The role of destination branding in tourism industry

Destination branding is relatively new marketing concept which demands special attention of the marketers who study progressive ways of building and promoting brands. Consequently, special attention is paid to tourist destination branding

The role of territorial identity in local development

Territorial identity is the result of a mechanism of interaction in which identity plays the role of cause and effect of territorial dynamics. The development of economic and productive collaborative relationships requires the creation of a strong territorial identity that will contribute to local development processes

A novel familial mutation in the PCSK1 gene that alters the oxyanion hole residue of proprotein convertase 1/3 and impairs its enzymatic activity.

Four siblings presented with congenital diarrhea and various endocrinopathies. Exome sequencing and homozygosity mapping identified five regions, comprising 337 protein-coding genes that were shared by three affected siblings. Exome sequencing identified a novel homozygous N309K mutation in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene, encoding the neuroendocrine convertase 1 precursor (PC1/3) which was recently reported as a cause of Congenital Diarrhea Disorder (CDD). The PCSK1 mutation affected the oxyanion hole transition state-stabilizing amino acid within the active site, which is critical for appropriate proprotein maturation and enzyme activity. Unexpectedly, the N309K mutant protein exhibited normal, though slowed, prodomain removal and was secreted from both HEK293 and Neuro2A cells. However, the secreted enzyme showed no catalytic activity, and was not processed into the 66 kDa form. We conclude that the N309K enzyme is able to cleave its own propeptide but is catalytically inert against in trans substrates, and that this variant accounts for the enteric and systemic endocrinopathies seen in this large consanguineous kindred

The role of destination branding in tourism industry

Destination branding is relatively new marketing concept which demands special attention of the marketers who study progressive ways of building and promoting brands. Consequently, special attention is paid to tourist destination branding

The role of territorial identity in local development

Territorial identity is the result of a mechanism of interaction in which identity plays the role of cause and effect of territorial dynamics. The development of economic and productive collaborative relationships requires the creation of a strong territorial identity that will contribute to local development processes

The natural history of primary sclerosing cholangitis in 781 children. A multicenter, international collaboration

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes

Oral Health Status and Salivary Properties in Relation to Gluten-free Diet in Children With Celiac Disease

ABSTRACT Background: Patients with celiac disease (CD) have a wide variety of symptoms, from being asymptomatic to having chronic diarrhea, abdominal pain, and extraintestinal symptoms. In the oral cavity, enamel defects and recurrent aphthous stomatitis are the most common symptoms. The aim of the study was to assess oral health, bacterial colonization and salivary buffering capacity of patients with CD at diagnosis were compared with patients with CD receiving a gluten-free diet (GFD) and healthy children. Methods: Three groups were prospectively investigated: newly diagnosed CD, CD treated with GFD, and a control group. All of the children were examined by pediatric dentists, and saliva samples were collected for bacterial and pH analysis. Results: Ninety children were enrolled in the study, 30 in each group. A higher prevalence of enamel hypoplasia (66%) was found in children with CD. Plaque index was significantly lower in the celiac-treated group, which correlated with oral health behavior: teeth brushing and frequency of eating between meals. Children receiving GFD brushed their teeth and used fluoride significantly more often than other children in the study. No difference between groups was found in snack consumption, mutans streptococci and lactobacilli counts in saliva, as well as pH and buffer capacity. Conclusions: A lower degree of plaque was found in children with CD receiving GFD. This finding could not be explained by salivary properties or bacteria, but rather by better oral hygiene. The results should raise the awareness of pediatric gastroenterologists toward oral health-related issues in children with CD

Phase I/II Trial of Liver-derived Mesenchymal Stem Cells in Pediatric Liver-based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome Patients

Background. Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases. Objective. This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy. Methods. Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti–human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis. Results. The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases. Conclusions. This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses