Nonsynonymous Variation in NKPD1 Increases Depressive Symptoms in European Populations.

Background: Despite high heritability, little success was achieved in mapping genetic determinants of depression-related traits by means of genome-wide association studies.

Methods: To identify genes associated with depressive symptomology, we performed a gene-based association analysis of nonsynonymous variation captured using exome-sequencing and exome-chip genotyping in a genetically isolated population from the Netherlands (n = 1999). Finally, we reproduced our significant findings in an independent population-based cohort (n = 1604).

An anterior cruciate ligament injury does not affect the neuromuscular function of the non-injured leg except for dynamic balance and voluntary quadriceps activation.

Purpose: The function of the anterior cruciate ligament (ACL) patients' non-injured leg is relevant in light of the high incidence of secondary ACL injuries on the contralateral side. However, the non-injured leg's function has only been examined for a selected number of neuromuscular outcomes and often without appropriate control groups. We measured a broad array of neuromuscular functions between legs of ACL patients and compared outcomes to age, sex, and physical activity matched controls.

[AbstractA woman with knee pain after a fall in childhood].

A 32-year-old woman presented with pain in her left knee ever since she had fallen down the stairs as a child and had landed on this knee. On the X-ray we saw two large patella fragments. We made the diagnosis of dislocated and subluxated fracture of the patella without consolidation.

Technical aspects of revision and functional outcome after revision of the Oxford unicompartmental knee arthroplasty.

Background: This study analysed the technical aspects of revision of the Oxford unicompartmental knee arthroplasty (OUKA) and functional results after revision.

Methods: In a historic cohort study we analysed all revised OUKAs that were primarily implanted at our clinic over a 10-year period (1998-2009). The primary aim was to investigate surgical difficulties encountered during revision surgery of the OUKA.

MRI signal intensity of anterior cruciate ligament graft after transtibial versus anteromedial portal technique (TRANSIG): design of a randomized controlled clinical trial.

Background: There are two primary surgical techniques to reconstruct the anterior cruciate ligament (ACL), transtibial (TT) technique and anteromedial portal (AMP) technique. Currently, there is no consensus which surgical technique elicits the best clinical and functional outcomes. MRI-derived measures of the signal intensity (SI) of the ACL graft have been described as an independent predictor of graft properties.

Exome-sequencing in a large population-based study reveals a rare Asn396Ser variant in the LIPG gene associated with depressive symptoms.

Despite a substantial genetic component, efforts to identify common genetic variation underlying depression have largely been unsuccessful. In the current study we aimed to identify rare genetic variants that might have large effects on depression in the general population. Using high-coverage exome-sequencing, we studied the exonic variants in 1265 individuals from the Rotterdam study (RS), who were assessed for depressive symptoms.

Progression of medial compartmental osteoarthritis 2-8 years after lateral closing-wedge high tibial osteotomy.

Purpose: The primary purpose of this study is to investigate the progression of medial osteoarthritis (OA) following lateral closing-wedge high tibial osteotomy (HTO). Secondary outcomes included functional and pain scores.

Methods: This prospective cohort study analysed 298 patients treated with lateral closing-wedge HTO surgery for medial compartmental OA.

Accounting for substitution and spatial heterogeneity in a labelled choice experiment.

Many environmental valuation studies using stated preferences techniques are single-site studies that ignore essential spatial aspects, including possible substitution effects. In this paper substitution effects are captured explicitly in the design of a labelled choice experiment and the inclusion of different distance variables in the choice model specification. We test the effect of spatial heterogeneity on welfare estimates and transfer errors for minor and major river restoration works, and the transferability of river specific utility functions, accounting for key variables such as site visitation, spatial clustering and income.

One versus two years of elastic compression stockings for prevention of post-thrombotic syndrome (OCTAVIA study): randomised controlled trial.

Objective:  To study whether stopping elastic compression stockings (ECS) after 12 months is non-inferior to continuing them for 24 months after proximal deep venous thrombosis.

Design:  Multicentre single blind non-inferiority randomised controlled trial.

Setting:  Outpatient clinics in eight teaching hospitals in the Netherlands, including one university medical centre.

A study of genetic and environmental contributions to structural brain changes over time in twins concordant and discordant for bipolar disorder.

