Genes and pathways underlying susceptibility to impaired lung function in the context of environmental tobacco smoke exposure.

Background: Studies aiming to assess genetic susceptibility for impaired lung function levels upon exposure to environmental tobacco smoke (ETS) have thus far focused on candidate-genes selected based on a-priori knowledge of potentially relevant biological pathways, such as glutathione S-transferases and ADAM33. By using a hypothesis-free approach, we aimed to identify novel susceptibility loci, and additionally explored biological pathways potentially underlying this susceptibility to impaired lung function in the context of ETS exposure.

Methods: Genome-wide interactions of single nucleotide polymorphism (SNP) by ETS exposure (0 versus ≥1 h/day) in relation to the level of forced expiratory volume in one second (FEV) were investigated in 10,817 subjects from the Dutch LifeLines cohort study, and verified in subjects from the Swiss SAPALDIA study (n = 1276) and the Dutch Rotterdam Study (n = 1156).

Is pain relief after vaginal mesh and/or sling removal durable long term?

Introduction And Hypothesis: This study was to review our experience of pain relief durability in women who experienced initial pain resolution after vaginal mesh and/or sling removal (VMSR).

Methods: A retrospective chart review of consecutive, nonneurogenic women who underwent VMSR for pain and reported persistent pain relief at the 6-month postoperative follow-up visit were assessed. Pre- and postoperative data collected were self-reported chief complaints, physical examination, other medical conditions associated with chronic pain, use of pain medications, Urogenital Distress Inventory-6 (in which question 6 specifically addresses pain), and the Numerical Pain Rating Scale (NPRS).

Evaluating the antifibrotic potency of galunisertib in a human ex vivo model of liver fibrosis.

Background And Purpose: Liver fibrosis is a major cause of liver-related mortality and, so far, no effective antifibrotic drug is available. Galunisertib, a TGF-β receptor type I kinase inhibitor, is a potential candidate for the treatment of liver fibrosis. Here, we evaluated the potency of galunisertib in a human ex vivo model of liver fibrosis.

Silica-Supported Au-Ag Catalysts for the Selective Hydrogenation of Butadiene.

Gold and silver are miscible over the entire composition range, and form an attractive combination for fundamental studies on bimetallic catalysts. Au-Ag catalysts have shown synergistic effects for different oxidation and liquid-phase hydrogenation reactions, but have rarely been studied for gas-phase hydrogenation. In this study 3 nm particles of Au, Ag and Au-Ag supported on silica (SBA-15) were investigated as catalysts for selective hydrogenation of butadiene in an excess of propene.

Hydrogen Bond Networks and Hydrophobic Effects in the Amyloid β Chain in Water: A Molecular Dynamics Study.

We have studied the conformational landscape of the C-terminal fragment of the amyloid protein Aβ in water using well-tempered metadynamics simulations and found that it resembles an intrinsically disordered protein. The conformational fluctuations of the protein are facilitated by a collective reorganization of both protein and water hydrogen bond networks, combined with electrostatic interactions between termini as well as hydrophobic interactions of the side chains. The stabilization of hydrophobic interactions in one of the conformers involves a collective collapse of the side chains along with a squeeze-out of water sandwiched between them.

Adverse Effects of Outcome Monitoring Feedback in Patients With Personality Disorders: A Randomized Controlled Trial in Day Treatment and Inpatient Settings.

This study aimed to evaluate the differential effect of outcome monitoring feedback to therapists and to patients on outcomes in cluster B, cluster C, and personality disorder not otherwise specified (PD-NOS) patients. Day treatment patients (n = 112) and inpatients (n = 94) were randomly assigned to a feedback to therapist (FbT), feedback to therapist and patient (FbTP), or no feedback (NFb) condition. Feedback was based on weekly administrations of the Outcome Questionnaire-45 (OQ-45).

Complex Energy Metabolic Changes in Heart Failure With Preserved Ejection Fraction and Heart Failure With Reduced Ejection Fraction.

Alterations in cardiac energy metabolism contribute to the severity of heart failure. However, the energy metabolic changes that occur in heart failure are complex, and are dependent not only on the severity and type of heart failure present, but also on the coexistence of common comorbidities such as obesity and type 2 diabetes. In this article we review the cardiac energy metabolic changes that occur in heart failure.

Short-Course Radiotherapy Followed by Neoadjuvant Bevacizumab, Capecitabine, and Oxaliplatin and Subsequent Radical Treatment in Primary Stage IV Rectal Cancer: Long-Term Results of a Phase II Study.

Background: In a Dutch phase II trial conducted between 2006 and 2010, short-course radiotherapy followed by systemic therapy with capecitabine, oxaliplatin, and bevacizumab as neoadjuvant treatment and subsequent radical surgical treatment of primary tumor and metastatic sites was evaluated. In this study, we report the long-term results after a minimum follow-up of 6 years.

Methods: Patients with histologically confirmed rectal adenocarcinoma with potentially resectable or ablatable metastases in liver or lungs were eligible.

Synthesis of pH-responsive N-acetyl-cysteine modified starch derivatives for oral delivery.

In this study, a novel type of pH-responsive polymer PyHES-NAC (2-hydroxy-3-(2-propynyloxy) propyl hydroxyethyl starch (PyHES)) - (N-acetyl-cysteine (NAC)) was synthesized. First, PyHES was prepared via hydrophobic modification of hydroxyl groups in hydroxyethyl starch (HES) with propynylglycidyl ether (PGE), and then pH-responsive carboxylic acid group was connected to propynyl group via thiol-yne click reaction with NAC. Aqueous PyHES-NAC solutions exhibited a good transference between hydrophobic (or self-assembly) and hydrophilic static along with the change of pH value and protective properties of drugs under acidic conditions.

