Post-genomic update on a classical candidate gene for coronary artery disease: ESR1.

BACKGROUND: After age, sex is the most important risk factor for coronary artery disease (CAD). The mechanism through which women are protected from CAD is still largely unknown, but the observed sex difference suggests the involvement of the reproductive steroid hormone signaling system. Genetic association studies of the gene-encoding Estrogen Receptor α (ESR1) have shown conflicting results, although only a limited range of variation in the gene has been investigated. METHODS AND RESULTS: We exploited information made available by advanced new methods and resources in complex disease genetics to revisit the question of ESR1's role in risk of CAD. We performed a meta-analysis of 14 genome-wide association studies (CARDIoGRAM discovery analysis, N=≈87,000) to search for population-wide and sex-specific associations between CAD risk and common genetic variants throughout the coding, noncoding, and flanking regions of ESR1. In addition to samples from the MIGen (N=≈6000), WTCCC (N=≈7400), and Framingham (N=≈3700) studies, we extended this search to a larger number of common and uncommon variants by imputation into a panel of haplotypes constructed using data from the 1000 Genomes Project. Despite the widespread expression of ERα in vascular tissues, we found no evidence for involvement of common or low-frequency genetic variation throughout the ESR1 gene in modifying risk of CAD, either in the general population or as a function of sex. CONCLUSIONS: We suggest that future research on the genetic basis of sex-related differences in CAD risk should initially prioritize other genes in the reproductive steroid hormone biosynthesis system.

