Drug Repurposing by Simulating Flow Through Protein-Protein Interaction Networks.

As drug development is extremely expensive, the identification of novel indications for in-market drugs is financially attractive. Multiple algorithms are used to support such drug repurposing, but highly reliable methods combining simulation of intracellular networks and machine learning are currently not available. We developed an algorithm that simulates drug effects on the flow of information through protein-protein interaction networks, and used support vector machine to identify potentially effective drugs in our model disease, psoriasis.

Splicing factors differentially expressed in psoriasis alter mRNA maturation of disease-associated EDA+ fibronectin.

The EDA+ fibronectin splicing variant is overexpressed in psoriatic non-lesional epidermis and sensitizes keratinocytes to mitogenic signals. However, regulation of its abundance is only partially understood. In our recent cDNA microarray experiment, we identified three SR-rich splicing factors-splicing factor, arginine/serine-rich 18 (SFRS18), peptidyl-prolyl cis-trans isomerase G (PPIG), and luc-7 like protein 3 (LUC7L3)-which might be implicated in the preactivated states of keratinocytes in psoriatic non-involved skin and could also contribute to the regulation of fibronectin mRNA maturation.

Sodium MRI of T1 High Signal Intensity in the Dentate Nucleus due to Gadolinium Deposition in Multiple Sclerosis.

Background And Purpose: Recently, several studies reported increased signal intensity (SI) of the dentate nucleus (DN) on unenhanced T1-weighted magnetic resonance imaging (MRI) as a possible consequence of multiple applications of gadolinium-based contrast agents. The aim of this study was to investigate with sodium ( Na) MRI possible tissue abnormalities of the DN in multiple sclerosis (MS) patients.

Methods: Sodium and conventional MRI were performed on a clinical 3T scanner.

Study of retinal neurodegeneration and maculopathy in diabetic Meriones shawi: A particular animal model with human-like macula.

The purpose of this work was to evaluate a potentially useful animal model, Meriones shawi (M.sh)-developing metabolic X syndrome, diabetes and possessing a visual streak similar to human macula-in the study of diabetic retinopathy and diabetic macular edema (DME). Type 2 diabetes (T2D) was induced by high fat diet administration in M.

Methodical Challenges and a Possible Resolution in the Assessment of Receptor Reserve for Adenosine, an Agonist with Short Half-Life.

The term receptor reserve, first introduced and used in the traditional receptor theory, is an integrative measure of response-inducing ability of the interaction between an agonist and a receptor system (consisting of a receptor and its downstream signaling). The underlying phenomenon, i.e.

[The probability of obstructive sleep apnea disorders emergence by odds ratio of main risk factors].

Introduction: The quality of sleep plays a serious role in the individual's daytime performace and state of health, there by it has a strong influence on the society.

Aim: The present study measures the probability developing and severity of obstructive sleep apnea syndrome, - which belongs to group of disorders of the respiratory - through odds ratio of leading risk factors.

Method: 127 persons were examined in the test.

Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany - A national case collection.

Background Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran that reverses its anticoagulant effects within minutes. It may exhibit the potential for patients under dabigatran therapy suffering ischemic stroke to regain eligibility for thrombolysis with rt-PA and may inhibit lesion growth in patients with intracerebral hemorrhage on dabigatran. Aims To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of ischemic stroke or intracranial hemorrhage.

Fluorinative ring-opening of cyclopropanes by hypervalent iodine reagents. An efficient method for 1,3-oxyfluorination and 1,3-difluorination.

A new method is presented for 1,3-difluorination and 1,3-oxyfluorination reactions. The process is based on iodonium mediated opening of 1,1-disubstituted cyclopropanes. The reaction proceeds with high chemo- and regioselectivity under mild reaction conditions typically at room temperature in a couple of hours.

Expansion of circulating follicular T helper cells associates with disease severity in childhood atopic dermatitis.

Follicular helper T (T) cells play crucial role in B-cell differentiation and antibody production. Although, atopic dermatitis (AD) is often associated with increased serum IgE levels, B-cell mediated responses have not been studied thoroughly. The aim of our study was to investigate the proportion of T-like cells in the disease.

Species specificity profiling of rat and human organic cation/carnitine transporter Slc22a5/SLC22A5 (Octn2/OCTN2).

The purpose of this study was to characterize the uptake of carnitine, the physiological substrate, and the uptake of 3-(2,2,2-trimethylhydrazinium)propionate, a consensus substrate by rat Octn2 and human OCTN2 transporters as well as to characterize drug-mediated inhibition of l-carnitine uptake by the rat and human orthologs overexpressed in CHO-K1 cells. l-carnitine and 3-(2,2,2-trimethylhydrazinium)propionate were found to be a lower affinity substrate for rat Octn2 (K = 32.66 ± 5.

MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjögren's syndrome.

The discovery of microRNAs (miRNAs) and their critical role in genetic control opened new avenues in understanding of various biological processes including immune cell lineage commitment, differentiation, proliferation and apoptosis. However, a given miRNA may have hundreds of different mRNA targets and a target might be regulated by multiple miRNAs, thus the characterisation of dysregulated miRNA expression profiles could give a better insight into the development of immunological disturbances in autoimmune diseases. The aim of our study was to examine the changes in miRNA expression profiles in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS).

Copper-Catalyzed, Stereoselective Cross-Coupling of Cyclic Allyl Boronic Acids with α-Diazoketones.

In this study, we present the synthesis of new, stereodefined allylboronic acids employed to investigate the stereochemistry of the Cu-catalyzed cross-coupling of allylboronic acids with α-diazoketones. According to our results, this reaction proceeds with retention of the relative configuration of the allylboronic acid substrate. We suggest that the stereoinduction step involves a syn S2'-type transmetalation of the allylboronic acid substrate with a Cu-carbene species.

