Association of Secondhand Smoke Exposure with Pediatric Invasive Bacterial Disease and Bacterial Carriage: A Systematic Review and Meta-analysis

Background: A number of epidemiologic studies have observed an association between secondhand smoke (SHS) exposure and pediatric invasive bacterial disease (IBD) but the evidence has not been systematically reviewed. We carried out a systematic review and meta-analysis of SHS exposure and two outcomes, IBD and pharyngeal carriage of bacteria, for Neisseria meningitidis (N. meningitidis), Haemophilus influenzae type B (Hib), and Streptococcus pneumoniae (S. pneumoniae). Methods and Findings: Two independent reviewers searched Medline, EMBASE, and selected other databases, and screened articles for inclusion and exclusion criteria. We identified 30 case-control studies on SHS and IBD, and 12 crosssectional studies on SHS and bacterial carriage. Weighted summary odd ratios (ORs) were calculated for each outcome and for studies with specific design and quality characteristics. Tests for heterogeneity and publication bias were performed. Compared with those unexposed to SHS, summary OR for SHS exposure was 2.02 (95% confidence interval [CI] 1.52–2.69) for invasive meningococcal disease, 1.21 (95% CI 0.69–2.14) for invasive pneumococcal disease, and 1.22 (95% CI 0.93–1.62) for invasive Hib disease. For pharyngeal carriage, summary OR was 1.68 (95% CI, 1.19–2.36) for N. meningitidis, 1.66 (95% CI 1.33–2.07) for S. pneumoniae, and 0.96 (95% CI 0.48–1.95) for Hib. The association between SHS exposure and invasive meningococcal and Hib diseases was consistent regardless of outcome definitions, age groups, study designs, and publication year. The effect estimates were larger in studies among children younger than 6 years of age for all three IBDs, and in studies with the more rigorous laboratory-confirmed diagnosis for invasive meningococcal disease (summary OR 3.24; 95% CI 1.72–6.13). Conclusions: When considered together with evidence from direct smoking and biological mechanisms, our systematic review and meta-analysis indicates that SHS exposure may be associated with invasive meningococcal disease. The epidemiologic evidence is currently insufficient to show an association between SHS and invasive Hib disease or pneumococcal disease. Because the burden of IBD is highest in developing countries where SHS is increasing, there is a need for high-quality studies to confirm these results, and for interventions to reduce exposure of children to SHS

Thrombocytosis is associated with worse survival in patients with hepatocellular carcinoma

Background & AimsThrombocytosis is associated with more aggressive tumour biology in many malignancies. There are limited data in patients with hepatocellular carcinoma (HCC), which often occurs in patients with cirrhosis and portal hypertension. We aimed to explore the prognostic value of thrombocytosis in two cohorts of patients with HCC.MethodsWe included 3561 patients from Taiwan and 1145 patients from the USA. Thrombocytopenia was defined as platelet count < 150à 109/L and thrombocytosis as - ¥Â 300 à  109/L at HCC diagnosis. We used multivariable Cox proportional hazard models to identify independent predictors of survival.ResultsThrombocytosis was present in 9.0% and 6.9% of Taiwan and USA patients respectively. Compared to patients with normal platelet counts and those with thrombocytopenia, patients with thrombocytosis had larger tumours, increased vascular invasion and a higher proportion had extrahepatic metastases in both cohorts. In multivariable analysis, thrombocytosis (aHR 1.40, 95% CI 1.23- 1.60) and thrombocytopenia (aHR 1.13, 95% CI 1.04- 1.23) were both associated with worse survival after adjusting for age, gender, liver disease aetiology, Child- Pugh score, maximal tumour size, tumour nodularity, vascular invasion, lymph node or distant metastasis, performance status and alpha- fetoprotein level. Patients with thrombocytosis had a median survival of 6 and 4 months in the Taiwan and USA cohorts, compared to 32 and 14 months for those with normal platelet counts and 38 and 16 months for thrombocytopenic patients.ConclusionThrombocytosis is independently associated with increased tumour burden and worse overall survival among HCC patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162769/2/liv14560.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162769/1/liv14560_am.pd

Thymic Selection Determines γδ T Cell Effector Fate: Antigen-Naive Cells Make Interleukin-17 and Antigen-Experienced Cells Make Interferon γ