The role of CTCFL/BORIS in Meiosis

The complexity of mammalian genome organization demands a complex interplay of DNA and proteins to orchestrate proper gene regulation. CTCF, a highly conserved, ubiquitously expressed protein has been postulated as a primary organizer of genome architecture because of its roles in transcriptional activation/repression, insulation and imprinting. Diverse regulatory functions are exerted through genome wide binding via a central eleven zinc finger DNA binding domain and an array of diverse protein-protein interactions through N- and C- terminal domains. CTCFL has been identified as a paralog of CTCF expressed only in spermatogenic cells of the testis. CTCF and CTCFL have a highly homologous DNA-binding domain, while the flanking amino acid sequences exhibit no significant similarity. Genome- wide mapping of CTCF binding sites has been carried out in many cell types, but no data exist for CTCFL apart from a few identified loci. The lack of high quality antibodies prompted us to generate an endogenously flag-tagged CTCFL mouse model using BAC recombination. IHC staining using anti-flag antibodies confirmed CTCFL localization to type Β spermatogonia and preleptotene spermatocytes and a mutually exclusive pattern of expression with CTCF. ChIP followed by high-throughput sequencing identified 10,382 binding sites showing 70% overlap but representing only 20% of CTCF sites. Consensus sequence analysis identified a significantly longer binding motif with prominently less ambiguity of base calling at every position. The significant difference between CTCF and CTCFL genomic binding patterns proposes that their binding to DNA is differentially regulated. Analysis of CTCFL binding to methylated regions on a genome wide scale identified approximately 1,000 loci. Methylation-independent binding of CTCFL might be at least one of the mechanisms that ensures distinct binding patterns of CTCF and CTCFL since CTCF binding is methylation- sensitive. Co-localization of CTCF with cohesin has been well established and analysis of CTCFL and SMC3 overlap identified around 3,300 binding sites from which two related but distinct consensus sequence motifs were derived. Because virtually all data for cohesin binding originate from mitotically proliferating cells, the anticipated overlap is expected to be considerably higher in meiotic cells. Meiosis-specific cohesin subunit Rec8 is specific for spermatocytes and 6 out of the 12 identified binding sites are also bound by CTCFL. In conclusion, this was the first genome-wide mapping of CTCFL binding sites in spermatocytes, the only cell type where CTCF is not expressed. CTCFL has a unique binding site repertoire distinct from CTCF, binds to methylated sequences and shows a significant overlap with cohesin binding sites. Future efforts will be oriented towards deciphering the role CTCFL plays in conversion of chromatin structure and function from mitotic to meiotic chromosomes. - La complexité de l'organisation du génome des mammifères exige une interaction particulière entre ADN et protéines pour orchestrer une régulation appropriée de l'expression des gènes. CTCFL, une protéine ubiquitaire très conservée, serait le principal organisateur de l'architecture du génome de par son rôle dans l'activation / la répression de la transcription, la protection et la localisation des gènes. Diverses régulations sont opérées, d'une part au travers d'interactions à différents endroits du génome par le biais d'un domaine protéique central de liaison à l'ADN à onze doigts de zinc, et d'autre part par des interactions protéine-protéine variées au niveau de leur domaine N- et C-terminal. CTCFL a été identifié comme un paralogue de CTCF exprimé uniquement dans les cellules spermatiques du testicule. CTCFL et CTCF ont un domaine de liaison à l'ADN très homologue, tandis que les séquences d'acides aminés situées de part et d'autre de ce domaine ne présentent aucune similitude. Une cartographie générale des sites de liaison au CTCF a été réalisée pour de nombreux types cellulaires, mais il n'existe aucune donnée pour CTCFL à l'exception de l'identification de quelques loci. L'absence d'anticorps de bonne qualité nous a conduit à générer un modèle murin portant un CTCFL endogène taggué grâce à un procédé de recombinaison BAC. Une coloration IHC à l'aide d'anticorps anti-FLAG a confirmé la présence de CTCFL au niveau des spermatogonies de type Β et des spermatocytes au stade préleptotène, et une distribution mutuellement exclusive avec CTCF. Une méthode de Chromatine Immunoprecipitation (ChIP) suivie d'un séquençage à haut débit a permis d'identifier 10.382 sites de liaison montrant 70% d'homologie mais ne représentant que 20% des sites CTCF. L'analyse de la séquence consensus révèle un motif de fixation à l'ADN nettement plus long et qui comporte bien moins de bases aléatoires à chaque position nucléotidique. La différence significative entre les séquences génomiques des sites de liaison au CTCF et CTCFL suggère que leur fixation à l'ADN est régulée différemment. Appliquée à l'échelle du génome, l'étude de l'interaction de CTCFL avec des régions méthylées de l'ADN a permis d'identifier environ 1.000 loci. Contrairement à CTCFL, la liaison de CTCF dépend de l'état de méthylation de l'ADN ; cette modification épigénétique constitue donc au moins un des mécanismes de régulation expliquant une localisation de CTCF et CTCFL à des sites distincts du génome. La co- localisation de CTCF avec la cohésine étant établie, l'analyse de la superposition des séquences de CTCFL avec la sous-unité SMC3 identifie environ 3.300 sites de liaison parmi lesquels deux mêmes motifs consensus distincts par leur séquence sont mis en évidence. La presque quasi-totalité des données sur la cohésine ayant été établie à partir de cellules en prolifération mitotique, il est probable que la similitude au sein des séquences consensus soit encore plus grande dans le cas des cellules en méiose. La sous-unité Rec8 de la cohésine propre à l'état de méiose est spécifiquement exprimée dans les spermatocytes. Or 6 des 12 sites de liaison identifiés sont également utilisés par CTCFL. Pour conclure, ce travail constitue la première cartographie à l'échelle du génome des sites de liaison de CTCFL dans les spermatocytes, seul type cellulaire où CTCFL n'est pas exprimé. CTCFL possède un répertoire unique de sites de fixation à l'ADN distinct de CTCF, se lie à des séquences méthylées et présente un nombre important de sites de liaison communs avec la cohésine. Les perspectives futures sont d'élucider le rôle de CTCFL dans le remodelage de la structure de la chromatine et de définir sa fonction dans le processus de méiose.

