Shaping mental health services in the community for refugees and elective migrants from former Yugoslavia

Background Although limited research has been conducted among displaced people it is clear mental health problems are more prevalent than among the general population. To plan services for current and future migrants it is important to establish whether differences in reasons for migration impact on the extent of mental health problems. Null Hypothesis The main hypothesis for this thesis is that there is no significant difference in the prevalence of common mental disorders in refugees compared to elective migrants. Methods A mixed-method research study is conducted in sequential order where a qualitative study gathered detailed and in-depth information to inform the design of a questionnaire employed in a historical cohort study. Findings Refugees are three times more likely to develop CMD than elective migrants (OR 3.0; 95% CI 1.5-6.1) but there is no difference in the severity of the illnesses. Multivariate analyses suggest that factors such as being a refugee and a female (OR 12, 95%CI 1.14 - 123.92), dissatisfaction with current employment (OR 5.56, 95%CI 1.72 - 17.92), dissatisfaction with living conditions 3.53 (1.11 - 11.21) and waiting for longer than a year for a Home Office decision on permission to remain in the United Kingdom 3.27 (1.37 - 7.77) were independent predictors for the common mental disorders among migrants to England from former Yugoslavia. Conclusion Although this study demonstrated a higher long-term prevalence of common mental disorders in asylum seekers and refugees compared to elective migrants it is important to emphasise that many migrants do not have any psychological problems and are economically active making a positive contribution to their host country. However, it is also important to recognise that long-term common mental disorders may be underestimated in previous research among refugee population. It is essential to provide accessible services in primary care settings that are culturally specific and acceptable to this specific population group

Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs

Activation of naive CD8+ T cells with antigen induces their differentiation into effector cytolytic T lymphocytes (CTLs). CTLs lyse infected or aberrant target cells by exocytosis of lytic granules containing the pore-forming protein perforin and a family of proteases termed granzymes. We show that effector CTL differentiation occurs in two sequential phases in vitro, characterized by early induction of T-bet and late induction of Eomesodermin (Eomes), T-box transcription factors that regulate the early and late phases of interferon (IFN) γ expression, respectively. In addition, we demonstrate a critical role for the transcription factor Runx3 in CTL differentiation. Runx3 regulates Eomes expression as well as expression of three cardinal markers of the effector CTL program: IFN-γ, perforin, and granzyme B. Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs

Deaths from Norovirus among the Elderly, England and Wales

Norovirus may be associated with ≈80 deaths/year

Women with learning disabilities and access to cervical screening: retrospective cohort study using case control methods

<p>Abstract</p> <p>Background</p> <p>Several studies in the UK have suggested that women with learning disabilities may be less likely to receive cervical screening tests and a previous local study in had found that GPs considered screening unnecessary for women with learning disabilities. This study set out to ascertain whether women with learning disabilities are more likely to be ceased from a cervical screening programme than women without; and to examine the reasons given for ceasing women with learning disabilities. It was carried out in Bury, Heywood-and-Middleton and Rochdale.</p> <p>Methods</p> <p>Carried out using retrospective cohort study methods, women with learning disabilities were identified by Read code; and their cervical screening records were compared with the Call-and-Recall records of women without learning disabilities in order to examine their screening histories. Analysis was carried out using case-control methods – 1:2 (women with learning disabilities: women without learning disabilities), calculating odds ratios.</p> <p>Results</p> <p>267 women's records were compared with the records of 534 women without learning disabilities. Women with learning disabilities had an odds ratio (OR) of 0.48 (Confidence Interval (CI) 0.38 – 0.58; <it>X</it>²: 72.227; p.value <.001) of receiving a cervical screening test; an OR of 2.05 (CI 1.88 – 2.22; <it>X</it>²: 24.236; p.value <.001) of being ceased from screening; and an OR of 0.14 (CI 0.001 – 0.28; <it>X</it>²: 286.341; p.value <0.001 of being a non-responder compared to age and practice-matched women without learning disabilities.</p> <p>Conclusion</p> <p>The reasons given for ceasing and/or not screening suggest that merely being coded as having a learning disability is <b>not </b>the sole reason for these actions. There are training needs among smear takers regarding appropriate reasons not to screen and providing screening for women with learning disabilities.</p

Runx proteins regulate Foxp3 expression

Runx proteins are essential for hematopoiesis and play an important role in T cell development by regulating key target genes, such as CD4 and CD8 as well as lymphokine genes, during the specialization of naive CD4 T cells into distinct T helper subsets. In regulatory T (T reg) cells, the signature transcription factor Foxp3 interacts with and modulates the function of several other DNA binding proteins, including Runx family members, at the protein level. We show that Runx proteins also regulate the initiation and the maintenance of Foxp3 gene expression in CD4 T cells. Full-length Runx promoted the de novo expression of Foxp3 during inducible T reg cell differentiation, whereas the isolated dominant-negative Runt DNA binding domain antagonized de novo Foxp3 expression. Foxp3 expression in natural T reg cells remained dependent on Runx proteins and correlated with the binding of Runx/core-binding factor β to regulatory elements within the Foxp3 locus. Our data show that Runx and Foxp3 are components of a feed-forward loop in which Runx proteins contribute to the expression of Foxp3 and cooperate with Foxp3 proteins to regulate the expression of downstream target genes

