Prevalence of overweight and obesity among migrants in Switzerland: association with country of origin.

Migrants tend to present higher overweight and obesity levels, but whether this relationship applies to all nationalities has seldom been studied. The present study aimed to assess the prevalence of overweight and obesity according to nationality in adults. Cross-sectional population-based samples. Five-year nationwide interview surveys (Swiss Health Surveys - SHS) from 1992 to 2007 (n 63 766) and a local examination survey (CoLaus Study in Lausanne 2004-2006, n 6743). Participants were separated into Swiss, French, German, Italian, Portuguese, Spanish nationals, those from the former Republic of Yugoslavia and from other European and other countries. Compared with Swiss nationals, German and French nationals presented a lower prevalence of overweight and obesity, whereas nationals from Italy, Spain, Portugal and the former Republic of Yugoslavia presented higher levels. Adjusting the SHS data for age, gender, education, smoking, leisure-time physical activity and survey year, a lower risk for overweight and obesity was found for German (OR = 0·80, 95 % CI 0·70, 0·92) and French (OR = 0·74, 95 % CI 0·61, 0·89) nationals, whereas higher risks were found for participants from Italy (OR = 1·45, 95 % CI 1·33, 1·58), Spain (OR = 1·36, 95 % CI 1·15, 1·61), Portugal (OR = 1·25, 95 % CI 1·06, 1·47) and the former Republic of Yugoslavia (OR = 1·98, 95 % CI 1·69, 2·32). Similar findings were observed in the CoLaus Study for Italian (OR = 1·63, 95 % CI 1·29, 2·06), Spanish (OR = 1·54, 95 % CI 1·17, 2·04) and Portuguese (OR = 1·49, 95 % CI 1·16, 1·91) participants and for those from the former Republic of Yugoslavia (OR = 5·34, 95 % CI 3·00, 9·50). Overweight and obesity are unevenly distributed among migrants in Switzerland. Migrants from Southern Europe and from the former Republic of Yugoslavia present higher prevalence rates. This suggests that preventive messages should be tailored to these specific populations.

Delayed diagnosis of acute ischemic stroke in children - a registry-based study in Switzerland.

QUESTIONS UNDER STUDY/PRINCIPLES: After arterial ischemic stroke (AIS) an early diagnosis helps preserve treatment options that are no longer available later. Paediatric AIS is difficult to diagnose and often the time to diagnosis exceeds the time window of 6 hours defined for thrombolysis in adults. We investigated the delay from the onset of symptoms to AIS diagnosis in children and potential contributing factors. METHODS: We included children with AIS below 16 years from the population-based Swiss Neuropaediatric Stroke Registry (2000-2006). We evaluated the time between initial medical evaluation for stroke signs/symptoms and diagnosis, risk factors, co-morbidities and imaging findings. RESULTS: A total of 91 children (61 boys), with a median age of 5.3 years (range: 0.2-16.2), were included. The time to diagnosis (by neuro-imaging) was <6 hours in 32 (35%), 6-12 hours in 23 (25%), 12-24 hours in 15 (16%) and >24 hours in 21 (23%) children. Of 74 children not hospitalised when the stroke occurred, 42% had adequate outpatient management. Delays in diagnosis were attributed to: parents/caregivers (n = 20), physicians of first referral (n = 5) and tertiary care hospitals (n = 8). A co-morbidity hindered timely diagnosis in eight children. No other factors were associated with delay to diagnosis. A total of 17 children were inpatients at AIS onset. CONCLUSIONS: One-third of children with AIS were diagnosed within six hours. Diagnostic delay was predominately caused by insufficient recognition of stroke symptoms. Increased public and expert awareness and immediate access to diagnostic imaging are essential. The ability of parents/caregivers and health professionals to recognise stroke symptoms in a child needs to be improved.

