Genetic Variants in TGF-β Pathway Are Associated with Ovarian Cancer Risk

The transforming growth factor-β (TGF-β) signaling pathway is involved in a diverse array of cellular processes responsible for tumorigenesis. In this case-control study, we applied a pathway-based approach to evaluate single-nucleotide polymorphisms (SNPs) in the TGF-β signaling pathway as predictors of ovarian cancer risk. We systematically genotyped 218 SNPs from 21 genes in the TGF-β signaling pathway in 417 ovarian cancer cases and 417 matched control subjects. We analyzed the associations of these SNPs with ovarian cancer risk, performed haplotype analysis and identified potential cumulative effects of genetic variants. We also performed analysis to identify higher-order gene-gene interactions influencing ovarian cancer risk. Individual SNP analysis showed that the most significant SNP was SMAD6: rs4147407, with an adjusted odds ratio (OR) of 1.60 (95% confidence interval [CI], 1.14–2.24, P = 0.0066). Cumulative genotype analysis of 13 SNPs with significant main effects exhibited a clear dose-response trend of escalating risk with increasing number of unfavorable genotypes. In gene-based analysis, SMAD6 was identified as the most significant gene associated with ovarian cancer risk. Haplotype analysis further revealed that two haplotype blocks within SMAD6 were significantly associated with decreased ovarian cancer risk, as compared to the most common haplotype. Gene-gene interaction analysis further categorized the study population into subgroups with different ovarian cancer risk. Our findings suggest that genetic variants in the TGF-β signaling pathway are associated with ovarian cancer risk and may facilitate the identification of high-risk subgroups in the general population

Effects of circadian disruption on physiology and pathology: from bench to clinic (and back)

Nested within the hypothalamus, the suprachiasmatic nuclei (SCN) represent a central biological clock that regulates daily and circadian (i.e., close to 24 h) rhythms in mammals. Besides the SCN, a number of peripheral oscillators throughout the body control local rhythms and are usually kept in pace by the central clock. In order to represent an adaptive value, circadian rhythms must be entrained by environmental signals or zeitgebers, the main one being the daily light?dark (LD) cycle. The SCN adopt a stable phase relationship with the LD cycle that, when challenged, results in abrupt or chronic changes in overt rhythms and, in turn, in physiological, behavioral, and metabolic variables. Changes in entrainment, both acute and chronic, may have severe consequences in human performance and pathological outcome. Indeed, animal models of desynchronization have become a useful tool to understand such changes and to evaluate potential treatments in human subjects. Here we review a number of alterations in circadian entrainment, including jet lag, social jet lag (i.e., desynchronization between body rhythms and normal time schedules), shift work, and exposure to nocturnal light, both in human subjects and in laboratory animals. Finally, we focus on the health consequences related to circadian/entrainment disorders and propose a number of approaches for the management of circadian desynchronization.Fil: Chiesa, Juan José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Duhart, José Manuel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Casiraghi, Leandro Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paladino, Natalia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bussi, Ivana Leda. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Über die genauere Lokalisation der Frakturen im Bereiche des Foramen opticum mit Hilfe der Radiographie

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State of zoonotic diseases 2011

De Staat van zoönosen 2011 geeft een overzicht van de mate waarin diverse zoönosen in het verslagjaar voorkomen, gecombineerd met de trends op de lange termijn. Het verslag bevat daarnaast enkele opmerkelijke voorvallen uit 2011 en behandelt jaarlijks een thema. Opmerkelijke voorvallen zoönosen uitgelicht Doorgaans vertonen de trends geen uitgesproken ontwikkelingen. Wel waren er een aantal opmerkelijke voorvallen zoals de uitbraken van E. coli O104 via kiemgroenten en Salmonella Newport. Een ander voorbeeld is het Schmallenbergvirus, een nieuw virus bij runderen en schapen dat tot misvormingen leidt bij kalveren en lammeren. Het RIVMCIb acht het zeer onwaarschijnlijk dat het virus een infectie bij de mens kan veroorzaken. Ook wordt de stand van zaken weergegeven van veegerelateerde MRSA en van de ziekte van Lyme. In het onderzoek naar de ziekte van Lyme is er steeds meer aandacht voor mensen die klachten hebben zonder dat daar duidelijke tekenen van infectie aan vooraf zijn gegaan, zoals de rode ring rondom de tekenbeet. Thema: 'Dieren onderweg' Het rapport wordt elk jaar afgesloten met een themahoofdstuk, dit keer getiteld 'Dieren onderweg'. Hierin wordt inzicht gegeven in de wet- en regelgeving voor de import van dieren en het reizen met dieren. Aangezien de verplaatsing van dieren tussen landen zoönotische risico's met zich mee kunnen brengen, is het van belang dat professionals, zoals GGD en dierenartsen, hiervan op de hoogte zijn. Bij dit thema wordt een onderscheid gemaakt tussen huisdieren, paardachtigen, landbouwhuisdieren en exotische dieren. Het is opmerkelijk hoeveel Nederlanders hun hond of kat meenemen op vakantie naar het buitenland. Echter, de kennis over de zoönotische risico's en naleving van veterinaire voorschriften is waarschijnlijk beperkt. Het reizen met dieren kan hierdoor een bedreiging vormen voor de dier- en volksgezondheid. Het laatste Nederlandse geval van insleep van rabiës in 2012 was dan ook het gevolg van de illegale invoer van een puppy vanuit Marokko.The State of Zoonotic Diseases 2011 is an overview of the occurrence of various zoonoses for that year and is combined with the trends for the long term. The report also contains a few striking incidents that occurred in 2011 and focuses on one theme each year. Striking incidents of zoonotic diseases explained Generally speaking the trends do not reveal any pronounced developments. There were, however, a number of striking incidents such as the outbreaks of E. coli 0104 through sprouting vegetables and Salmonella Newport. Another example is that of the Schmallenberg virus, a new virus in cattle and sheep that causes congenital malformations in lambs and calves. The Centre for Infectious Disease Control (CIb) at the National Institute for Public Health and the Environment (RIVM) thinks that it is highly unlikely that the virus can cause an infection in humans. The report also contains the state of affairs for livestockassociated MRSA and for Lyme disease. Research on Lyme disease is increasingly focusing on people who have symptoms without having had prior clear signs of infection, such as the red ring that surrounds a tick bite. Theme: Animals en route Each year the report ends with a chapter on a special theme; this year the title of that chapter is Animals en route. This chapter highlights the legal and regulatory requirements for importing animals and for travelling with animals. Bearing in mind that the transfer of animals between countries can bring zoonotic risks with it, professionals such as those working at the Public Health Services (GGD) and veterinarians should be aware of these regulations. In this chapter a distinction has been made between pets, the horse family, farm animals and exotic animals. It is striking to note how many Dutch people take their dog or cat on holiday abroad. People's knowledge with regard to the zoonotic risks and their adherence to veterinary regulations is probably limited. Travelling with animals may therefore constitute a threat for the health of both animals and humans. The last incident of a case of rabies being brought into the Netherlands (in 2012) was the result of a puppy being illegally imported from Morocco.NVW