Public Policy and Ageing in Northern Ireland: Identifying Levers for Change

Public Policy and Ageing in Northern Ireland: Identifying Levers for Change Judith Cross, Policy Officer with the Centre for Ageing Research Development in Ireland (CARDI)��������Introduction Identifying a broad range of key public policy initiatives as they relate to age can facilitate discussion and create new knowledge within and across government to maximise the opportunities afforded by an ageing population. This article looks at how examining the current public policy frameworks in Northern Ireland can present opportunities for those working in this field for the benefit of older people. Good policy formulation needs to be evidence-based, flexible, innovative and look beyond institutional boundaries. Bringing together architects and occupational therapists, for example, has the potential to create better and more effective ways relevant to health, housing, social services and government departments. Traditional assumptions of social policy towards older people have tended to be medically focused with an emphasis on care and dependency. This in turn has consequences for the design and delivery of services for older people. It is important that these assumptions are challenged as changes in thinking and attitudes can lead to a redefinition of ageing, resulting in policies and practices that benefit older people now and in the future. Older people, their voices and experiences, need to be central to these developments. The Centre for Ageing Research and Development in Ireland The Centre for Ageing Research and Development in Ireland (CARDI) (1) is a not for profit organisation developed by leaders from the ageing field across Ireland (North and South) including age sector focused researchers and academics, statutory and voluntary, and is co-chaired by Professor Robert Stout and Professor Davis Coakley. CARDI has been established to provide a mechanism for greater collaboration among age researchers, for wider dissemination of ageing research information and to advance a research agenda relevant to the needs of older people in Ireland, North and South. Operating at a strategic level and in an advisory capacity, CARDI�۪s work focuses on promoting research co-operation across sectors and disciplines and concentrates on influencing the strategic direction of research into older people and ageing in Ireland. It has been strategically positioned around the following four areas: Identifying and establishing ageing research priorities relevant to policy and practice in Ireland, North and South;Promoting greater collaboration and co-operation on ageing research in order to build an ageing research community in Ireland, North and South;Stimulating research in priority areas that can inform policy and practice relating to ageing and older people in Ireland, North and South;Communicating strategic research issues on ageing to raise the profile of ageing research in Ireland, North and South, and its role in informing policy and practice. Context of Ageing in Ireland Ireland �۪s population is ageing. One million people aged 60 and over now live on the island of Ireland. By 2031, it is expected that Northern Ireland�۪s percentage of older people will increase to 28% and the Republic of Ireland�۪s to 23%. The largest increase will be in the older old; the number aged 80+ is expected to triple by the same date. However while life expectancy has increased, it is not clear that life without disability and ill health has increased to the same extent. A growing number of older people may face the combined effects of a decline in physical and mental function, isolation and poverty. Policymakers, service providers and older people alike recognise the need to create a high quality of life for our ageing population. This challenge can be meet by addressing the problems relating to healthy ageing, reducing inequalities in later life and creating services that are shaped by, and appropriate for, older people. Devolution and Structures of Government in Northern Ireland The Agreement (2) reached in the Multi-Party Negotiations in Belfast 1998 established the Northern Ireland Assembly which has full legislative authority for all transferred matters. The majority of social and economic public policy such as; agriculture, arts, education, health, environment and planning is determined by the Northern Ireland Assembly at Stormont. There are 11 Government Departments covering the main areas of responsibility with 108 elected Members of the Legislative Assembly (MLA�۪s). The powers of the Northern Ireland Assembly do not cover ��� reserved�۪ matters or ��� excepted�۪ matters . These are the responsibility of Westminster and include issues such as, tax, social security, policing, justice, defence, immigration and foreign affairs. Northern Ireland has 18 elected Members of Parliament (MP�۪s) to the House of Commons. Public Policy Context in Northern Ireland The economic, social and political consequence of an ageing population is a challenge for policy makers across government. Considering the complex and diverse causal factors that contribute to ageing in Northern Ireland, there are a number of areas of government policy at regional, national and international levels that are likely to impact in this area. International The Madrid International Plan of Action on Ageing (3) and the Research Agenda on Ageing for the 21st Century (4) provide important mechanisms for furthering research into ageing. The United Kingdom has signed up to these. The Madrid International Plan of Action on Ageing commits member states to a systematic review of the Plan of Action through Regional Implementation Strategies. The United Kingdom�۪s Regional Implementation Strategy covers Northern Ireland. National At National level, pension and social security are high on the agenda. The Pensions Act (5) became law in 2007 and links pensions increases with earnings as opposed to prices from 2012. Additional credits for people raising children and caring for older people to boost their pensions were introduced. Some protections are included for those who lost occupational pensions as a result of underfunded schemes being wound up before April 2005. In relation to State Pensions and benefits, this Act will bring changes to state pensions in future. The Act now places the Pension Credit element which is up-rated in line with or above earnings, on a permanent, statutory footing. Regional At regional level there are a number of age related public policy initiatives that have the potential to impact positively on the lives of older people in Northern Ireland. Some are specific to ageing such as the Ageing in an Inclusive Society (6) and others by their nature are cross-cutting such as Lifetime Opportunities: Governments Anti-Poverty Strategy for Northern Ireland (7). The main public policy framework in Northern Ireland is the Programme for Government: Building a Better Future, 2008-2011(PfG) (8) . The PfG, is the overarching high level policy framework for Northern Ireland and provides useful principles for ageing research and public policy in Northern Ireland. The PfG vision is to build a peaceful, fair and prosperous society in Northern