Pre-migration traumatic experiences, post-migration perceived discrimination and substance use among Russian and Kurdish migrants-a population-based study

Background and aims The associations between traumatic events, substance use and perceived discrimination have been rarely studied among migrants in host countries. We examined whether pre-migration potentially traumatic experiences (PTEs) or perceived discrimination (PD) are associated with substance use among migrants with voluntary (Russians) and forced (Kurds) migration backgrounds. Design Cross-sectional interview and health examination data from the Finnish Migrant Health and Wellbeing Study were used. The target sample (n = 1000 for each group) was drawn from the national population register using stratified random sampling by participants' country of birth and native language. Setting Population-based data were collected from six cities in Finland during 2010-12. Participants The participation rates were 68% (Russians) and 59% (Kurds). The analytical sample size varied (Russians n = 442-687, Kurds n = 459-613), as some participants completed only interview, health examination or short interview. The majority of Kurds had a refugee background (75%) while Russians had mainly migrated for other reasons (99%). Measurements The three main outcomes were self-reported binge drinking, daily smoking and life-time cannabis use. PTEs and PD were self-reported in the interview. Socio-demographic background, migration-related factors and current affective symptoms were adjusted for. Findings Among Kurds, PTEs were associated with binge drinking [adjusted odds ratio (aOR) = 2.65, 95% confidence interval (CI) = 1.30-5.42] and PD was associated with life-time cannabis use (aOR = 3.89, 95% CI = 1.38-10.97) after adjusting for contextual factors. Among Russians, PTEs were associated with life-time cannabis use adjusting for contextual factors (aOR = 2.17, 95% CI = 1.12-4.18). Conclusions In Finland, pre-migration traumatic experiences appear to be associated with life-time cannabis use among the Russian migrant population (voluntary migration) and binge drinking among the Kurdish migrant population (forced migration). Perceived discrimination in Finland appears to be associated with life-time cannabis use among Kurdish migrants.Peer reviewe

Microbiota composition of simultaneously colonized mice housed under either a gnotobiotic isolator or individually ventilated cage regime

Germ-free rodents colonized with microbiotas of interest are used for host-microbiota investigations and for testing microbiota-targeted therapeutic candidates. Traditionally, isolators are used for housing such gnotobiotic rodents due to optimal protection from the environment, but research groups focused on the microbiome are increasingly combining or substituting isolator housing with individually ventilated cage (IVC) systems. We compared the effect of housing systems on the gut microbiota composition of germ-free mice colonized with a complex microbiota and housed in either multiple IVC cages in an IVC facility or in multiple open-top cages in an isolator during three generations and five months. No increase in bacterial diversity as assessed by 16S rRNA gene sequencing was observed in the IVC cages, despite not applying completely aseptic cage changes. The donor bacterial community was equally represented in both housing systems. Time-dependent clustering between generations was observed in both systems, but was strongest in the IVC cages. Different relative abundance of a Rikenellaceae genus contributed to separate clustering of the isolator and IVC communities. Our data suggest that complex microbiotas are protected in IVC systems, but challenges related to temporal dynamics should be addressed

Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention

Abstract On the basis of the abundance of specific bacterial genera, the human gut microbiota can be divided into two relatively stable groups that might have a role in personalized nutrition. We studied these simplified enterotypes as prognostic markers for successful body fat loss on two different diets. A total of 62 participants with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in fiber/whole grain or an Average Danish Diet for 26 weeks. Participants were grouped into two discrete enterotypes by their relative abundance of Prevotella spp. divided by Bacteroides spp. (P/B ratio) obtained by quantitative PCR analysis. Modifications of dietary effects of pre-treatment P/B group were examined by linear mixed models. Among individuals with high P/B the NND resulted in a 3.15 kg (95% confidence interval (CI): 1.55; 4.76, P&lt;0.001) larger body fat loss compared with ADD, whereas no differences was observed among individuals with low P/B (0.88 kg (95% CI: −0.61; 2.37, P=0.25)). Consequently, a 2.27 kg (95% CI: 0.09; 4.45, P=0.041) difference in responsiveness to the diets were found between the two groups. In summary, subjects with high P/B ratio appeared more susceptible to lose body fat on diets high in fiber and whole grain than subjects with a low P/B ratio.</jats:p

High Mercury Concentrations of European Perch (Perca fluviatilis) in Boreal Headwater Lakes with Variable History of Acidification and Recovery

