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Adherence describes how a patient follows a medical regime recommended by a healthcare provider. Poor treatment adherence represents a complex and challenging problem of international healthcare systems, as it has a substantial impact on clinical outcomes and patient safety and constitutes an important financial burden. Since it is one of the most common causes of treatment failure, it is extremely important for physicians to reliably distinguish between non‐adherence and non‐response. This systematic review aims to summarize the current literature on treatment adherence in dermatology, focusing on chronic inflammatory skin diseases such as psoriasis, atopic dermatitis and acne. A systematic literature search was performed using the PubMed Database, including articles from 2008 to 2018. Low treatment adherence is a multidimensional phenomenon defined by the interplay of numerous factors and should under no circumstances be considered as the patient's fault alone. Factors influencing treatment adherence in dermatology include patient characteristics and beliefs, treatment efficacy and duration, administration routes, disease chronicity and the disease itself. Moreover, the quality of the physician‐patient relationship including physician‐time available for the patient plays an important role. Understanding patients' adherence patterns and the main drivers of non‐adherence creates opportunities to improve adherence in the future. Strategies to increase treatment adherence range from reminder programs to simplifying prescriptions or educational interventions. Absolute adherence to treatment may not be realistically achievable, but efforts need to be made to raise awareness in order to maximize adherence as far as possible. [ABSTRACT FROM AUTHOR]

We report on the observation of inertial-ballistic and mode-controlled rectification in mesoscopic GaAs/AlGaAs cross junctions. The cross junctions are composed of two current injecting branches which oppositely merge under an injection angle ϕ (90° ≥⃒ ϕ ≥⃒ 30°) into a straight central voltage stem. Ballistic electron transport is indicated by negative bend resistance which develops for ϕ = 90° in bend resistance configuration. Rectification is observed at both ends of the voltage stem. The mode-controlled signal at the upper end of the stem is found to be nearly independent from ϕ. The inertial-ballistic signal obtained from the potential difference between both ends of the stem vanishes for ϕ = 90° and increases with decreasing ϕ. Rectification is studied for different top-gate voltages and temperatures. [ABSTRACT FROM AUTHOR]

Abstract: Magneto-ballistic transport is studied in a mesoscopic four-terminal junction with broken symmetry in the classical ballistic transport regime. Depending on the measurement configuration the device acts as a non-centrosymmetric Hall junction or a ballistic rectifier. In Hall configuration the absolute value of the Hall voltage depends on the current polarity. This nonlinearity is attributed to a current-polarity-dependent feeding of ballistic electrons into the Hall probes. A centrosymmetric reference sample shows the well-known linear Hall characteristic. In rectifier configuration the rectified inertial-ballistic signal is superimposed by the Hall component. The inertial-ballistic component is maintained in perpendicular magnetic fields exceeding . [Copyright &y& Elsevier]

Ballistic rectification is demonstrated in a nanoscale waveguide cross junction consisting of a straight voltage stem channel and current-injecting branches which oppositely merge into the stem under an angle [lowercase_phi_synonym]<90°. According to a simple billiardlike picture for both current directions, the injected electrons are deflected at the opposite boundary, thus charging one arm of the stem according to their preferential momentum component. The rectification efficiency has a maximum value of 2.6% and shows a characteristic voltage dependence, which is explained by the availability of unoccupied states in the voltage stem at low voltage and by carrier heating at high voltage. [ABSTRACT FROM AUTHOR]

A first attempt at the three-dimensional evaluation of naturally initiated surface connected and internal fatigue cracks is presented. Fatigue crack initiation and growth in air and vacuum environments have been investigated through X-ray microtomography in air and vacuum environments at elevated temperatures (350 °C), accompanied by post-mortem electron microscopy of the fracture surfaces. In vacuum ( < 10 −5 mbar), multiple internal and surface-connected crack initiation was observed, but only the surface-connected cracks grew. In contrast, fewer cracks formed in air, these were mostly surface-connected and all were observed to grow. In all instances the initiation features were associated with globular primary α . An improved fatigue life was found in vacuum, which was mostly a consequence of delayed initiation, but was also due to slower fatigue crack propagation. The non-propagation of internal cracks was taken to imply that even the good laboratory vacuum obtained here was insufficient to simulate the conditions obtained for an internal crack in a component. The crack shape evolved towards a semi-circular shape a / c = 1 in air during fatigue crack growth, whilst the vacuum cracks remained semi-elliptical ( a / c ≃ 1.4 ). This was taken to imply that oxide-induced crack closure played a role in fatigue crack growth in air. [ABSTRACT FROM AUTHOR]