Autosomal Recessive Posterior Microphthalmos/Nanophthalmos is Caused by Loss-of-function Mutations in LOC646960, a Novel Gene Encoding a Trypsin-like Serine Protease

Purpose: Posterior microphthalmos (MCOP)/nanophthalmos (NNO) is a developmental anomaly characterized by extreme hyperopia due to short axial length. The population of the Faroe Islands shows a high prevalence of an autosomal recessive form (arMCOP). The gene mutated in arMCOP is not yet known.Methods: Genetic mapping by linkage analysis using microsatellite and single nucleotide polymorphisms, mutation analysis by PCR and sequencing, molecular modellingResults: Having refined the position of the disease locus (MCOP6) in an interval of 250 kb in chromosome 2q37.1 in Faroese families, we detected 3 mutations in a novel gene, LOC646960: Patients of 10 different Faroese families were either homozygous (n=22) for c.926G>C (p.Trp309Ser) or compound heterozygous (n=6) for c.926G>C and c.526C>G (p.Arg176Gly), whereas a homozygous 1 bp duplication (c.1066dupC) was identified in patients with arNNO from a Tunisian family. In two unrelated patients with MCOP, no LOC646960 mutation was found. LOC646960 is expressed in the human adult retina and RPE. The expression of the mouse homologue in the eye can be first detected at E17 and is highest in adults. The predicted protein is a 603 amino acid long secreted trypsin-like serine peptidase. c.1066dupC should result in a functional null allele. Molecular modelling of the p.Trp309Ser mutant suggests that both affinity and reactivity of the enzyme towards in vivo substrates are substantially reduced.Conclusions: Postnatal growth of the eye is important for proper development of the refractive components (emmetropization), and is mainly due to elongation of the posterior segment from 10-11 mm at birth to 15-16 mm at the age of 13 years. Optical defocus leads to changes in axial length by moving the retina towards the image plane. arMCOP may theoretically be explained, in line with the expression pattern of LOC646960, by a postnatal growth retardation of the posterior segment.

Mirror therapy in children with hemiplegia: a pilot study.

Mirror therapy, which provides the visual illusion of a functional paretic limb by using the mirror reflection of the non-paretic arm, is used in the rehabilitation of hemiparesis after stroke in adults. We tested the effectiveness and feasibility of mirror therapy in children with hemiplegia by performing a pilot crossover study in ten participants (aged 6-14 y; five males, five females; Manual Ability Classification System levels: one at level I, two at level II, four at level III, three at level IV) randomly assigned to 15 minutes of daily bimanual training with and without a mirror for 3 weeks. Assessments of maximal grasp and pinch strengths, and upper limb function measured by the Shriner's Hospital Upper Extremity Evaluation were performed at weeks 0 (baseline), 3, 6 (intervention), and 9 (wash-out). Testing of grasp strength behind the mirror improved performance by 15% (p=0.004). Training with the mirror significantly improved grasp strength (with mirror +20.4%, p=0.033; without +5.9%, p>0.1) and upper limb dynamic position (with mirror +4.6%, p=0.044; without +1.2%, p>0.1), while training without a mirror significantly improved pinch strength (with mirror +6.9%, p>0.1; without +21.9%, p=0.026). This preliminary study demonstrates the feasibility of mirror therapy in children with hemiplegia and that it may improve strength and dynamic function of the paretic arm.

The dexamethasone-induced inhibition of proliferation, migration, and invasion in glioma cell lines is antagonized by macrophage migration inhibitory factor (MIF) and can be enhanced by specific MIF inhibitors.

Glioblastomas (GBMs) are the most frequent and malignant brain tumors in adults. Glucocorticoids (GCs) are routinely used in the treatment of GBMs for their capacity to reduce the tumor-associated edema. Few in vitro studies have suggested that GCs inhibit the migration and invasion of GBM cells through the induction of MAPK phosphatase 1 (MKP-1). Macrophage migration inhibitory factor (MIF), an endogenous GC antagonist is up-regulated in GBMs. Recently, MIF has been involved in tumor growth and migration/invasion and specific MIF inhibitors have been developed on their capacity to block its enzymatic tautomerase activity site. In this study, we characterized several glioma cell lines for their MIF production. U373 MG cells were selected for their very low endogenous levels of MIF. We showed that dexamethasone inhibits the migration and invasion of U373 MG cells, through a glucocorticoid receptor (GR)- dependent inhibition of the ERK1/2 MAPK pathway. Oppositely, we found that exogenous MIF increases U373 MG migration and invasion through the stimulation of the ERK1/2 MAP kinase pathway and that this activation is CD74 independent. Finally, we used the Hs 683 glioma cells that are resistant to GCs and produce high levels of endogenous MIF, and showed that the specific MIF inhibitor ISO-1 could restore dexamethasone sensitivity in these cells. Collectively, our results indicate an intricate pathway between MIF expression and GC resistance. They suggest that MIF inhibitors could increase the response of GBMs to corticotherapy.

