Relationship between Levels of Brain-Derived Neurotrophic Factor and Metabolic Parameters in Patients with Type 2 Diabetes Mellitus

Background and Aim. Studies have suggested that brain-derived neurotrophic factor (BDNF) plays a role in glucose and lipid metabolism and inflammation. The aim of this study was to evaluate the relationship between serum BDNF levels and various metabolic parameters and inflammatory markers in patients with type 2 diabetes mellitus (T2DM). Materials and Methods. The study included 88 T2DM patients and 33 healthy controls. Fasting blood samples were obtained from the patients and the control group. The serum levels of BDNF were measured with an ELISA kit. The current paper introduces a receiver-operating characteristic (ROC) generalization curve to identify cut-off for the BDNF values in type 2 diabetes patients. Results. The serum levels of BDNF were significantly higher in T2DM patients than in the healthy controls (206.81 ± 107.32 pg/mL versus 130.84 ± 59.81 pg/mL; P<0.001). They showed a positive correlation with the homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.28; P<0.05), the triglyceride level (r=0.265; P<0.05), and white blood cell (WBC) count (r=0.35; P<0.001). In logistic regression analysis, age (P<0.05), body mass index (BMI) (P<0.05), C-reactive protein (CRP) (P<0.05), and BDNF (P<0.01) were independently associated with T2DM. In ROC curve analysis, BDNF cut-off was 137. Conclusion. The serum BDNF level was higher in patients with T2DM. The BDNF had a cut-off value of 137. The findings suggest that BDNF may contribute to glucose and lipid metabolism and inflammation

Heterogeneity of pollen food allergy syndrome in seven Southern European countries: The @IT.2020 multicenter study

Background Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. Objectives To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. Methods As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. Results Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). Conclusions PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics

“Whole” vs. “fragmented” approach to EAACI pollen season definitions: A multicenter study in six Southern European cities

Background: The adequate definition of pollen seasons is essential to facilitate a correct diagnosis, treatment choice, and outcome assessment in patients with seasonal allergic rhinitis. A position paper by the European Academy of Allergy and Clinical Immunology (EAACI) proposed season definitions for Northern and Middle Europe. Objective: To test the pollen season definitions proposed by EAACI in six Mediterranean cities for seven pollen taxa. Methods: As part of the @IT.2020 multi-center study, pollen counts for Poaceae, Oleaceae, Fagales, Cupressaceae, Urticaceae (Parietaria spp.), and Compositae (Ambrosia spp., Artemisia spp.) were collected from January 1 to December 31, 2018. Based on these data, pollen seasons were identified according to EAACI criteria. A unified monitoring period for patients in AIT trials was created and assessed for feasibility. Results: The analysis revealed a great heterogeneity between the different locations in terms of pattern and length of the examined pollen seasons. Further, we found a fragmentation of pollen seasons in several segments (max. 8) separated by periods of low pollen counts (intercurrent periods). Potential monitoring periods included often many recording days with low pollen exposure (max. 341 days). Conclusion: The Mediterranean climate leads to challenging pollen exposure times. Monitoring periods for AIT trials based on existing definitions may include many intermittent days with low pollen concentrations. Therefore, it is necessary to find an adapted pollen season definition as individual solution for each pollen and geographical area

Genome-wide characterization of circulating metabolic biomarkers

Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1,2,3,4,5,6,7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8,9,10,11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Activation of beta-Catenin by mutation of the gene in cultivated hepatoma cells