Ireland, with respect for the rule of law. A number of Public Service Agreements (PSA) aligned to the PfG confirm key actions that will be taken to support the priorities that the Government aim to achieve over the next three years. For example objective 2 of PSA 7: Making Peoples�۪ Lives Better: Drive a programme across Government to reduce poverty and address inequality and disadvantage, refers to taking forward strategic action to promote social inclusion for older people; and to deliver a strong independent voice for older people. The Office of the First Minister and deputy First Minister (OFMDFM) have recently appointed an Interim Older People�۪s Advocate, Dame Joan Harbison to provide a focus for older peoples issues across Government. Ageing in an Inclusive Society is the cross-departmental strategy for older people in Northern Ireland and was launched in March 2005. It sets out the approach to be taken across Government to promote and support the inclusion of older people. The vision coupled with six strategic objectives form the basis of the action plans accompanying the strategy. The vision is: ���To ensure that age related policies and practices create an enabling environment, which offers everyone the opportunity to make informed choices so that they may pursue healthy, active and positive ageing.�۝ (Ageing in an Inclusive Society, Office of the First Minister and Deputy First Minister, 2005) Action planning and maintaining momentum across government in relation to this strategy has proved to be slower than anticipated. It is proposed to refresh this Strategy in line with Opportunity Age ��� meeting the challenges of ageing in the 21st Century (9). There are a number of policy levers elsewhere which can also be used to promote the positive aspects of an ageing society. The Investing for Health (10) and A Healthier Future:A 20 Year Vision for Health and Well-being in Northern Ireland (11), seek to ensure that the overall vision for health and wellbeing is achievable and provides a useful framework for ageing policy and research in the health area. These health initiatives have the potential to positively impact on the quality of life of older people and provide a useful framework for improving current policy and practice. In addition to public policy initiatives, the anti-discrimination frameworks in terms of employment in Northern Ireland cover age as well as a range of other grounds. Goods facilitates and services are currently excluded from the Employment Equality (age) Regulations (NI) 2006 (12). Supplementing the anti-discrimination measures, Section 75 of the Northern Ireland Act 1998 (13), unique to Northern Ireland, places a statutory obligation on public authorities in fulfilling their functions to promote equality of opportunity across nine grounds, one of which is age(14). This positive duty has the potential to make a real difference to the lives of older people in Northern Ireland. Those affected by policy decisions must be consulted and their interests taken into account. This provides an opportunity for older people and their representatives to participate in public policy-making, right from the start of the process. Policy and Research Interface ���Ageing research is vital as decisions in relation to policy and practice and resource allocation will be made on the best available information�۝. (CARDI�۪s Strategic Plan 2008-2011) As outlined earlier, CARDI has been established to bridge the gap to ensure that research reaches those involved in making policy decisions. CARDI is stimulating the ageing research agenda in Ireland through a specific research fund that has a policy and practice focus. My work is presently focusing on helping to build a greater awareness of the key policy levers and providing opportunities for those within research and policy to develop closer links. The development of this shared understanding by establishing these links between researchers and policy makers is seen as the best predictor for research utilization. It is important to acknowledge and recognise that researchers and policy makers operate in different institutional, political and cultural contexts. Research however needs to ���resonate�۪ with the contextual factors in which policy makers operate. Conclusions Those working within the public policy field recognise all too often that the development of government policies and initiatives in respect of age does not guarantee that they will result in changes in actual provision of services, despite Government recommendations and commitments. The identification of public policy initiatives as they relate to age has the potential to highlight persistent and entrenched difficulties that social policy has previously failed to address. Furthermore, the identification of these difficulties can maximise the opportunities for progressing these across government. A focus on developing effective and meaningful targets to ensure measurable outcomes in public policy for older people can assist in this. Access to sound, credible and up-to-date evidence will be vital in this respect. As well as a commitment to working across departmental boundaries to effect change. Further details: If you would like to discuss this paper or for further information about CARDI please contact: Judith Cross, Policy Officer, Centre for Ageing Research and Development in Ireland CARDI). t: +44 (0) 28 9069 0066; m: +353 (0) 867 904 171; e: judith@cardi.ie ; or visit our website at: www.cardi.ie References 1) Centre for Ageing Research and Development in Ireland (2008) Strategic Plan 2008-2011. Belfast. CARDI 2) The Agreement: Agreement Reached in the Multi-Party Negotiations. Belfast 1998 3) Madrid International Plan of Action on Ageing. http://www.un.org/ageing/ 4) UN Programme on Ageing (2007) Research Agenda on Ageing for the 21st Century: 2007 Update. New York. New York. UN Programme on Ageing and the International Association of Gerontology and Geriatrics. 5) The Pensions Act 2007 Chapter 22 6) Office of the First Minister and deputy First Minister (2005). Ageing in an Inclusive Society. Belfast. OFMDFM Central Anti-Poverty Unit. 7) Office of the First Minister and deputy First Minister (2005). Lifetime Opportunities: Government�۪s Anti-Poverty and Social Inclusion Strategy for Northern Ireland. Belfast. OFMDFM Central Anti-Poverty Unit. 8) Northern Ireland Executive (2008) Building a Better Future: Programme for Government 2008-2011. Belfast. OFMDFM Economic Policy Unit. 9) Department for Work and Pensions, (2005) Opportunity Age: Meeting the Challenges of Ageing in the 21 st Century. London. DWP. 10) Department of Health, Social Services and Public Safety (DHSS&PS) (2002) Investing for Health. Belfast. DHSS&PS. 11) Department of Health, Social Services and Public Safety (DHSS&PS) (2005) A Healthier Future:A 20 Year Vision for Health and Well-being in Northern Ireland Belfast. DHSS&PS. �� 12) The Employment Equality (Age) Regulations (Northern Ireland) 2006 SR2006 No.261 13) The Northern Ireland Act 1998, Part VII, S75 14) The nine grounds covered under S75 of the Northern Ireland Act are: gender, religion, race, sexual orientation, those with dependents, disability, political opinion, marital status and age.

