Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking

Twin studies indicate that additive genetic effects explain most of the variance in nicotine dependence (ND), a construct emphasizing habitual heavy smoking despite adverse consequences, tolerance and withdrawal. To detect ND alleles, we assessed cigarettes per day (CPD) regularly smoked, in two European populations via whole genome association techniques. In these approximately 7500 persons, a common haplotype in the CHRNA3-CHRNA5 nicotinic receptor subunit gene cluster was associated with CPD (nominal P=6.9 x 10(-5)). In a third set of European populations (n= approximately 7500) which had been genotyped for approximately 6000 SNPs in approximately 2000 genes, an allele in the same haplotype was associated with CPD (nominal P=2.6 x 10(-6)). These results (in three independent populations of European origin, totaling approximately 15 000 individuals) suggest that a common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to ND

VI-RADS for bladder cancer: current applications and future developments

Bladder cancer (BCa) is among the ten most frequent cancers globally. It is the tumor with the highest lifetime treatment-associated costs, and among the tumors with the heaviest impacts on postoperative quality of life. The purpose of this article is to review the current applications and future perspectives of the Vesical Imaging Reporting and Data System (VI-RADS). VI-RADS is a newly developed scoring system aimed at standardization of MRI acquisition, interpretation, and reporting for BCa. An insight will be given on the BCa natural history, current MRI applications for local BCa staging with assessment of muscle invasiveness, and clinical implications of the score for disease management. Future applications include risk stratification of nonmuscle invasive BCa, surveillance, and prediction and monitoring of therapy response. Level of Evidence: 3. Technical Efficacy Stage: 2

Dynamical and stationary critical behavior of the Ising ferromagnet in a thermal gradient

In this paper we present and discuss results of Monte Carlo numerical simulations of the two-dimensional Ising ferromagnet in contact with a heat bath that intrinsically has a thermal gradient. The extremes of the magnet are at temperatures $T_1<T_c<T_2$, where $T_c$ is the Onsager critical temperature. In this way one can observe a phase transition between an ordered phase ($TT_c$) by means of a single simulation. By starting the simulations with fully disordered initial configurations with magnetization $m\equiv 0$ corresponding to $T=\infty$, which are then suddenly annealed to a preset thermal gradient, we study the short-time critical dynamic behavior of the system. Also, by setting a small initial magnetization $m=m_0$, we study the critical initial increase of the order parameter. Furthermore, by starting the simulations from fully ordered configurations, which correspond to the ground state at T=0 and are subsequently quenched to a preset gradient, we study the critical relaxation dynamics of the system. Additionally, we perform stationary measurements ($t\rightarrow\infty$) that are discussed in terms of the standard finite-size scaling theory. We conclude that our numerical simulation results of the Ising magnet in a thermal gradient, which are rationalized in terms of both dynamic and standard scaling arguments, are fully consistent with well established results obtained under equilibrium conditions

The PsyCoLaus study: methodology and characteristics of the sample of a population-based survey on psychiatric disorders and their association with genetic and cardiovascular risk factors.

ABSTRACT: BACKGROUND: The Psychiatric arm of the population-based CoLaus study (PsyCoLaus) is designed to: 1) establish the prevalence of threshold and subthreshold psychiatric syndromes in the 35 to 66 year-old population of the city of Lausanne (Switzerland); 2) test the validity of postulated definitions for subthreshold mood and anxiety syndromes; 3) determine the associations between psychiatric disorders, personality traits and cardiovascular diseases (CVD), 4) identify genetic variants that can modify the risk for psychiatric disorders and determine whether genetic risk factors are shared between psychiatric disorders and CVD. This paper presents the method as well as somatic and sociodemographic characteristics of the sample. METHODS: All 35 to 66 year-old persons previously selected for the population-based CoLaus survey on risk factors for CVD were asked to participate in a substudy assessing psychiatric conditions. This investigation included the Diagnostic Interview for Genetic Studies to elicit diagnostic criteria for threshold disorders according to DSM-IV and algorithmically defined subthreshold syndromes. Complementary information was gathered on potential risk and protective factors for psychiatric disorders, migraine and on the morbidity of first-degree family members, whereas the collection of DNA and plasma samples was part of the original somatic study (CoLaus). RESULTS: A total of 3,691 individuals completed the psychiatric evaluation (67% participation). The gender distribution of the sample did not differ significantly from that of the general population in the same age range. Although the youngest 5-year band of the cohort was underrepresented and the oldest 5-year band overrepresented, participants of PsyCoLaus and individuals who refused to participate revealed comparable scores on the General Health Questionnaire, a self-rating instrument completed at the somatic exam. CONCLUSIONS: Despite limitations resulting from the relatively low participation in the context of a comprehensive and time-consuming investigation, the PsyCoLaus study should significantly contribute to the current understanding of psychiatric disorders and comorbid somatic conditions by: 1) establishing the clinical relevance of specific psychiatric syndromes below the DSM-IV threshold; 2) determining comorbidity between risk factors for CVD and psychiatric disorders; 3) assessing genetic variants associated with common psychiatric disorders and 4) identifying DNA markers shared between CVD and psychiatric disorders

