Effects of dietary broccoli on human in vivo drug metabolizing enzymes: evaluation of caffeine, oestrone and chlorzoxazone metabolism

Ingestion of cruciferous vegetables may prevent chemically inducedcarcinogenesis by their influence on specific cytochrome P450enzymes (CYP) and phase II drug metabolizing enzymes in humansand rodents. Thus CYP enzymes are involved in transformationof procarcinogens, mutagens, steroid hormones and a large varietyof other endogenous and exogenous components. In order to learnmore about the influence of cruciferous vegetables on drug metabolizingenzymes in man two CYP enzymespreviously suggested to be inducedby vegetables were selected in an in vivo experiment in humans.Sixteen healthy non-smoking subjects, two females and 14 males,were exposed to three different types of diets and afterwardsassayed for CYP1A2 catalysed caffeine metabolites and for CYP2E1catalysed 6-hydroxylation of chlorzoxazone. Further, 2-hydroxyoestrone:16     

Association analyses suggest GPR24 as a shared susceptibility gene for bipolar affective disorder and schizophrenia.

Linkage analyses suggest that chromosome 22q12-13 may harbor a shared susceptibility locus for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of a sample from the Faeroe Islands we have previously reported association between both disorders and microsatellite markers in a 3.6 cM segment on 22q13. The present study investigated three candidate genes located in this segment: GPR24, ADSL, and ST13. Nine SNPs located in these genes and one microsatellite marker (D22S279) were applied in an association analysis of two samples: an extension of the previously analyzed Faeroese sample comprising 28 distantly related cases (17 BPD, 11 SZ subjects) and 44 controls, and a Scottish sample including 162 patients with BPD, 103 with SZ, and 200 controls. In both samples significant associations were observed in both disorders with predominantly GPR24 SNPs and haplotypes. In the Faeroese sample overall P-values of 0.0009, 0.0054, and 0.0023 were found for haplotypes in BPD, SZ, and combined cases, respectively, and in the Scottish sample overall P-values of 0.0003, 0.0005, and 0.016 were observed for similar groupings. Specific haplotypes showed associations with lowest P-values of 7 x 10(-5) and 0.0006 in the combined group of cases from the Faeroe Islands and Scotland, respectively. The G protein-coupled receptor 24 encoded by GPR24 binds melanin-concentrating hormone (MCH) and has been implicated with feeding behavior, energy metabolism, and regulation of stress and mood. To our knowledge this is the first study reporting association between GPR24 and BPD and SZ, suggesting that GPR24 variants may confer susceptibility to both disorders.     

Tympanometry in three-year-old children. I. A regional prevalence study on the distribution of tympanometric results in a non-selected population of 3-year-old children

Epidemiological data on middle-ear pathology during pre-school age are lacking the striking frequency of middle-ear symptoms in this age group. To evaluate the applicability of the impedance test in the younger age groups and to make an epidemiological study of the distribution of tympanogram types in a normal group of pre-school children, an attempt was made to examine all 523 3-year-olds in a limited geographic area. 1005 ears in 504 children (96.4% of those invited) were fully investigated with tympanometry and otoscopy with Siegle's speculum within 4 weeks. 62.8% of the ears showed type A tympanometric curves, 9.8% type B and 27.4% type C. Bilateral type A tympanometric curves were found in 276 children (55.4%). The prevalence of abnormal tympanometry proved to be unexpectedly high in both sexes. This finding is discussed. Even with the use of conventional technique and standard equipment, the 3-year-old clientele presented no testing problems.     

Improving Asthma Control through Asthma Action Plans: A Quality Improvement Project at a Midwest Community Clinic

This urban community clinic had poor asthma outcomes compared to the state of Minnesota. The standard of care supports an annual Asthma Action Plan (AAP). However, the majority of patients at this clinic had not received one. This quality improvement project aimed to improve asthma control, measured by an asthma control test of at least 20, through AAP implementation supported by all team members. The clinic’s interdisciplinary champion group implemented workflow changes via practice facilitation and Plan-Do-Study-Act cycles. Asthma control rates increased from 23% to 58% in adults and 45% to 63% in children over one year, a statistically significant change.     

