The gene encoding the immunoregulatory signaling molecule CMRF-35A localized to human chromosome 17 in close proximity to other members of the CMRF-35 family

The immunoregulatory signaling (IRS) family includes several molecules, which play major roles in the regulation of the immune response. The CMRF-35A and CMRF-35H molecules are two new members of the IRS family of molecules, that are found on a wide variety of haemopoietic lineages. The extracellular functional interactions of these molecules is presently unknown, although CMRF-35H on initiate an inhibitory signal and is internalized when cross-linked. In this paper, we described the gene structure for the CMRF-35A gene and its localization to human chromosome 17. The gene consists of four exons spanning approximately 4.5 kb. Exon 1 encodes the 5' untranslated region and leader sequence, exon 2 encodes the immunoglobulin (Ig)-like domain, exon 3 encodes the membrane proximal region and exon 4 encodes the transmembrane region, the cytoplasmic tail and the 3' untranslated region. A region in the 5' flanking sequence of the CMRF-35A gene, that promoted expression of a reporter gene was identified. The genes for the CMRF-35A and CMRF-35H molecules are closely linked on chromosome 17. Similarity between the Ig-like exons and the preceding intron of the two genes suggests exon duplication was involved in their evolution. We also identified a further member of the CMRF-35 family, the CMRF-35J pseudogene. This gene appears to have arisen by gene duplication of the CMRF-35A gene. These three loci-the CMRF-35A, CMRF-35J and CMRF-35H genes-form a new complex of IRS genes on chromosome 17.

Making decisions about treatment for localized prostate cancer

Objective To describe the decision-making processes used by men diagnosed with localized prostate cancer who were considering treatment. Patients and methods Men newly diagnosed with localized prostate cancer from outpatient urology clinics and urologist's private practices were approached before treatment. Their decision-making processes and information-seeking behaviour was assessed; demographic information was also obtained. Results Of 119 men approached, 108 (90%) were interviewed; 91% reported non-systematic decision processes, with deferral to the doctor, positive and negative recollections of others' cancer experiences, and the pre-existing belief that surgery is a better cancer treatment being most common. For systematic information processing the mean (SD, range) number of items considered was 4.19 (2.28, 0-11), with 57% of men considering four or fewer treatment/medical aspects of prostate cancer. Men most commonly considered cancer stage (59%), urinary incontinence (55%) and impotence (51%) after surgery, and low overall mortality (45%). Uncertainty about probabilities for cure was reported by 43% of men and fear of cancer spread by 37%. Men also described uncertainty about the probabilities of side-effects (27%), decisional uncertainty (25%) and anticipated decisional regret (18%). Overall, 73% of men sought information about prostate cancer from external sources, most commonly the Internet, followed by family and friends. Conclusions In general, men did not use information about medical treatments comprehensively or systematically when making treatment decisions, and their processing of medical information was biased by their previous beliefs about cancer and health. These findings have implications for the provision of informational and decisional support to men considering prostate cancer treatment.

Genetic characterization of pilin glycosylation and phase variation in Neisseria meningitidis

Pili of Neisseria meningitidis are a key virulence factor, being the major adhesin of this capsulate organism and contributing to specificity for the human host. Pili are post-translationally modified by addition of either an O-linked trisaccharide, Gal (beta1-4) Gal (alpha1-3) 2,4-diacetamido-2,4,6-trideoxyhexose or an O-linked disaccharide Gal (alpha1,3) GlcNAc. The role of these structures in meningococcal pathogenesis has not been resolved. In previous studies we identified two separate genetic loci, pglA and pglBCD, involved in pilin glycosylation. Putative functions have been allocated to these genes; however, there are not enough genes to account for the complete biosynthesis of the described structures, suggesting additional genes remain to be identified. In addition, it is not known why some strains express the trisaccharide structure and some the disaccharide structure. In order to find additional genes involved in the biosynthesis. of these structures, we used the recently published group A strain Z2491 and group B strain MC58 Neisseria meningitidis genomes and the unfinished Neisseria meningitidis group C strain FAM18 and Neisseria gonorrhoeae strain FA1090 genomes to identify novel genes involved in pilin glycosylation, based on homology to known oligosaccharide biosynthetic genes. We identified a new gene involved in pilin glycosylation designated pglE and examined four additional genes pgIB/B2, pglF, pglG and pglH. A strain survey revealed that pglE and pglF were present in each strain examined. The pglG, pglH and pgIB2 polymorphisms were not found in strain C311#3 but were present in a large number of clinical isolates. Insertional mutations were constructed in pglE and pglF in N. meningitidis strain C311#3, a strain with well-defined lipopolysaccharide (LPS) and pilin-linked glycan structures. Increased gel migration of the pilin subunit molecules of pglE and pglF mutants was observed by Western analysis, indicating truncation of the trisaccharide structure. Antisera specific for the C311#3 trisaccharide failed to react with pilin from these pglE and pglF mutants. GC-MS analysis of the sugar composition of the pglE mutant showed a reduction in galactose compared with C311#3 wild type. Analysis of amino acid sequence homologies has suggested specific roles for pglE and pglF in the biosynthesis of the trisaccharide structure. Further, we present evidence that pglE, which contains heptanucleotide repeats, is responsible for the phase variation between trisaccharide and disaccharide structures in strain C311#3 and other strains. We also present evidence that pglG, pglH and pgIB2 are potentially phase variable.

