Asthma prevalence and risk factors in schoolchildren of the city of São Paulo, Brazil

OBJETIVO: Analisar a prevalência de asma e possíveis fatores de risco associados. MÉTODOS: Estudo transversal, integrante do International Study of Asthma and Allergies in Childhood. Participaram 561 escolares de seis a sete anos de idade, provenientes de 35 escolas públicas da cidade de São Paulo, escolhidas por sorteio, em 2002. A amostra incluiu 168 asmáticos e 393 não asmáticos, que responderam questionário constituído por 33 questões referentes a dados pessoais, familiares e ambientais. A associação entre asma e fatores de risco foi avaliada pela análise de regressão logística, considerando-se nível de significância estatística de 5%. RESULTADOS: Entre os escolares, 31,2% referiam sibilos nos 12 meses anteriores à entrevista. Os fatores de risco significativamente associados à asma foram: sexo masculino (OR=2,4;IC 95%: 1,4;4,2), mãe fumante no primeiro ano de vida (OR=2,0; IC 95%: 1,1;3,8), presença de eczema em locais característicos (OR=3,0; IC 95%:1,2; 7,6) e rinoconjuntivite (OR=2,4;IC 95%: 1,2; 4,8). CONCLUSÕES: A prevalência de asma na região estudada foi elevada e os fatores de risco relacionados foram: sexo masculino, sintomas de rinoconjuntivite no último ano, mãe fumante no primeiro ano de vida e presença de eczema em locais característicos.OBJECTIVE: To assess asthma prevalence and potential risk factors associated. METHODS: Cross-sectional study part of the International Study of Asthma and Allergies in Childhood. A total of 561 schoolchildren aged 6-7 years from 35 public schools in the city of São Paulo (Southeastern Brazil) were drawn to participate in the study, in 2002. The sample consisted of 168 asthmatic and 393 non-asthmatic children who answered a questionnaire comprising 33 questions on personal, family and environmental information. The association between asthma and the risk factors studied was assessed by logistic regression analysis at a 5% statistical significance. RESULTS: Among the schoolchildren studied, 31.2% reported wheezing in the 12 months preceding the interview. The following risk factors were significantly associated with asthma: male gender (OR=2.4; 95% CI: 1.4;4.2), maternal smoking in the child's first year of life (OR=2.0; 95% CI: 1.1;3.8), eczema on characteristic body areas (OR=3.0; 95% CI: 1.2;7.6) and rhinoconjunctivitis (OR=2.4; 95% CI: 1.2;4.8). CONCLUSIONS: Asthma prevalence in the study area was high and the risk factors identified were male gender, rhinoconjunctivitis in last year, maternal smoking in the child's first year of life and eczema on characteristic body areas

Disparities in appendicitis rupture rate among mentally ill patients

<p>Abstract</p> <p>Background</p> <p>Many studies have been carried out that focus on mental patients' access to care for their mental illness, but very few pay attention on these same patients' access to care for their physical diseases. Acute appendicitis is a common surgical emergency. Our population-based study was to test for any possible association between mental illness and perforated appendicitis. We hypothesized that there are significant disparities in access to timely surgical care between appendicitis patients with and without mental illness, and more specifically, between patients with schizophrenia and those with another major mental illness.</p> <p>Methods</p> <p>Using the National Health Insurance (NHI) hospital-discharge data, we compared the likelihood of perforated appendix among 97,589 adults aged 15 and over who were hospitalized for acute appendicitis in Taiwan between the years 1997 to 2001. Among all the patients admitted for appendicitis, the outcome measure was the odds of appendiceal rupture vs. appendicitis that did not result in a ruptured appendix.</p> <p>Results</p> <p>After adjusting for age, gender, ethnicity, socioeconomic status (SES) and hospital characteristics, the presence of schizophrenia was associated with a 2.83 times higher risk of having a ruptured appendix (odds ratio [OR], 2.83; 95% confidence interval [CI], 2.20–3.64). However, the presence of affective psychoses (OR, 1.15; 95% CI: 0.77–1.73) or other mental disorders (OR, 1.58; 95% CI: 0.89–2.81) was not a significant predictor for a ruptured appendix.</p> <p>Conclusion</p> <p>These findings suggest that given the fact that the NHI program reduces financial barriers to care for mentally ill patients, they are still at a disadvantage for obtaining timely treatment for their physical diseases. Of patients with a major mental illness, schizophrenic patients may be the most vulnerable ones for obtaining timely surgical care.</p

Molecular Mechanisms Generating and Stabilizing Terminal 22q13 Deletions in 44 Subjects with Phelan/McDermid Syndrome

