Observation of Live Ticks (Haemaphysalis flava) by Scanning Electron Microscopy under High Vacuum Pressure

Scanning electron microscopes (SEM), which image sample surfaces by scanning with an electron beam, are widely used for steric observations of resting samples in basic and applied biology. Various conventional methods exist for SEM sample preparation. However, conventional SEM is not a good tool to observe living organisms because of the associated exposure to high vacuum pressure and electron beam radiation. Here we attempted SEM observations of live ticks. During 1.5×10−3 Pa vacuum pressure and electron beam irradiation with accelerated voltages (2–5 kV), many ticks remained alive and moved their legs. After 30-min observation, we removed the ticks from the SEM stage; they could walk actively under atmospheric pressure. When we tested 20 ticks (8 female adults and 12 nymphs), they survived for two days after SEM observation. These results indicate the resistance of ticks against SEM observation. Our second survival test showed that the electron beam, not vacuum conditions, results in tick death. Moreover, we describe the reaction of their legs to electron beam exposure. These findings open the new possibility of SEM observation of living organisms and showed the resistance of living ticks to vacuum condition in SEM. These data also indicate, for the first time, the usefulness of tick as a model system for biology under extreme condition

Delta1 Expression, Cell Cycle Exit, and Commitment to a Specific Secretory Fate Coincide within a Few Hours in the Mouse Intestinal Stem Cell System

The stem cells of the small intestine are multipotent: they give rise, via transit-amplifying cell divisions, to large numbers of columnar absorptive cells mixed with much smaller numbers of three different classes of secretory cells - mucus-secreting goblet cells, hormone-secreting enteroendocrine cells, and bactericide-secreting Paneth cells. Notch signaling is known to control commitment to a secretory fate, but why are the secretory cells such a small fraction of the population, and how does the diversity of secretory cell types arise? Using the mouse as our model organism, we find that secretory cells, and only secretory cells, pass through a phase of strong expression of the Notch ligand Delta1 (Dll1). Onset of this Dll1 expression coincides with a block to further cell division and is followed in much less than a cell cycle time by expression of Neurog3 – a marker of enteroendocrine fate – or Gfi1 – a marker of goblet or Paneth cell fate. By conditional knock-out of Dll1, we confirm that Delta-Notch signaling controls secretory commitment through lateral inhibition. We infer that cells stop dividing as they become committed to a secretory fate, while their neighbors continue dividing, explaining the final excess of absorptive over secretory cells. Our data rule out schemes in which cells first become committed to be secretory, and then diversify through subsequent cell divisions. A simple mathematical model shows how, instead, Notch signaling may simultaneously govern the commitment to be secretory and the choice between alternative modes of secretory differentiation

Dysregulation of the transcription factors SOX4, CBFB and SMARCC1 correlates with outcome of colorectal cancer

The aim of this study was to identify deregulated transcription factors (TFs) in colorectal cancer (CRC) and to evaluate their relation with the recurrence of stage II CRC and overall survival. Microarray-based transcript profiles of 20 normal mucosas and 424 CRC samples were used to identify 51 TFs displaying differential transcript levels between normal mucosa and CRC. For a subset of these we provide in vitro evidence that deregulation of the Wnt signalling pathway can lead to the alterations observed in tissues. Furthermore, in two independent cohorts of microsatellite-stable stage II cancers we found that high SOX4 transcript levels correlated with recurrence (HR 2.7; 95% CI, 1.2–6.0; P=0.01). Analyses of ∼1000 stage I–III adenocarcinomas, by immunohistochemistry, revealed that patients with tumours displaying high levels of CBFB and SMARCC1 proteins had a significantly better overall survival rate (P=0.0001 and P=0.0275, respectively) than patients with low levels. Multivariate analyses revealed that a high CBFB protein level was an independent predictor of survival. In conclusion, several of the identified TFs seem to be involved in the progression of CRC

Multi-Level Interactions between the Nuclear Receptor TRα1 and the WNT Effectors β-Catenin/Tcf4 in the Intestinal Epithelium