Psicopatia e traços da personalidade em estudantes universitários

RESUMO: No presente estudo é investigada a existência de relações entre a psicopatia e os traços de personalidade em estudantes universitários. Este estudo tem como objectivo o estabelecimento de correlações entre os traços psicopáticos e as dimensões da personalidade decorrentes do Modelo dos Cinco Factores em estudantes universitários. A amostra é constituída por 400 estudantes universitários, provenientes de várias universidades da zona de Lisboa, de vários cursos universitários e de ambos os sexos, de forma aleatória. As idades dos sujeitos constituintes da amostra estão compreendidas entre os 17 e os 46 anos de idade (M = 24,26 e DP = 4,435). Por forma a atingir o objectivo proposto para este estudo, recorreu-se à aplicação de um questionário sócio-demográfico e de três medidas de avaliação, nomeadamente: a Escala PDS (Paulhus Deception Scale) de Delroy L. Paulhus, Ph.D. (1998), a Escala LSRP (Levenson Self-Report Psychopathy Scale) de Levenson, Kiehl e Fitzpatrick (1995) e o Inventário NEO-PI-R (Inventário de Personalidade NEO Revisto) de Costa e McCrae (1992), sendo que existe a aferição desta medida de avaliação para a população portuguesa dos autores Lima e Simões (1997). De acordo com os resultados obtidos, podemos constatar que existem associações significativas entre as dimensões da Personalidade e as dimensões da Psicopatia. Verificou-se que os indivíduos que possuem índices elevados de Neuroticismo e baixos indíces de Extroversão e Abertura à Experiência possuem uma maior propensão para apresentarem características psicopáticas. Por outro lado, também se constatou que os indivíduos que possuem baixos índices de Amabilidade e Conscienciosidade apresentam também uma maior probabilidade de possuírem características psicopáticas. ABSTRACT: In the present study, it is investigated the existence of relationships between psychopathy and personality traits in university students. The goal of this study is the establishment of correlations between psychopathic traits and the personality dimensions, recurring from the five factor model in university students. The sample is composed by 400 university students, from various universities in the Lisbon area, from different courses and from both genders, randomly picked. The ages of the subjects in the sample are in between 17 and 46 years old (M = 24,26 and SD = 4,435). By means of reaching the goal proposed for this study, there were applied a socio-demographic questionnaire and three evaluation measures, namely the PDS Scale (Paulhus Deception Scale) from Delroy L. Paulhus, Ph.D. (1998), the LSRP Scale (Levenson Self-Report Psychopathy Scale) from Levenson, Kiehl e Fitzpatrick (1995) and the NEO-PI-R Inventory (Revised NEO Personality Inventory) from de Costa e McCrae (1992), as there is an admeasurement from this measure for the portuguese population from authors Lima e Simões (1997). Considering the obtained results, we can state that there exist significant associations between the Personality dimensions and the Psychopathy dimensions. It was verified that the individuals that possess high indexes of Neuroticism and low indexes of Extroversion and Openness, have a higher propensity to present psychopathic characteristics. On the other hand, it was also found that the individuals that possess low indexes of Lovability and Consciousness also present a higher probability of having psychopathic characteristics.

