The NLRP3 inflammasome in health and disease: the good, the bad and the ugly.

While interleukin (IL)-1β plays an important role in combating the invading pathogen as part of the innate immune response, its dysregulation is responsible for a number of autoinflammatory disorders. Large IL-1β activating platforms, known as inflammasomes, can assemble in response to the detection of endogenous host and pathogen-associated danger molecules. Formation of these protein complexes results in the autocatalysis and activation of caspase-1, which processes precursor IL-1β into its secreted biologically active form. Inflammasome and IL-1β activity is required to efficiently control viral, bacterial and fungal pathogen infections. Conversely, excess IL-1β activity contributes to human disease, and its inhibition has proved therapeutically beneficial in the treatment of a spectrum of serious, yet relatively rare, heritable inflammasomopathies. Recently, inflammasome function has been implicated in more common human conditions, such as gout, type II diabetes and cancer. This raises the possibility that anti-IL-1 therapeutics may have broader applications than anticipated previously, and may be utilized across diverse disease states that are linked insidiously through unwanted or heightened inflammasome activity.

The Inter-municipal Cooperation in Switzerland and the Trend towards Amalgamation

In Switzerland, the ongoing reforms of fiscal federalism put municipalities under increased fiscal stress. A majority of the municipalities had responded by increasing the cooperation with neighbouring municipalities over the last few years. Simultaneously, many discuss or are directly involved in a possible amalgamation project. Accordingly, the paper aimed at describing how cooperation has presently developed between Swiss municipalities, in order to illustrate the existing trend towards amalgamation. Current surveys helped us estimate the growing importance of inter-municipal arrangements together with the surge of amalgamations. A further goal was to investigate if cantonal financial incentives to municipal amalgamation essentially benefit the cantonal community, following the fiscal equivalence principle, or if they rather benefit amalgamating municipalities. In reality, equivalence does not exist. However, this may possibly be the condition to reduce inequality among amalgamating municipalities.

Nonclassical measurement error with applications to labor and development issues

Zero correlation between measurement error and model error has been assumed in existing panel data models dealing specifically with measurement error. We extend this literature and propose a simple model where one regressor is mismeasured, allowing the measurement error to correlate with model error. Zero correlation between measurement error and model error is a special case in our model where correlated measurement error equals zero. We ask two research questions. First, we wonder if the correlated measurement error can be identified in the context of panel data. Second, we wonder if classical instrumental variables in panel data need to be adjusted when correlation between measurement error and model error cannot be ignored. Under some regularity conditions the answer is yes to both questions. We then propose a two-step estimation corresponding to the two questions. The first step estimates correlated measurement error from a reverse regression; and the second step estimates usual coefficients of interest using adjusted instruments.

Prevalence of thinness in children and adolescents in the Seychelles: comparison of two international growth references.

BACKGROUND: : Thinness in children and adolescents is largely under studied, a contrast with abundant literature on under-nutrition in infants and on overweight in children and adolescents. The aim of this study is to compare the prevalence of thinness using two recently developed growth references, among children and adolescents living in the Seychelles, an economically rapidly developing country in the African region. METHOD: S: Weight and height were measured every year in all children of 4 grades (age range: 5 to 16 years) of all schools in the Seychelles as part of a routine school-based surveillance program. In this study we used data collected in 16,672 boys and 16,668 girls examined from 1998 to 2004. Thinness was estimated according to two growth references: i) an international survey (IS), defining three grades of thinness corresponding to a BMI of 18.5, 17.0 and 16.0 kg/m2 at age 18 and ii) the WHO reference, defined here as three categories of thinness (-1, -2 and -3 SD of BMI for age) with the second and third named "thinness" and "severe thinness", respectively. RESULTS: : The prevalence of thinness was 21.4%, 6.4% and 2.0% based on the three IS cut-offs and 27.7%, 6.7% and 1.2% based on the WHO cut-offs. The prevalence of thinness categories tended to decrease according to age for both sexes for the IS reference and among girls for the WHO reference. CONCLUSION: The prevalence of the first category of thinness was larger with the WHO cut-offs than with the IS cut-offs while the prevalence of thinness of "grade 2" and thinness of "grade 3" (IS cut-offs) was similar to the prevalence of "thinness" and "severe thinness" (WHO cut-offs), respectively.

Seroepidemiology of Herpes Simplex virus type 1 and 2 in Western and Southern Switzerland in adults aged 25-74 in 1992-93: a population-based study.

