Early fecal microbiota composition in children who later develop celiac disease and associated autoimmunity

Objectives: Several studies have reported that the intestinal microbiota composition of celiac disease (CD) patients differs from healthy individuals. The possible role of gut microbiota in the pathogenesis of the disease is, however, not known. Here, we aimed to assess the possible differences in early fecal microbiota composition between children that later developed CD and healthy controls matched for age, sex and HLA risk genotype.

Materials and methods: We used 16S rRNA gene sequencing to examine the fecal microbiota of 27 children with high genetic risk of developing CD. Nine of these children developed the disease by the age of 4 years. Stool samples were collected at the age of 9 and 12 months, before any of the children had developed CD. The fecal microbiota composition of children who later developed the disease was compared with the microbiota of the children who did not have CD or associated autoantibodies at the age of 4 years. Delivery mode, early nutrition, and use of antibiotics were taken into account in the analyses.

Results: No statistically significant differences in the fecal microbiota composition were found between children who later developed CD (n?=?9) and the control children without disease or associated autoantibodies (n?=?18).

Conclusions: Based on our results, the fecal microbiota composition at the age of 9 and 12 months is not associated with the development of CD. Our results, however, do not exclude the possibility of duodenal microbiota changes or a later microbiota-related trigger for the disease.     

Adrenal gland tumorigenesis after gonadectomy in mice is a complex genetic trait driven by epistatic loci

Postgonadectomy adrenocortical tumorigenesis is a strain-specific phenomenon in inbred mice, assumed to be caused by elevated LH secretion and subsequent ectopic LH receptor (LHR) overexpression in adrenal gland. However, the molecular mechanisms of this cascade of events remain unknown. In this study, we took advantage of the mouse strain dependency of the phenotype to unravel its genetic basis. Our results present the first genome-wide screening related to this pathology in two independent F2 and backcross populations generated between the neoplastic DBA/2J and the nonsusceptible C57BL/6J strains. Surprisingly, the postgonadectomy elevation of serum LH was followed by similar up-regulation of adrenal LHR expression in both parental strains and their crosses, irrespective of their tumor status, indicating that it is not the immediate cause of the tumorigenesis. Linkage analysis revealed one major significant locus for the tumorigenesis on chromosome 8, modulated by epistasis with another quantitative trait locus on chromosome 18. Weight gain, a secondary phenotype after gonadectomy, showed a significant but separate quantitative trait locus on chromosome 7. Altogether, postgonadectomy adrenocortical tumorigenesis in DBA/2J mice is a dominant trait that is not a direct consequence of adrenal LHR expression but is driven by a complex genetic architecture. Analysis of candidate genes in the tumorigenesis linkage region showed that Sfrp1 (secreted frizzled-related protein 1), a tumor suppressor gene, is differentially expressed in the neoplastic areas. These findings may have relevance to the human pathogenesis of macronodular adrenal hyperplasia and adrenocortical tumors in postmenopausal women and why some of them develop obesity.     

Functioning and preferences for improvement of health among patients with juvenile idiopathic arthritis in early adulthood using the WHO ICF model

OBJECTIVE: To evaluate functioning and preferences for health among young adult patients with juvenile idiopathic arthritis (JIA) and controls. The WHO International Classification of Functioning, Disability and Health (ICF) was used as a framework. METHODS: The patient files of a rheumatology hospital were screened to identify patients with juvenile arthritis born 1976 to 1980. Functioning was measured by the Finnish version of the Multidimensional Health Assessment Questionnaire (MDHAQ) within the framework of the ICF. Preferences in improvement of health were measured by the Finnish version of the Arthritis Impact Measurement Scales 2. Age and sex matched controls from the community were selected from the Finnish population registry. RESULTS: In all, 123 patients with a mean age of 23 (SD 21-26) years participated in the followup study. The mean time from diagnosis to followup was 16.2 years. Among them, 35% (n = 43) were in remission at followup. Lower levels of functioning for 3 ICF components were found in patients with active disease compared to controls. JIA patients with active disease had more pain and lower levels of mobility, self-care, and domestic and social life compared to controls. Patients with active disease differed from those in remission with pain in preferences for improvement of health. CONCLUSION: Patients with active disease need active treatment and rehabilitation to maintain functioning and decrease pain. The ICF offers a promising model to examine the outcomes of adult patients with JIA. Application of the MDHAQ is supported by our evaluation studies in young adults with JIA.     

Polymorphisms in androgen and estrogen receptor genes: effects on male aging

Besides lifestyle and environmental factors, the life-long exposure to the endocrine milieu of gonadal steroids is a determining factor to gender specific features of aging. In contrast to women, men do not experience a sudden cessation of gonadal function comparable to menopause. However, cross-sectional and longitudinal population studies demonstrate that the hormones with anabolic actions (e.g. testosterone [T], growth hormone, insulin-like growth factor [IGF]-1, dehydroepiandrosterone) do decrease progressively with aging in healthy men, and chronic systemic illnesses accelerate this process. In addition, estrogen has recently been established to be essential for normal physiology of the male. The slow progressive decline of the hypothalamic-pituitary-gonadal (HPG) function is thought to be responsible for many common signs and symptoms of aging men, such as general weakness, sexual dysfunction, and increased fat mass. There is a large inter-individual variation in sex hormone levels cross-sectionally within given age groups as well as longitudinally with aging. A contributing factor to this variability are the numerous functionally significant polymorphisms that have been detected in the receptors for androgen and estrogen. In this review, we summarize the recent information on some common polymorphisms in androgen and estrogen receptor genes and their effect on gender specific and aging-related symptoms and diseases of men.     

