Angina Severity and Symptom Improvement Are Associated With Diagnostic Acetylcholine Provocation Dose in Vasospastic Angina.

Background: A coronary function test (CFT) is the recommended diagnostic test to identify coronary vasomotor dysfunction as a cause of symptoms in patients with angina and nonobstructive coronary arteries (ANOCA). Acetylcholine is the commonly used pharmacological agent for spasm provocation. We aimed to investigate an association between severity of symptoms and provocative acetylcholine dose.

Clinical Features and Outcomes of Pediatric -Related Dilated Cardiomyopathy.

Background: Although genetic variants in are the most frequent cause of pediatric genetic dilated cardiomyopathy (DCM), there are no studies available describing this entity. We sought to describe clinical features, analyze variant location, and explore predictors of bad prognosis in pediatric -related DCM.

Methods And Results: We evaluated clinical records from 44 patients (24 men; median age at diagnosis, 0.

Intracellular localisation and extracellular release of Y RNA and Y RNA binding proteins.

Cells can communicate via the release and uptake of extracellular vesicles (EVs), which are nano-sized membrane vesicles that can transfer protein and RNA cargo between cells. EVs contain microRNAs and various other types of non-coding RNA, of which Y RNA is among the most abundant types. Studies on how RNAs and their binding proteins are sorted into EVs have mainly focused on comparing intracellular (cytoplasmic) levels of these RNAs to the extracellular levels in EVs.

Accuracy of urgency allocation in patients with shortness of breath calling out-of-hours primary care: a cross-sectional study.

Background: In out-of-hours primary care (OHS-PC), semi-automatic decision support tools are often used during telephone triage. In the Netherlands, the Netherlands Triage Standard (NTS) is used. The NTS is mainly expert-based and evidence on the diagnostic accuracy of the NTS' urgency allocation against clinically relevant outcomes for patients calling with shortness of breath (SOB) is lacking.

Assessment of carnitine excretion and its ratio to plasma free carnitine as a biomarker for primary carnitine deficiency in newborns.

In the Netherlands, newborns are referred by the newborn screening (NBS) Program when a low free carnitine (C0) concentration (<5 μmol/l) is detected in their NBS dried blood spot. This leads to ~85% false positive referrals who all need an invasive, expensive and lengthy evaluation. We investigated whether a ratio of urine C0 / plasma C0 (Ratio) can improve the follow-up protocol for primary carnitine deficiency (PCD).

Risk of osteoporosis in testicular germ cell tumour survivors: A systematic review of the literature.

Context: Testicular germ cell tumour (TGCT) survivors are potentially at risk of developing osteoporosis, because of increased risk for disturbed bone remodelling associated with hypogonadism and anti-cancer treatment. A number of studies show bone loss and increased fracture risk in TGCT survivors, but data are scarce. There are no clinical guidelines or recommendations issued to address skeletal health in this group of patients potentially at high risk for osteoporosis.

Recurrence risk of venous thromboembolism associated with systemic lupus erythematosus: A retrospective cohort study.

Background: Recurrence risk of systemic lupus erythematosus (SLE)-associated venous thromboembolism (VTE) is unclear.

Aim: To determine the recurrence risk of SLE-associated VTE overall and by presence of provoking factors and SLE flares.

Methods: A multicenter, retrospective cohort study was conducted among patients with first SLE-associated VTE who discontinued anticoagulation.

Human regulatory T cells locally differentiate and are functionally heterogeneous within the inflamed arthritic joint.

Objective: Tregs are crucial for immune regulation, and environment-driven adaptation of effector (e)Tregs is essential for local functioning. However, the extent of human Treg heterogeneity in inflammatory settings is unclear.

Methods: We combined single-cell RNA- and TCR-sequencing on Tregs derived from three to six patients with juvenile idiopathic arthritis (JIA) to investigate the functional heterogeneity of human synovial fluid (SF)-derived Tregs from inflamed joints.

Hyperosmolar expansion medium improves nucleus pulposus cell phenotype.

Background: Repopulating the degenerated intervertebral disc (IVD) with tissue-specific nucleus pulposus cells (NPCs) has already been shown to promote regeneration in various species. Yet the applicability of NPCs as cell-based therapy has been hampered by the low cell numbers that can be extracted from donor IVDs and their potentially limited regenerative capacity due to their degenerated phenotype. To optimize the expansion conditions, we investigated the effects of increasing culture medium osmolarity during expansion on the phenotype of dog NPCs and their ability to produce a healthy extracellular matrix (ECM) in a 3D culture model.

Causal Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Peripheral Artery Disease: A Mendelian Randomization Approach.