γδ T cells contribute uniquely to host immune competence, but how they do so remain unclear. Here, by analyzing T10/T22-specific γδ T cells in mice with different T10/T22 expression patterns, we find that encountering antigen in the thymus is neither required nor inhibitory for the development of these cells. Instead, ligand recognition determines which of two distinct functional subsets γδ T cells will become. When triggered through the TCR, lymphoid-γδ T cells that encounter ligand during development produce IFNγ, while those that develop in the absence of ligand make IL-17, a major inducer of granulopoiesis during inflammation. Indeed, we find large fractions of IL-17+ γδ T cells from the draining lymph nodes immediately after peptide/CFA immunization and days before the appearance of antigen specific IL-17+ αβ T cells. This suggests a critical role for γδ T cells as ‘initial providers’ of IL-17 in an inflammatory response to novel antigens

Undifferentiated round cell sarcoma with BCOR internal tandem duplications (ITD) or YWHAE fusions:a clinicopathologic and molecular study

Until recently, undifferentiated round cell sarcomas (URCS) in infants have been considered a wastebasket diagnosis, composed of various pathologic entities and lacking consistent genetic alterations. The recent identification of recurrent BCOR internal tandem duplications (ITD) and less common alternative YWHAE\u2013NUTM2B/E fusions in half of infantile URCS and the majority of so-called primitive myxoid mesenchymal tumors of infancy (PMMTI) suggests a common pathogenesis with clear cell sarcoma of the kidney which also harbors the same genetic alterations. These tumors also share a similar morphology and immunoprofile, including positivity for BCOR, cyclin D1, and SATB2. In this study, we investigate the largest cohort to date of genetically confirmed URCS and PMMTI with BCOR ITD or YWHAE fusions to better define their morphologic spectrum and clinical behavior. Twenty-eight cases harbored BCOR ITD and five YWHAE fusions, occurring in 29 infants and 4 children, 19 males and 14 females. Microscopically, 20 were classified as URCS and 13 as PMMTI. Follow-up was available in 25 patients, with 14 (56%) succumbing to their diseases at a mean duration of 18-months follow-up (range: 2\u201362). Six patients remained with no evidence of disease at a mean follow-up of 63 months (range: 4\u2013192), four patients were still alive with disease (mean follow-up: 46 months, range: 4\u2013120), and one died of other causes. Local recurrence and distant metastasis were each observed in 11/25 (44%) of the patients. The overall survival was 42% at 3 years and 34% at 5 years (median survival: 26 months). There was no statistically significant survival difference between cases diagnosed as URCS and PMMTI and between those with BCOR ITD and YWHAE fusions

Morfometría geométrica aplicada en la evaluación de la vía aérea superior: revisión narrativa

29 p.La morfometría geométrica es un método tridimensional que obtiene la forma geométrica de las estructuras biológicas de un organismo, para comparar estas estructuras entre las mismas especies o diferentes especies, y así detectar variaciones morfológicas. La morfometría geométrica es ampliamente usada en distintas áreas de las ciencias para describir la diversidad morfológica con mayor precisión y detalles que los métodos convencionales, como la cefalometría lateral. La morfometría geométrica es usada en ortodoncia, principalmente para estudiar formas dentales y estructuras craneofaciales. Sin embargo, en ortodoncia hay déficit de estudios de morfometría geométrica para evaluar la vía aérea superior. La evaluación de la vía aérea superior es importante en ortodoncia, debido a su estrecha relación con el desarrollo de las estructuras craneofaciales. En la presente revisión narrativa, identificamos que la morfometría geométrica se usa para reconocer diferencias significativas del dimorfismo sexual de diferentes estructuras de la vía aérea superior. También, se usa para planificar tratamientos ortodónticos y comparar los cambios de la vía aérea superior luego de realizado el tratamiento. Además, con la morfometría geométrica puede diferenciarse estructuras morfológicas de la vía aérea superior entre pacientes con y sin síndrome de apnea/hipopnea obstructiva del sueño. Debido a la complejidad morfológica de la vía aérea superior, la evaluación de sus estructuras requiere un método más completo que los métodos convencionales. La morfometría geométrica usa imágenes bidimensionales en diferentes planos, o directamente imágenes tridimensionales, con esto, otorga mayor información y una mejor interpretación gráfica, lo que permite evaluar completamente las estructuras estudiadas. // ABSTRACT: Geometric morphometrics is a three-dimensional method that obtains the geometric shape of the biological structures of an organism, to compare these structures between the same species or different species, and thus detect morphological variations. Geometric morphometrics is widely used in different areas of science to describe morphological diversity with greater precision and detail than conventional methods, such as lateral cephalometry. Geometric morphometrics is used in orthodontics, mainly to study tooth shapes and craniofacial structures. However, in orthodontics there is a deficit of geometric morphometrics studies to evaluate the upper airway. The evaluation of the upper airway is important in orthodontics, due to its close relationship with the development of craniofacial structures. In the present narrative review, we identify that geometric morphometrics is used to recognize significant differences in the sexual dimorphism of different upper airway structures. Also, it is used to plan orthodontic treatments and to compare the changes of the upper airway after the treatment. Furthermore, with geometric morphometrics, morphological structures of the upper airway can be differentiated between patients with and without obstructive sleep apnea / hypopnea syndrome. Due to the morphological complexity of the upper airway, the evaluation of its structures requires a more complete method tan conventional ones. Geometric morphometrics uses two-dimensional images in different planes, or three-dimensional images directly, with this, it gives more information and a better graphic interpretation, which allows the studied structures to be fully evaluated