BACKGROUND: Genital herpes is one of the most prevalent sexually-transmitted diseases, and accounts for a substantial morbidity. Genital herpes puts newborns at risk for very severe disease and also increases the risk of horizontal HIV transmission. It thus stands as an important public health problem. The recent availability of type-specific gG-based assays detecting IgG against HSV-1 and HSV-2 allows to establish the prevalence of each subtype. Worldwide, few data have been published regarding the seroprevalence in general populations of HSV-2, the major causative agent for genital herpes, while no data exist regarding the Swiss population. METHODS: To evaluate the prevalence of IgG antibodies against HSV-1 and HSV-2 in Switzerland, we used a population-based serum repository from a health examination survey conducted in the Western and Southern area of Switzerland in 1992-93. A total of 3,120 sera were analysed by type-specific gG-based ELISA and seroprevalence was correlated with available volunteers characteristics by logistic regression. RESULTS: Overall, seroprevalence rates were 80.0 +/- 0.9% (SE, 95% CI: 78.1-81.8) for HSV-1 and 19.3 +/- 0.9% (SE, 95% CI: 17.6-21.1) for HSV-2 in adults 35-64 year old. HSV-1 and HSV-2 seroprevalence increased with age, with a peak HSV-2 seroprevalence in elderly gentlemen, possibly a seroarcheological evidence of sexually transmitted disease epidemics during World War II. Risk factors for HSV-2 infection included female sex, marital status other than married, and size of town of residence larger than 1500 inhabitants. Unexpectedly and conversely to HSV-1, HSV-2 seroprevalence increased with educational level. HSV-2 infection was less prevalent among HSV-1 infected individuals when compared to HSV-1 uninfected individuals. This effect was most apparent among women at high risk for HSV-2 infection. CONCLUSIONS: Our data demonstrate that by the early nineties, HSV-2 had spread quite largely in the Swiss population. However, the epidemiology of HSV-2 in Switzerland presents paradoxical characteristics, e.g. positive correlation with education level, that have not been observed elsewhere.

Epidemiologie der letalen Missbildungen in der Schweiz. [Epidemiology of fatal abnormalities in Switzerland].

Official certificates of stillbirth and infant death are analysed in the birth cohort of 1979-81. Congenital malformations account for approx. 40% of infant mortality. Cantonal differences in malformation rates are not explained by different incidence of such malformations only, but also by differences in lethality. Incidence of Anencephaly is examined in detail.

Current standards and progress in understanding and treatment of GIST.

Gastrointestinal stromal tumours (GIST), despite being rare, pose a relevant medical problem from the viewpoint of diagnosis and management. GIST are fragile, liable to metastasize and often located in delicate structures. Surgical options, therefore, are limited. In the last decade an improved understanding of the molecular mechanisms of the disease has resulted in novel modes of treatment. The introduction of systemic tyrosine kinase inhibitor therapy with imatinib has significantly improved the outcome of the disease and prolonged the survival of GIST patients. For many patients the acute threat of a deadly cancer has been transformed into a manageable chronic condition. Drug safety, tolerability and compliance, subjects of concern in all long-term therapies, have proven to be acceptable for the tyrosine kinase inhibitor imatinib. The present paper provides a compact overview of the epidemiology, pathophysiology and morphology of GIST, with special reference to the underlying molecular biology. Relevant aspects of diagnosis, therapy and monitoring of the disease are reviewed with particular emphasis on the available clinical evidence and recent guidelines.

Cellular Derivatives and Efficacy in Wound and Scar Management

Biologicals have been used for decades in biopharmaceutical topical preparations. Because cellular therapies are rou-tinely used in the clinic they have gained significant attention. Different derivatives are possible from different cell and tissue sources, making the selection of cell types and establishment of consistent cell banks crucial steps in the initial whole-cell bioprocessing. Various cell and tissue types have been used in treatment of skin wounds including autolo-gous and allogenic skin cells, platelets, placenta and amniotic extracts from either human or animal sources. Experience with progenitor cells show that they may provide an interesting cell choice due to facility of out-scaling and known properties for wound healing without scar. Using defined animal cell lines to develop cell-free derivatives may provide initial starting material for pharmaceutical formulations that help in overall stability. Cell lines derived from ovine tis-sue (skin, muscle, connective tissue) can be developed in short periods of time and consistency of these cell lines was monitored by cellular life-span, protein concentrations, stability and activity. Each cell line had long culture periods up to 37 - 41 passages and protein measures for each cell line at passages 2 - 15 had only 1.4-fold maximal difference. Growth stimulation activity towards two target skin cell lines (GM01717 and CRL-1221; 40 year old human males) at concentrations ranging up to 6 μg/ml showed 2-3-fold (single extracts) and 3-7-fold (co-cultured extracts) increase. Proteins from co-culture remained stable up to 1 year in pharmaceutical preparations shown by separation on SDS- PAGE gels. Pharmaceutical cell-free preparations were used for veterinary and human wounds and burns. Cell lines and cell-free extracts can show remarkable consistency and stability for preparation of biopharmaceutical creams, moreover when cells are co-cultured, and have positive effects for tissue repair.

The oral cancer epidemic in central and eastern Europe.