High dissolved organic carbon and low pH are often associated with elevated mercury content of fish in boreal lakes, but less is known about the fish mercury dynamics in lakes recovering from acidification stress. We measured total mercury concentration (THg) in muscle of European perch (Perca fluviatilis) and evaluated the overall correlation with environmental and growth variables in 24 boreal headwater lakes in the 2010s. We found negative correlations of length-corrected perch THg with lake pH and perch growth, but no correlation with dissolved organic carbon. The main emphasis in the present study was focused to a subset of ten lakes in southern Finland with known perch THg during severe acidification in the 1980-1990s. The comparison of perch THg concentrations in the 2010s with values determined in the 1980-1990s showed a sharp increase in most acidic lakes where the perch populations suffered from severe acid stress in the 1980s. This increase was attributed to growth condensation caused by sharp decrease in perch growth during recovery of reproduction capacity and the consequent increases in population densities of perch. Our results highlight the importance of perch growth rate and population density for understanding the variability of fish Hg in boreal headwater lakes, where recovery from acidification can lead to higher mercury concentration of fish in certain cases.Peer reviewe

Psychotic experiences are associated with health anxiety and functional somatic symptoms in preadolescence

Background: Health anxiety (HA) is an increasing public health problem related to increased health service costs, and associated with functional somatic symptoms (FSS) and considerable personal suffering. Abnormal bodily experiences which may resemble HA and FSS are common in psychotic disorders, but a potential link between HA and psychosis vulnerability in childhood is largely unexplored. The current study estimates the association between subclinical psychotic experiences (PE) and HA and FSS in a general population cohort of preadolescents. Methods: The study population consisted of 1,572 11–12-year-old children from the Copenhagen Child Cohort 2000. PE were comprehensibly assessed as either present or not present using the Kiddie Schedule of Affective Disorders and Schizophrenia psychosis section. HA and FSS were assessed by self-report on validated questionnaires. Additional variables on general psychopathology, puberty, and chronic somatic illness were also obtained. Results: Psychotic experiences were associated with the top 10% high scores of HA (Odds Ratio (OR) 3.2; 95% CI: 2.1–4.8) and FSS (OR 4.6; 95% CI: 3.1–6.9) in univariate analyses. After mutual adjustment, the association was reduced to (HA: OR 2.3; 95% CI: 1.5–3.5; FSS: OR 3.7; 95% CI: 2.4–4.7), suggesting interdependence. Further adjustment for potential confounders and general psychopathology only reduced the associations slightly: HA OR 2.2 (95% CI: 1.4–3.4); FSS OR 3.3 (95% CI: 2.1–5.2). Secondary analyses of subdimensions of HA showed that PE were associated with fears (OR 3.0; 95% CI: 2.0–4.6) and daily impact of HA symptoms (OR 5.0; 95% CI: 3.4–7.5), but not help seeking (OR 1.2; 95% CI: 0.7–2.1). Conclusions: This is the first study to investigate the associations between PE and HA and FSS, respectively. PE were significantly associated with HA and FSS over and above general psychopathology in preadolescence. Individuals with PE expressed high levels of health-related fears and daily impact, but no corresponding help-seeking behavior

The predictive validity of the Strengths and Difficulties Questionnaire in preschool age to identify mental disorders in preadolescence

The Strengths and Difficulties Questionnaire (SDQ) is a brief, widely used instrument to screen for mental health problems in children and adolescents. The SDQ predictive algorithms developed for the SDQ, synthesize information from multiple informants regarding psychiatric symptoms and their impact on daily life. This study aimed to explore the validity of the SDQ predictive algorithms used in preschool age to predict mental disorders in preadolescence. The study population comprises 1176 children from the Copenhagen Child Cohort 2000 (CCC2000) assessed at age 5-7 years by the SDQ and reassessed at 11-12 years with the Development and Well Being Assessment (DAWBA) for evaluation of ICD-10 mental disorders. Odds Ratios (ORs), sensitivities, specificities, positive predictive values (PPVs) and negative predictive values (NPVs) were calculated for the SDQ predictive algorithms regarding ICD-10 diagnoses of hyperkinetic-inattentive-, behavioural- and emotional disorders. Significant ORs ranging from 2.3-36.5 were found for the SDQ predictive algorithms in relation to the corresponding diagnoses. The highest ORs were found for hyperkinetic and inattentive disorders, and the lowest for emotional disorders. Sensitivities ranging from 4.5-47.4, specificities ranging from 83.0-99.5, PPVs ranging from 5.0-45.5 and NPVs ranging from 90.6-99.0 were found for the SDQ predictive algorithms in relation to the diagnoses. The results support that the SDQ predictive algorithms are useful for screening at preschool-age to identify children at an increased risk of mental disorders in preadolescence. However, early screening with the SDQ predictive algorithms cannot stand alone, and repeated assessments of children are needed to identify, especially internalizing, mental health problems

Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib: a case report

BACKGROUND: Anaplastic lymphoma kinase-positive non-small cell lung carcinoma patients are generally highly responsive to the dual anaplastic lymphoma kinase and MET tyrosine kinase inhibitor crizotinib. However, they eventually acquire resistance to this drug, preventing the anaplastic lymphoma kinase inhibitors from having a prolonged beneficial effect. The molecular mechanisms responsible for crizotinib resistance are beginning to emerge, e.g., in some anaplastic lymphoma kinase-positive non-small cell lung carcinomas the development of secondary mutations in this gene has been described. However, the events behind crizotinib-resistance currently remain largely uncharacterized. Thus, we report on an anaplastic lymphoma kinase-positive non-small cell lung carcinoma patient with concomitant occurrence of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations upon development of crizotinib-resistance. CASE PRESENTATION: A 61-year-old Caucasian never-smoking male was diagnosed with anaplastic lymphoma kinase -positive pulmonary adenocarcinoma, stage T4N3M1b. Treatment with crizotinib initially resulted in complete objective response in the thorax and partial response in the abdomen, but after 8 months of therapy the patient acquired resistance and progressed. Biopsies from new metastases revealed development of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations concomitant with the original anaplastic lymphoma kinase gene rearrangement and without signs of anaplastic lymphoma kinase fusion gene amplification or secondary anaplastic lymphoma kinase mutations. CONCLUSION: To our knowledge, this is the first report of an anaplastic lymphoma kinase-positive pulmonary adenocarcinoma, which upon emergence of crizotinib resistance acquired 2 new somatic mutations in the epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog genes, respectively, concomitant with the original anaplastic lymphoma kinase rearrangement. Thus, these 3 driver mutations, usually considered mutually exclusive, may coexist in advanced non-small cell lung carcinoma that becomes resistant to crizotinib, presumably because heterogeneous tumor clones utilize epidermal growth factor receptor and/or V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling to circumvent the inhibition of anaplastic lymphoma kinase-mediated signaling by crizotinib. The identification of new targetable somatic mutations by tumor re-biopsy may help clarify the mechanism behind the development of the acquired crizotinib resistance and pave the way for combined strategies involving multiple targeted therapies

Functional coupling analysis suggests link between the obesity gene FTO and the BDNF-NTRK2 signaling pathway

<p>Abstract</p> <p>Background</p> <p>The Fat mass and obesity gene (FTO) has been identified through genome wide association studies as an important genetic factor contributing to a higher body mass index (BMI). However, the molecular context in which this effect is mediated has yet to be determined. We investigated the potential molecular network for FTO by analyzing co-expression and protein-protein interaction databases, Coxpresdb and IntAct, as well as the functional coupling predicting multi-source database, FunCoup. Hypothalamic expression of FTO-linked genes defined with this bioinformatics approach was subsequently studied using quantitative real time-PCR in mouse feeding models known to affect FTO expression.</p> <p>Results</p> <p>We identified several candidate genes for functional coupling to FTO through database studies and selected nine for further study in animal models. We observed hypothalamic expression of Profilin 2 (Pfn2), cAMP-dependent protein kinase catalytic subunit beta (Prkacb), Brain derived neurotrophic factor (Bdnf), neurotrophic tyrosine kinase, receptor, type 2 (Ntrk2), Signal transducer and activator of transcription 3 (Stat3), and Btbd12 to be co-regulated in concert with Fto. Pfn2 and Prkacb have previously not been linked to feeding regulation.</p> <p>Conclusions</p> <p>Gene expression studies validate several candidates generated through database studies of possible FTO-interactors. We speculate about a wider functional role for FTO in the context of current and recent findings, such as in extracellular ligand-induced neuronal plasticity via NTRK2/BDNF, possibly via interaction with the transcription factor CCAAT/enhancer binding protein β (C/EBPβ).</p

Structure and tissue distribution of some retinoid-binding proteins

Vitamin A has, apart from its function in the visual pigments, general effects on several organs. Early signs of vitamin A deficiency include keratinization of epithelia and hyperkeratosis of the skin. To elucidate a generalized function for vitamin A, we have taken the approach of tracing the vitamin from its storage site in the liver via its blood transport by the retinol-binding protein (RBP) to its uptake by susceptible cells. We have also examined the intracellular occurrence of vitamin A as regards its binding to specific receptor proteins. Here we summarize data on the amino acid sequences of several vitamin A-binding proteins. The finding that CRBP and CRABP, the two intracellular proteins, are homologous to each other, to a myelin protein, and to a fatty acid-binding protein may shed light on the functions of these proteins. Retinoic acid, which binds to CRABP but not CRBP, induces differentiation of teratocarcinoma cells. This is accompanied by a lowering of the CRABP concentration, an increase of the CRBP level, and an increase in the uptake of retinol from RBP. The epidermis contains both CRBP and CRABP, and their distributions are rather similar. However, in contrast to CRBP, CRABP is most abundant in cells lining the hair follicles. CRBP occurs in greatest relative amounts in the outer layers of the epidermis. Since techniques have been developed to measure CRBP and CRABP, normal and disease-affected skin may now be explored as to quantity and cellular distribution of the retinoid-binding proteins