The PompeQoL questionnaire: Development and validation of a new measure for children and adolescents with Pompe disease

Genetic disorders pose great challenges for affected individuals and their families, as they must cope with the irreversible nature of the disease and a life‐long dependence on medical assistance and treatment. Children and adolescents dealing with Pompe disease (PD) often struggle to keep up with their peers in physical activities. To gain valuable insights into their subjective experiences and better understand their perception and coping related to daily challenges linked to their condition and treatment, the use of standardized questionnaires is crucial. This study introduces the novel PompeQoL 1.0 questionnaire for children and adolescents with PD, designed for comprehensive assessment of both disease‐specific FDH and HRQoL through self‐ and proxy reports. Content validity was ensured through patients' and parents' involvement at the initial stages of development and in subsequent cognitive debriefing process. Participants found the questionnaire easy to understand, answerable, relevant, and comprehensive. Adjustments based on feedback from patients and their parents improved its utility as a patient‐ and observer‐reported outcome measure. After careful item examination, 52 items were selected, demonstrating moderate to excellent test–retest reliability for most scales and initial evidence for satisfactory construct validity. The PompeQoL questionnaire stands as a valuable screening instrument for both clinical and research purposes. Future research should prioritize additional revisions and larger validation studies, focusing on testing the questionnaire in clinical practice and trials. Nevertheless, the PompeQoL 1.0 stands out as the first standardized measure providing insights into disease‐specific FDH and HRQoL among children and adolescents with various forms of PD

Organic Agriculture

Consumers are increasingly aware of the health- and safety-related implications of the food which they can buy in the market. At the same time, households have become more aware of their environmental responsibilities. Regarding the production of food, a crucial and multifunctional role is played by agriculture. The way vegetables, fruits, and other crops are grown and how livestock is raised has an impact on the environment and landscape. Operations performed by farmers, such as water management, can be dangerous for the soil and the whole ecosystem. Consequently, there is a search for natural ways of sustaining the impact of agriculture on the environment. In this context, one of the most popular ideas is organic agriculture. In the literature on the subject, there are many concepts that some authors consider to be synonymous even as others argue that these terms are not interchangeable. There is, for example, "organic agriculture," "alternative agriculture," "sustainable agriculture," "ecological agriculture," "biological agriculture," "niche farming," "community-supported agriculture," and "integrated pest management." Very often, techniques and products related to organic agriculture are described by marketing experts with the use of abbreviations such as "bio" and "eco." Products with such markings and labels are increasingly popular in stores that often give them separate shelves for their sale. Despite the higher price compared to conventional products, they are increasingly sought by consumers. The entry examines the various impacts of organic agriculture with a view to these trends

Impact of a school-based intervention to promote fruit intake: a cluster randomized controlled trial

OBJECTIVE: There is evidence that fruit consumption among school children is below the recommended levels. This study aims to examine the effects of a dietary education intervention program me, held by teachers previously trained in nutrition, on the consumption of fruit as a dessert at lunch and dinner, among children 6-12 years old. STUDY DESIGN: This is a randomized trial with the schools as the unit of randomisation. METHODS: A total of 464 children (239 female, 6-12years) from seven elementary schools participated in this cluster randomized controlled trial. Three schools were allocated to the intervention and four to the control group. For the intervention schools, we delivered professional development training to school teachers (12 sessions of 3 h each). The training provided information about nutrition, healthy eating, the importance of drinking water and healthy cooking activities. After each session, teachers were encouraged to develop classroom activities focused on the learned topics. Sociodemographic was assessed at baseline and anthropometric, dietary intake and physical activity assessments were performed at baseline and at the end of the intervention. Dietary intake was evaluated by a 24-h dietary recall and fruit consumption as a dessert was gathered at lunch and dinner. RESULTS: Intervened children reported a significant higher intake in the consumption of fruit compared to the controlled children at lunch (P = 0.001) and at dinner (P = 0.012), after adjusting for confounders. CONCLUSIONS: Our study provides further support for the success of intervention programmes aimed at improving the consumption of fruit as a dessert in children.CIEC – Research Centre on Child Studies, IE, UMinho (FCT R&D unit 317), Portuga

Stabilization of mismatch repair gene PMS2 by glycogen synthase kinase 3β is implicated in the treatment of cervical carcinoma

