Metallothionein genes: no association with Crohn's disease in a New Zealand population

Metallothioneins (MTs) are excellent candidate genes for Inflammatory Bowel Disease (IBD) and have previously been shown to have altered expression in both animal and human studies of IBD. This is the first study to examine genetic variants within the MT genes and aims to determine whether such genetic variants have an important role in this disease. 28 tag SNPs in genes MT1 (subtypes A, B, E, F, G, H, M, X), MT2, MT3 and MT4 were selected for genotyping in a well-characterized New Zealand dataset consisting of 406 patients with Crohn's Disease and 638 controls. We did not find any evidence of association for MT genetic variation with CD. The lack of association indicates that genetic variants in the MT genes do not play a significant role in predisposing to CD in the New Zealand population

The influence of age on the female/male ratio of treated incidence rates in depression

BACKGROUND: Poor data exist on the influence of psychosocial variables on the female/male ratio of depression because of the small number of cases and the resulting limited numbers of variables available for investigation. For this investigation a large number of first admitted depressed patients (N = 2599) was available which offered the unique opportunity to calculate age specific sex ratios for different marital and employment status categories. METHODS: Age and sex specific population based depression rates were calculated for first ever admissions for single year intervals. Moving averages with interpolated corrections for marginal values in the age distribution were employed. RESULTS: For the total group the female/male ratio of depression showed an inverted U-shape over the life-cycle. This pattern was influenced by the group of married persons, which showed a sex-ratio of 3:1 between the age of 30–50, but ratios of around 1:1 at younger and older ages. For not married persons the female/male ratio was already around 2:1 at the age of 18 and rose to 2.5:1 in mid-life and declined to 1 at around 55. The almost parallel decline of depression rates in employed men and women resulted in a female/male ratio of about 2:1 from age 18 to age 50 and became 1 after the age of 60. The female/male ratio among the not employed was about 1, in mid-life it became negative. CONCLUSIONS: Our analyses show that the gender-gap in first admitted depressed patients is age dependent and that psychosocial factors modify the sex ratio

Paracrine cellular senescence exacerbates biliary injury and impairs regeneration

Senescence has been suggested as causing biliary cholangiopathies but how this is regulated is unclear. Here, the authors generate a mouse model of biliary senescence by deleting Mdm2 in bile ducts and show that inhibiting TGFβ limits senescence-dependent aggravation of cholangiopathies

Nutrition, Diabetes and Tuberculosis in the Epidemiological Transition

BACKGROUND: Diabetes prevalence and body mass index reflect the nutritional profile of populations but have opposing effects on tuberculosis risk. Interactions between diabetes and BMI could help or hinder TB control in growing, aging, urbanizing populations. METHODS AND FINDINGS: We compiled data describing temporal changes in BMI, diabetes prevalence and population age structure in rural and urban areas for men and women in countries with high (India) and low (Rep. Korea) TB burdens. Using published data on the risks of TB associated with these factors, we calculated expected changes in TB incidence between 1998 and 2008. In India, TB incidence cases would have increased (28% from 1.7 m to 2.1 m) faster than population size (22%) because of adverse effects of aging, urbanization, changing BMI and rising diabetes prevalence, generating an increase in TB incidence per capita of 5.5% in 10 years. In India, general nutritional improvements were offset by a fall in BMI among the majority of men who live in rural areas. The growing prevalence of diabetes in India increased the annual number of TB cases in people with diabetes by 46% between 1998 and 2008. In Korea, by contrast, the number of TB cases increased more slowly (6.1% from 40,200 to 42,800) than population size (14%) because of positive effects of urbanization, increasing BMI and falling diabetes prevalence. Consequently, TB incidence per capita fell by 7.8% in 10 years. Rapid population aging was the most significant adverse effect in Korea. CONCLUSIONS: Nutritional and demographic changes had stronger adverse effects on TB in high-incidence India than in lower-incidence Korea. The unfavourable effects in both countries can be overcome by early drug treatment but, if left unchecked, could lead to an accelerating rise in TB incidence. The prevention and management of risk factors for TB would reinforce TB control by chemotherapy

