Compliance with international guidelines for chronic inflammatory neuropathies

ERare diseases’ management guidelines are produced with the primary aim of improving practice and standards of care for patients and may represent a useful framework for clinical practice. The EFNS/PNS (European Federation of Neurological Societies/Peripheral Nerve Society) guidelines for CIDP (chronic inflammatory demyelinating polyneuropathy) and MMN (multifocal motor neuropathy) were last published in 2010 (1, 2). Enthusiasm of the audience for whom they are produced, arguably primarily non‐sub‐specialists, is however largely unexplored. Compliance to these guidelines by neuromuscular and/or peripheral nerve specialists has not been investigated

Helicobacter Genotyping and Detection in Peroperative Lavage Fluid in Patients with Perforated Peptic Ulcer

Introduction and Objectives Certain Helicobacter pylori genotypes are associated with peptic ulcer disease; however, little is known about associations between the H. pylori genotype and perforated peptic ulcer (PPU). The primary aim of this study was to evaluate which genotypes are present in patients with PPU and which genotype is dominant in this population. The secondary aim was to study the possibility of determining the H. pylori status in a way other than by biopsy. Materials and Methods Serum samples, gastric tissue biopsies, lavage fluid, and fluid from the nasogastric tube were collec

Design and characterization of dielectric filled TM110_{110} microwave cavities for ultrafast electron microscopy

Microwave cavities oscillating in the TM$_{110}$ mode can be used as dynamic electron-optical elements inside an electron microscope. By filling the cavity with a dielectric material it becomes more compact and power efficient, facilitating the implementation in an electron microscope. However, the incorporation of the dielectric material makes the manufacturing process more difficult. Presented here are the steps taken to characterize the dielectric material, and to reproducibly fabricate dielectric filled cavities. Also presented are two versions with improved capabilities. The first, called a dual-mode cavity, is designed to support two modes simultaneously. The second has been optimized for low power consumption. With this optimized cavity a magnetic field strength of 2.84 $\pm$ 0.07 mT was generated at an input power of 14.2 $\pm$ 0.2 W. Due to the low input powers and small dimensions, these dielectric cavities are ideal as electron-optical elements for electron microscopy setups

Sympatric speciation and extinction driven by environment dependent sexual selection

A theoretical model is studied to investigate the possibility of sympatric speciation driven by sexual selection and ecological diversi¢cation. In particular, we focus on the rock-dwelling haplochromine cichlid species in Lake Victoria. The high speciation rate in these cichlids has been explained by their apparent ability to specialize rapidly to a large diversity of feeding niches. Seehausen and colleagues, however, demonstrated the importance of sexual selection in maintaining reproductive barriers between species. Our individual-orientated model integrates both niche di¡erentiation and a Fisherian runaway process, which is limited by visibility constraints. The model shows rapid sympatric speciation or extinction of species, depending on the strength of sexual selection

Detection of the tulip breaking virus (TBV) in tulips using optical sensors

The tulip breaking virus (TBV) causes severe economic losses for countries that export tulips such as the Netherlands. Infected plants have to be removed from the field as soon as possible. There is an urgent need for a rapid and objective method of screening. In this study, four proximal optical sensing techniques for the detection of TBV in tulip plants were evaluated and compared with a visual assessment by crop experts as well as with an ELISA (enzyme immunoassay) analysis of the same plants. The optical sensor techniques used were an RGB color camera, a spectrophotometer measuring from 350 to 2500 nm, a spectral imaging camera covering a spectral range from 400 to 900 nm and a chlorophyll fluorescence imaging system that measures the photosynthetic activity. Linear discriminant classification was used to compare the results of these optical techniques and the visual assessment with the ELISA score. The spectral imaging system was the best optical technique and its error was only slightly larger than the visual assessment error. The experimental results appear to be promising, and they have led to further research to develop an autonomous robot for the detection and removal of diseased tulip plants in the open field. The application of this robot system will reduce the amount of insecticides and the considerable pressure on labor for selecting diseased plants by the crop expert. © 2010 The Author(s

Impact of Combined Clenbuterol and Metoprolol Therapy on Reverse Remodelling during Mechanical Unloading

Clenbuterol (Cl), a β2 agonist, is associated with enhanced myocardial recovery during left ventricular assist device (LVAD) support, and exerts beneficial remodelling effects during mechanical unloading (MU) in rodent heart failure (HF). However, the specific effects of combined Cl+β1 blockade during MU are unknown.We studied the chronic effects (4 weeks) of β2-adrenoceptor (AR) stimulation via Cl (2 mg/kg/day) alone, and in combination with β1-AR blockade using metoprolol ((Met), 250 mg/kg/day), on whole heart/cell structure, function and excitation-contraction (EC) coupling in failing (induced by left coronary artery (LCA) ligation), and unloaded (induced by heterotopic abdominal heart transplantation (HATx)) failing rat hearts. Combined Cl+Met therapy displayed favourable effects in HF: Met enhanced Cl's improvement in ejection fraction (EF) whilst preventing Cl-induced hypertrophy and tachycardia. During MU combined therapy was less beneficial than either mono-therapy. Met, not Cl, prevented MU-induced myocardial atrophy, with increased atrophy occurring during combined therapy. MU-induced recovery of Ca2+ transient amplitude, speed of Ca2+ release and sarcoplasmic reticulum Ca2+ content was enhanced equally by Cl or Met mono-therapy, but these benefits, together with Cl's enhancement of sarcomeric contraction speed, and MU-induced recovery of Ca2+ spark frequency, disappeared during combined therapy.Combined Cl+Met therapy shows superior functional effects to mono-therapy in rodent HF, but appears inferior to either mono-therapy in enhancing MU-induced recovery of EC coupling. These results suggest that combined β2-AR simulation +β1-AR blockade therapy is likely to be a safe and beneficial therapeutic HF strategy, but is not as effective as mono-therapy in enhancing myocardial recovery during LVAD support

Multigene panel sequencing of established and candidate melanoma susceptibility genes in a large cohort of Dutch non-CDKN2A/CDK4 melanoma families.