Impact of rheumatoid arthritis in oral surgery and implantology treatment based on literature.

Rheumatoid arthritis (RA) is an autoimmune disease that results in a chronic, systemic inflammatory disorder that principally attacks synovial joints. The pathology of the disease process often leads to the destruction of articular cartilage and the bone. Normal bone remodeling cycle requires the balance between bone resorption and bone deposition which is determined by the activities of two principle cell types, namely, osteoclasts and osteoblasts.

Synthesis of Benzyl-, Allyl-, and Allenyl-boronates via Copper-Catalyzed Borylation of Alcohols.

Alcohols are among the most abundant and readily available organic feedstocks in industrial processes. The direct catalytic functionalization of sp C-O bonds of alcohols remains the main challenge in this field. Here, we report a copper-catalyzed synthesis of benzyl-, allyl-, and allenyl-boronates from benzylic, allylic, and propargylic alcohols, respectively.

Stimulus-triggered enhancement of chilling tolerance in zebrafish embryos.

Background: Cryopreservation of zebrafish embryos is still an unsolved problem despite market demand and massive efforts to preserve genetic variation among numerous existing lines. Chilled storage of embryos might be a step towards developing successful cryopreservation, but no methods to date have worked.

Methods: In the present study, we applied a novel strategy to improve the chilling tolerance of zebrafish embryos by introducing a preconditioning hydrostatic pressure treatment to the embryos.

Critical appraisal of advance directives given by patients with fatal acute stroke: an observational cohort study.

Background: Advance directives (AD) imply the promise of determining future medical treatment in case of decisional incapacity. However, clinical practice increasingly indicates that standardized ADs often fail to support patients' autonomy. To date, little data are available about the quality and impact of ADs on end-of-life decisions for incapacitated acute stroke patients.

Diagnostic and Prognostic Relevance of Magnetic Resonance Imaging and Electrophysiological Findings in Acute Spinal Ischemia.

Objective: Our purpose was to classify the rare entity of spontaneous spinal ischemia with clinical, magnetic resonance-tomographic, and electrophysiological parameters to determine criteria for outcome prediction.

Methods: We analyzed the stroke registry database of the University Hospital Mannheim, Germany, from 2004 to 2010 for patients with a diagnosis of vascular spinal cord ischemia.

Results: Ten patients were identified (mean age 65 years [range 50-83], 5 women).

Opinions of sports clinical practice chiropractors, with sports specialty training and those without, about chiropractic research priorities in sports health care: a centering resonance analysis.

Introduction: A Canadian sports chiropractic research agenda has yet to be defined. The Delphi method can be utilized to achieve this purpose; however, the sample of experts who participate can influence the results. To better inform sample selection for future research agenda development, we set out to determine if differences in opinions about research priorities exist between chiropractors who have their sports specialty designation and those who do not.

Hepatitis E Virus in Wild Boars and Spillover Infection in Red and Roe Deer, Germany, 2013-2015.

To determine animal hepatitis E virus (HEV) reservoirs, we analyzed serologic and molecular markers of HEV infection among wild animals in Germany. We detected HEV genotype 3 strains in inner organs and muscle tissues of a high percentage of wild boars and a lower percentage of deer, indicating a risk for foodborne infection of humans.

Recent Advances in the Preparation and Application of Allylboron Species in Organic Synthesis.

In this Perspective we will highlight the most important recent breakthroughs in selective allylboron chemistry (both the synthesis and application of these species). In addition we will provide an outlook toward the future of this promising subfield of organic synthesis.

Myostatin propeptide mutation of the hypermuscular mice decreases the formation of myostatin and improves insulin sensitivity.

The TGFβ family member myostatin (growth/differentiation factor-8) is a negative regulator of skeletal muscle growth. The hypermuscular mice carry the 12-bp deletion in the sequence encoding the propeptide region of the precursor promyostatin, and additional modifier genes of the genetic background contribute to determine the full expression of the phenotype. In this study, by using mice strains carrying mutant or wild-type myostatin alleles with the genetic background and nonmutant myostatin with the wild-type background, we studied separately the effect of the mutation or the genetic background on morphology, metabolism, and signaling.

Size matters for lice on birds: Coevolutionary allometry of host and parasite body size.

Body size is one of the most fundamental characteristics of all organisms. It influences physiology, morphology, behavior, and even interspecific interactions such as those between parasites and their hosts. Host body size influences the magnitude and variability of parasite size according to Harrison's rule (HR: positive relationship between host and parasite body sizes) and Poulin's Increasing Variance Hypothesis (PIVH: positive relationship between host body size and the variability of parasite body size).

Idarucizumab as Antidote to Intracerebral Hemorrhage under Treatment with Dabigatran.

Background And Purpose: Non-vitamin K anticoagulants (NOAC) such as dabigatran have become important therapeutic options for the prevention of stroke. Until recently, there were only nonspecific agents to reverse their anticoagulant effects in a case of emergency. Idarucizumab, an antibody fragment targeting dabigatran, is the first specific antidote for a NOAC to be approved, but real-world experience is limited.

Implicit Learning in Transient Global Amnesia and the Role of Stress.

Transient global amnesia (TGA) is a disorder with reversible anterograde disturbance of explicit memory, frequently preceded by an emotionally or physically stressful event. By using magnetic resonance imaging (MRI) following an episode of TGA, small hippocampal lesions have been observed. Hence it has been postulated that the disorder is caused by the stress-related transient inhibition of memory formation in the hippocampus.