Intestinal homeostasis results from complex cross-regulation of signaling pathways; their alteration induces intestinal tumorigenesis. Previously, we found that the thyroid hormone nuclear receptor TRα1 activates and synergizes with the WNT pathway, inducing crypt cell proliferation and promoting tumorigenesis. Here, we investigated the mechanisms and implications of the cross-regulation between these two pathways in gut tumorigenesis in vivo and in vitro. We analyzed TRα1 and WNT target gene expression in healthy mucosae and tumors from mice overexpressing TRα1 in the intestinal epithelium in a WNT-activated genetic background (vil-TRα1/Apc mice). Interestingly, increased levels of β-catenin/Tcf4 complex in tumors from vil-TRα1/Apc mice blocked TRα1 transcriptional activity. This observation was confirmed in Caco2 cells, in which TRα1 functionality on a luciferase reporter-assay was reduced by the overexpression of β-catenin/Tcf4. Moreover, TRα1 physically interacted with β-catenin/Tcf4 in the nuclei of these cells. Using molecular approaches, we demonstrated that the binding of TRα1 to its DNA target sequences within the tumors was impaired, while it was newly recruited to WNT target genes. In conclusion, our observations strongly suggest that increased β-catenin/Tcf4 levels i) correlated with reduced TRα1 transcriptional activity on its target genes and, ii) were likely responsible for the shift of TRα1 binding on WNT targets. Together, these data suggest a novel mechanism for the tumor-promoting activity of the TRα1 nuclear receptor

An exploratory study of the costs and consequences of prenatal care in the Family Health Program.

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Estudo exploratório de custos e conseqüências do pré-natal no Programa Saúde da Família

OBJECTIVE: To assess costs and consequences of prenatal care on perinatal morbidity and mortality. METHODS: Evaluation study using two types of analysis: implementation and efficiency analysis, carried out at 11 Family Health Units in the Recife, Northeastern Brazil, in 2006. The costs were calculated by means of the activity-based costing technique and the cost-effectiveness ratio was calculated for each consequence. Data sources were information systems of the Ministry of Health and worksheets of costs provided by the Health Department of Recife and Instituto de Medicina Integral Prof. Fernando Figueira. Healthcare units with implemented or partially implemented prenatal care were compared in terms of their cost-effectiveness and perinatal results. RESULTS: In 64% of the units, prenatal care was implemented with a mean total cost of R$39,226.88 and variation of R$ 3,841,87 to R$8,765.02 per healthcare unit. In the units with partially implemented prenatal care (36$ 30,092.61 (R$4,272.12 to R$ 11,774.68). The mean cost per pregnant woman was R$196.13 with implemented prenatal care and R$ 150.46 with partially implemented prenatal care. A higher proportion of low birth weight, congenital syphilis, perinatal and fetal deaths was found in the partially implemented group. CONCLUSIONS: Prenatal care is cost-effective for several studied consequences. The adverse effects measured by the health indicators were lower in the units with implemented prenatal care. The mean cost in the partially implemented group was higher, which suggests a possible waste of resources, as the teams' productivity is insufficient for the installed capacity.OBJETIVO: Avaliar custos e conseqüências da assistência pré-natal na morbimortalidade perinatal. MÉTODOS: Estudo avaliativo com dois tipos de análise - de implantação e de eficiência, realizado em 11 Unidades de Saúde da Família do Recife, PE, em 2006. Os custos foram apurados pela técnica activity-based costing e a razão de custo-efetividade foi calculada para cada conseqüência. As fontes de dados foram sistemas de informação do Ministério da Saúde e planilhas de custos da Secretaria de Saúde do Recife e do Instituto de Medicina Integral Prof. Fernando Figueira. As unidades de saúde com pré-natal implantado ou parcial foram comparadas quanto ao seu custo-efetividade e resultados perinatais. RESULTADOS: Em 64% das unidades, o pré-natal estava implantado com custo médio total de R$39.226,88 e variação de R$ 3.841,87 a R$8.765,02 por Unidade de Saúde. Nas unidades parcialmente implantadas (36$ 30.092,61 (R$4.272,12 a R$ 11.774,68). O custo médio por gestante foi de R$196,13 com pré-natal implantado e R$ 150,46 no parcial. Encontrou-se maior proporção de baixo peso ao nascer, sífilis congênita, óbitos perinatais e fetais no grupo parcialmente implantado. CONCLUSÕES: Pré-natal é custo-efetivo para várias conseqüências estudadas. Os efeitos adversos medidos pelos indicadores de saúde foram menores nas unidades com pré-natal implantado. O custo médio no grupo parcialmente implantado foi mais elevado, sugerindo possível desperdício de recursos, uma vez que a produtividade das equipes é insuficiente para a capacidade instalada.OBJETIVO: Evaluar costos y consecuencias de la asistencia prenatal en la morbimortalidad perinatal. MÉTODOS: Estudio evaluativo con dos tipos de análisis: de implantación y de eficiencia, realizado en 11 Unidades de Salud de la Familia de Recife, Sureste de Brasil, en 2006. Los costos fueron mejorados por la técnica activity-based costing y la razón de costo-efectividad fue calculada para cada consecuencia. Las fuentes de datos fueron sistemas de información del Ministerio de la Salud y planillas de costos de la Secretaria de la Salud de Recife y del Instituto de Medicina Integral Prof. Fernando Figueira. Las unidades de salud con prenatal implantado o parcial fueron comparadas con relación a su costo-efectividad y resultados perinatales. RESULTADOS: En 64% de las unidades, el prenatal estaba implantado con costo promedio total de R$39.226,88 y variación de R$ 3.841,87 a R$8.765,02 por unidad de salud. En las unidades parcialmente implantadas (36$ 30.092,61 (R$4.272,12 a R$ 11.774,68). El costo promedio por gestante fue de R$196,13 con prenatal implantado y R$ 150,46 en el parcial. Se encontró mayor proporción de bajo peso al nacer, sífilis congénita, óbitos perinatales y fetales en el grupo parcialmente implantado. CONCLUSIONES: El prenatal es costo-efectivo para varias consecuencias estudiadas. Los efectos adversos medidos por los indicadores de salud fueron menores en las unidades con prenatal implantado. El costo promedio en el grupo parcialmente implantado fue más elevado, sugiriendo posible desperdicio de recursos, dado que la productividad de los equipos es suficiente para la capacidad instalada