Germline mutations in the major melanoma susceptibility gene CDKN2A explain genetic predisposition in only 10-40% of melanoma-prone families. In our study we comprehensively characterized 488 melanoma cases from 451 non-CDKN2A/CDK4 families for mutations in 30 established and candidate melanoma susceptibility genes using a custom-designed targeted gene panel approach. We identified (likely) pathogenic variants in established melanoma susceptibility genes in 18 families (n = 3 BAP1, n = 15 MITF p.E318K; diagnostic yield 4.0%). Among the three identified BAP1-families, there were no reported diagnoses of uveal melanoma or malignant mesothelioma. We additionally identified two potentially deleterious missense variants in the telomere maintenance genes ACD and TERF2IP, but none in the POT1 gene. MC1R risk variants were strongly enriched in our familial melanoma cohort compared to healthy controls (R variants: OR 3.67, 95% CI 2.88-4.68, p <0.001). Several variants of interest were also identified in candidate melanoma susceptibility genes, in particular rare (pathogenic) variants in the albinism gene OCA2 were repeatedly found. We conclude that multigene panel testing for familial melanoma is appropriate considering the additional 4% diagnostic yield in non-CDKN2A/CDK4 families. Our study shows that BAP1 and MITF are important genes to be included in such a diagnostic test

Optimizing adalimumab treatment in psoriasis with concomitant methotrexate (OPTIMAP): study protocol for a pragmatic, single-blinded, investigator-initiated randomized controlled trial

markdownabstract__Background:__ The introduction of anti-tumor necrosis factor medications has revolutionized the treatment of psoriasis with achievement of treatment goals (Psoriasis Area and Severity Index score 75, remission) that are not usually met with conventional systemics. Nevertheless, some patients continue to experience persistent disease activity or treatment failure over time. Strategies to optimize treatment outcomes include the use of concomitant methotrexate, which has demonstrated beneficial effects on pharmacokinetics and treatment efficacy in psoriasis and other inflammatory diseases. __Methods:__ This is an investigator-initiated, multicenter randomized controlled trial (RCT) designed to compare the combination treatment of adalimumab and methotrexate with adalimumab monotherapy in patients with psoriasis. The primary outcome is adalimumab drug survival at week 49. Other outcomes include improvement in disease severity and quality of life, tolerability, and safety. Moreover, anti-adalimumab antibodies and adalimumab serum concentrations will be measured and correlations between genotypes and clinical outcomes will be assessed. Patient recruitment started in March 2014. Up to now, 36 patients have been randomized. Many more patients have been (pre)screened. A total of 93 patients is desired to meet an adequate sample size. In our experience, the main limitation for recruitment is prior adalimumab therapy and intolerability or toxicity for methotrexate in the past. __Discussion:__ OPTIMAP is the first RCT to examine combination therapy with adalimumab and methotrexate in a psoriasis population. With data derived from this study we expect to provide valuable clinical data on long-term treatment outcomes. These data will be supported by assessment of the impact of concomitant methotrexate on adalimumab pharmacokinetics. Furthermore, the influence of several single nucleotide polymorphisms on adalimumab response will be analyzed in order to support the development of a more personalized approach for this targeted therapy. Trial registration:NTR4499. Registered on 7 April 2014

Lung MRI and impairment of diaphragmatic function in Pompe disease

Background: Pompe disease is a progressive metabolic myopathy. Involvement of respiratory muscles leads to progressive pulmonary dysfunction, particularly in supine position. Diaphragmatic weakness is considered to be the most important component. Standard spirometry is to some extent indicative but provides too little insight into diaphragmatic dynamics. We used lung MRI to study diaphragmatic and chest-wall movements in Pompe disease. Methods: In ten adult Pompe patients and six volunteers, we acquired two static spirometer-controlled MRI scans during maximum inspiration and expiration. Images were manually segmented. After normalization for lung size, changes in lung dimensions between inspiration and expiration were used for analysis; normalization was based on the cranial-caudal length ratio (representing vertical diaphragmatic displacement), and the anterior-posterior and left-right length ratios (representing chest-wall movements due to thoracic muscles). Results: We observed striking dysfunction of the diaphragm in Pompe patients; in some patients the diaphragm did not show any displacement. Patients had smaller cranial-caudal length ratios than volunteers (p &lt; 0.001), indicating diaphragmatic weakness. This variable strongly correlated with forced vital capacity in supine position (r = 0.88) and postural drop (r = 0.89). While anterior-posterior length ratios also differed between patients and volunteers (p = 0.04), left-right length ratios did not (p = 0.1). Conclusions: MRI is an innovative tool to visualize diaphragmatic dynamics in Pompe patients and to study chest-walland diaphragmatic movements in more detail. Our data indicate that diaphragmatic displacement may be severely disturbed in patients with Pompe disease