Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial

PMCID: PMC3691177This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

High morbid-mortability and reduced level of osteoporosis diagnosis among elderly people who had hip fractures in São Paulo City

OBJECTIVE: To know the morbid-mortality following an osteoporotic hip fracture in elderly patients living in São Paulo. PATIENTS AND METHODS: This study evaluated prospectively all patient over 60 years admitted in 2 school-hospitals in the city of São Paulo in a following 6-month period due to a osteoporotic proximal femur fracture. All of them filled up the Health Assessment Questionnaire (HAQ) and had their chart reviewed. After 6 months they were re-interviewed. Linear regression analysis was utilized to determine the factors related to functional ability. RESULTS: 56 patients were included (mean age 80.7 ± 7.9 years old, 80.4% females). After the 6-month follow up the mortality rate was 23.2%. Only 30% of the patients returned to their previous activities, and 11.6% became totally dependent. Factors related to worse functional ability after fracture were HAQ before fracture, institutionalization after fracture and age (r² 0.482). The diagnosis of osteoporosis was informed only by 13.9% of them, and just 11.6% received any treatment for that. CONCLUSION: Our results showed the great impact of these fractures on mortality and in the functional ability of these patients. Nevertheless, many of our physicians do not inform the patients about the diagnosis of osteoporosis and, consequently, the treatment of this condition is jeopardized.As fraturas osteoporóticas de fêmur proximal trazem graves conseqüências quanto à morbimortalidade e à qualidade de vida, mas desconhece-se este impacto no Brasil. OBJETIVO: Conhecer a morbimortalidade decorrente deste tipo de fraturas em idosos na cidade de São Paulo. MÉTODOS: Foram incluídos todos os pacientes com mais de 60 anos internados por fraturas de fêmur proximal durante seis meses, em dois hospitais de São Paulo. Os pacientes preencheram o questionário de capacidade funcional (HAQ), tiveram seu prontuário examinado e foram reavaliados após seis meses. Utilizou-se a análise de regressão linear para determinar os fatores relacionados à capacidade funcional. RESULTADOS: Cinqüenta e seis pacientes foram incluídos no estudo (80,7 ± 7,9 anos; 80,4% mulheres). A mortalidade em seis meses foi de 23,2%. Apenas 30% retornaram plenamente às suas atividades prévias e 11,6% tornaram-se completamente dependentes. Os fatores que mais bem conseguiram prever pior capacidade funcional após a fratura foram HAQ pré-fratura, institucionalização pós-fratura e idade (r² 0,482). Somente 13,9% receberam o diagnóstico de osteoporose e 11,6% iniciaram algum tratamento. CONCLUSÕES: Os resultados do presente estudo demonstram o impacto deste tipo de fraturas sobre a mortalidade e a capacidade funcional. Entretanto, a falha médica no diagnóstico e na orientação de tratamento da osteoporose permanece elevada.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaSanta Casa de Misericórdia de São Paulo Departamento de OrtopediaUNIFESP-EPM EPMUNIFESP, EPM, EPMSciEL

Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

The immune response is crucial for protection against disease; however, immunological imbalances can lead to heart and digestive tract lesions in chagasic patients. Several studies have evaluated the cellular and humoral immune responses in chagasic patients in an attempt to correlate immunological findings with clinical forms of Chagas disease. Moreover, immunoglobulins and cytokines are important for parasitic control and are involved in lesion genesis. Here, cytokine and IgG isotype production were studied, using total epimastigote antigen on sera of chagasic patients with indeterminate (IND, n = 27) and cardiac (CARD, n = 16) forms of the disease. Samples from normal, uninfected individuals (NI, n = 30) were use as controls. The results showed that sera from both IND and CARD patients contained higher levels of Trypanosoma cruzi-specific IgG1 (IgG1) antibodies than sera from NI. No difference in IgG2 production levels was observed between NI, IND and CARD patients, nor was a difference in IL-10 and IFN-³ production detected in the sera of IND, CARD and NI patients. However, IND patients displayed a positive correlation between IL-10 and IFN-³ levels in serum, while CARD patients showed no such correlation, indicating an uncontrolled inflammatory response in CARD patients. These findings support the hypothesis that a lack of efficient regulation between IFN-³ and IL-10 productions in CARD patients may lead to cardiac immunopathology.CNP

Stomach cancer and occupational exposure to asbestos: a meta-analysis of occupational cohort studies