Risk factors for basal cell carcinoma: a case-control study

A controlled trial was performed with the purpose of investigating which factors could be considered of significant risk for the development of basal cell carcinoma. A total of 259 cases of basal cell carcinoma diagnosed from July 1991 to July 1992 were compared with 518 controls matched for age and sex. All subjects in both groups were white. Protocol data were submitted to statistical analysis by the chi-square test and by multiple conditional logistic regression analysis and the following conclusions were reached: 1) light skin color (types I and II of the Fitzpatrick classification), odds ratio of 2.8; outdoor work under constant sunlight, odds ratio of 5.0; the presence of actinic lesions due to exposure to the sun, odds ratio of 4.9, are risk factors perse. 2) Type III skin in the Fitzpatrick classification only represents a risk factor when the patient reports a history of intense sunburns, but not in the absence of such a history. 3) Sunburns per se do not represent a risk factor althorig the point made in item 2 of these conclusions is valid. 4) Other suspected risk factors whose significance was not confirmed by multiple conditioned logistic regression analysis were: residence in rural areas, light eyes and blond hair color, extent of the awareness of the "sun x skin cancer" relationship, familial occurrence of skin cancer, excessive exposure to the sun, and freckles appearing in childhood.

Depressão e ansiedade em adolescentes de escolas públicas e privadas

OBJETIVO: Identificar prevalência de depressão e de ansiedade em adolescentes matriculados e freqüentando escolas públicas e privadas da cidade do Recife - Pernambuco. MÉTODOS: Por meio de estudo de prevalência, de base populacional, admitindo população de 10.414 alunos das redes pública e privada, prevalência de depressão e transtornos depressivos de 20,3%, precisão de 5% e nível de significância de 0,05, a amostragem aleatória e estratificada incluiu 243 alunos, do ensino fundamental e médio de 11 escolas, com idade de 14 a 16 anos. As variáveis foram: idade, religião, tipo, adscrição e porte da escola, escolaridade, tempo de estudo, condição estudantil e laboral, características do núcleo familiar, sexo, estado civil, tipo de pele segundo escala de Fitzpatrick (investigadas por questionário demográfico) e grau de depressão e de ansiedade pelas escalas de Hamilton. Para análise estatística, empregou-se programa Statistical Package for Social Sciences. RESULTADOS: As prevalências de sintomas depressivos expressivos e de ansiedade igualaram-se a 59,9% e 19,9%, respectivamente. Foram significativas as associações de sintomas depressivos de intensidade grave com o sexo feminino e a crença religiosa diferentes da corrente do cristianismo. A ideação suicida/tentativa de suicídio foi referida por 34,3% dos estudantes. Houve associação significativa de ideação suicida com grau leve ou moderado de sintomas depressivos e moderado de ansiedade, assim como de tentativa de suicídio com sintomas depressivos graves, estudo em escola privada e ansiedade severa. CONCLUSÕES: A gravidade das características psicopatológicas em uma idade tão jovem está a merecer uma intervenção psicossocial para reduzir suas repercussões para o futuro.

Can Early Intervention Policies Improve Well-being? Evidence from a randomized controlled trial

Many authors have proposed incorporating measures of well-being into evaluations of public policy. Yet few evaluations use experimental design or examine multiple aspects of well-being, thus the causal impact of public policies on well-being is largely unknown. In this paper we examine the effect of an intensive early intervention program on maternal well-being in a targeted disadvantaged community. Using a randomized controlled trial design we estimate and compare treatment effects on global well-being using measures of life satisfaction, experienced well-being using both the Day Reconstruction Method (DRM) and a measure of mood yesterday, and also a standardized measure of parenting stress. The intervention has no significant impact on negative measures of well-being, such as experienced negative affect as measured by the DRM and global measures of well-being such as life satisfaction or a global measure of parenting stress. Significant treatment effects are observed on experienced measures of positive affect using the DRM, and a measure of mood yesterday. The DRM treatment effects are primarily concentrated during times spent without the target child which may reflect the increased effort and burden associated with additional parental investment. Our findings suggest that a maternal-focused intervention may produce meaningful improvements in experienced well-being. Incorporating measures of experienced affect may thus alter cost-benefit calculations for public policies.

Commissioning for equity. Inequalities in access to revascularisation in the NHS and in the independent sector. A technical report

This document describes the methodology for examining inequalities in access to revascularisation in the NHS and in the independent sector. It is a technical report.

Commissioning for equity. Stop gaps: equity of access to London's stop smoking services

This briefing looks at who is making use of NHS stop smoking services in the London area.