To monitor recent trends in oral and pharyngeal cancer mortality in 38 European countries, we analyzed data provided by the World Health Organization over the period 1975-2004. Joinpoint analysis was used to identify significant changes in trends. In the European Union (EU), male mortality rates rose by 2.1% per year between 1975 and 1984, by 1.0% between 1984 and 1993, and declined by 1.3% between 1993 and 2004, to reach an overall age-standardized rate of 6.1/100,000 in 2000-2004. Mortality rates were much lower in women, and the rate in the EU rose by 0.9% per year up to 2000, and levelled off to 1.1/100,000 in 2000-2004. In France and Italy - which had the highest rates in the past - male rates have steadily declined during the last two decades (annual percent change, APC=-4.8% in 1998-2004 in France, and -2.6% in 1986-2003 in Italy). Persisting rises were, however, observed in several central and eastern European countries, with exceedingly high rates in Hungary (21.1/100,000; APC=6.9% in 1975-1993 and 1.4% in 1993-2004) and Slovakia (16.9/100,000; APC=0.14% in 1992-2004). In middle aged (35 to 64) men, oral and pharyngeal cancer mortality rates in Hungary (55.2/100,000) and Slovakia (40.8/100,000) were comparable to lung cancer rates in several major European countries. The highest rates for women were in Hungary (3.3/100,000; APC=4.7% in 1975-2004) and Denmark (1.6/100,000; APC=1.3% in 1975-2001). Oral and pharyngeal cancer mortality essentially reflects the different patterns in tobacco smoking and alcohol drinking, including drinking patterns and type of alcohol in central Europe. (c) 2009 UICC.

Prevalence of overweight and obesity in children and adolescents in Seychelles : results of the School Screening Program in 2013

Results related to overweight and obesity in 2013: Participation to the school screening program was satisfactory in 2013, but a bit less than in previous years (4220 children seen out of a total of approximately 6000 eligible ones). Less than maximal participation to the screening program can relate to different factors, e.g.; a trend for obese children to decline participation; lack of time of school nurses to complete the screening program due to competing duties at health centre level. Good organization by the school nurses and adequate facilities for screening are also important factors for a good conduct of the screening program.

Adaptation en français et en allemand d'une échelle de pression des pairs pour jeunes adultes : le Peer Pressure Inventory [Adaptation of a peer pressure scale in French and German: the Peer Pressure Inventory].

BACKGROUND: Peer pressure is regarded as an important determinant of substance use, sexual behavior and juvenile delinquency. However, few peer pressure scales are validated, especially in French or German. Little is known about the factor structure of such scales or the kind of scale needed: some scales takes into account both peer pressure to do and peer pressure not to do, while others consider only peer pressure to do. The aim of the present study was to adapt French and German versions of the Peer Pressure Inventory, which is one of the most widely used scales in this field. We considered its factor structure and concurrent validity. METHODS: Five thousand eight hundred and sixty-seven young Swiss men filled in a questionnaire on peer pressure, substance use, and other variables (conformity, involvement) in a cohort study. RESULTS: We identified a four-factor structure, with the three factors of the initial Peer Pressure Inventory (involvement, conformity, misconduct) and adding a new one (relationship with girls). A non-valued scale (from no peer pressure to peer pressure to do only) showed stronger psychometric qualities than a valued scale (from peer pressure not to do to peer pressure to do). Concurrent validity was also good. Each behavior or attitude was significantly associated with peer pressure. CONCLUSION: Peer pressure seems to be a multidimensional concept. In this study, peer pressure to do showed the strongest influence on participants. Indeed, peer pressure not to do did not add anything useful. Only peer pressure to do affected young Swiss men's behaviors and attitudes and was reliable.

Circulating insulin-like growth factor-I in pregnancy and maternal risk of breast cancer.

BACKGROUND: Elevated serum concentrations of insulin-like growth factor (IGF)-1 have been associated with increased risk of breast cancer. Previously, we reported a similar association in samples obtained during pregnancy. The current study was conducted to further characterize the association of IGF-1 during pregnancy with maternal breast cancer risk. METHODS: A case-control study was nested within the Finnish Maternity Cohort. The study was limited to primiparous women less than 40 years of age, who donated blood samples during early (median, 12 weeks) pregnancy and delivered a single child at term. Seven hundred and nineteen women with invasive breast cancer were eligible. Two controls (n = 1,434) were matched to each case on age and date at blood donation. Serum IGF-1 concentration was measured using an Immulite 2000 analyzer. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).RESULTS: No significant associations were observed between serum IGF-1 concentrations and breast cancer risk in both the overall analysis (OR 1.08 (95% CI 0.80-1.47) and in analyses stratified by histological subtype, lag-time to cancer diagnosis, age at pregnancy or age at diagnosis.CONCLUSIONS: There was no association between IGF-1 and maternal breast cancer risk during early pregnancy in this large nested case-control study.Impact:Serum IGF-1 concentrations during early pregnancy may not be related to maternal risk of breast cancer.