Background We investigated the causal associations between the genetic liability to cardiovascular and lifestyle risk factors and peripheral artery disease (PAD), using a Mendelian randomization approach. Methods and Results We performed a 2-sample inverse-variance weighted Mendelian randomization analysis, multiple sensitivity analyses to assess pleiotropy and multivariate Mendelian randomization analyses to assess mediating/confounding factors. European-ancestry genomic summary data (<5×10) for type 2 diabetes, lipid-fractions, smoking, alcohol and coffee consumption, physical activity, sleep, and education level were selected.

Safety and biodegradability of a synthetic dural sealant patch (Liqoseal) in a porcine cranial model.

Background: Liqoseal consists of a watertight layer of poly(ester)ether urethane and an adhesive layer containing polyethylene glycol--hydroxysuccinimide (PEG-NHS). It is designed to prevent cerebrospinal fluid (CSF) leakage after intradural surgery. This study assessed the safety and biodegradability of Liqoseal in a porcine craniotomy model.

In Vivo Induction of Regulatory T Cells Via CTLA-4 Signaling Peptide to Control Autoimmune Encephalomyelitis and Prevent Disease Relapse.

Regulatory T cells play a key role in immune tolerance to self-antigens, thereby preventing autoimmune diseases. However, no drugs targeting Treg cells have been approved for clinical trials yet. Here, a chimeric peptide is generated by conjugation of the cytoplasmic domain of CTLA-4 (ctCTLA-4) with dNP2 for intracellular delivery, dNP2-ctCTLA-4, and evaluated Foxp3 expression during Th0, Th1, Treg, and Th17 differentiation dependent on TGF-.

Patient-relevant health outcomes for hemophilia care: Development of an international standard outcomes set.

Background: Patient-relevant health outcomes for persons with hemophilia should be identified and prioritized to optimize and individualize care for persons with hemophilia. Therefore, an international group of persons with hemophilia and multidisciplinary health care providers set out to identify a globally applicable standard set of health outcomes relevant to all individuals with hemophilia.

Methods: A systematic literature search was performed to identify possible health outcomes and risk adjustment variables.

Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical.

Chronic back and neck pain is a prevalent disability, often caused by degeneration of the intervertebral disc. Because current treatments for this condition are less than satisfactory, a great deal of effort is being applied to develop new solutions, including regenerative strategies. However, the path from initial promising idea to clinical use is fraught with many hurdles to overcome.

Predictive value of a bleeding score for postpartum hemorrhage.

Background: A reliable screening tool that could contribute to the identification of women with an increased risk of postpartum hemorrhage would be of great clinical significance.

Objectives: The aim of this study was to examine the added predictive value of a bleeding assessment tool for postpartum hemorrhage exceeding 1000 mL.

Patients/methods: Prospective two-center cohort study among 1147 pregnant women visiting the outpatient clinic or the maternity ward who completed a bleeding assessment tool prior to birth.

National cohort study on postoperative risks after surgery for submucosal invasive colorectal cancer.

Background: The decision to perform surgery for patients with T1 colorectal cancer hinges on the estimated risk of lymph node metastasis, residual tumour and risks of surgery. The aim of this observational study was to compare surgical outcomes for T1 colorectal cancer with those for more advanced colorectal cancer.

Methods: This was a population-based cohort study of patients treated surgically for pT1-3 colorectal cancer between 2009 and 2016, using data from the Dutch ColoRectal Audit.

Successful fishing for nucleus pulposus progenitor cells of the intervertebral disc across species.

Background: Recently, Tie2/TEK receptor tyrosine kinase (Tie2 or syn. angiopoietin-1 receptor) positive nucleus pulposus progenitor cells were detected in human, cattle, and mouse. These cells show remarkable multilineage differentiation capacity and direct correlation with intervertebral disc (IVD) degeneration and are therefore an interesting target for regenerative strategies.

Discordant NIPT result in a viable trisomy-21 pregnancy due to prolonged contribution to cfDNA by a demised trisomy-14 cotwin.

One of the confounders in noninvasive prenatal testing (NIPT) is the vanishing twin phenomenon. Prolonged contribution to the maternal Cell-free DNA (cfDNA) pool by cytotrophoblasts representing a demised, aneuploid cotwin may lead to a false-positive outcome for a normal, viable twin. We show that a vanishing trisomy-14 twin contributes to cfDNA for more than 2 weeks after demise.

Barriers and carriers: a multicenter survey of nurses' barriers and facilitators to monitoring of nurse-sensitive outcomes in intensive care units.

Aim: To identify nurses' barriers and facilitators to monitoring of nurse-sensitive outcomes in intensive care units (ICUs), and to explore influential nurse characteristics and work environment factors.

Design: A cross-sectional survey in three Dutch ICUs between October 2013 - June 2014.

Methods: A questionnaire with questions regarding facilitators and three types of barriers: knowledge, attitude and behaviour.