Sulfatase modifying factor 1 (SUMF1) is associated with Chronic Obstructive Pulmonary Disease.

Background: It has been observed that mice lacking the sulfatase modifying factor (Sumf1) developed an emphysema-like phenotype. However, it is unknown if SUMF1 may play a role in Chronic Obstructive Pulmonary Disease (COPD) in humans. The aim was to investigate if the expression and genetic regulation of SUMF1 differs between smokers with and without COPD.

Monitoring Protein-Unbound Valproic Acid Serum Concentrations in Clinical Practice.

Background: Valproic acid (VPA) is an effective antiepileptic drug and mood stabilizer. A key characteristic of VPA is its high and saturable protein binding at higher concentrations. Although the unbound concentration of VPA is responsible for its pharmacological activity, total drug concentrations are monitored in routine clinical practice.

Evidence for ontogenetically and morphologically distinct alternative reproductive tactics in the invasive Round Goby Neogobius melanostomus.

Alternative reproductive tactics are characterized by the occurrence of discrete alternative morphs that differ in behavioural, morphological and physiological traits within the same sex. Although much effort has been made to describe the behaviour, morphology and physiology of such alternative morphs, less effort has been invested investigating how much overlap there is in the characteristics of such morphs in natural populations. We studied random population samples of the invasive Round Goby Neogobius melanostomus from five different localities in the river Rhine system in the Netherlands.

Effects of the Functionalization of the Ordered Mesoporous Carbon Support Surface on Iron Catalysts for the Fischer-Tropsch Synthesis of Lower Olefins.

Ordered mesoporous carbon (CMK-3) with different surface modifications is applied as a support for Fe-based catalysts in the Fischer-Tropsch to olefins synthesis (FTO) with and without sodium and sulfur promoters. Different concentrations of functional groups do not affect the size (3-5 nm) of Fe particles in the fresh catalysts but iron (carbide) supported on N-enriched CMK-3 and a support with a lower concentration of functional groups show higher catalytic activity under industrially relevant FTO conditions (340 °C, 10 bar, H/CO=2) compared to a support with an O-enriched surface. The addition of promoters leads to more noticeable enhancements of the catalytic activity (3-5 times higher) and the selectivity to C-C olefins (≈2 times higher) than surface functionalization of the support.

Nepafenac 0.3% after Cataract Surgery in Patients with Diabetic Retinopathy: Results of 2 Randomized Phase 3 Studies.

Purpose: To demonstrate the efficacy and safety of once-daily nepafenac 0.3% ophthalmic suspension versus vehicle, based on clinical outcomes, after cataract surgery in patients with diabetes.

Design: Two prospective, randomized, multicenter, double-masked, vehicle-controlled phase 3 studies.

Management of Severe Pancreatic Fistula After Pancreatoduodenectomy.

Importance: Postoperative pancreatic fistula is a potentially life-threatening complication after pancreatoduodenectomy. Evidence for best management is lacking.

Objective: To evaluate the clinical outcome of patients undergoing catheter drainage compared with relaparotomy as primary treatment for pancreatic fistula after pancreatoduodenectomy.

Longitudinal measurement invariance of the Dutch Outcome Questionnaire-45 in a clinical sample.

Purpose: In the absence of measurement invariance across measurement occasions, change scores based on pretest-posttest measurements may be inaccurate representations of real change on the latent variable. In this study, we examined whether measurement invariance held in the Dutch version of Outcome Questionnaire-45 (OQ-45).

Method: Using secondary data analysis of a sample of N = 540 Dutch outpatients, we tested the stability of the factorial structure (gamma change) and the metric and scalar invariance (beta change) across pretest and posttest measurements using a combination of factor analysis and item response theory methodology.

Psychometric properties of the Dutch version of the Treatment Support Measure (TSM) parent and youth form.

Unlabelled: The Treatment Support Measure (TSM) Parent and Youth were created to help clinicians with actionable feedback when youths are not making sufficient progress in treatment. This study examined the psychometric properties of the Dutch TSM Parent and TSM Youth. Parents (n = 172) and youth (n = 122) were recruited at 2 outpatient mental health care institutions.

Obesity and type 2 diabetes have additive effects on left ventricular remodelling in normotensive patients-a cross sectional study.

Background: It is unclear whether obesity and type 2 diabetes (T2D), either alone or in combination, induce left ventricular hypertrophy (LVH) independent of hypertension. In the current study, we provide clarity on this issue by rigorously analysing patient left ventricular (LV) structure via clinical indices and via LV geometric patterns (more commonly used in research settings). Importantly, our sample consisted of hypertensive patients that are routinely screened for LVH via echocardiography and normotensive patients that would normally be deemed low risk with no further action required.

Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD.

From Optimization to Mapping: An Evolutionary Algorithm for Protein Energy Landscapes.

Stochastic search is often the only viable option to address complex optimization problems. Recently, evolutionary algorithms have been shown to handle challenging continuous optimization problems related to protein structure modeling. Building on recent work in our laboratories, we propose an evolutionary algorithm for efficiently mapping the multi-basin energy landscapes of dynamic proteins that switch between thermodynamically stable or semi-stable structural states to regulate their biological activity in the cell.

Evidence for large-scale gene-by-smoking interaction effects on pulmonary function.

Background: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV 1 (forced expiratory volume in 1 second) or FEV 1 /FVC (FEV 1 /forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered.

No convincing association between genetic markers and respiratory symptoms: results of a GWA study.

Background: Respiratory symptoms are associated with accelerated lung function decline, and increased hospitalization and mortality rates in the general population. Although several environmental risk factors for respiratory symptoms are known, knowledge on genetic risk factors is lacking. We aim to identify genetic variants associated with respiratory symptoms by genome-wide association (GWA) analyses.