Triggering infections in reactive arthritis.

Certain microbes like yersinia, salmonella, shigella, campylobacter, chlamydia, and possibly gonococcus can trigger reactive arthritis especially in patients of the HLA-B27 type. In the present study we have used serological and culture methods to identify the probable triggering infection in 50 consecutive HLA-B27 positive patients diagnosed as having reactive arthritis. The two most common triggering agents thus identified were Yersinia enterocolitica (12 patients) and Chlamydia trachomatis (11 patients). In addition six patients had high antistreptolysin O titres and two high teichoic acid antibody titres suggesting group A streptococci and Staphylococcus aureus as triggering agents. In 13 patients no preceding infection could be identified. The identity of the infective agent seems to have very little effect on the clinical picture of the reactive arthritis - the only difference between the various aetiological groups in the present material was absence of fever in the patients with a preceding C. trachomatis infection, of whom only one out of 11 had a temperature greater than or equal to 38 degrees C, whereas 13 of 16 patients with a preceding enterobacterial, and five of the eight patients with a streptococcal or staphylococcal infection had raised temperatures.     

N-glycan structures and associated gene expression reflect the characteristic N-glycosylation pattern of human hematopoietic stem and progenitor cells

OBJECTIVE: Cell surface glycans contribute to the adhesion capacity of cells and are essential in cellular signal transduction. Yet, the glycosylation of hematopoietic stem and progenitor cells (HSPC), such as CD133+ cells, is poorly explored. MATERIALS AND METHODS: N-glycan structures of cord blood-derived CD133+ and CD133- cells were analyzed with mass spectrometric profiling and exoglycosidase digestion, cell surface glycan epitopes with lectin binding assay, and expression of N-glycan biosynthesis-related genes with microarray analysis. RESULTS: Over 10% difference was demonstrated in the N-glycan profiles of CD133+ and CD133- cells. Biantennary complex-type N-glycans were enriched in CD133+ cells. Of the genes regulating the synthesis of these structures, CD133+ cells overexpressed MGAT2 and underexpressed MGAT4. Moreover, the amount of high-mannose type N-glycans and terminal alpha2,3-sialylation was increased in CD133+ cells. Elevated alpha2,3-sialylation was supported by the overexpression of ST3GAL6. CONCLUSION: Our work presents new information on the characters of HSPCs. The new knowledge of HSPC-specific N-glycosylation advances their identification and provides tools to promote HSPC homing and mobilization or targeting to specific tissues.     

Ultrasound screening for fetal anomalies in southern Sweden: a population-based study

BACKGROUND: The accuracy of ultrasound in the diagnosis of congenital malformations has been the subject of many studies. Most of these are hospital-based studies over a limited period of years presenting high detection rates and also relatively high incidence of major malformations. We present here a large population-based study over a long period of years. METHODS: The prenatal diagnoses are compared with the diagnoses of the newborns and aborted fetuses, including autopsy results. The detection rate of some common structural malformations is studied. RESULTS: The overall detection rate of malformations in our study was 28.4%. We noticed an improved detection rate of heart defects and cleft lip during the study period. The prevalence of malformations in the population was 2.6%. The false positive diagnoses were few, 54 cases, and mainly of a mild nature. CONCLUSIONS: Ultrasound screening of fetal malformations in our population has a low false positive rate and even though the overall sensitivity is low, 28.4%, the detection rate for many common structural malformations is relatively good.     

Abdominal obesity and alcohol use modify the impact of genetic risk for incident advanced liver disease in the general population

Background & Aims

Genetic variants, abdominal obesity and alcohol use are risk factors for incident liver disease (ILD). We aimed to study whether variants either alone or when aggregated into genetic risk scores (GRSs) associate with ILD, and whether waist-hip ratio (WHR) or alcohol use interacts with this risk.

Methods

Our study included 33 770 persons (mean age 50 years, 47% men) who participated in health-examination surveys (FINRISK 1992–2012 or Health 2000) with data on alcohol use, WHR and 63 genotypes associated with liver disease. Data were linked with national health registers for liver-related outcomes (hospitalizations, malignancies and death). Exclusions were baseline clinical liver disease. Mean follow-up time was 12.2 years. Cox regression analyses between variants and ILD were adjusted for age, sex and BMI.

Results

Variants in PNPLA3, IFNL4, TM6SF2, FDFT1, PPP1R3B, SERPINA1 and HSD17B13 were associated with ILD. GRSs calculated from these variants were not associated with WHR or alcohol use, but were exponentially associated with ILD (up to 25-fold higher risk in high versus low score). The risk of ILD in individuals with high GRS and high WHR or alcohol use compared with those with none of these risk factors was increased by up to 90-fold. GRSs provided new prognostic information particularly in individuals with high WHR.

Conclusions

The effect of multiple genetic variants on the risk of ILD is potentiated by abdominal obesity and alcohol use. Simple GRSs may help to identify individuals with adverse lifestyle who are at a particularly high risk of ILD.     

Persistent organic pollutants associate with liver disease in a Finnish general population sample

Background and Aims

Persistent organic pollutants (POPs) have multiple adverse effects on human health. Recent studies show a possible association with liver disease, but population-based data are scarce. In this population-based study, we studied the associations between POPs and biomarkers of liver disease and incident liver disease.

Methods

This study consisted of 2789 adults that participated in the environmental toxin subset of the Finnish health-examination survey, FINRISK 2007. Toxins were measured from serum samples, and standard liver tests and dynamic aspartate aminotransferase-alanine aminotransferase ratio (dAAR) were measured as biomarkers of liver function. Associations between POPs and the biomarkers were then analysed using linear regression. Associations between POPs and incident liver disease (n = 36) were analysed by Cox regression.