Conventional and diffusion-weighted magnetic resonance imaging findings of benign fibromatous paratesticular tumor: a case report

<p>Abstract</p> <p>Introduction</p> <p>The vast majority of paratesticular masses are benign. Magnetic resonance imaging of the scrotum may provide valuable information in the pre-operative work-up of scrotal masses, by allowing the precise localization of the lesion and helping in characterizing its nature. Diffusion-weighted magnetic resonance imaging is an evolving technique that can be used to improve tissue characterization, when interpreted with the findings of conventional magnetic resonance sequences. We present the case of an adenomatoid tumor of the tunica albuginea, with abundant fibrosis evaluated by magnetic resonance imaging of the scrotum, including both conventional and diffusion-weighted sequences. To the best of our knowledge, there are very few reports in the English literature regarding the magnetic resonance imaging features of this rare benign paratesticular tumor and no report on the diffusion-weighted magnetic resonance findings. We discuss the value of magnetic resonance imaging in the pre-operative diagnosis of benign fibromatous paratesticular tumors and differential diagnosis.</p> <p>Case presentation</p> <p>A 45-year-old Caucasian man was referred to us with a palpable left scrotal mass. Magnetic resonance imaging of his scrotum revealed the presence of a multilobular left paratesticular mass, mainly detected with very low signal intensity on T2-weighted images and restricted diffusion on apparent diffusion coefficient maps. These findings were suggestive of a fibrous component, and were confirmed on histology following lesion excision.</p> <p>Conclusion</p> <p>Magnetic resonance imaging of the scrotum, by using both conventional and diffusion-weighted sequences, could have a potential role in the evaluation of scrotal masses.</p

FUS MUTATIONS IN SPORADIC AMYOTROPHIC LATERAL SCLEROSIS: CLINICAL AND GENETIC ANALYSIS

Fused in sarcoma (FUS) or translocation in liposarcoma (TLS), a DNA/RNA-binding protein, causes a dominant autosomal inherited form of amyotrophic lateral sclerosis (ALS), ALS 6. Its main role in neurodegeneration is highlighted by the presence of cytoplasmic accumulation of its mutant protein form in ALS patients. To further define the frequency and spectrum of FUS gene mutations, we have performed a molecular screening of a cohort of 327 Italian patients from Southern Italy with sporadic ALS (SALS). We identified 4 patients carrying 3 different missense mutations and several polymorphisms. Two different substitutions occurring in the same amino acidic position have been observed in 2 patients: R521G and R521C respectively; P525L mutation has been found in 2 additional cases. Most of the patients with FUS mutations showed early symptom onset and had short disease survival. We also detected 4 different polymorphic variants (3=-untranslated region [UTR] variant, c.*41G.A; c.52313ins[GAGGTG]; c.335-15del[TTTT]; and rs13331793) in 9 patients from within our cohort. This study underlines the importance of population-based mutation screening of newly identified genes. \ua9 2011 Elsevier Inc. All rights reserved

Genetic Associations with Gestational Duration and Spontaneous Preterm Birth

BACKGROUND Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. METHODS We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P<5.0x10(-8)) or an association with suggestive significance (P<1.0x10(-6)) in the discovery set. RESULTS In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother-infant dyads suggested that these variants act at the level of the maternal genome. CONCLUSIONS In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement.Peer reviewe

Conceptualizing pathways linking women's empowerment and prematurity in developing countries.

BackgroundGlobally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity.MethodsThe key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors.ResultsThere is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving access to and receipt of recommended health services during pregnancy and delivery to help prevent prematurity and improve survival of premature babies.ConclusionsWomen's empowerment is an important distal factor that affects prematurity through several intervening factors. Improving women's empowerment will help prevent prematurity and improve survival of preterm babies. Research to empirically show the links between women's empowerment and prematurity is however needed