In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17–74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS

SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras

SHANK3, a synaptic scaffold protein and actin regulator, is widely expressed outside of the central nervous system with predominantly unknown function. Solving the structure of the SHANK3 N-terminal region revealed that the SPN domain is an unexpected Ras-association domain with high affinity for GTP-bound Ras and Rap G-proteins. The role of Rap1 in integrin activation is well established but the mechanisms to antagonize it remain largely unknown. Here, we show that SHANK1 and SHANK3 act as integrin activation inhibitors by sequestering active Rap1 and R-Ras via the SPN domain and thus limiting their bioavailability at the plasma membrane. Consistently, SHANK3 silencing triggers increased plasma membrane Rap1 activity, cell spreading, migration and invasion. Autism-related mutations within the SHANK3 SPN domain (R12C and L68P) disrupt G-protein interaction and fail to counteract integrin activation along the Rap1-RIAM-talin axis in cancer cells and neurons. Altogether, we establish SHANKs as critical regulators of G-protein signalling and integrin-dependent processes

Genetic predisposition to mosaic Y chromosome loss in blood.

Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism1-5, yet our knowledge of the causes and consequences of this is limited. Here, using a computational approach, we estimate that 20% of the male population represented in the UK Biobank study (n = 205,011) has detectable LOY. We identify 156 autosomal genetic determinants of LOY, which we replicate in 757,114 men of European and Japanese ancestry. These loci highlight genes that are involved in cell-cycle regulation and cancer susceptibility, as well as somatic drivers of tumour growth and targets of cancer therapy. We demonstrate that genetic susceptibility to LOY is associated with non-haematological effects on health in both men and women, which supports the hypothesis that clonal haematopoiesis is a biomarker of genomic instability in other tissues. Single-cell RNA sequencing identifies dysregulated expression of autosomal genes in leukocytes with LOY and provides insights into why clonal expansion of these cells may occur. Collectively, these data highlight the value of studying clonal mosaicism to uncover fundamental mechanisms that underlie cancer and other ageing-related diseases.This research has been conducted using the UK Biobank Resource under application 9905 and 19808. This work was supported by the Medical Research Council [Unit Programme number MC_UU_12015/2]. Full study-specific and individual acknowledgements can be found in the supplementary information

Meeting the challenges of implementing rapid genomic testing in acute pediatric care

Authors: Stark, Z. Lunke, S. Brett, G. Tan, N. Stapleton, R. Kumble, S. Yeung, A. Phelan, D. Chong, B. Fernandez, M.F. Marum, J.E. Hunter, M. Jarmolowicz, A. Yael Prawer, Y. Riseley, J.R. Regan, M. Elliott, J. Melissa Martyn, M. Best, S. Tan, T. Clara L Gaff, C.L. and White, S.M

Policies and clinical practices relating to the management of gestational diabetes mellitus in the public health sector, South Africa – a qualitative study

BACKGROUND: Women with a prior gestational diabetes have an increased lifetime risk of developing type 2 diabetes. Although post-partum follow-up for GDM women is essential to prevent progression to type 2 diabetes, it is poorly attended. The need for health systems interventions to support postpartum follow-up for GDM women is evident, but there is little knowledge of actual current practice. The aim of this study was to explore current policies and clinical practices relating to antenatal and post-natal care for women with GDM in South Africa, as well as health sector stakeholders’ perspectives on the barriers to – and opportunities for – delivering an integrated mother - baby health service that extends beyond the first week post-partum, to the infant’s first year of life. METHODS: Following a document review of policy and clinical practice guidelines, in-depth interviews were conducted with 11 key informants who were key policy makers, health service managers and clinicians working in the public health services in South Africa’s two major cities (Johannesburg and Cape Town). Data were analysed using qualitative content analysis procedures. RESULTS: The document review and interviews established that it is policy that health services adhere to international guidelines for GDM diagnosis and management, in addition to locally developed guidelines and protocols for clinical practice. All key informants confirmed that lack of postpartum follow-up for GDM women is a significant problem. Health systems barriers include fragmentation of care and the absence of standardised postnatal care for post-GDM women. Key informants also raised patient - related challenges including lack of perceived future risk of developing type 2 diabetes and non-attendance for postpartum follow up, as barriers to postnatal care for GDM women. All participants supported integrated primary health services but cautioned against overloading health workers. CONCLUSION: Although there is alignment between international guidelines, local policy and reported clinical practice in the management of GDM, there is a gap in continuation of care in the postpartum period. Health systems interventions that support and facilitate active follow-up for women with prior GDM are needed if high rates of progression to type 2 diabetes are to be avoided

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified