Novel Pathogenic PRSS1 Variant p.Glu190Lys in a Case of Chronic Pancreatitis

Mutations in the PRSS1 (serine protease 1) gene encoding human cationic trypsinogen cause hereditary pancreatitis or may be associated with sporadic chronic pancreatitis. The mutations exert their pathogenic effect either by increasing intra-pancreatic trypsinogen activation (trypsin pathway) or by causing proenzyme misfolding and endoplasmic reticulum stress (misfolding pathway). Here we report a novel heterozygous c.568G>A (p.Glu190Lys) variant identified in a case with chronic pancreatitis. The parents of the index patient had no history of pancreatitis but were unavailable for genetic testing. Functional characterization revealed 2.5-fold increased autoactivation of the mutant trypsinogen relative to wild type. Unlike many other clinically relevant PRSS1 mutations, p.Glu190Lys did not alter the chymotrypsin C (CTRC)-dependent degradation of trypsinogen nor did it increase CTRC-mediated processing of the trypsinogen activation peptide. Cellular secretion of the mutant protein was unchanged indicating normal folding behavior. Based on the genetic and functional evidence, we classify the p.Glu190Lys PRSS1 variant as likely pathogenic, which stimulates autoactivation of cationic trypsinogen independently of CTRC

A public health threat in Hungary: obesity, 2013

Background: In Hungary, the last wide-range evaluation about nutritional status of the population was completed in 1988. Since then, only limited data were available. Our aim was to collect, analyze and present updated prevalence data. Methods. Anthropometric, educational and morbidity data of persons above 18 y were registered in all geographical regions of Hungary, at primary care encounters and within community settings. Results: Data (BMI, waist circumference, educational level) of 40,331 individuals (16,544 men, 23,787 women) were analyzed. Overall prevalence for overweight was 40.4% among men, 31.3% among women, while for obesity 32.0% and 31.5%, respectively. Abdominal obesity was 37.1% in males, 60.9% in females. Among men, the prevalence of overweight-obesity was: under 35 y = 32.5%-16.2%, between 35-60 y = 40.6%-34.7%, over 60 y = 44.3%-36.7%. Among women, in the same age categories were: 17.8%-13.8%, 29.7%-29.0%, and 36.9%-39.0%. Data were presented according to age by decades as well. The highest odds ratio of overweight (OR: 1.079; 95% CI [1.026-1.135]) was registered by middle educational level, the lowest odds ratio of obesity (OR: 0.500; 95% CI [0.463-0.539]) by the highest educational level. The highest proportion of obese people lived in villages (35.4%) and in Budapest (28.9%). Distribution of overweighed persons were: Budapest (37.1%), other cities (35.8%), villages (33.8%). Registered metabolic morbidities were strongly correlated with BMIs and both were inversely related to the level of urbanization. Over the previous decades, there has been a shift in the distribution of population toward being overweight and moreover obese, it was most prominent among males, mainly in younger generation. Conclusions: Evaluation covered 0.53% of the total population over 18 y and could be very close to the proper national representativeness. The threat of obesity and related morbidities require higher public awareness and interventions

An appraisal: How notifiable infectious diseases are reported by Hungarian family physicians

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Diabetes Stimulates Osteoclastogenesis by Acidosis-Induced Activation of Transient Receptor Potential Cation Channels

Patients with type 1 diabetes have lower bone mineral density and higher risk of fractures. The role of osteoblasts in diabetes-related osteoporosis is well acknowledged whereas the role of osteoclasts (OCLs) is still unclear. We hypothesize that OCLs participate in pathological bone remodeling. We conducted studies in animals (streptozotocin-induced type 1 diabetic mice) and cellular models to investigate canonical and non-canonical mechanisms underlying excessive OCL activation. Diabetic mice show an increased number of active OCLs. In vitro studies demonstrate the involvement of acidosis in OCL activation and the implication of transient receptor potential cation channel subfamily V member 1 (TRPV1). In vivo studies confirm the establishment of local acidosis in the diabetic bone marrow (BM) as well as the ineffectiveness of insulin in correcting the pH variation and osteoclast activation. Conversely, treatment with TRPV1 receptor antagonists re-establishes a physiological OCL availability. These data suggest that diabetes causes local acidosis in the BM that in turn increases osteoclast activation through the modulation of TRPV1. The use of clinically available TRPV1 antagonists may provide a new means to combat bone problems associated with diabetes

Feel4Diabetes healthy diet score: Development and evaluation of clinical validity

Background: The aim of this paper is to present the development of the Feel4Diabetes Healthy Diet Score and to evaluate its clinical validity. Methods: Study population consisted of 3268 adults (63% women) from high diabetes risk families living in 6 European countries. Participants filled in questionnaires at baseline and after 1 year, reflecting the dietary goals of the Feel4Diabetes intervention. Based on these questions the Healthy Diet Score was constructed, consisting of the following components: breakfast, vegetables, fruit and berries, sugary drinks, whole-grain cereals, nuts and seeds, low-fat dairy products, oils and fats, red meat, sweet snacks, salty snacks, and family meals. Maximum score for each component was set based on its estimated relative importance regarding T2DM risk, higher score indicating better quality of diet. Clinical measurements included height, weight, waist circumference, heart rate, blood pressure, and fasting blood sampling, with analyses of glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides. Analysis of (co) variance was used to compare the Healthy Diet Score and its components between countries and sexes using baseline data, and to test differences in clinical characteristics between score categories, adjusted for age, sex and country. Pearson''s correlations were used to study the association between changes from baseline to year 1 in the Healthy Diet Score and clinical markers. To estimate reproducibility, Pearson''s correlations were studied between baseline and 1 year score, within the control group only. Results: The mean total score was 52.8 ± 12.8 among women and 46.6 ± 12.8 among men (p < 0.001). The total score and its components differed between countries. The change in the Healthy Diet Score was significantly correlated with changes in BMI, waist circumference, and total and LDL cholesterol. The Healthy Diet Score as well as its components at baseline were significantly correlated with the values at year 1, in the control group participants. Conclusion: The Feel4Diabetes Healthy Diet Score is a reproducible method to capture the dietary information collected with the Feel4Diabetes questionnaire and measure the level of and changes in the adherence to the dietary goals of the intervention. It gives a simple parameter that associates with clinical risk factors in a meaningful manner