Concurrent versus simultaneous use of alcohol and non-medical use of prescription drugs: is simultaneous use worse for mental, social, and health issues?

Abstract This study investigated the difference between concurrent and simultaneous use of alcohol and non-medical use of prescription drugs (NMUPD) in relation to mental, social, and health issues. The 544 study participants of the Swiss ongoing Cohort Study on Substance Use Risk Factors (C-SURF) had a combined use of alcohol with NMUPD during the previous 12 months. Alcohol-related problems (i.e., dependence and consequences), as well as mental, social, and health concerns (i.e., depression, general mental/physical health, and social/health consequences), were assessed. The simultaneous use of alcohol and NMUPD proved to be a greater risk factor for mental, social, and health issues than concurrent use. This study adds information regarding simultaneous polydrug use, which results in distinct effects compared to concurrent use, including important social, psychosocial, and health-related consequences.

Cardiac rotation and relaxation after anterolateral myocardial infarction.

BACKGROUND: Both systolic and diastolic dysfunction have been observed in patients with anterolateral myocardial infarction. Diastolic dysfunction is related to disturbances in relaxation and diastolic filling. OBJECTIVE: To analyse cardiac rotation, regional shortening and diastolic relaxation in patients with anterolateral infarction. METHODS: Cardiac rotation and relaxation in controls and patients with chronic anterolateral infarction were assessed by myocardial tagging. Myocardial tagging is based on magnetic resonance imaging and allows us to label specific myocardial regions for imaging cardiac motion (rotation, translation and radial displacement). A rectangular grid was placed on the myocardium (basal, equatorial and apical short-axis plane) of each of 18 patients with chronic anterolateral infarction and 13 controls. Cardiac rotation, change in area and shortening of circumference were determined in each case. RESULTS: The left ventricle in controls performs a systolic wringing motion with a clockwise rotation at the base and a counterclockwise rotation at the apex when viewed from the apex. During relaxation a rotational motion in the opposite direction (namely untwisting) can be observed. In patients with anterolateral infarction, there is less systolic rotation at the apex and diastolic untwisting is delayed and prolonged in comparison with controls. In the presence of a left ventricular aneurysm (n = 4) apical rotation is completely lost. There is less shortening of circumference in infarcted and remote regions. CONCLUSIONS: The wringing motion of the myocardium might be an important mechanism involved in maintaining normal cardiac function with minimal expenditure of energy. This mechanism no longer operates in patients with left ventricular aneurysms and operates significantly less than normal in those with anterolateral hypokinaesia. Diastolic untwisting is significantly delayed and prolonged in patients with anterolateral infarction, which could explain the occurrence of diastolic dysfunction in these patients.