Clinical usefulness of FDG-PET/CT scan imaging in the management of posttransplant lymphoproliferative disease.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is, aside skin cancer, the most common malignancy occurring after solid organ transplant in adults. Fluorodeoxyglucose (FDG) positron emission tomography (PET) has proved useful in the management of lymphomas. METHODS: We report our experience with the use of FDG-PET inline with computed tomography (CT) scanning in the management of four transplant recipients with histologically confirmed PTLD, including three monomorphic PTLDs and one polymorphic PTLD. RESULTS: FDG-PET/CT scan at diagnosis showed increased FDG uptake in all examined PTLD lesions, and the disease was upstaged on the basis of FDG-PET/CT scan results over conventional CT scanning in one patient. At the end of treatment, PET/CT scans no longer demonstrated FDG uptake in the original PTLD lesions in all patients. Complete remission of disease persisted for at least 1 year after diagnosis in all. CONCLUSIONS: Our results strongly support that FDG-PET scanning is highly specific for diagnosis and follow-up of PTLD. The clinical relevance of including FDG-PET/CT scanning in the management of PTLD should be evaluated in a larger prospective cohort study.

Specific Silencing of the REST Target Genes in Insulin-Secreting Cells Uncovers Their Participation in Beta Cell Survival.

The absence of the transcriptional repressor RE-1 Silencing Transcription Factor (REST) in insulin-secreting beta cells is a major cue for the specific expression of a large number of genes. These REST target genes were largely ascribed to a function of neurotransmission in a neuronal context, whereas their role in pancreatic beta cells has been poorly explored. To identify their functional significance, we have generated transgenic mice expressing REST in beta cells (RIP-REST mice), and previously discovered that REST target genes are essential to insulin exocytosis. Herein we characterized a novel line of RIP-REST mice featuring diabetes. In diabetic RIP-REST mice, high levels of REST were associated with postnatal beta cell apoptosis, which resulted in gradual beta cell loss and sustained hyperglycemia in adults. Moreover, adenoviral REST transduction in INS-1E cells led to increased cell death under control conditions, and sensitized cells to death induced by cytokines. Screening for REST target genes identified several anti-apoptotic genes bearing the binding motif RE-1 that were downregulated upon REST expression in INS-1E cells, including Gjd2, Mapk8ip1, Irs2, Ptprn, and Cdk5r2. Decreased levels of Cdk5r2 in beta cells of RIP-REST mice further confirmed that it is controlled by REST, in vivo. Using siRNA-mediated knock-down in INS-1E cells, we showed that Cdk5r2 protects beta cells against cytokines and palmitate-induced apoptosis. Together, these data document that a set of REST target genes, including Cdk5r2, is important for beta cell survival.

Deviant trajectories of cortical maturation in 22q11.2 deletion syndrome (22q11DS): a cross-sectional and longitudinal study.

