HLA Class II (DR, DQ, DP) Genes Were Separately Associated With the Progression From Seroconversion to Onset of Type 1 Diabetes Among Participants in Two Diabetes Prevention Trials (DPT-1 and TN07).

Objective: To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D).

Research Design And Methods: Next-generation targeted sequencing was used to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants from the Diabetes Prevention Trial-1 and Randomized Diabetes Prevention Trial with Oral Insulin sponsored by TrialNet. By the linkage disequilibrium, DQA1 and DQB1 are haplotyped to form DQ haplotypes; DP and DR haplotypes are similarly constructed.

Autoimmune susceptible HLA class II motifs facilitate the presentation of modified neoepitopes to potentially autoreactive T cells.

Rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes (T1D), and celiac disease (CD), are strongly associated with susceptible HLA class II haplotypes. The peptide-binding pockets of these molecules are polymorphic, thus each HLA class II protein presents a distinct set of peptides to CD4 T cells. Peptide diversity is increased through post-translational modifications, generating non-templated sequences that enhance HLA binding and/or T cell recognition.

Association of HLA-DQ Heterodimer Residues -18β and β57 With Progression From Islet Autoimmunity to Diabetes in the Diabetes Prevention Trial-Type 1.

Objective: The purpose was to test the hypothesis that the HLA-DQαβ heterodimer structure is related to the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D).

Research Design And Methods: Next-generation targeted sequencing was used to genotype HLA-DQA1-B1 class II genes in 670 subjects in the Diabetes Prevention Trial-Type 1 (DPT-1). Coding sequences were translated into DQ α- and β-chain amino acid residues and used in hierarchically organized haplotype (HOH) association analysis to identify motifs associated with diabetes onset.

The KAG motif of HLA-DRB1 (β71, β74, β86) predicts seroconversion and development of type 1 diabetes.

Background: HLA-DR4, a common antigen of HLA-DRB1, has multiple subtypes that are strongly associated with risk of type 1 diabetes (T1D); however, some are risk neutral or resistant. The pathobiological mechanism of HLA-DR4 subtypes remains to be elucidated.

Methods: We used a population-based case-control study of T1D (962 patients and 636 controls) to decipher genetic associations of HLA-DR4 subtypes and specific residues with susceptibility to T1D.

Next-Generation HLA Sequence Analysis Uncovers Seven HLA-DQ Amino Acid Residues and Six Motifs Resistant to Childhood Type 1 Diabetes.

HLA-DQA1 and -DQB1 genes have significant and potentially causal associations with autoimmune type 1 diabetes (T1D). To follow up on the earlier analysis on high-risk HLA-DQ2.5 and DQ8.

Motifs of Three HLA-DQ Amino Acid Residues (α44, β57, β135) Capture Full Association With the Risk of Type 1 Diabetes in DQ2 and DQ8 Children.

HLA-DQA1 and -DQB1 are strongly associated with type 1 diabetes (T1D), and DQ8.1 and DQ2.5 are major risk haplotypes.

MOLECULAR CHARACTERIZATION OF FECAL ISOLATED FROM ZOO ANIMALS.

Accredited zoos and animal parks play an important role in animal health research and conservation, providing important insights on matters of public health including zoonotic infectious diseases and antimicrobial resistance (AMR). The emergence and spread of AMR is a complex phenomenon that jeopardizes human and animal health and also threatens the long-term survival of endangered species. The presence of β-lactamases in clinical isolates is particularly significant as they can jeopardize the efficacy of critically important antimicrobials.

Combined Action of Piperitenone Epoxide and Antibiotics Against Clinical Isolates of and .

The aim of this study was to determine the antimicrobial efficiency of piperitenone epoxide (PEO) - a principal component of various aromatic plants' essential oil - in combination with various antibiotics against 28 strains of and 10 strains of isolated from clinical samples. essential oil, initially collected by hydrodistillation, was then subjected to flush column chromatography affording PEO of high purity. Minimum inhibitory concentrations of PEO alone and in combination with various concentrations of antibiotics were assessed using the microdilution method.