Detection of calicivirus from fecal samples from children with acute gastroenteritis in the West Central region of Brazil

The objective of this study was to describe the circulation of caliciviruses in the West Central region of Brazil and its correlation with children's gender and age, as well as with the year and months of the sample collection. Reverse transcriptase-polymerase chain reaction was performed to detect the human calicivirus genome in 1006 fecal samples that were collected in Goiânia (n = 696) and Brasília (n = 310). Viral RNA was detected in 8.6% of the samples. No significant difference in viral prevalence was found regarding gender, age or year of the sample. However, it was observed that in Goiânia, there is a higher incidence of caliciviruses from September to March. The analysis employing three primer pairs demonstrated that the Ni/E3 or JV12/13 primer pairs, which detect norovirus (NoV), detected 41 positive samples while the 289/290 primer pair, which detects NoV or sapovirus, detected the remaining 46 samples. Calicivirus circulates in the West Central region of Brazil and for better detection of this virus it is important to use more than one primer pair. Also, we conclude that the seasonality presented by this virus is related to higher humidity in the period.

Cell proliferation and interferon-gamma response to recombinant MBP-3, NarL, MT-10.3, and 16kDa Mycobacterium tuberculosis antigens in Brazilian tuberculosis patients

Human pulmonary tuberculosis (TB) is a worldwide public health problem. In resistant individuals, control of the infection mainly requires development of a Th1 cell immune response with production of cytokines, of which interferon-gamma (IFN-gamma)plays an important role. Several antigens from Mycobacterium tuberculosis complex has been described for use in vaccine development or for diagnostic purposes, however little evaluation has been done in endemic area for TB. The proliferative and IFN-gamma human T cell immune responses, to four recombinant proteins (MBP-3, NarL, MT-10.3, 16 kDa) and PPD, of 38 Brazilian TB patients (6 untreated and 32 treated) and 67 controls (38 positive and 29 negative tuberculin skin test - TST) were compared. The highest reactivity mean rate was obtained with PPD followed by 16 kDa in TB patients. While most of the patients (87%) and controls (> 64%) respond to the PPD, 16kDa was more specifically recognized (> 21%) although less sensitive (54%). When TB patients were divided according to treatment status, opposite to PPD, higher average level of IFN-gamma was induced by 16kDa in untreated (505 pg/ml) compared to treated TB patients and TST+ (269.8 pg/ml x 221.6pg/ml, respectively), although the difference was not significant. These data show that in contrast with the other recombinant proteins, the stimulatory potency of 16kDa to induce proliferative and INF-gamma response was more effective and is more recognized by active TB untreated patients, eliciting in control individuals a more selective immune response than PPD.

Trypanosoma cruzi high infectivity in vitro is related to cardiac lesions during long-term infection in Beagledogs

Trypanosoma cruzi is a hemoflagelate parasite associated with heart dysfunctions causing serious problems in Central and South America. Beagle dogs develop the symptoms of Chagas disease in humans, and could be an important experimental model for better understanding the immunopathogenic mechanisms involved in the chagasic infection. In the present study we investigated the relation among biological factors inherent to the parasite (trypomastigote polymorphism and in vitro infectivity) and immunoglobulin production, inflammation, and fibrosis in the heart of Beagle dogs infected with either T. cruzi Y or Berenice-78 strains. In vitro infectivity of Vero cells as well as the extension of cardiac lesions in infected Beagle was higher for Y strain when compared to Berenice-78 strain. These data suggested that in vitro infectivity assays may correlate with pathogenicity in vivo. In fact, animals infected with Y strain, which shows prevalence of slender forms and high infectivity in vitro, presented cardiomegaly, inflammation, and fibrosis in heart area. Concerning the immunoglobulin production, no statistically significant difference was observed for IgA, IgM or IgG levels among T. cruzi infected animals. However, IgA together IgM levels have shown to be a good marker for the acute phase of Chagas disease.