Endothelial Wnt/β-catenin signaling inhibits glioma angiogenesis and normalizes tumor blood vessels by inducing PDGF-B expression

Endothelial Wnt/β-catenin signaling is necessary for angiogenesis of the central nervous system and blood–brain barrier (BBB) differentiation, but its relevance for glioma vascularization is unknown. In this study, we show that doxycycline-dependent Wnt1 expression in subcutaneous and intracranial mouse glioma models induced endothelial Wnt/β-catenin signaling and led to diminished tumor growth, reduced vascular density, and normalized vessels with increased mural cell attachment. These findings were corroborated in GL261 glioma cells intracranially transplanted in mice expressing dominant-active β-catenin specifically in the endothelium. Enforced endothelial β-catenin signaling restored BBB characteristics, whereas inhibition by Dkk1 (Dickkopf-1) had opposing effects. By overactivating the Wnt pathway, we induced the Wnt/β-catenin–Dll4/Notch signaling cascade in tumor endothelia, blocking an angiogenic and favoring a quiescent vascular phenotype, indicated by induction of stalk cell genes. We show that β-catenin transcriptional activity directly regulated endothelial expression of platelet-derived growth factor B (PDGF-B), leading to mural cell recruitment thereby contributing to vascular quiescence and barrier function. We propose that reinforced Wnt/β-catenin signaling leads to inhibition of angiogenesis with normalized and less permeable vessels, which might prove to be a valuable therapeutic target for antiangiogenic and edema glioma therapy

Multilaboratory assessment of Epstein-Barr virus serologic assays: the case for standardization

IgA antibodies targeting Epstein-Barr virus (EBV) have been proposed for screening for nasopharyngeal carcinoma (NPC). However, methods differ, and the antigens used in these assays differ considerably between laboratories. To enable formal comparisons across a range of established EBV serology assays, we created a panel of 66 pooled serum samples and 66 pooled plasma samples generated from individuals with a broad range of IgA antibody levels. Aliquots from these panels were distributed to six laboratories and were tested by 26 assays measuring antibodies against VCA, EBNA1, EA-EBNA1, Zta, or EAd antigens. We estimated the correlation between assay pairs using Spearman coefficients (continuous measures) and percentages of agreement (positive versus negative, using predefined positivity cutoffs by each assay developer/manufacturer). While strong correlations were observed between some assays, considerable differences were also noted, even for assays that targeted the same protein. For VCA-IgA assays in serum, two distinct clusters were identified, with a median Spearman coefficient of 0.41 (range, 0.20 to 0.66) across these two clusters. EBNA1-IgA assays in serum grouped into a single cluster with a median Spearman coefficient of 0.79 (range, 0.71 to 0.89). Percentages of agreement differed broadly for both VCA-IgA (12% to 98%) and EBNA1-IgA (29% to 95%) assays in serum. Moderate-to-strong correlations were observed across assays in serum that targeted other proteins (correlations ranged from 0.44 to 0.76). Similar results were noted for plasma. We conclude that standardization of EBV serology assays is needed to allow for comparability of results obtained in different translational research studies across laboratories and populations

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