BACKGROUND: A recent Monographs Working Group of the International Agency for Research on Cancer concluded that there is limited evidence for a causal association between exposure to asbestos and stomach cancer. METHODS: We performed a meta-analysis to quantitatively evaluate this association. Random effects models were used to summarise the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. RESULTS: We identified 40 mortality cohort studies from 37 separate papers, and cancer incidence data were extracted for 15 separate cohorts from 14 papers. The overall meta-SMR for stomach cancer for total cohort was 1.15 (95% confidence interval 1.03–1.27), with heterogeneous results across studies. Statistically significant excesses were observed in North America and Australia but not in Europe, and for generic asbestos workers and insulators. Meta-SMRs were larger for cohorts reporting a SMR for lung cancer above 2 and cohort sizes below 1000. CONCLUSIONS: Our results support the conclusion by IARC that exposure to asbestos is associated with a moderate increased risk of stomach cancer

Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism

Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of genetic loci. The convergence of ASD variants have been investigated using various approaches, including protein interactions extracted from the published literature. However, these datasets are frequently incomplete, carry biases and are limited to interactions of a single splicing isoform, which may not be expressed in the disease-relevant tissue. Here we introduce a new interactome mapping approach by experimentally identifying interactions between brain-expressed alternatively spliced variants of ASD risk factors. The Autism Spliceform Interaction Network reveals that almost half of the detected interactions and about 30% of the newly identified interacting partners represent contribution from splicing variants, emphasizing the importance of isoform networks. Isoform interactions greatly contribute to establishing direct physical connections between proteins from the de novo autism CNVs. Our findings demonstrate the critical role of spliceform networks for translating genetic knowledge into a better understanding of human diseases

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Following damage, the majority of bone marrow-derived airway cells express an epithelial marker

<p>Abstract</p> <p>Background</p> <p>Adult-derived bone marrow stem cells are capable of reconstituting the haematopoietic system. However there is ongoing debate in the literature as to whether bone marrow derived cells have the ability to populate other tissues and express tissue specific markers. The airway has been an organ of major interest and was one of the first where this was demonstrated. We have previously demonstrated that the mouse airway can be repopulated by side population bone marrow transplanted cells. Here we investigate the frequency and phenotypic nature of these bone marrow derived cells.</p> <p>Methods</p> <p>Female mice were engrafted with male whole bone marrow or side population (SP) cells and subjected to detergent-induced damage after 3 months. Donor cells were identified by Y chromosome fluorescence in situ hybridisation and their phenotype was assessed by immunohistochemistry on the same sections. Slides were visualised by a combination of widefield and deconvolved microscopy and whole cells were analysed on cytospin preparations.</p> <p>Results</p> <p>The frequencies of engraftment of male cells in the airway of mice that show this (9/10), range from 1.0 – 1.6% with whole marrow and 0.6 – 1.5% with SP cells. Undamaged controls have only between 0.1 and 0.2% male cells in the trachea. By widefield microscopy analysis we find 60.2% (53/88) of male donor derived cells express cytokeratins as a marker of epithelial cells. These results were reinforced using deconvolved microscopy and scored by two independent investigators. In addition cytospin analysis of cells dissociated from the damaged trachea of engrafted mice also reveals donor derived Y chromosome positive cells that are immunopositive for cytokeratin. Using cytokeratin and the universal haematopoietic marker CD45 immunohistochemistry, we find the donor derived cells fall into four phenotypic classes. We do not detect cytokeratin positive cells in whole bone marrow using cytokeratin immunostaining and we do not detect any cytokeratin mRNA in SP or bone marrow samples by RT-PCR.</p> <p>Conclusion</p> <p>The appearance of bone marrow derived cells in the tracheal epithelium is enriched by detergent-induced tissue damage and the majority of these cells express an epithelial marker. The cytokeratin positive donor derived cells in the tracheal epithelium are not present in the injected donor cells and must have acquired this novel phenotype <it>in vivo</it>.</p

Normal Hematopoietic Stem Cell Function in Mice with Enforced Expression of the Hippo Signaling Effector YAP1

The Hippo pathway has recently been implicated in the regulation of organ size and stem cells in multiple tissues. The transcriptional cofactor yes-associated protein 1 (Yap1) is the most downstream effector of Hippo signaling and is functionally repressed by the upstream components of the pathway. Overexpression of YAP1 stimulates proliferation of stem and progenitor cells in many tissues, consistent with inhibition of Hippo signaling. To study the role of Hippo signaling in hematopoietic stem cells (HSCs), we created a transgenic model with inducible YAP1 expression exclusively within the hematopoietic system. Following 3 months induction, examination of blood and bone marrow in the induced mice revealed no changes in the distribution of the hematopoietic lineages compared to control mice. Moreover, the progenitor cell compartment was unaltered as determined by colony forming assays and immunophenotyping. To address whether YAP1 affects the quantity and function of HSCs we performed competitive transplantation experiments. We show that ectopic YAP1 expression does not influence HSC function neither during steady state nor in situations of hematopoietic stress. This is in sharp contrast to effects seen on stem- and progenitor cells in other organs and suggests highly tissue specific functions of the Hippo pathway in regulation of stem cells