Patterns of pain freedom response in 497 cases with classical trigeminal neuralgia and at least one year of follow-up treated by gamma knife radiosurgery

Purpose: To identify patterns of initially pain freedom response in patients with classical trigeminal neuralgia (CTN) with Gamma Knife surgery (GKS) and to compare their associated hypoesthesia and recurrence rates. Methods: In this study we analysed only 497 patients treated between July 1992 and November 2010, with a follow-up longer than 1 year, after excluding megadolichobasilar artery and multiple sclerosis related trigeminal neuralgia, as well as the second GKS treatments so as to have only cases with CTN and single radiosurgical treatment. GKS using a Gamma Knife (model B or C or Perfexion) was performed, based on both MRI and computer tomography (CT) targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.8 mm (range 4.5-14) anteriorly to the emergence of the nerve. A median maximum dose of 85 Gy (range 70-90) was delivered. After empiric methods but also by using a chart with clear cut-off periods of pain free distribution, we were able to divide the initially pain free patients into 3 separate groups: within the first 48 hours, after 48 hours till 30 days and after 30 days, respectively. Results: The median follow- up period was 43.75 months (range 12-174.41). Four hundred and fifty-four patients (91.75%) were initially pain free in a median time of 10 days (range 1-459): 169 (37.2%) became pain free within the first 48 hours (pf<=48 h), compared to 194 (42.8%) between the 3-rd day and the day 30 (pf (>48 h, <=30 d)), inclusively and 91 (20%) patients after 30 days (pf>30d). Differences in terms of postoperative hypoesthesia were found with a p value of 0.014 as follows: the group pf<=48 h had 18 (13.7%) compared to pf (>48 h, <=30 d) with 30 (19%) and pf>30d with 22 (30.5%) patients developing a postoperative GKS hypoesthesia. One hundred and fifty seven (34.4%) patients initially pain free experienced a recurrence with a median delay of 24 months (range 0.62-150.06). There were no statistically significant differences between the three groups concerning recurrence (p value of 0.515). Conclusions: An important number of patients (169 cases, 37.2%) became pain free in the first 48 hours. Hypoesthesia rate was higher within the group becoming pain free after 30 days with a statistically significant difference between the three populations (p= 0.014). Further analysis will eventually help to elucidate the differences observed among groups.

Association of insecticide use and alteration on Aedes aegypti susceptibility status

Dengue and dengue hemorrhagic fever, vector-borne diseases transmitted by the mosquito Aedes aegypti, are presently important public health problems in Brazil. As the strategy for disease control is based on vector control through the use of insecticides, the development of resistance is a threat to programs efficacy. The objective of this study was to compare the Aedes aegypti susceptibility in nine vector populations from the state of São Paulo and seven from Northeast region of Brazil, since there was a difference on group of insecticide used between the areas. Bioassays with larvae and adult were performed according to the World Health Organization methods.The results showed higher resistance levels to organophosphates group in populations from the Northeast region where this group was used for both larvae and adult control than in São Paulo where organophosphates were used for larvae and pyretroids for adult control. Resistance to pyretroids in adults was widespread in São Paulo after ten years of use of cypermethrin while in vector populations from the Northeast region it was punctual. The difference in resistance profile between the areas is in accordance to the group of insecticide used.

Hirschsprung's disease: the "Swiss roll" technique revisited.

PURPOSE: During pull-through for Hirschsprung's disease (HSCR), the assessment of innervation is mainly based on the presence of ganglion cells when conventional Hematoxylin and Eosin (HE) staining is used. In hypoganglionosis, the evaluation is difficult. We adapted a standardized methodology for the examination of resected bowel after HSCR surgery, using the technique described by Moolenbeek on rodent intestine and later by Meier-Ruge in children. We have analysed the entire innervation of surgically resected bowels and compared the results with the follow up of patients. METHODS: Three longitudinal strips of colon were harvested from the mesenteric, anti-mesenteric and intermediate part in the whole length of resected colon of six patients with HSCR. Each strip was divided into two parts. One of the contiguous strips was assessed with HE and Hematoxylin-Phloxin-Safran, and the other one with acetylcholinesterase (AChE) histochemistry. We analyzed the distribution of ganglion cells and nerve arrangement along the strips with both techniques and compared the results obtained in the three different regions of the bowel. RESULTS: There was no significant difference in the pattern of innervation circumferentially. There was a correlation between a progressive increase of AChE activity and nerve hypertrophy and a decrease of ganglion cells from the proximal to the distal part of the resected colon in the submucosa and the myenteric plexus. Nerve hypertrophy and AChE-positive reaction in the mucosa were found at the resection border in patients who presented postoperative complications. CONCLUSIONS: Simultaneous assessment of nerve cells, nerve fibers and AChE activity is important in the evaluation of the innervation of the bowel segment proximal to the aganglionic zone. The method described is feasible and can be adapted to older children and adults with larger bowels. These results point out the importance of assessing nerve fibers in intraoperative biopsies during pull-through procedures to prevent uncomplete surgical bowel resection.

Drogues et psychose: que faire [Drugs and psychoses: what to do?]

Substance abuse co morbidity is frequent in psychotic disorders. General practitioners are frequently involved in such treatments. In order to be able to face this complex task, it is important to be able to identify early symptoms of psychosis in a patient abusing substances, to make the difference between psychotic symptoms and intoxication or withdrawal symptoms, to know basic principles of treatment and the type of medication used in such interventions, and finally to know when specialised treatment or hospital admission are required. This paper reviews epidemiological and diagnostic elements, outlines the various treatment stages, the type of medication currently used in such situations and provides a brief description of motivational interview techniques.

Effects of increased intensity of intermittent training in runners with differing VO2 kinetics.

The purpose of this study was to test the hypothesis that athletes having a slower oxygen uptake ( VO(2)) kinetics would benefit more, in terms of time spent near VO(2max), from an increase in the intensity of an intermittent running training (IT). After determination of VO(2max), vVO(2max) (i.e. the minimal velocity associated with VO(2max) in an incremental test) and the time to exhaustion sustained at vVO(2max) ( T(lim)), seven well-trained triathletes performed in random order two IT sessions. The two IT comprised 30-s work intervals at either 100% (IT(100%)) or 105% (IT(105%)) of vVO(2max) with 30-s recovery intervals at 50% of vVO(2max) between each repeat. The parameters of the VO(2) kinetics (td(1), tau(1), A(1), td(2), tau(2), A(2), i.e. time delay, time constant and amplitude of the primary phase and slow component, respectively) during the T(lim) test were modelled with two exponential functions. The highest VO(2) reached was significantly lower ( P<0.01) in IT(100%) run at 19.8 (0.9) km(.)h(-1) [66.2 (4.6) ml(.)min(-1.)kg(-1)] than in IT(105%) run at 20.8 (1.0) km(.)h(-1) [71.1 (4.9) ml(.)min(-1.)kg(-1)] or in the incremental test [71.2 (4.2) ml(.)min(-1.)kg(-1)]. The time sustained above 90% of VO(2max) in IT(105%) [338 (149) s] was significantly higher ( P<0.05) than in IT(100%) [168 (131) s]. The average T(lim) was 244 (39) s, tau(1) was 15.8 (5.9) s and td(2) was 96 (13) s. tau(1) was correlated with the difference in time spent above 90% of VO(2max) ( r=0.91; P<0.01) between IT(105%) and IT(100%). In conclusion, athletes with a slower VO(2) kinetics in a vVO(2max) constant-velocity test benefited more from the 5% rise of IT work intensity, exercising for longer above 90% of VO(2max) when the IT intensity was increased from 100 to 105% of vVO(2max).

Impact of moisture on survival of Aedes aegypti eggs and ovicidal activity of Metarhizium anisopliae under laboratory conditions

The effect of relative humidity (43%, 75%, 86% and > 98%) on Aedes aegypti eggs treated with Metarhizium anisopliae or water only was tested for up to a six months exposure at 25ºC. Survival of larvae inside eggs was clearly affected by the lowest humidity (43%) tested, and eclosion diminished at all humidities after increasing periods of exposure. M. anisopliae showed to have a strong ovicidal activity only at humidity close to saturation. No difference of activity was found between conidia and hyphal bodies tested. This fungus affected larvae inside eggs and has potential as a control agent of this important vector in breeding sites with high moisture.