<p>Abstract</p> <p>Background</p> <p>PMS2 expression loss was reported in a variety of human. However, its importance has not been fully understood in cervical carcinoma. The aim of this study was to determine the expression of PMS2 in cervical carcinoma and evaluate the significance of mismatch repair gene PMS2 regulated by glycogen synthase kinase 3β (GSK-3β) in chemosensitivity.</p> <p>Methods</p> <p>We examined PMS2 and phosphorylated GSK-3β(<it>s</it>9) expression in cervical carcinoma tissues using immunohistochemical staining. Furthermore, we detected PMS2 expression in HeLa cells and evaluate the interaction with GSK-3β after transfection with GSK-3β by small interference RNA (siRNA), co-immunoprecipitation and immunoblotting. We also evaluated the effect of PMS2 transfection on HeLa cells' chemosensitivity to cisplatin treatment.</p> <p>Results</p> <p>We found significant downregulation of PMS2 in cervical carcinoma, which was negatively associated with phosphorylated GSK-3β (<it>s</it>9). Furthermore, we demonstrated GSK-3β transfection was able to interact with PMS2 and enhance PMS2 production in HeLa cells, and increased PMS2 production was responsible for enhanced chemosensitivity.</p> <p>Conclusions</p> <p>Our results provide the evidence that stabilization of PMS2 production by GSK-3β was important to improve chemosensitization, indicating the significance of GSK-3β-related PMS2 downregulation in the development of cervical carcinoma and in developing a potential strategy for chemotherapy.</p

Pathways to Injury in Chronic Pancreatitis: Decoding the Role of the High-Risk SPINK1 N34S Haplotype Using Meta-Analysis

Background: The complex interactions between recurrent trypsin-mediated pancreatic injury, alcohol-associated pancreatic injury and SPINK1 polymorphisms in chronic pancreatitis (CP) are undefined. We hypothesize that CP occurs as a result of multiple pathological mechanisms (pathways) that are initiated by different metabolic or environmental factors (etiologies) and may be influenced differentially by downstream genetic risk factors. We tested this hypothesis by evaluating the differences in effect size of the high risk SPINK1 N34S haplotype on CP from multiple etiologies after combining clinical reports of SPINK1 N34S frequency using meta-analysis. Methods and Findings: The Pubmed and the Embase databases were reviewed. We studied 24 reports of SPINK1 N34S in CP (2,421 cases, 4,857 controls) using reported etiological factors as surrogates for pathways and multiple meta-analyses to determine the differential effects of SPINK1 N34S between alcoholic and non-alcoholic etiologies. Using estimates of between-study heterogeneity, we sub-classified our 24 studies into four specific clusters. We found that SPINK1 N34S is strongly associated with CP overall (OR 11.00; 95% CI: 7.59-15.93), but the effect of SPINK1 N34S in alcoholic CP (OR 4.98, 95% CI: 3.16-7.85) was significantly smaller than in idiopathic CP (OR 14.97, 95% C.I. = 9.09-24.67) or tropical CP (OR 19.15, 95% C.I. = 8.83-41.56). Studies analyzing familial CP showed very high heterogeneity suggestive of a complex etiology with an I2 = 80.95%. Conclusion: The small effect of SPINK1 N34S in alcoholic subjects suggests that CP is driven through a different pathway that is largely trypsin-independent. The results also suggest that large effect sizes of SPINK1 N34S in small candidate gene studies in CP may be related to a mixture of multiple etiologic pathways leading to the same clinical endpoint. © 2008 Aoun MD et al

Partial loss of heterozygosity events at the mutated gene in tumors from MLH1/MSH2 large genomic rearrangement carriers