Results

Organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and several perfluorinated alkyl substances exhibited statistically significant positive associations with several biomarkers of liver injury (betacoefficient per SD 0.04–0.14, p < 0.05). These associations were stronger in subgroups of individuals with obesity or non-alcoholic fatty liver disease. OCPs, PCBs and perfluoro-octanoic acid also had significant positive associations with dAAR, which can be used to predict risk of incident severe liver outcomes (beta coefficient per SD 0.05–0.08, p < 0.05). OCPs and PCBs were also significantly and positively associated with incident liver disease (hazard ratio per SD 1.82 95% CI 1.21–2.73, p < 0.01 and hazard ratio per SD 1.69, 95% CI 1.07–2.68, p < 0.05 respectively).

Conclusions

Several POPs show positive associations with markers of liver injury and incident liver disease, suggesting that environmental toxins are important risk factors for chronic liver disease.     

An association between both low and high birth weight and increased disorganized and negative symptom severity in schizophrenia and other psychoses

Longitudinal cohort studies have implicated an association between both low and high birth weight and increased schizophrenia risk. In this study, we investigated the effect of birth weight on the symptom severity of psychotic disorders including schizophrenia in a Finnish schizophrenia family study sample. We used a multivariate GEE (General Estimating Equation) regression model to investigate the association of birth weight and symptom severity in 282 subjects with a primary psychotic disorder, 178 of whom had a diagnosis of schizophrenia. The Scales for the Assessment of Positive and Negative Symptoms (SAPS and SANS) were used as a measure of symptom severity. Sex, place of birth and year of birth were adjusted for in the model. Both low and high birth weight were associated with more severe symptoms with respect to bizarre behaviour, affective flattening and attentional impairment. In addition, low birth weight was associated with more severe symptoms with respect to positive formal thought. Our findings suggest that both low and high birth weight can influence the symptom severity of psychotic disorders. Our results implicate an association between both low and high birth weight and disorganized and negative symptoms.     

Neuron navigator 3 alterations in nervous system tumors associate with tumor malignancy grade and prognosis

Copy number changes or reduced expression of the Neuron navigator 3 (NAV3) gene occurs in neuroblastomas and malignancies of epithelial or lymphoid origin. To elucidate whether NAV3 has a role in the tumorigenesis of nervous system tumors in general, we studied central and peripheral nervous system tumors for NAV3 copy number changes. In search for common tumorigenic denominators, we analyzed 113 central and peripheral nervous system tumors, including glial tumors (grades I–IV gliomas), medulloblastomas, and neuroblastomas. NAV3 copy number changes were studied by fluorescence in situ hybridization and correlated to survival analyses. To identify target genes of NAV3 deletion, NAV3 was silenced by siRNA in glioblastoma cell lines and gene expression profiles were analyzed by Agilent 4×44k dual‐color microarrays. Selected upregulations were confirmed by immunohistochemistry and quantitative polymerase chain reaction. We found NAV3 amplifications to dominate in neuronally differentiated tumors, whereas glial tumors showed almost equal proportions of NAV3 deletion and amplification. However, Grade IV gliomas had more frequent NAV3 deletions than grades I–III gliomas. Silencing of NAV3 in glioma cell lines led to the upregulation of receptor genes associated with gonadotropin‐releasing hormone and Jak‐Stat signaling pathways. Kaplan–Meier analysis of the entire clinical tumor material showed association between NAV3 amplifications and favorable prognosis, as well as NAV3 deletions and unfavorable prognosis. With Cox regression model, a hazard ratio of 0.51 was observed for NAV3 amplifications and 1.36 for NAV3 deletions. We conclude that NAV3 may be a potential new prognostic biomarker and a potential therapeutic target. © 2012 Wiley Periodicals, Inc.     

Adolescents’ Attitudes on Smoking Are Related to Experimentation with Smoking,Daily Smoking and Best Friends’ Smoking in Two Karelias in Finland and in Russia

Purpose

Becoming a smoker usually starts during adolescence and is a dynamic process involving experimentation before the establishment of daily smoking. It has been suggested that adolescents who smoke differ from those who do not in their attitudes to smoking. The purpose of this study was to find out whether attitudes related to smoking legislation and restrictions, social pressures in smoking and image of smokers are associated with smoking experimentation, daily smoking and best friends’ smoking.

Method

The data were gathered with a self-administered questionnaire in North Karelia, Eastern Finland and in the Pitkyaranta district, Republic of Karelia, Russia. The respondents were 15-year-old 9th grade pupils in local schools. In Pitkyaranta, the data analyses covered pupils in all eight schools in the area (n?=?179). In North Karelia, the data analyses comprised of selected eight schools (n?=?601). Data were analysed with exploratory factor analysis.

Results

The models revealed that attitudes related to restrictions and social pressure were significantly associated with experimenting with smoking [OR (95 % CI) 7.923 (5.787–10.847)], daily smoking [OR (95 % CI) 9.575 (6.727–13.628)] and the likelihood of best friends’ smoking [OR (95 % CI) 3.154 (2.579–3.858)]. The stronger the young peoples’ attitudes and opinions, for example, towards restrictions and with more difficulties in refusing smoking, the higher the likelihood for smoking experimentations, daily smoking as well as the likelihood for their best friends’ smoking. The country and factor interactions were not associated with smoking experimentations, daily smoking or best friends’ smoking.

Conclusion

Regardless of cultural background, adolescents who smoke have more positive attitudes to smoking, and perceive more social support for smoking, than do adolescents who do not smoke. The study stresses the similarity of the results in both Karelia’s despite the enormous differences in culture, economy and public policy.