Das Protein Beta-Catenin hat zwei wichtige Aufgaben in der Zelle: Zum einen ist es ge-meinsam mit Cadherinen an der physikalischen Verankerung benachbarter Zellen be-teiligt, zum anderen wirkt es als Transkriptionsfaktor im Zellkern. Zahlreiche Studien belegen seine wichtige Funktion während der Embryonalentwicklung; Darüber hinaus ist es auch im adulten Organismus an der Steuerung von Zellteilung und -differenzierung beteiligt. Das CTNNB1-Gen, das beim Menschen für Beta-Catenin kodiert, ist in etwa 30% der menschlichen hepatozellulären Karzinome durch Mutation verändert; Besonders häufig sind Mutationen in Hepatoblastomen. Mutationen treten auch in experimentell erzeugten Tumoren auf. In Lebertumoren von Mäusen, die mit dem Modell-Tumorpromotor Phenobarbital (PB) behandelt worden waren, waren in etwa 80% der Fälle Mutationen im Catnb-Gen, dem Maus-Orthologen des CTNNB1-Gens, nach-zuweisen. Dagegen zeigten Hepatome aus Tieren ohne PB-Behandlung keine Catnb-Mutationen. Im Rahmen der vorliegenden Arbeit wurden Hepatomlinien aus Mäusen und Ratten analysiert, die z. T. im Labor etabliert worden waren oder aus anderen Quellen zur Verfügung standen. Keine der Linien stammte aus einem Tumor eines mit PB behandelten Tieres. Ziel der Arbeit war, die verschiedenen Linien bezüglich ihres Catnb-Mutationsstatus molekulargenetisch zu charakterisieren. Die Analysen erfolgten auf der Ebene der DNA, der RNA und auf der Proteinebene. Insgesamt wurden 14 Linien untersucht. Hierbei wurden folgende Ergebnisse erzielt: - Die überwiegende Zahl der untersuchten Linien (10/14) zeigten Aberrationen im Catnb-Gen, die in der Regel auf der RNA-Ebene bestätigt werden konnten und häufig Auswirkungen auf das Laufverhalten des Proteins bei der gelelektrophoretischen Trennung hatten. - Der in den Zelllinien beobachtete Typ der Aberrationen unterscheidet sich gravierend von jenen Mutationsmustern, die in den Tumoren selbst beobachtet werden. Häufig traten Deletionen im Gen auf, die zu einer partiellen Verkürzung des Proteins im aminoterminalen Bereich führten. In den Primärtumoren der Maus wurden dagegen ausschließlich Punktmutationen beobachtet. Die Daten weisen darauf hin, dass die Mutationen im Catnb-Gen erst während der Kultivierung der Linien in vitro entstanden sind und den mutierten Zellen dort einen Selektionsvorteil verschaffen. Hier besteht vermutlich eine Analogie zum Selektionsdruck einer in vivo PB-Behandlung.The protein beta-Catenin has two important functions in the cell: On the one hand it is involved together with Cadherins in the physical anchorage of neighbouring cells, on the other hand it acts as a transcription factor in the nucleus. It's important role in regulation of cell polarity during embryonal development is well established.In the adult organism it controls cell division and differentiation. Beta-Catenin is encoded by CTNNB1/Catnb (human and mouse orthologues). CTNNB1 is mutated approximately 30 % of human hepatocellular carcinomas. Mutations are also very frequent in hepatoblastomas. In liver tumors of mice, which had been treated with the model tumor promoter phenobarbital, mutations in the Catnb gene were detected in approximately 80 % of the cases. By contrast, hepatomas from mice not treated with Phenobarbital did not show Catnb mutations. In the present study cells from various mouse or rat hepatoma lines, most of which were established previously in our laboratory were investigated for the presence of mutations in Catnb. In addition, analyses at the level of the RNA and protein were carried out. The following results were obtained: - The majority of the examined lines (10/14) showed aberrations in the Catnb gene, which could be generally confirmed by sequence analysis of the RNA level and Western analysis of the protein. - The types of aberrations observed in the cell lines differed differed from those seen in mouse liver tumors: Cell lines frequently harbored deletions within the gene, elimination parts of the aminoterminal part of the protein. By contrast, the predominant type of mutation of the primary tumors were point mutatations. The data suggest that the mutations in the Catnb gene had developed only during the cultivation of the lines in vitro providing the mutated cells with a selective advantage, resembling the situation given in vivo during promotion with phenobarbital treatment

Relationship between Thyroid Hormone Levels and Crime Type: A Controlled Study in Prisoners

Various factors cause aggression, which can be related to imbalance of T3 and T4 hormones, which can act as neurotransmitters and are reported to be elevated during aggression. This indicates changes in the hypothalamic-pituitary-thyroid axis that cause long-term changes in aggressive behaviour, especially in criminals. Moreover, mental and behavioural disorders possibly occur in individuals with impairment in thyroid hormone balance. The main rationale for this study was to asses if high T3, high T4, and low TSH hormones may have an effect on aggression-related crime tendency. Furthermore, the study aimed to measure levels of thyroid hormones in prisoners and to examine relationships of the hormone levels with crime rates. Our study was conducted in Ankara Sincan Closed Prisons. The study group consisted of 208 male volunteers who were imprisoned and the control group included 82 male volunteers who were not imprisoned. Prisoners in the study group were divided into two groups: those who committed aggression-related crime (Group A, n = 96) and prisoners convicted of other crimes (Group B, n = 112). Pulse rates, T3, T4, and thyroid-stimulating hormone (TSH) levels, and theT3/T4 ratio were measured in these prisoners. Data were analysed using the Wilcoxon rank sum test and chi-square Fisher’s exact test to test for any statistically significant differences. Results showed that toxic goitre rates, T3 and T4 values, and pulse rates were significantly higher in Group A than in the control group. Significant increase in T3 and T4 levels and the presence of toxic goitre were associated with aggression-related crime. These examinations should be performed on prisoners in general, especially those convicted of violent crimes. Additional rehabilitation and research programs should also be developed for such patients

Knowledge Management And Learning Capability To Enhance Organizational Innovativeness

AbstractXXI century is witnessing the rise of innovation and innovativeness as one of the main drivers of industrial competition. Innovation becomes increasingly crucial in creating and maintaining an organization's competitive advantage, as well as its contributions to growth and wealth [i]. In other words innovation itself is a strong competitive strategy to achieve world-class manufacturing and servicing status and compete effectively in global markets [ii]. Learning capabilities of a firm in context of knowledge management are claimed that as one of the main drivers of innovativeness. Even there are some efforts to consider these concepts together; they are mostly studied as separately in today's “management theory jungle”. Thus, this paper aims to offer a holistic approach for building organizational innovativeness on the basis of Knowledge Management (KM) and Organizational Learning Capabilities (OLC)