Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis.

Selenium-binding protein 1 (SELENBP1) has been associated with several cancers, although its exact role is unknown. We show that SELENBP1 is a methanethiol oxidase (MTO), related to the MTO in methylotrophic bacteria, that converts methanethiol to HO, formaldehyde, and HS, an activity not previously known to exist in humans. We identified mutations in SELENBP1 in five patients with cabbage-like breath odor.

Identifying patients at risk for severe exacerbations of asthma: development and external validation of a multivariable prediction model.

Background: Preventing exacerbations of asthma is a major goal in current guidelines. We aimed to develop a prediction model enabling practitioners to identify patients at risk of severe exacerbations who could potentially benefit from a change in management.

Methods: We used data from a 12-month primary care pragmatic trial; candidate predictors were identified from GINA 2014 and selected with a multivariable bootstrapping procedure.

Behavior of neuropathic pain in mice following chronic constriction injury comparing silk and catgut ligatures.

Introduction: Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system and is common after surgery. Neuropathic pain can persist without an obvious injury. In this study we aim to validate a murine chronic constriction injury model as a model for neuropathic pain research and determine if silk or catgut ligatures induced most stable neuropathic pain behavior.

Cardiovascular response to exercise training in the systemic right ventricle of adults with transposition of the great arteries.

Key Points: Patients with transposition of the great arteries (TGA) and systemic right ventricles have premature congestive heart failure; there is also a growing concern that athletes who perform extraordinary endurance exercise may injure the right ventricle. Therefore we felt it essential to determine whether exercise training might injure a systemic right ventricle which is loaded with every heartbeat. Previous studies have shown that short term exercise training is feasible in TGA patients, but its effect on ventricular function is unclear.

Pain is not systematically registered in Dutch medical oncology outpatients.

Background: Systematic pain registration and assessment with a visual analog scale (VAS) or numeric rating scale (NRS) at each visit are key recommendations in one of the most recent guidelines on cancer pain management. It is unclear whether this recommendation is applied.

Objectives: The aim was to explore registration of pain in medical records of patients visiting the medical oncology outpatient clinic.

Resveratrol attenuates NF-κB-binding activity but not cytokine production in mechanically ventilated mice.

Background: Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-κB are proposed to play a crucial role in the MV-induced inflammatory response. Resveratrol (RVT) exhibits anti-inflammatory effects in vitro and in vivo supposedly by interfering with TLR4 signaling and NF-κB.

Prevalence and correlates of psychotropic drug use in community-dwelling people with young-onset dementia: the NeedYD-study.

Background: Young-onset dementia (YOD) is defined as dementia that develops before the age of 65 years. The prevalence and type of neuropsychiatric symptoms (NPS) in YOD differ from patients with late onset dementia. NPS in dementia patients are often treated with psychotropic drugs.

First results of a European multi-center registry of patients with anorectal malformations.

Background: The European consortium on anorectal malformations (ARM-NET) was established to improve the health care of patients and to identify genetic and environmental risk factors. The aim of the present study was to present the first results on clinical data of a large European cohort of ARM patients based on our registry.

Methods: In 2010, the registry was established including patient characteristics and data on diagnosis, surgical therapy, and outcome regarding complications.

Is the quality of data in an electronic medical record sufficient for assessing the quality of primary care?

Objective: Quality indicators for the treatment of type 2 diabetes are often retrieved from a chronic disease registry (CDR). This study investigates the quality of recording in a general practitioner's (GP) electronic medical record (EMR) compared to a simple, web-based CDR.

Methods: The GPs entered data directly in the CDR and in their own EMR during the study period (2011).

Validity, reliability and discriminative capacity of an electronic quality of life instrument (Pelican) for childhood asthma in the Netherlands.

Purpose: To assess psychometric properties of the Pelican instrument, an online Dutch self-administered Quality of Life instrument for childhood asthma for scientific and clinical use.

Methods: A cohort study was done in two asthma populations and healthy children. One asthma population had assessment at start, 4 and 8 weeks.

Natural killer cells generated from cord blood hematopoietic progenitor cells efficiently target bone marrow-residing human leukemia cells in NOD/SCID/IL2Rg(null) mice.

Natural killer (NK) cell-based adoptive immunotherapy is an attractive adjuvant treatment option for patients with acute myeloid leukemia. Recently, we reported a clinical-grade, cytokine-based culture method for the generation of NK cells from umbilical cord blood (UCB) CD34⁺ hematopoietic progenitor cells with high yield, purity and in vitro functionality. The present study was designed to evaluate the in vivo anti-leukemic potential of UCB-NK cells generated with our GMP-compliant culture system in terms of biodistribution, survival and cytolytic activity following adoptive transfer in immunodeficient NOD/SCID/IL2Rg(null) mice.

Communication in cross-cultural consultations in primary care in Europe: the case for improvement. The rationale for the RESTORE FP 7 project.

The purpose of this paper is to substantiate the importance of research about barriers and levers to the implementation of supports for cross-cultural communication in primary care settings in Europe. After an overview of migrant health issues, with the focus on communication in cross-cultural consultations in primary care and the importance of language barriers, we highlight the fact that there are serious problems in routine practice that persist over time and across different European settings. Language and cultural barriers hamper communication in consultations between doctors and migrants, with a range of negative effects including poorer compliance and a greater propensity to access emergency services.

Oncologic multidisciplinary team meetings: evaluation of quality criteria.

