23 research outputs found

    Tobacco Exposure Enhances Human Papillomavirus 16 Oncogene Expression via EGFR/PI3K/Akt/c-Jun Signaling Pathway in Cervical Cancer Cells

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    High-risk human papillomavirus (HR-HPV) infection is not a sufficient condition for cervical cancer development because most infections are benign and naturally cleared. Epidemiological studies revealed that tobacco smoking is a cofactor with HR-HPV for cervical cancer initiation and progression, even though the mechanism by which tobacco smoke cooperates with HR-HPV in this malignancy is poorly understood. As HR-HPV E6/E7 oncoproteins overexpressed in cervical carcinomas colocalize with cigarette smoke components (CSC), in this study we addressed the signaling pathways involved in a potential interaction between both carcinogenic agents. Cervical cancer-derived cell lines, CaSki (HPV16; 500 copies per cell) and SiHa (HPV16; 2 copies per cell), were acutely exposed to CSC at various non-toxic concentrations and we found that E6 and E7 levels were significantly increased in a dose-dependent manner. Using a reporter construct containing the luciferase gene under the control of the full HPV16 long control region (LCR), we also found that p97 promoter activity is dependent on CSC. Non-synonymous mutations in the LCR-resident TPA (12-O-tetradecanoylphorbol 13-acetate)-response elements (TRE) had significantly decreased p97 promoter activation. Phosphoproteomic arrays and specific inhibitors revealed that CSC-mediated E6/E7 overexpression is at least in part reliant on EGFR phosphorylation. In addition, we showed that the PI3K/Akt pathway is crucial for CSC-induced E6/E7 overexpression. Finally, we demonstrated that HPV16 E6/E7 overexpression is mediated by JUN. overexpression, c-Jun phosphorylation and recruitment of this transcription factor to TRE sites in the HPV16 LCR. We conclude that acute exposure to tobacco smoke activates the transcription of HPV16 E6 and E7 oncogenes through p97 promoter activation, which involves the EGFR/PI3K/Akt/C-Jun signaling pathway activation in cervical cancer cells

    Efectos del genotipo, tamaño de la camada y el sexo sobre las características de la canal y el perfil de ácidos grasos en corderos de pelo

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    The effect of the genotype (Pelibuey vs Katahdin), type of lambing (single vs. double) and sex (males vs. females) on the characteristics of the carcass and its cuts, in addition to the fatty acid profile of the loin were evaluated in 66 lambs slaughtered at weaning. The yield of the carcass and ribs were higher (P<0.05) in the Pelibuey breed. Slaughter weight, carcass weight and rib yield were higher (P<0.01) in single-born lambs, while the yield of shoulder and leg were lower (P<0.01) than in double-born lambs. The proportion of soft tissue of the different cuts was higher (P<0.05), but that of bone was lower (P< 0.05) in single-born lambs than in double-born lambs. Females had a higher (P<0.05) proportion of soft tissue and a lower proportion of bone (P<0.01) than males. The concentrations of C18:1n7 and C20:4n-6 were higher (P<0.05) in the Pelibuey breed than in the Katahdin breed, while the C22:5n-3 and C22:6n-3 were lower. The percentage of monounsaturated fatty acids was higher (P<0.05) in the meat of single-born lambs, while that of total polyunsaturated fatty acids and n-3 was higher (P<0.05) in double-born lambs. The characteristics of the carcass, the tissue composition of the commercial cuts and the fatty acid profile in hair sheep slaughtered at weaning varied more due to the type of lambing than due to the genotype or sex.El efecto del genotipo (Pelibuey vs Katahdin), tipo de parto (simple vs dobles) y sexo (machos vs. hembras) sobre las características de la canal y de sus cortes, además del perfil de ácidos grasos del lomo fueron evaluados en 66 corderos sacrificados al destete. El rendimiento de la canal y del costillar fue mayor (P<0.05) en la raza Pelibuey. El peso al sacrificio, peso de canal y rendimiento del costillar fue mayor (P<0.01) en crías de parto simple, mientras que el rendimiento de paleta y pierna fue menor (P< 0.01) que en crías de parto doble. La proporción del tejido blando de los diferentes cortes fue mayor (P<0.05), pero el de hueso fue menor (P< 0.05) en crías de parto simple que las de parto doble. Las hembras tuvieron mayor (P<0.05) proporción de tejido blando y menor proporción de hueso (P<0.01) que los machos. Las concentraciones de C18:1n7 y C20:4n-6 fueron mayores (P< 0.05) en la raza Pelibuey que, en la Katahdin, mientras que los C22:5n-3 y C22:6n-3 fueron menores. El porcentaje de ácidos grasos monoinsaturados fue mayor (P<0.05) en la carne de crías de partos simples, en tanto que el de los ácidos grasos poliinsaturados totales y n-3 fue mayor (P<0.05) en crías de partos dobles. Las características de la canal, la composición tisular de los cortes comerciales y el perfil de ácidos grasos en ovinos de pelo sacrificados al destete mostraron más cambios por el tipo de parto que por el genotipo o el sexo

    Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

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    Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

    Valor monetario de la leche materna en Bolivia

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    Objetivos. Estimar el volumen de leche materna consumido por los niños bolivianos de < 36 meses de edad y el valor monetario de la sustitución de dicho volumen de leche materna con sucedáneos comerciales. Métodos. Para el análisis se tuvieron en cuenta la distribución de la población infantil por grupos de edad, la prevalencia de las diferentes prácticas de lactancia materna (exclusiva o parcial) en cada grupo de edad, el volumen promedio de leche materna consumido por los lactantes de un grupo de edad determinado y el costo de la producción y sustitución de la leche materna. Resultados. Los lactantes bolivianos consumen anualmente más de 161 millones de litros de leche materna, lo que representa un volumen promedio de 573 mL/día por cada lactante menor de un año. El valor monetario de la leche materna consumida por los lactantes bolivianos asciende a US274millonesanuales.Elcostopromediodesustituirlalechematernaconsucedaˊneoscomercialesenunlactanteamamantadoadecuadamenteelprimeran~odevidaasciendeaUS 274 millones anuales. El costo promedio de sustituir la leche materna con sucedáneos comerciales en un lactante amamantado adecuadamente el primer año de vida asciende a US 407. Discusión. Para que la formulación y consolidación de políticas y programas de protección, promoción y apoyo a la lactancia materna sean una realidad, los líderes políticos de Bolivia han de tomar conciencia del enorme valor monetario de la leche materna

    Virtual Teams in Times of Pandemic: Factors That Influence Performance

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    In the digital age, the global software development sector has been a forerunner in implementing new ways and configurations for remote teamwork using information and communication technologies on a widespread basis. Crises and technological advances have influenced each other to bring about changes in the ways of working. In the 70’s of the last century, in the middle of the so-called oil crisis, the concept of teleworking was defined using remote computer equipment to access office equipment and thus avoid moving around using traditional vehicles. Then from the 90s, with the advent of communications and the widespread use of the Internet, the first virtual work teams were implemented in software development companies that already had some of the important characteristics needed to work in this way, such as, cultural diversity, characterized tasks, geographical distribution of members, communication, interdependence of tasks, leadership, cohesion, empowerment, confidence, virtuality. This manuscript groups the main factors into different models proposed by the literature and also analyzes the results of a study conducted in the midst of the Covid-19 crisis on 317 software development teams that had to work in virtual teams (VT). The results of the quantitative methodology with structural equation modeling based on variance using the partial least squares route method are analyzed. The results of the research focus on some determinants that can directly affect the performance of the virtual team. A first determinant is communication in relation to the tasks. The second is trust in relation to leadership, empowerment and cohesion. The results of virtual teams provide information that can serve as a basis for future research lines for the implementation of virtual work strategies in post-pandemic work
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