22q11.2 deletion syndrome (22q11DS) is associated with an increased susceptibility to develop schizophrenia. Despite a large body of literature documenting abnormal brain structure in 22q11DS, cerebral changes associated with brain maturation in 22q11DS remained largely unexplored. To map cortical maturation from childhood to adulthood in 22q11.2 deletion syndrome, we used cerebral MRI from 59 patients with 22q11DS, aged 6 to 40, and 80 typically developing controls; three year follow-up assessments were also available for 32 patients and 31 matched controls. Cross-sectional cortical thickness trajectories during childhood and adolescence were approximated in age bins. Repeated-measures were also conducted with the longitudinal data. Within the group of patients with 22q11DS, exploratory measures of cortical thickness differences related to COMT polymorphism, IQ, and schizophrenia were also conducted. We observed deviant trajectories of cortical thickness changes with age in patients with 22q11DS. In affected preadolescents, larger prefrontal thickness was observed compared to age-matched controls. Afterward, we observed greater cortical loss in 22q11DS with a convergence of cortical thickness values by the end of adolescence. No compelling evidence for an effect of COMT polymorphism on cortical maturation was observed. Within 22q11DS, significant differences in cortical thickness were related to cognitive level in children and adolescents, and to schizophrenia in adults. Deviant trajectories of cortical thickness from childhood to adulthood provide strong in vivo cues for a defect in the programmed synaptic elimination, which in turn may explain the susceptibility of patients with 22q11DS to develop psychosis.

Trends in the association between height and socioeconomic indicators in France, 1970-2003

Average physical stature has increased dramatically during the 20th century in many populations across the world with few exceptions. It remains unclear if social inequalities in height persist despite improvements in living standards in the welfare economies of Western Europe. We examined trends in the association between height and socioeconomic indicators in adults over three decades in France. The data were drawn from the French Decennial Health Surveys: a multistage, stratified, random survey of households, representative of the population, conducted in 1970, 1980, 1991, and 2003. We categorised age into 10-year bands, 25-34, 35-44, 45-54 and 55-64 years. Education and income were the two socioeconomic measures used. The slope index of inequality (SII) was used as a summary index of absolute social inequalities in height. The results show that average height increased over this period; men and women aged 25-34 years were 171.9 and 161.2 cm tall in 1970 and 177.0 and 164.0 cm in 2003, respectively. However, education-related inequalities in height remained unchanged over this period and in men were 4.48 cm (1970), 4.71 cm (1980), 5.58 cm (1991) and 4.69 cm (2003), the corresponding figures in women were 2.41, 2.37, 3.14 and 2.96 cm. Income-related inequalities in height were smaller and much attenuated after adjustment for education. These results suggest that in France, social inequalities in adult height in absolute terms have remained unchanged across the three decades under examination.

Comparison of two oral probiotic preparations in a randomized crossover trial highlights a potentially beneficial effect of Lactobacillus paracasei NCC2461 in patients with allergic rhinitis.

BACKGROUND: There is promising but conflicting evidence to recommend the addition of probiotics to foods for prevention and treatment of allergy. Based on previous studies with fermented milk containing Lactobacillus paracasei NCC2461, we aimed to compare the effect of a powder form of the latter probiotic with the effect of a blend of Lactobacillus acidophilus ATCC SD5221 and Bifidobacterium lactis ATCC SD5219 in patients with allergic rhinitis. METHODS: A double-blind, randomized, cross-over study, involving 31 adults with allergic rhinitis to grass pollen, was performed outside the grass pollen season (registration number: NCT01233154). Subjects received each product for 4-weeks in two phases separated by a wash-out period of 6 to 8 weeks. A nasal provocation test was performed before and after each 4-week product intake period, and outcome parameters (objective and subjective clinical symptoms; immune parameters) were measured during and/or 24 hours after the test. RESULTS: Out of the 31 subject enrolled, 28 completed the study. While no effect was observed on nasal congestion (primary outcome), treatment with NCC2461 significantly decreased nasal pruritus (determined by VAS), and leukocytes in nasal fluid samples, enhanced IL-5, IL-13 and IL-10 production by peripheral blood mononuclear cells in an allergen specific manner and tended to decrease IL-5 secretion in nasal fluid, in contrast to treatment with the blend of L. acidophilus and B. lactis. CONCLUSIONS: Despite short-term consumption, NCC2461 was able to reduce subjective nasal pruritus while not affecting nasal congestion in adults suffering from grass pollen allergic rhinitis. The associated decrease in nasal fluid leukocytes and IL-5 secretion, and the enhanced IL-10 secretion in an allergen specific manner may partly explain the decrease in nasal pruritus. However, somewhat unexpected systemic immune changes were also noted. These data support the study of NCC2461 consumption in a seasonal clinical trial to further demonstrate its potentially beneficial effect.