Pharmaceutical cost and multimorbidity with type 2 diabetes mellitus using electronic health record data

© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.[EN] Background: The objective of the study is to estimate the frequency of multimorbidity in type 2 diabetes patients classified by health statuses in a European region and to determine the impact on pharmaceutical expenditure. Methods: Cross-sectional study of the inhabitants of a southeastern European region with a population of 5,150,054, using data extracted from Electronic Health Records for 2012. 491,854 diabetic individuals were identified and selected through clinical codes, Clinical Risk Groups and diabetes treatment and/or blood glucose reagent strips. Patients with type 1 diabetes and gestational diabetes were excluded. All measurements were obtained at individual level. The prevalence of common chronic diseases and co-occurrence of diseases was established using factorial analysis. Results: The estimated prevalence of diabetes was 9.6 %, with nearly 70 % of diabetic patients suffering from more than two comorbidities. The most frequent of these was hypertension, which for the groups of patients in Clinical Risk Groups (CRG) 6 and 7 was 84.3 % and 97.1 % respectively. Regarding age, elderly patients have more probability of suffering complications than younger people. Moreover, women suffer complications more frequently than men, except for retinopathy, which is more common in males. The highest use of insulins, oral antidiabetics (OAD) and combinations was found in diabetic patients who also suffered cardiovascular disease and neoplasms. The average cost for insulin was 153€ and that of OADs 306€. Regarding total pharmaceutical cost, the greatest consumers were patients with comorbidities of respiratory illness and neoplasms, with respective average costs of 2,034.2€ and 1,886.9€. Conclusions: Diabetes is characterized by the co-occurrence of other diseases, which has implications for disease management and leads to a considerable increase in consumption of medicines for this pathology and, as such, pharmaceutical expenditure.This study was financed by a grant from the Fondo de Investigaciones de la Seguridad Social Instituto de Salud Carlos III, the Spanish Ministry of Health (FIS PI12/0037).Sancho Mestre, C.; Vivas Consuelo, DJJ.; Alvis, L.; Romero, M.; Usó Talamantes, R.; Caballer Tarazona, V. (2016). Pharmaceutical cost and multimorbidity with type 2 diabetes mellitus using electronic health record data. BMC Health Services Research. 16(394):1-8. https://doi.org/10.1186/s12913-016-1649-2S1816394Whiting DR, Guariguata L, Weil C, Shaw J. 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