Health Inequalities Intervention Toolkit

This Health Inequalities Intervention Toolkit, developed jointly by the Association of Public Health Observatories and the Department of Health, focuses on improving life expectancy and infant mortality rates, especially in disadvantaged areas. Based on local authority boundaries, it is designed to assist evidence-based local service planning and commissioning, including Joint Strategic Needs Assessments. The Toolkit does this by providing information on the diseases, which are causing low life expectancy in individual areas, enabling good local priority setting. The Toolkit was originally designed to support achievement of the national Public Service Agreement target to: "Reduce health inequalities by 10% by 2010 as measured by infant mortality and life expectancy at birth." Although the PSA target has now ended, the Toolkit should still be useful to the NHS and local government, supporting planning to narrow inequalities in life expectancy and infant mortality

Mapping health inequalities across London

Analysis of infant mortality and life expectancy across London by various dimensions of inequality- socioeconomic; gender; geographical, and trends

Indications of public health in the English regions - 4: Ethnicity and health

Part 4 of the Indications of Public Health for England. This report focuses on race equality and inequality terms of health and health care between ethnic groups in England. A separate Executive Summary is available (it is included in this full version of the report).

A male with unilateral microphthalmia reveals a role for TMX3 in eye development.

Anophthalmia and microphthalmia are important birth defects, but their pathogenesis remains incompletely understood. We studied a patient with severe unilateral microphthalmia who had a 2.7 Mb deletion at chromosome 18q22.1 that was inherited from his mother. In-situ hybridization showed that one of the deleted genes, TMX3, was expressed in the retinal neuroepithelium and lens epithelium in the developing murine eye. We re-sequenced TMX3 in 162 patients with anophthalmia or microphthalmia, and found two missense substitutions in unrelated patients: c.116G>A, predicting p.Arg39Gln, in a male with unilateral microphthalmia and retinal coloboma, and c.322G>A, predicting p.Asp108Asn, in a female with unilateral microphthalmia and severe micrognathia. We used two antisense morpholinos targeted against the zebrafish TMX3 orthologue, zgc:110025, to examine the effects of reduced gene expression in eye development. We noted that the morphant larvae resulting from both morpholinos had significantly smaller eye sizes and reduced labeling with islet-1 antibody directed against retinal ganglion cells at 2 days post fertilization. Co-injection of human wild type TMX3 mRNA rescued the small eye phenotype obtained with both morpholinos, whereas co-injection of human TMX3(p.Arg39Gln) mutant mRNA, analogous to the mutation in the patient with microphthalmia and coloboma, did not rescue the small eye phenotype. Our results show that haploinsufficiency for TMX3 results in a small eye phenotype and represents a novel genetic cause of microphthalmia and coloboma. Future experiments to determine if other thioredoxins are important in eye morphogenesis and to clarify the mechanism of function of TMX3 in eye development are warranted.

International variation in management of screen-detected ductal carcinoma in situ of the breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) incidence has grown with the implementation of screening and its detection varies across International Cancer Screening Network (ICSN) countries. The aim of this survey is to describe the management of screen-detected DCIS in ICSN countries and to evaluate the potential for treatment related morbidity. METHODS: We sought screen-detected DCIS data from the ICSN countries identified during 2004-2008. We adopted standardised data collection forms and analysis and explored DCIS diagnosis and treatment processes ranging from pre-operative diagnosis to type of surgery and radiotherapy. RESULTS: Twelve countries contributed data from a total of 15 screening programmes, all from Europe except the United States of America and Japan. Among women aged 50-69years, 7,176,050 screening tests and 5324 screen-detected DCIS were reported. From 21% to 93% of DCIS had a pre-operative diagnosis (PO); 67-90% of DCIS received breast conservation surgery (BCS), and in 41-100% of the cases this was followed by radiotherapy; 6.4-59% received sentinel lymph node biopsy (SLNB) only and 0.8-49% axillary dissection (ALND) with 0.6% (range by programmes 0-8.1%) being node positive. Among BCS patients 35% received SLNB only and 4.8% received ALND. Starting in 2006, PO and SLNB use increased while ALND remained stable. SLNB and ALND were associated with larger size and higher grade DCIS lesions. CONCLUSIONS: Variation in DCIS management among screened women is wide and includes lymph node surgery beyond what is currently recommended. This indicates the presence of varying levels of overtreatment and the potential for its reduction.