Rationale, Aims And Objectives: To develop a guideline with quality criteria for an optimal structure and functioning of a multidisciplinary team meeting (MTM), and to assess to what extent the Dutch MTMs complied with these criteria.

Method: A literature search and expert opinions were used to develop a guideline for optimal MTMs. In order to assess adherence to the guideline, we conducted interviews with MTM chairs and observed general and tumour-specific MTMs in seven hospitals.

Significance of complete 1p/19q co-deletion, IDH1 mutation and MGMT promoter methylation in gliomas: use with caution.

The histopathological diagnosis of diffuse gliomas often lacks the precision that is needed for tailored treatment of individual patients. Assessment of the molecular aberrations will probably allow more robust and prognostically relevant classification of these tumors. Markers that have gained a lot of interest in this respect are co-deletion of complete chromosome arms 1p and 19q, (hyper)methylation of the MGMT promoter and IDH1 mutations.

Targeting of 111In-labeled dendritic cell human vaccines improved by reducing number of cells.

Purpose: Anticancer dendritic cell (DC) vaccines require the DCs to relocate to lymph nodes (LN) to trigger immune responses. However, these migration rates are typically very poor. Improving the targeting of ex vivo generated DCs to LNs might increase vaccine efficacy and reduce costs.

Outcome prediction in moderate and severe traumatic brain injury: a focus on computed tomography variables.

Background: With this study we aimed to design validated outcome prediction models in moderate and severe traumatic brain injury (TBI) using demographic, clinical, and radiological parameters.

Methods: Seven hundred consecutive moderate or severe TBI patients were included in this observational prospective cohort study. After inclusion, clinical data were collected, initial head computed tomography (CT) scans were rated, and at 6 months outcome was determined using the extended Glasgow Outcome Scale.

Targeting CD4(+) T-helper cells improves the induction of antitumor responses in dendritic cell-based vaccination.

To evaluate the relevance of directing antigen-specific CD4(+) T helper cells as part of effective anticancer immunotherapy, we investigated the immunologic and clinical responses to vaccination with dendritic cells (DC) pulsed with either MHC class I (MHC-I)-restricted epitopes alone or both MHC class I and II (MHC-I/II)-restricted epitopes. We enrolled 33 stage III and IV HLA-A*02:01-positive patients with melanoma in this study, of whom 29 were evaluable for immunologic response. Patients received intranodal vaccinations with cytokine-matured DCs loaded with keyhole limpet hemocyanin and MHC-I alone or MHC-I/II-restricted tumor-associated antigens (TAA) of tyrosinase and gp100, depending on their HLA-DR4 status.

Insight into the dynamics, localization and magnitude of antigen-specific immune responses by [(18)F]FLT PET imaging.

In order for cellular therapeutics to succeed, comprehensive monitoring of the transplanted cells in vivo is required i.e., their localization, functionality and numbers in a longitudinal manner.

Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness.

Using exome sequencing, we identify SERAC1 mutations as the cause of MEGDEL syndrome, a recessive disorder of dystonia and deafness with Leigh-like syndrome, impaired oxidative phosphorylation and 3-methylglutaconic aciduria. We localized SERAC1 at the interface between the mitochondria and the endoplasmic reticulum in the mitochondria-associated membrane fraction that is essential for phospholipid exchange. A phospholipid analysis in patient fibroblasts showed elevated concentrations of phosphatidylglycerol-34:1 (where the species nomenclature denotes the number of carbon atoms in the two acyl chains:number of double bonds in the two acyl groups) and decreased concentrations of phosphatidylglycerol-36:1 species, resulting in an altered cardiolipin subspecies composition.

Rationale, design, and implementation protocol of the Dutch clinical practice guideline pain in patients with cancer: a cluster randomised controlled trial with Short Message Service (SMS) and Interactive Voice Response (IVR).

Background: One-half of patients with cancer have pain. In nearly one out of two cancer patients with pain, this was undertreated. Inadequate pain control still remains an important problem in this group of patients.

Role of the calcium-sensing receptor in reducing the risk for calcium stones.

The tight control of blood Ca2+ levels within a narrow range is essential for the performance of vital physiologic functions. Muscle contraction, neuronal excitation, and intracellular signaling processes acquisitively require Ca2+. It is the concerted action of intestine, bone, and kidney that controls the Ca2+ balance through the regulation of intestinal absorption, bone (de)mineralization, and renal excretion of Ca2+, respectively.

Assessing the information desire of patients with advanced cancer by providing information with a decision aid, which is evaluated in a randomized trial: a study protocol.

Background: There is a continuing debate on the desirability of informing patients with cancer and thereby involving them in treatment decisions. On the one hand, information uptake may be hampered, and additional stress could be inflicted by involving these patients. On the other hand, even patients with advanced cancer desire information on risks and prognosis.

MAPK pathway activation through BRAF gene fusion in pilocytic astrocytomas; a novel oncogenic fusion gene with diagnostic, prognostic, and therapeutic potential.

Recently, a new mechanism for activation of B-RAF was identified resulting from a tandem duplication, generating a fusion protein with constitutive BRAF activity and thereby activating the MAPK pathway. Different fusion variants involving BRAF and KIAA1549 were demonstrated, present in 80% of pilocytic astrocytomas in children. As the KIAA1549-BRAF fusion gene is detected at a much lower frequency in diffuse low-grade astrocytomas and survival was much longer than expected in the patients with a 'non-pilocytic' astrocytoma carrying the fusion gene, identification of this fusion gene can be of diagnostic and prognostic value.