<p>Abstract</p> <p>Background</p> <p>Depending on the population studied, large genomic rearrangements (LGRs) of the mismatch repair (<it>MMR</it>) genes constitute various proportions of the germline mutations that predispose to hereditary non-polyposis colorectal cancer (HNPCC). It has been reported that loss of heterozygosity (LOH) at the LGR region occurs through a gene conversion mechanism in tumors from <it>MLH1</it>/<it>MSH2 </it>deletion carriers; however, the converted tracts were delineated only by extragenic microsatellite markers. We sought to determine the frequency of LGRs in Slovak HNPCC patients and to study LOH in tumors from LGR carriers at the LGR region, as well as at other heterozygous markers within the gene to more precisely define conversion tracts.</p> <p>Methods</p> <p>The main <it>MMR </it>genes responsible for HNPCC, <it>MLH1</it>, <it>MSH2</it>, <it>MSH6</it>, and <it>PMS2</it>, were analyzed by MLPA (multiplex ligation-dependent probe amplification) in a total of 37 unrelated HNPCC-suspected patients whose <it>MLH1/MSH2 </it>genes gave negative results in previous sequencing experiments. An LOH study was performed on six tumors from LGR carriers by combining MLPA to assess LOH at LGR regions and sequencing to examine LOH at 28 SNP markers from the <it>MLH1 </it>and <it>MSH2 </it>genes.</p> <p>Results</p> <p>We found six rearrangements in the <it>MSH2 </it>gene (five deletions and dup5-6), and one aberration in the <it>MLH1 </it>gene (del5-6). The <it>MSH2 </it>deletions were of three types (del1, del1-3, del1-7). We detected LOH at the LGR region in the single <it>MLH1 </it>case, which was determined in a previous study to be LOH-negative in the intragenic D3S1611 marker. Three tumors displayed LOH of at least one SNP marker, including two cases that were LOH-negative at the LGR region.</p> <p>Conclusion</p> <p>LGRs accounted for 25% of germline <it>MMR </it>mutations identified in 28 Slovakian HNPCC families. A high frequency of LGRs among the <it>MSH2 </it>mutations provides a rationale for a MLPA screening of the Slovakian HNPCC families prior scanning by DNA sequencing. LOH at part of the informative loci confined to the <it>MLH1 </it>or <it>MSH2 </it>gene (heterozygous LGR region, SNP, or microsatellite) is a novel finding and can be regarded as a partial LOH. The conversion begins within the gene, and the details of conversion tracts are discussed for each case.</p

Organic Agriculture

Consumers are increasingly aware of the health- and safety-related implications of the food which they can buy in the market. At the same time, households have become more aware of their environmental responsibilities. Regarding the production of food, a crucial and multifunctional role is played by agriculture. The way vegetables, fruits, and other crops are grown and how livestock is raised has an impact on the environment and landscape. Operations performed by farmers, such as water management, can be dangerous for the soil and the whole ecosystem. Consequently, there is a search for natural ways of sustaining the impact of agriculture on the environment. In this context, one of the most popular ideas is organic agriculture. In the literature on the subject, there are many concepts that some authors consider to be synonymous even as others argue that these terms are not interchangeable. There is, for example, "organic agriculture," "alternative agriculture," "sustainable agriculture," "ecological agriculture," "biological agriculture," "niche farming," "community-supported agriculture," and "integrated pest management." Very often, techniques and products related to organic agriculture are described by marketing experts with the use of abbreviations such as "bio" and "eco." Products with such markings and labels are increasingly popular in stores that often give them separate shelves for their sale. Despite the higher price compared to conventional products, they are increasingly sought by consumers. The entry examines the various impacts of organic agriculture with a view to these trends

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

Glucose control during a driving training in patients with type 1 and type 2 diabetes mellitus - a randomised, controlled trial

AIM: To investigate the effect of prolonged acute mental stress by means of a driving training on glucose control in patients with type 1 and type 2 diabetes mellitus. METHODS: 39 patients with insulin-treated diabetes (18 type 1, 21 type 2 diabetes) were exposed to mental stress by means of a 2 h-driving training. The training session started 15 min after intake of a standard meal. Blood glucose, blood pressure, heart rate, salivary cortisol, and subjective stress perception were monitored in regular intervals and compared to a control day. RESULTS: On the stress testing day, blood pressure rose from 142/86±16/9 mmHg to 162/95±22/11 mmHg (p<0.001), heart rate from 72±11 bpm to 86±16 bpm (p<0.001) and subjective stress perception from 1.4±0.6 to 4.7±2.5 points (p<0.001). Salivary cortisol concentrations increased from a median of 5.1 nmol/l (Interquartile Range (IQR) 3.5-7.5 nmol/l) at baseline to 7.7 nmol/l (IQR 4.7-12.8 nmol/l, p<0.001), all these measurements remained stable on the control day. Glucose control showed no significant difference on the stress testing day compared to the control day (mean difference over time=0.22 mmol/l, 95%-CI -1.5 to +1.9 mmol/l, p=0.794). A multivariate linear regression and correlation analysis showed no association of demographic characteristics (diabetes type, age, body mass index (BMI), diabetes duration, HbA1c), objective or subjective stress parameters with the course of glucose concentrations during the driving training. CONCLUSIONS: Although a 2 h-driving training causes increased subjective and objective stress parameters, glucose control is maintained in patients with insulin-treated diabetes