game-based eHealth interventions are believed to address adherence issues by making the intervention more accessible and engaging.

Reflecting on the Importance of Family Building and Fertility Preservation: Transgender People's Experiences with Starting Gender-Affirming Treatment as an Adolescent.

Purpose: We aimed to investigate how adults, who started gender-affirming hormone treatment during adolescence, reflect on their reproductive decisions.

Methods: We recruited transgender and gender-diverse (TGD) people who visited our gender identity clinic and commenced medical treatment in adolescence at least 9 years ago. We collected data through an online survey.

Risk and Protective Factors of Psychosocial Functioning in Survivors of Childhood Cancer: Results of the DCCSS-LATER Study.

Objective: This study examines the association between psychosocial risk and protective factors and a wide range of psychosocial outcomes including emotional, social, cognitive, and physical domains in childhood cancer survivors (CCS).

Methods: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963-2001) part 2 (age ≥ 18 years, diagnosed < 18 years, ≥ 5 years since diagnosis) completed questionnaires on psychosocial risk and protective factors (Benefit and Burden Scale, Illness Cognition Questionnaire, Rosenberg Self-Esteem Scale, and Impact of Cancer Scale), and psychosocial outcomes (Hospital Anxiety and Depression Scale, Self-Rating Scale for Post-Traumatic Stress Disorder, TNO-AZL Questionnaire for Adult Health-Related Quality of Life, and Short Form-36). Associations were assessed with regression analysis, adjusting for attained age, sex, number of health conditions, and time since diagnosis, while correcting for multiple testing (p < 0.

Long-Term Risk of Subsequent Neoplasms in 5-Year Survivors of Childhood Neuroblastoma: A Dutch Childhood Cancer Survivor Study-LATER 3 Study.

Purpose: Neuroblastoma survivors have an increased risk of developing subsequent malignant neoplasms (SMNs), but the risk of subsequent nonmalignant neoplasms (SNMNs) and risk factors are largely unknown. We analyzed the long-term risks and associated risk factors for developing SMNs and SNMNs in a well-characterized cohort of 5-year neuroblastoma survivors.

Methods: We included 563 5-year neuroblastoma survivors from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort, diagnosed during 1963-2014.

The differential impact of early graft dysfunction in kidney donation after brain death and after circulatory death: Insights from the Dutch National Transplant Registry.

Kidneys donated after circulatory death (DCD) perform similarly to kidneys donated after brain death (DBD). However, the respective incidences of delayed graft function (DGF) differ. This questions the donor type-specific impact of early graft function on long-term outcomes.

Breaking Rossby waves drive extreme precipitation in the world's arid regions.

More than a third of the world's population lives in drylands and is disproportionately at risk from hydrometeorological hazards such as drought and flooding. While weather systems governing precipitation formation in humid regions have been widely explored, our understanding of the atmospheric processes generating precipitation in arid regions remains fragmented at best. Here we show, using a variety of precipitation datasets, that Rossby wave breaking is a key atmospheric driver of precipitation in arid regions worldwide.