Adult native septic arthritis: 10 years in review in order to establish local guidelines on empiric antibiotic therapy.

Objective: Antibiotic stewardship includes development of practice guidelines incorporating local microbiology and resistance patterns. In case of septic arthritis (SA), addition of vancomycin to the empiric therapy and broad-spectrum antibiotherapy in some clinical settings are subjects of discussion. Our objective was to review the local epidemiology of native septic arthritis in adults, in order to establish local guidelines for empiric therapy. Methods: Retrospective study based on positive synovial fluid cultures and hospital discharge diagnoses of SA obtained from 1999 to 2008 in patients _16 years. Medical records were reviewed to assess the diagnosis and complete relevant clinical information. Results: During this ten-year period, we identified 233 SA on native joints in 231 patients. 107 episodes (46%) were obtained through positive synovial fluid cultures, and 126 episodes (54%) through the discharge diagnosis. 147 SA (63%) were large joint infections (LJI). 35 SA (15%) occurred in intravenous drug users. Preexisting arthropathy was present in 51% of cases. 42% of patients with small joint infection (SJI) were diabetic, vs. 23% with LJI (p = 0.003). When available, synovial fluid direct examination was positive in 35% of cases. Etiologic agents are reported in the table. Five of the 11 MRSA SA (45%) occurred in known carriers. SJI were more frequently polymicrobial (24% vs. 1%, p<0.001). For LJI, an empiric treatment with amoxicillin/clavulanate (A/C) would have been appropriate in 85% of cases. MRSA (8 cases) and tuberculous (7 cases) arthritis would have been the most frequently untreated pathogens. Addition of vancomycin to A/C in MRSA carriers would rise the adequacy to 87%. In contrast, A/C would cover only 75% of SJI (82% if restricted to non-diabetic patients). MRSA (3 cases) and P. aeruginosa (9 cases, 7 monomicrobial) would be the main untreated pathogens. An anti-pseudomonal penicillin would have been appropriate in 94% of cases of SJI (P = 0.002 vs. A/C, p = 0.19 if diabetic patients not included). Conclusions: Treatment with A/C seems adequate for empiric coverage of LJI in our setting. Broad-spectrum antibiotherapy was significantly superior for SJI in diabetic patients, due to different causative bacteria. In an area of low MRSA incidence, our results do not justify a systematic empiric therapy for MRSA, which should be considered in a known carrier.

Socioeconomic determinants of dietary patterns in low- and middle-income countries : a systematic review

BACKGROUND: In high-income countries, high socioeconomic status (SES) is generally associated with a healthier diet, but whether social differences in dietary intake are also present in low- and middle-income countries (LMICs) remains to be established. OBJECTIVE: We performed a systematic review of studies that assessed the relation between SES and dietary intake in LMICs. DESIGN: We carried out a systematic review of cohort and cross-sectional studies in adults in LMICs and published between 1996 and 2013. We assessed associations between markers of SES or urban and rural settings and dietary intake. RESULTS: A total of 33 studies from 17 LMICs were included (5 low-income countries and 12 middle-income countries; 31 cross-sectional and 2 longitudinal studies). A majority of studies were conducted in Brazil (8), China (6), and Iran (4). High SES or living in urban areas was associated with higher intakes of calories; protein; total fat; cholesterol; polyunsaturated, saturated, and monounsaturated fatty acids; iron; and vitamins A and C and with lower intakes of carbohydrates and fiber. High SES was also associated with higher fruit and/or vegetable consumption, diet quality, and diversity. Although very few studies were performed in low-income countries, similar patterns were generally observed in both LMICs except for fruit intake, which was lower in urban than in rural areas in low-income countries. CONCLUSIONS: In LMICs, high SES or living in urban areas is associated with overall healthier dietary patterns. However, it is also related to higher energy, cholesterol, and saturated fat intakes. Social inequalities in dietary intake should be considered in the prevention and control of noncommunicable diseases in LMICs.