Drug Resistance Rates of Mycobacterium tuberculosis at a Private Referral Center in Korea

The goals of this study were to identify first-line drug resistance in new and previously treated tuberculosis (TB) cases and to determine risk factors for multidrug-resistant TB (MDR-TB) at a private referral center in Korea. All patients with culture-confirmed pulmonary TB over a 2-yr period between July 2002 and June 2004 were prospectively included in this study. In total, 637 patients were included; 512 (80.4%) were new cases, and 125 (19.6%) were previously treated cases. Resistance to at least one first-line drug was identified in 11.7% of new cases and 41.6% of previously treated cases. MDR-TB was detected in 3.9% of new cases and 27.2% of previously treated cases. The proportion of extensively drug-resistant TB among MDR-TB patients was 16.7% (9/54). Factors associated with MDR-TB included age under 45 yr, previous TB treatment, and the presence of cavitation on chest radiography. Rates of first-line drug resistance are high, particularly in previously treated patients, in the private sector in Korea. This underscores the need for an improved control program, coupled with early diagnosis of MDR-TB, to reduce the spread and development of resistance

The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns

T-bet acts as a functional repressor in association with Bcl-6 to antagonize SOCS1, SOCS3, TCF-1, and late-stage IFN-γ to regulate Th1 development

Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3+ inducible regulatory T cells

Forkhead box P3 (FOXP3)+CD4+CD25+ inducible regulatory T (iT reg) cells play an important role in immune tolerance and homeostasis. In this study, we show that the transforming growth factor-β (TGF-β) induces the expression of the Runt-related transcription factors RUNX1 and RUNX3 in CD4+ T cells. This induction seems to be a prerequisite for the binding of RUNX1 and RUNX3 to three putative RUNX binding sites in the FOXP3 promoter. Inactivation of the gene encoding RUNX cofactor core-binding factor-β (CBFβ) in mice and small interfering RNA (siRNA)-mediated suppression of RUNX1 and RUNX3 in human T cells resulted in reduced expression of Foxp3. The in vivo conversion of naive CD4+ T cells into Foxp3+ iT reg cells was significantly decreased in adoptively transferred CbfbF/F CD4-cre naive T cells into Rag2−/− mice. Both RUNX1 and RUNX3 siRNA silenced human T reg cells and CbfbF/F CD4-cre mouse T reg cells showed diminished suppressive function in vitro. Circulating human CD4+ CD25high CD127− T reg cells significantly expressed higher levels of RUNX3, FOXP3, and TGF-β mRNA compared with CD4+CD25− cells. Furthermore, FOXP3 and RUNX3 were colocalized in human tonsil T reg cells. These data demonstrate Runx transcription factors as a molecular link in TGF-β–induced Foxp3 expression in iT reg cell differentiation and function

Stochastic Cytokine Expression Induces Mixed T Helper Cell States

During eukaryotic development, the induction of a lineage-specific transcription factor typically drives differentiation of multipotent progenitor cells, while repressing that of alternative lineages. This process is often mediated by some extracellular signaling molecules, such as cytokines that can bind to cell surface receptors, leading to activation and/or repression of transcription factors. We explored the early differentiation of naive CD4 T helper (Th) cells into Th1 versus Th2 states by counting single transcripts and quantifying immunofluorescence in individual cells. Contrary to mutually exclusive expression of antagonistic transcription factors, we observed their ubiquitous co-expression in individual cells at high levels that are distinct from basal-level co-expression during lineage priming. We observed that cytokines are expressed only in a small subpopulation of cells, independent from the expression of transcription factors in these single cells. This cell-to-cell variation in the cytokine expression during the early phase of T helper cell differentiation is significantly larger than in the fully differentiated state. Upon inhibition of cytokine signaling, we observed the classic mutual exclusion of antagonistic transcription factors, thus revealing a weak intracellular network otherwise overruled by the strong signals that emanate from extracellular cytokines. These results suggest that during the early differentiation process CD4 T cells acquire a mixed Th1/Th2 state, instructed by extracellular cytokines. The interplay between extracellular and intracellular signaling components unveiled in Th1/Th2 differentiation may be a common strategy for mammalian cells to buffer against noisy cytokine expression.National Cancer Institute (U.S.). Physical Sciences-Oncology Center (U54CA143874)National Institutes of Health (U.S.) (Pioneer Award)National Institutes of Health (U.S.) (Grant R01-GM068957