Objectives There is convergent evidence for an important role of interleukin-16 ( IL-16) in the pathogenesis of multiple sclerosis ( MS). IL-16 serves as a chemoattractant for different immune cells that are involved in developing lesions. Here, we compared IL-16 levels of MS patients and controls and addressed the long-term effect of IFN- β, the most common immunomodulatory MS therapy, on IL-16 serum levels in MS patients over 2 years. Beyond this, we analysed the expression of IL-16 in two CD4+ T-cell subsets, Th1 and Th17 cells, which are important autoimmune mediators and affected by IFN- β treatment, derived from myelin-specific T-cell transgenic mice. Materials and methods IL-16 serum levels of 17 controls and of 16 MS patients before therapy and at months 1, 2, 3, 6, 9, 12 and 24 during IFN- β1a therapy were determined by ELISA. MRI was performed before therapy, at months 12 and 24. IL-16 expression of in vitro differentiated murine myelin oligodendrocyte glycoprotein ( MOG)-specific Th1 and Th17 cells was quantified by real-time PCR. Results Before therapy, MS patients showed significantly elevated IL-16 levels compared with controls irrespective of disease activity determined by MRI. Therapy with IFN- β1a led to a significant linear decrease in IL-16 serum levels beginning after 2 months. MOG-specific Th17 cells expressed more IL-16 than Th1 cells. Conclusions Reduction in increased IL-16 levels may be of relevance for the therapeutic effect of IFN- β1a in MS. Easily accessible IL-16 serum levels hold a potential as biomarker of treatment efficacy in MS. [ABSTRACT FROM AUTHOR]

Nischwitz S, Cepok S, Kroner A, Wolf C, Knop M, Müller-Sarnowski F, Pfister H, Rieckmann P, Hemmer B, Ising M, Uhr M, Bettecken T, Holsboer F, Müller-Myhsok B, Weber F. More CLEC16A gene variants associated with multiple sclerosis. Acta Neurol Scand: 2011: 123: 400-406. © 2010 John Wiley & Sons A/S. Recently, associations of several single-nucleotide polymorphisms (SNPs) within the CLEC16A gene with multiple sclerosis (MS), type-I diabetes, and primary adrenal insufficiency were reported. We performed linkage disequilibrium (LD) fine mapping with 31 SNPs from this gene, searching for the region of highest association with MS in a German sample consisting of 603 patients and 825 controls. Four SNPs located in intron 19 of the CLEC16A gene were found associated. We could replicate the finding for SNP rs725613 and were able to show for the first time the association of rs2041670, rs2080272 and rs998592 with MS. All described base polymorphisms are mapping to one LD block of approximately 50 kb within intron 19 of the CLEC16A gene, suggesting a pivotal role of this region for susceptibility of MS and possibly also for other autoimmune diseases. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is the most common chronic inflammatory neurologic disorder diagnosed in young adults and, due to its chronic course, is responsible for a substantial economic burden. MS is considered to be a multifactorial disease in which both genetic and environmental factors intervene. The well-established human leukocyte antigen (HLA) association does not completely explain the genetic impact on disease susceptibility. However, identification and validation of non-HLA-genes conferring susceptibility to MS has proven to be difficult probably because of the small individual contribution of each of these genes. Recently, associations with two single nucleotide polymorphisms (SNPs) in the IL2RA gene (rs12722489, rs2104286) and one SNP in the IL7RA gene (rs6897932) have been reported by several groups. These three SNPs were genotyped in a French and a German population of MS patients using the hME assay by the matrix-assisted laser desorption/ionization time of flight technology (Sequenom, San Diego, CA, USA). We show that these SNPs do contribute to the risk of MS in these two unrelated European MS patient populations with odds ratios varying from 1.1 to 1.5. The discovery and validation of new genetic risk factors in independent populations may help toward the understanding of MS pathogenesis by providing valuable information on biological pathways to be investigated.Genes and Immunity (2008) 9, 259–263; doi:10.1038/gene.2008.14; published online 20 March 2008 [ABSTRACT FROM AUTHOR]

Peroxisomes are eukaryotic organelles that function in numerous metabolic pathways and defects in peroxisome function can cause serious developmental brain disorders such as adrenoleukodystrophy (ALD). Peroxisomal membrane proteins (PMPs) play a crucial role in regulating peroxisome function. Therefore, PMP homeostasis is vital for peroxisome function. Recently, we established that certain PMPs are degraded by the Ubiquitin Proteasome System yet little is known about how faulty/non-functional PMPs undergo quality control. Here we have investigated the degradation of Pxa1p, a fatty acid transporter in the yeast Saccharomyces cerevisiae. Pxa1p is a homologue of the human protein ALDP and mutations in ALDP result in the severe disorder ALD. By introducing two corresponding ALDP mutations into Pxa1p (Pxa1MUT), fused to mGFP, we show that Pxa1MUT-mGFP is rapidly degraded from peroxisomes in a proteasome-dependent manner, while wild type Pxa1-mGFP remains relatively stable. Furthermore, we identify a role for the ubiquitin ligase Ufd4p in Pxa1MUT-mGFP degradation. Finally, we establish that inhibiting Pxa1MUT-mGFP degradation results in a partial rescue of Pxa1p activity in cells. Together, our data demonstrate that faulty PMPs can undergo proteasome-dependent quality control. Furthermore, our observations may provide new insights into the role of ALDP degradation in ALD. Unlabelled Image • Pxa1p is a yeast peroxisomal fatty acid transporter and homologue of human ALDP. • Mutations in ALDP cause the severe disease adrenoleukodystrophy. • A mutant form of Pxa1p (Pxa1MUT) is degraded by the proteasome system. • Ufd4p, a cytosolic E3 ligase, is involved in the degradation of peroxisomal Pxa1MUT. • Inhibition of Pxa1MUT degradation partially rescues Pxa1p activity in cells. [ABSTRACT FROM AUTHOR]