Cardiovascular risk factor profiles and their social gradient from adolescence to age 74 in a Swiss region.

BACKGROUND: Few European studies have investigated how cardiovascular risk factors (CRF) in adults relate to those observed in younger generations. OBJECTIVE: To explore this issue in a Swiss region using two population health surveys of 3636 adolescents ages 9-19 years and 3299 adults ages 25-74 years. METHODS: Age patterns of continuous CRF were estimated by robust locally weighted regression and those of high-risk groups were calculated using adult criteria with appropriate adjustment for children. RESULTS: Gender differences in height, weight, blood pressure, and HDL cholesterol observed in adults were found to emerge in adolescents. Overweight, affecting 10-12% of adolescents, was increasing steeply in young adults (three times among males and twice among females) in parallel with inactivity. Median age at smoking initiation was decreasing rapidly from 18 to 20 years in young adults to 15 in adolescents. A statistically significant social gradient in disfavor of the lower education level was observed for overweight in all age groups of women above 16 (odds ratios (ORs) 2.4 to 3.3, P < 0.01), for inactivity in adult males (ORs 1.6 to 2.0, P < 0.05), and for regular smoking in older adolescents (OR 1.9 for males, 2.7 for females, P < 0.005), but not for elevated blood pressure. CONCLUSION: Discontinuities in the cross-sectional age patterns of CRF indicated the emergence of a social gradient and the need for preventive actions against the early adoption of persistent unhealthy behaviors, to which low-educated girls and women are particularly exposed.

Context- and Prosody-Driven ERP Markers for Dialog Focus Perception in Children.

The development of language proficiency extends late into childhood and includes not only producing or comprehending sounds, words and sentences, but likewise larger utterances spanning beyond sentence borders like dialogs. Dialogs consist of information units whose value constantly varies within a verbal exchange. While information is focused when introduced for the first time or corrected in order to alter the knowledge state of communication partners, the same information turns into shared knowledge during the further course of a verbal exchange. In many languages, prosodic means are used by speakers to highlight the informational value of information foci. Our study investigated the developmental pattern of event-related potentials (ERPs) in three age groups (12, 8 and 5 years) when perceiving two information focus types (news and corrections) embedded in short question-answer dialogs. The information foci contained in the answer sentences were either adequately marked by prosodic means or not. In so doing, we questioned to what extent children depend on prosodic means to recognize information foci or whether contextual means as provided by dialog questions are sufficient to guide focus processing.Only 12-year-olds yield prosody-independent ERPs when encountering new and corrective information foci, resembling previous findings in adults. Focus processing in the 8-year-olds relied upon prosodic highlighting, and differing ERP responses as a function of focus type were observed. In the 5-year-olds, merely prosody-driven ERP responses were apparent, but no distinctive ERP indicating information focus recognition. Our findings reveal substantial alterations in information focus perception throughout childhood that are likely related to long-lasting maturational changes during brain development.

Gonadal alterations in male whitefish Coregonus fatioi: no evidence for genetic damage reducing viability in early life stages.

In recent years, numerous cases of morphological gonadal alterations in fish have been recorded throughout the world and across a wide range of species. In the whitefish Coregonus fatioi from the pre-alpine Lake Thun (Switzerland), the frequency of gonadal alterations is particularly high and the variety of alteration types large. Little is known about the proximal causes and the direct consequences of these morphological features on population persistence. In particular, the potential for the observed alterations to be the phenotypic expression of reduced genetic quality has not yet been addressed. In this study, we used offspring survival during embryogenesis as a proximate indicator of male genetic quality and tested whether the presence of gonadal alterations in males is an indicator of reduced quality. Embryos resulted from in vitro fertilizations of gametes from 126 males and females. We found no significant correlation between embryo survival and gonadal alteration in adults. Our findings suggest that in C. fatioi of Lake Thun, alterations in gonad morphology are not a phenotypic expression of variation in genetic quality.