A modified flow cytometry method for objective estimation of human CD4 regulatory T cells (CD4 Tregs) in peripheral blood, via CD4/CD25/CD45RO/FoxP3 labeling.

Background: Several methods exist for flow-cytometric estimation of human peripheral blood CD4 T regulatory cells (CD4 Tregs).

Methods: We report our experience with the estimation of human CD4 Tregs via three different characterizations using flow cytometry (CD25 FoxP3 , CD25 CD127 FoxP3 , and CD4 CD25 CD45ROFoxP3 ) in normal subjects. We have used these methods on the control populations from two studies (32 and 36 subjects, respectively), the latter two methods retrospectively on the subjects of the first study.

Discriminative T cell recognition of cross-reactive islet-antigens is associated with HLA-DQ8 transdimer-mediated autoimmune diabetes.

Human leukocyte antigen (HLA)-DQ8 transdimer (HLA-DQA1*0501/DQB1*0302) confers exceptionally high risk in autoimmune diabetes. However, little is known about HLA-DQ8 transdimer-restricted CD4 T cell recognition, an event crucial for triggering HLA-DQ8 transdimer-specific anti-islet immunity. Here, we report a high degree of epitope overlap and T cell promiscuity between susceptible HLA-DQ8 and HLA-DQ8 transdimer.

Eleven Amino Acids of HLA-DRB1 and Fifteen Amino Acids of HLA-DRB3, 4, and 5 Include Potentially Causal Residues Responsible for the Risk of Childhood Type 1 Diabetes.

Next-generation targeted sequencing of HLA-DRB1 and HLA-DRB3, -DRB4, and -DRB5 (abbreviated as DRB345) provides high resolution of functional variant positions to investigate their associations with type 1 diabetes risk and with autoantibodies against insulin (IAA), GAD65 (GADA), IA-2 (IA-2A), and ZnT8 (ZnT8A). To overcome exceptional DR sequence complexity as a result of high polymorphisms and extended linkage disequilibrium among the DR loci, we applied a novel recursive organizer (ROR) to discover disease-associated amino acid residues. ROR distills disease-associated DR sequences and identifies 11 residues of DRB1, sequences of which retain all significant associations observed by DR genes.

Derivation and validation of a cardiovascular risk score for prediction of major acute cardiovascular events in non-alcoholic fatty liver disease; the importance of an elevated mean platelet volume.

Background: Atherosclerotic cardiovascular disease is a key cause of morbidity in non-alcoholic fatty liver disease (NAFLD) but appropriate means to predict major acute cardiovascular events (MACE) are lacking.

Aim: To design a bespoke cardiovascular risk score in NAFLD.

Methods: A retrospective derivation (2008-2016, 356 patients) and a prospective validation (2016- 2017, 111 patients) NAFLD cohort study was performed.

DRB4*01:01 Has a Distinct Motif and Presents a Proinsulin Epitope That Is Recognized in Subjects with Type 1 Diabetes.

DRB4*01:01 (DRB4) is a secondary HLA-DR product that is part of the high-risk DR4/DQ8 haplotype that is associated with type 1 diabetes (T1D). DRB4 shares considerable homology with HLA-DR4 alleles that predispose to autoimmunity, including DRB1*04:01 and DRB1*04:04. However, the DRB4 protein sequence includes distinct residues that would be expected to alter the characteristics of its binding pockets.

Exercise Training Attenuates the Development of Cardiac Autonomic Dysfunction in Diabetic Rats.

Background/aim: Exercise training usually complements pharmacological therapy of type 1 diabetes mellitus, however, little is known about its impact on cardiac autonomic neuropathy. Our aim was to evaluate the impact of exercise on electrocardiographic parameters and heart rate variability in diabetic rats.

Materials And Methods: Wistar rats were randomly assigned to four groups (n=12): Sedentary control (SC), sedentary diabetic (SD), exercise control (EC), and exercise diabetic (ED).