Intravenous streptokinase treatment and serum C-reactive protein in patients with acute myocardial infarction

Serum concentrations of C-reactive protein were studied in 23 patients with acute myocardial infarction. In 14 patients who did not receive thrombolytic treatment there was a linear relation between infarct size (determined by serial creatine kinase-MB determinations and thallium-201 isotope emission tomography) and the C-reactive protein response. The correlation coefficient between the concentration-time integrals of creatine kinase-MB and C-reactive protein was 0.96. The correlation coefficient between the creatine kinase-MB concentration-time integral and the peak serum value of C-reactive protein was 0.93. In the nine patients who received intravenous streptokinase treatment there was also a positive correlation between the concentration-time integrals of creatine kinase-MB and C-reactive protein. The relation, however, depended on the success of the treatment. In patients with successful reperfusion the C-reactive protein response was only approximately 20% of that in patients in whom reperfusion failed or who received no thrombolytic treatment and who were matched by infarct size. When thrombolysis was successful the correlation coefficient between the concentration-time integrals of creatine kinase-MB and C-reactive protein was 0.86. Daily measurement of serum C-reactive protein is useful in evaluating infarct size in patients with acute myocardial infarction who do not receive thrombolytic treatment. In patients treated with streptokinase C-reactive protein concentrations may be used to assess the success of thrombolysis.     

Children's postoperative pain at home: family interview study

The purpose of this study was to: (i) describe the methods that are used in the identification and management of postoperative pain in children aged 1-7 years after minor outpatient surgery at home; (ii) to identify parents' perceptions regarding children's pain and pain medication; and (iii) to examine parents' perceptions of discharge advice. Family interviews with inductive content analysis were used to gather information from families of 17 Finnish children undergoing minor outpatient surgery at a university hospital in Finland. Versatile methods were employed by the parents in the identification and management of children's postoperative pain subsequent to discharge from the hospital. The children expressed that they had experienced pain relief through the administration of pain medication, eating ice-cream and playing. The results indicate a need for further research in order to identify what elements of parents' perceptions of children's pain and pain medication should receive additional attention. In addition, the content, methods of providing and timing of discharge advice need to be developed in order to help parents with their efforts to achieve maximum pain relief in children after surgery.     

Parents' roles in using non-pharmacological methods in their child's postoperative pain alleviation

Increasingly nowadays, parents participate more fully in the care of their hospitalized children. The purpose of this study was to describe parents' utilization of selected non-pharmacological methods in relieving their hospitalized child's (aged 8-12 years) postoperative pain, and factors related to this function. Data were collected by a questionnaire survey completed by parents (n=192) with a child hospitalized on a paediatric surgical ward in the five university hospitals of Finland. The response rate was 90%. Results indicated that non-pharmacological methods, such as emotional support and helping with daily activities, were well utilized whereas cognitive-behavioural and physical methods were less frequently used strategies. Certain background factors specific to the parents and their hospitalized children were significantly related to the non-pharmacological methods used by the parents. The hospitalized child's gender, the time of the surgical procedure, and the parents' assessments of their child's pain intensity, were especially significantly related to many of these strategies. The findings of this study could be used in clinical practice to improve guidance provided to parents regarding interventions for children's pain relief.     

Association between habitual dietary intake and lipoprotein subclass profile in healthy young adults

Background and aimsNutritional epidemiology is increasingly shifting its focus from studying single nutrients to the exploration of the whole diet utilizing dietary pattern analysis. We analyzed associations between habitual diet (including macronutrients, dietary patterns, biomarker of fish intake) and lipoprotein particle subclass profile in young adults.Methods and resultsComplete dietary data (food-frequency questionnaire) and lipoprotein subclass profile (via nuclear magnetic resonance spectroscopy) were available for 663 subjects from the population-based FinnTwin12 study (57% women, age: 21–25 y). The serum docosahexaenoic to total fatty acid ratio was used as a biomarker of habitual fish consumption. Factor analysis identified 5 dietary patterns: “Fruit and vegetables”, “Meat”, “Sweets and desserts”, “Junk food” and “Fish”. After adjustment for sex, age, body mass index, waist circumference, physical activity, smoking status and alcohol intake, the “Junk food” pattern was positively related to serum triglycerides (r = 0.12, P = 0.002), a shift in the subclass distribution of VLDL toward larger particles (r = 0.12 for VLDL size, P < 0.001) and LDL toward smaller particles (r = ?0.15 for LDL size, P < 0.001). In addition, higher scores on this pattern were positively correlated with concentrations of small, dense HDL (r = 0.16, P < 0.001). Habitual fish intake associated negatively with VLDL particle diameter (“Fish” pattern and biomarker) and positively with HDL particle diameter (biomarker).ConclusionsOur results suggest that in young adults, higher habitual fish consumption is related to favorable subclass distributions of VLDL and HDL, while junk food intake is associated with unfavorable alterations in the distribution of all lipoprotein subclasses independent of adiposity and other lifestyle factors.