Rapid HIV testing program implementation: lessons from the emergency department

Background: The US Centers for Disease Control and Prevention (CDC) guidelines and the World Health Organization (WHO) both recommend HIV testing in health-care settings. However, neither organization provides prescriptive details regarding how these recommendations should be adapted into clinical practice in an emergency department. Methods: We have implemented an HIV-testing program in the ED of a major academic medical center within the scope of the Universal Screening for HIV Infection in the Emergency Room (USHER) Trial—a randomized clinical trial evaluating the feasibility and cost-effectiveness of HIV screening in this setting. Results and conclusion: Drawing on our collective experiences in establishing programs domestically and internationally, we offer a practical framework of lessons learned so that others poised to embark on such HIV testing programs may benefit from our experiences

Low prevalence of H. pylori Infection in HIV-Positive Patients in the Northeast of Brazil

<p>Abstract</p> <p>Background</p> <p>This study conducted in Northeastern Brazil, evaluated the prevalence of <it>H. pylori </it>infection and the presence of gastritis in HIV-infected patients.</p> <p>Methods</p> <p>There were included 113 HIV-positive and 141 age-matched HIV-negative patients, who underwent upper gastrointestinal endoscopy for dyspeptic symptoms. <it>H. pylori </it>status was evaluated by urease test and histology.</p> <p>Results</p> <p>The prevalence of <it>H. pylori </it>infection was significantly lower (p < 0.001) in HIV-infected (37.2%) than in uninfected (75.2%) patients. There were no significant differences between <it>H. pylori </it>status and gender, age, HIV viral load, antiretroviral therapy and the use of antibiotics. A lower prevalence of <it>H. pylori </it>was observed among patients with T CD4 cell count below 200/mm³; however, it was not significant. Chronic active antral gastritis was observed in 87.6% of the HIV-infected patients and in 780.4% of the control group (p = 0.11). <it>H. pylori </it>infection was significantly associated with chronic active gastritis in the antrum in both groups, but it was not associated with corpus chronic active gastritis in the HIV-infected patients.</p> <p>Conclusion</p> <p>We demonstrated that the prevalence of <it>H. pylori </it>was significantly lower in HIV-positive patients compared with HIV-negative ones. However, corpus gastritis was frequently observed in the HIV-positive patients, pointing to different mechanisms than <it>H. pylori </it>infection in the genesis of the lesion.</p

Evaluation of invasive and non-invasive methods for the diagnosis of Helicobacter pylori infection in symptomatic children and adolescents