This is the first longitudinal twin study examining genetic and environmental contributions to the association between liability to bipolar disorder (BD) and changes over time in global brain volumes, and global and regional measures of cortical surface area, cortical thickness and cortical volume. A total of 50 twins from pairs discordant or concordant for BD (monozygotic: 8 discordant and 3 concordant pairs, and 1 patient and 3 co-twins from incomplete pairs; dizygotic: 6 discordant and 2 concordant pairs, and 1 patient and 7 co-twins from incomplete pairs) underwent magnetic resonance imaging twice. In addition, 57 twins from healthy twin pairs (15 monozygotic and 10 dizygotic pairs, and 4 monozygotic and 3 dizygotic subjects from incomplete pairs) were also scanned twice.

Genetic variants in RBFOX3 are associated with sleep latency.

Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency.

Retooling institutional support infrastructure for clinical research.

Clinical research activities at academic medical centers are challenging to oversee. Without effective research administration, a continually evolving set of regulatory and institutional requirements can divert investigator and study team attention away from a focus on scientific gain, study conduct, and patient safety. However, even when the need for research administration is recognized, there can be struggles over what form it should take.

Evaluation of Sysmex XN-1000 High-Sensitive Analysis (hsA) Research Mode for Counting and Differentiating Cells in Cerebrospinal Fluid.

Objectives: Counting cells in cerebrospinal fluid (CSF) using automated analyzers is generally problematic due to low precision at low cell numbers. To overcome this limitation, Sysmex (Kobe, Japan) developed the high-sensitive analysis (hsA) research mode specifically for counting cells in fluids that contain low cell counts. We evaluated this mode by counting RBCs, WBCs, and differentiated WBCs in CSF samples.

Genetic Variation in Schizophrenia Liability is Shared With Intellectual Ability and Brain Structure.

Background: Alterations in intellectual ability and brain structure are important genetic markers for schizophrenia liability. How variations in these phenotypes interact with variance in schizophrenia liability due to genetic or environmental factors is an area of active investigation. Studying these genetic markers using a multivariate twin modeling approach can provide novel leads for (genetic) pathways of schizophrenia development.

Efficacy and Safety of Outpatient Treatment Based on the Hestia Clinical Decision Rule with or without N-Terminal Pro-Brain Natriuretic Peptide Testing in Patients with Acute Pulmonary Embolism. A Randomized Clinical Trial.

Rationale: Outpatient treatment of pulmonary embolism (PE) may lead to improved patient satisfaction and reduced healthcare costs. However, trials to assess its safety and the optimal method for patient selection are scarce.

Objectives: To validate the utility and safety of selecting patients with PE for outpatient treatment by the Hestia criteria and to compare the safety of the Hestia criteria alone with the Hestia criteria combined with N-terminal pro-brain natriuretic peptide (NT-proBNP) testing.

The association between hippocampal volume and life events in healthy twins.

Hippocampal volume deficits have been linked to life stress. However, the degree to which genes and environment influence the association between hippocampal volume and life events is largely unknown. In total, 123 healthy twins from monozygotic and dizygotic twin pairs underwent magnetic resonance imaging (MRI), and 57 healthy twins were interviewed with the Life Events and Difficulties Schedule (LEDS), with an overlap of 54 twins undergoing both MRI and the life events interview.

Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma.

The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging.

Incomplete Reossification After Craniosynostosis Surgery.

A patient with unicoronal craniosynostosis was treated by an open cranial vault remodeling procedure at 11 months of age. A calvarial defect persists at the site of the sagittal suture at 7 years follow-up. This unexpected outcome led us to evaluate current literature on incidence and possible causes of incomplete reossification after craniosynostosis surgery.

Increased risk of psychosis in patients with hearing impairment: Review and meta-analyses.

Several studies suggest hearing impairment as a risk factor for psychosis. Hearing impairment is highly prevalent and potentially reversible, as it can be easily diagnosed and sometimes improved. Insight in the association between hearing impairment and psychosis can therefore contribute to prevention of psychosis.

ACTG2 variants impair actin polymerization in sporadic Megacystis Microcolon Intestinal Hypoperistalsis Syndrome.

Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (MMIHS) is a rare congenital disorder, in which heterozygous missense variants in the Enteric Smooth Muscle actin γ-2 (ACTG2) gene have been recently identified. To investigate the mechanism by which ACTG2 variants lead to MMIHS, we screened a cohort of eleven MMIHS patients, eight sporadic and three familial cases, and performed immunohistochemistry, molecular modeling and molecular dynamics (MD) simulations, and in vitro assays. In all sporadic cases, a heterozygous missense variant in ACTG2 was identified.