Midwife and Doula Information on the Web: An Analysis of Websites that Provide Information About Pregnancy and Childbirth

This study analyzed midwife and doula information on pregnancy and childbirth websites originating in the U.S. A two-fold sampling process of top Google search results and purposive sampling of pregnancy and childbirth websites was used. Most websites published articles about midwives and doulas making it relatively easy to find information if one were to search, but not necessarily if browsing commonly used websites. Themes on the websites’ scant discussion forums evidenced readers’ interest in midwife and doula services. Findings reveal a need to make discussion forums and midwife and doula services more accessible on pregnancy and childbirth websites.     

Impact of gender on the risk of AIDS-defining illnesses and mortality in Danish HIV-1-infected patients: A nationwide cohort study

Abstract Background: Gender differences in the risk of AIDS-defining illness (ADI) and mortality have been reported in the HIV-1-infected (HIV-positive) population, with conflicting findings. We aimed to assess the impact of gender on the risk of ADI and death in HIV-positive patients infected sexually. Methods: This was a population-based, nationwide cohort study of incident Danish HIV-positive individuals infected by sexual contact. Outcomes were progression to AIDS and death. We used Cox proportional hazards models and Poisson regression analyses to calculate the risk of progression to AIDS and mortality rate ratios (MRR) between risk groups and compared these with the general Danish population. Results: We identified 587 heterosexually infected women, 583 men who have sex with women (MSW), and 1089 men who have sex with men (MSM). The total follow-up time was 13,708 person-y. At the time of HIV diagnosis MSM had a lower prevalence of AIDS compared to MSW. Women and MSW presented more often with tuberculosis and less often with AIDS-defining cancers compared to MSM. In the adjusted analyses we observed no differences in progression to AIDS. In the adjusted analyses of risk of death, there were no differences between the 3 risk groups, although we saw a trend towards a higher risk of death in older MSW. MSM had a lower risk of death compared to the background population than women and MSW. Conclusions: In the Danish HIV population, gender has no major impact on progression to AIDS or mortality. Differences in these factors between women, MSW, and MSM are mainly due to confounding from race and CD4 + cell count at diagnosis.     

Life-Time Adversities,Reported Thirteen Years After a Suicide Attempt: Relationship to Recovery, 5HTTLPR Genotype,and Past and Present Morbidity

In this study, we investigated how adversities related to past and present morbidity, and genotype. Forty-two, suicide attempters and 22 matched control patients were followed-up after 13 years. Life-time adversities were explored in an interview, and the patients were reassessed psychiatrically. The serotonin-transporter-linked promotor region (5-HTTLPR) was typed. More adversities were reported by suicide attempters than controls, and by still-ill than recovered suicide attempters. Adversities reported at follow-up were related to psychiatric morbidity at follow-up, but not to morbidity 13 years earlier. The 5-HTTLPR, genotype was associated with reported adversities, but not chances of recovery. Adversities potentially affected chronic morbidity. 5-HTTLPR genotype did not affect long-term recovery.     

Hypophosphorylated TCR/CD3zeta signals through a Grb2-SOS1-Ras pathway in Lck knockdown cells

Despite the loss of proximal TCR-dependent signaling events, downstream T cell responses are paradoxically augmented in T cells with siRNA-mediated Lck knockdown (Methi et al., J. Immunol. 2005. 175: 7398-7406). This indicates that alternative Lck-independent pathways of T cell activation exist or that low levels of Lck elicit other signals than normal T cell activation. Here we report the recruitment of Grb2-SOS1 to CD3zeta of the TCR complex after prolonged anti-CD3 (OKT3) stimulation in T cells with Lck knockdown. Grb2 bound to incompletely phosphorylated ITAM1 with the pY-Y configuration in a solid-phase assay, but was excluded by ZAP-70 in the doubly phosphorylated pY-pY conformation. Ras and ERK1/2 activation was augmented after prolonged stimulation in T cells with Lck knockdown compared to control, leading to increased activation of the proximal IL-2 promoter (NFAT-AP-1). Finally, the phosphorylation of Ras-GAP was strongly suppressed in Lck knockdown cells, indicating that a Ras negative feedback mechanism is dependent on Lck.