CONTEXT: Multiple diagnostic methods are available for the detection of Helicobacter pylori infection, but at present no single one can be used as the gold standard. OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of 3 invasive and 2 non-invasive methods for detection of Helicobacter pylori infection in symptomatic children and adolescents. DESIGN: Prospective cohort study SETTING: Peptic Disease outpatients service, Discipline of Pediatric Gastroenterology, Universidade Federal de São Paulo (UNIFESP) / Escola Paulista de Medicina. PATIENTS: Forty-seven patients who underwent endoscopy because of dyspeptic symptoms. DIAGNOSTIC METHODS: Endoscopy with gastric biopsies for 3 invasive (rapid urease test, histology and culture) and 2 non-invasive methods (a commercial ELISA serology and 13carbon urea breath test - isotope ratio mass spectrometry) for detection of Helicobacter pylori infection. MAIN MEASUREMENTS: Sensitivity, specificity, positive and negative predictive values of each method and agreement and disagreement rates between the methods. RESULTS: Forty-seven patients [mean age, 11y9mo (SD 2y10mo), 27 female and 20 male]; 62% of them were Helicobacter pylori-positive. All methods agreed in 61%, and were negative in 21% and positive in 40%. The greatest concordance between 2 methods occurred between the invasive methods: histology and rapid urease test (89.6%) and histology and culture (87.5%). The greatest sensitivity, considering Helicobacter pylori-positive cases, for any combination of 3 or more tests, was achieved by the rapid urease test (S=100%), followed by histology, serology and 13carbon-urea breath test (S=93.1%) and lastly by culture (S=79.3%). The highest specificity was obtained by histology (100%) and culture (100%), followed by the rapid urease test (84.2%), serology (78.9%) and 13carbon-urea breath test (78.9%). CONCLUSIONS: Our results suggest that among invasive methods, an association between the rapid urease test and histology constituted the best choice for the detection of Helicobacter pylori infection. If results of histology and the rapid urease test are different, serology may be recommended.CONTEXTO: Vários métodos diagnósticos estão disponíveis para a detecção da infecção por Helicobacter pylori (Hp), porém, até o presente momento, não há um teste que possa ser utilizado isoladamente como padrão-ouro. OBJETIVO: Avaliar a acurácia de três métodos invasivos e dois não-invasivos na detecção da infecção por Hp em crianças e adolescentes sintomáticos. TIPO DE ESTUDO: Estudo coorte prospectivo. LOCAL: Ambulatório de Doença Péptica, Disciplina de Gastroenterologia Pediátrica, Universidade Federal de São Paulo (UNIFESP) / Escola Paulista de Medicina. PACIENTES: 47 pacientes sintomáticos que realizaram exame endoscópico devido a sintomas dispépticos. MÉTODOS DIAGNÓSTICOS: Exame endoscópico com biopsias gástricas para três métodos invasivos (teste rápido da urease, histologia e cultura) e dois métodos não-invasivos (teste sorológico ELISA industrializado e teste respiratório com uréia marcada com Carbono13). VARIÁVEIS ESTUDADAS: Sensibilidade, especificidade, valor preditivo positivo e negativo de cada método e taxas de concordância e discordância entre os métodos. RESULTADOS: 47 pacientes [idade média de 11a9m (DP 2a10m), 27 do sexo feminino e 20 do masculino], 62% deles com infecção por Hp. Todos os 5 métodos concordaram em 61%, sendo negativo em 21% e positivo em 40%. As maiores concordâncias entre dois métodos ocorreram entre os métodos invasivos: histologia e teste rápido da urease (89,6%) e entre a histologia e cultura (87,5%). A maior sensibilidade, considerando como Hp positivo, qualquer combinação de 3 ou mais testes, foi encontrada no teste rápido da urease (S=100%), seguido pela histologia, sorologia e o teste respiratório com uréia marcada com Carbono13 (S=93,1%) e por fim a cultura (S=79,3%). A maior especificidade foi obtida pela histologia e cultura (100%), seguidos pelo teste rápido da urease (84,2%), sorologia (78,9%) e teste respiratório com uréia marcada com Carbono13 (78,9%). CONCLUSÕES: Nossos resultados sugerem que, entre os métodos invasivos, a associação do teste rápido da urease e histologia constituem a melhor escolha para a detecção da infecção por Hp. Se os resultados da histologia e do teste rápido da urease forem discordantes é recomendada a sorologia.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Pediatric DepartmentUNIFESP, EPM, Pediatric DepartmentSciEL

The interplay between structure and agency in shaping the mental health consequences of job loss

Main themes that emerged from the qualitative exploration of the psychological distress of job loss included stress, changes to perceived control, loss of self-esteem, shame and loss of status, experiencing a grieving process, and financial strain. Drawing on two models of agency we identified the different ways workers employed their agency, and how their agency was enabled, but mainly constrained, when dealing with job loss consequences. Respondents’ accounts support the literature on the moderating effects of economic resources such as redundancy packages. The results suggest the need for policies to put more focus on social, emotional and financial investment to mediate the structural constraints of job loss. Our study also suggests that human agency must be understood within an individual’s whole of life circumstances, including structural and material constraints, and the personal or interior factors that shape these circumstances.The authors acknowledge support from the National Health and Medical Research Council Capacity Building Grant (324724). The research was supported by the SA Department of Health and the SA Department of Families and Communities through the Human Services Research and Innovation Program (HSRIP), and the Australian Research Council Linkage Program (LP0562288), with the Department of Health (DOH) serving as Industry Partner. Professor Fran Baum was supported by an ARC Federation Fellowship and Drs Newman and Ziersch by the SA Premier’s Science and Research Fund

Ginger Stimulates Hematopoiesis via Bmp Pathway in Zebrafish

) has been widely used in traditional medicine; however, to date there is no scientific research documenting the potential of ginger to stimulate hematopoiesis. expression in the caudal hematopoietic tissue area. We further confirmed that Bmp/Smad pathway mediates this hematopoiesis promoting effect of ginger by using the Bmp-activated Bmp type I receptor kinase inhibitors dorsomorphin, LND193189 and DMH1.Our study provides a strong foundation to further evaluate the molecular mechanism of ginger and its bioactive components during hematopoiesis and to investigate their effects in adults. Our results will provide the basis for future research into the effect of ginger during mammalian hematopoiesis to develop novel erythropoiesis promoting agents