Multivariate analysis of the milk coagulation process in ovine breeds from Spain.

In Spain, ewe milk is mainly used for cheesemaking, and farming systems have traditionally been based on the use of autochthonous breeds. However, in recent years, the progressive introduction of highly productive foreign breeds in Spanish farms has led to an increasing interest in the characterization of dairy sheep breeds to evaluate whether genetic selection schemes should focus on productivity or milk technological aptitude. The purpose of this work was to explore milk composition and coagulation to classify 4 of the main dairy sheep breeds used in Spain.

Cross-cultural Adaptation and Validation of the Greek Voice Handicap Index-10 (GVHI-10) With Additional Receiver Operating Characteristic Analysis.

Objective(s): The use of subjective evaluation tools are proven useful and of high clinical value in the case of voice disordered population. For that type of evaluation, self-assessment questionnaires about the severity of the voice like Voice Handicap Index-30 (VHI-30) have been developed. The VHI-30 is the most studied tool which includes psychometrically robustness while guiding physician's therapeutic decision making.

Biodiversity and Microbial Resistance of Lactobacilli Isolated From the Traditional Greek Cheese Kopanisti.

Kopanisti is a Greek artisan cheese produced from raw milk in the island of Mykonos, Greece. The milk is left to rest for 12-24 h and then the rennet is added. After its formation the curd is left to drain for 2-3 days and is ready either for consumption (as tyrovolia fresh cheese), or with the addition of extra salt, the curd is left to ripen through further fermentation and surface development of Penicillium fungi, aprocess leading to the production of the traditional Greek cheese Kopanisti.

Swallowing and Aspiration Risk: A Critical Review of Non Instrumental Bedside Screening Tests.

Background And Purpose: The presence of dysphagia and aspiration in stroke patients is associated with increased mortality and morbidity. Early recognition and management of these two conditions via reliable, minimally invasive bedside procedures before complications arise remains challenging in everyday clinical practice. This study reviews the available bedside screening tools for detecting swallowing status and aspiration risk in acute stroke by qualitatively observing reference population study design, clinical flexibility, reliability and applicability to acute-care settings.

Rates and Correlations of Psychiatric Drug Administration in a Rehabilitation Center.

Background: Physical injury has been associated with the development of several psychopathological manifestations. Less is known about the use of psychiatric medication in those patients.

Objectives: This study aimed to explore the use of psychiatric medication by patients been admitted in a rehabilitation center in a tertiary care teaching hospital and to inquire for the correlations of such drug administration.

Genomic diversity and population structure of three autochthonous Greek sheep breeds assessed with genome-wide DNA arrays.

In the present study, genome-wide genotyping was applied to characterize the genetic diversity and population structure of three autochthonous Greek breeds: Boutsko, Karagouniko and Chios. Dairy sheep are among the most significant livestock species in Greece numbering approximately 9 million animals which are characterized by large phenotypic variation and reared under various farming systems. A total of 96 animals were genotyped with the Illumina's OvineSNP50K microarray beadchip, to study the population structure of the breeds and develop a specialized panel of single-nucleotide polymorphisms (SNPs), which could distinguish one breed from the others.

Tablet-Based Application for Objective Measurement of Motor Fluctuations in Parkinson Disease.

Background: The motor subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) has limited applicability for the assessment of motor fluctuations in the home setting.

Methods: To assess whether a self-administered, tablet-based application can reliably quantify differences in motor performance using two-target finger tapping and forearm pronation-supination tasks in the ON (maximal dopaminergic medication efficacy) and OFF (reemergence of parkinsonian deficits) medication states, we recruited 11 Parkinson disease (PD) patients (age, 60.6 ± 9.

Investigating pH based evaluation of fetal heart rate (FHR) recordings.

Cardiotocography (CTG) is a standard tool for the assessment of fetal well-being during pregnancy and delivery. However, its interpretation is associated with high inter- and intra-observer variability. Since its introduction there have been numerous attempts to develop computerized systems assisting the evaluation of the CTG recording.