The biological activity of hybrids
2 was evaluated in vitro on human uterine and ovarian cancers. The molecules present high affinity for the estrogen receptor alpha. The cytotoxicity and the ...affinity of
2 are explained by molecular modeling analysis.
We have recently reported the synthesis of a series of original 17β-estradiol-linked platinum(II) hybrid molecules. The biological activity of these compounds was evaluated in vitro on estrogen dependent and independent (ER
+ and ER
−) human uterine and ovarian cancers. The hybrid molecules present higher affinity than that of 17β-estradiol for the estrogen receptor alpha (ERα). The cytotoxicity and the affinity of the hybrid molecules are explained using molecular modeling analysis. This study further confirms that the derivatives made of a 2-(2′-aminoethyl)pyridine ligand displayed superior activity against the cell lines particularly when the connecting arm is 8–10 carbon atoms long. Molecular modeling shows that a long side chain can facilitate the access of the platinum(II) moiety to DNA. The novel compounds also prove to be moderately cytotoxic against platinum resistant endometrial and ovarian cancer cell lines.
The first intention of this research is to test if Wells and Gubar's model (1966) of consumer behavior, based on the life cycle, still explains the Canadian population's consumption behavior. A ...second objective, if warranted, is to determine the possibility to segment the Canadian population based on life cycles with the aim of explaining garment/apparel consumption. Using the Survey of Household Spending from Statistics Canada (2009), this article analyses total clothing expenditures and their subcategories of expenses for women and girls, men and boys, and children. Each expense is analyzed using two different data: (1) gross amount of money spent annually and (2) percentage of the category on household total spending. The three hypotheses of this research are validated, confirming (H1) the non-representativeness of Wells and Gubar's model; (H2) the importance of integrating single households in the life-cycle model since their purchase behaviors are significantly different from those of traditional households; (H3) the possibility to segment based on life-cycle criteria to better understand Canadian realities.
In human endometrial cancer, the fourth most common cancer in women, tumor suppressor phosphatase tensin homologue (PTEN) is frequently mutated. In the presence of a mutated PTEN protein, Akt ...phosphorylation levels are increased leading to the activation of this survival pathway. Numerous studies indicated that COX-2 is inappropriately induced and up-regulated in a number of malignant cancer cells. COX-2 plays an important role in tumor cell biology, taking part actively in angiogenesis particularly via the production of prostaglandin E2 (PGE2). The present study was undertaken to determine the involvement of PI 3-K/Akt pathway in the regulation of COXs expression and PGE2 synthesis. Three different human endometrial cancer cell lines known to have wild-type PTEN (HEC 1-A) or a mutated inactive PTEN protein (RL 95-2 and Ishikawa) were used for these studies. Results showed that Akt phosphorylation was high in mutated PTEN cells. RT-PCR studies revealed that Akt1 and Akt2 were the regulated forms whereas Akt3 mRNA was nearly undetectable. COX-2 mRNA expression and protein levels were high in these cells compared to wild-type PTEN cells as demonstrated by RT-PCR and Western analysis respectively. PGE2 production was higher in mutated-PTEN expressing phospho-Akt and COX-2 compared to wild-type PTEN cells. Inhibition of PI 3-K with Wortmannin and LY294002 blocked Akt phosphorylation and inhibited expression of COX-2 in mutated-PTEN cells. Inhibition of Akt phosphorylation with specific PI 3-K inhibitors and down-regulation of COX-2 increased apoptosis in human endometrial cancer cells. Likewise, transfection of mutated-PTEN cells with a dominant negative Akt vector, resulted in COX-2 down-regulation and activation of apoptosis, as demonstrated by Hoechst nuclear staining. On the opposite, activation of Akt using a constitutively active expression vector, resulted in the up-regulation of COX-2 protein expression. Specific inhibition of COX-2 with NS-398 induced apoptosis in COX-2 expressing human endometrial cancer cells. It is concluded that the PI 3-K/Akt survival pathway is involved in the regulation of COX-2 and PGE2 synthesis in human endometrial cancer cells.
The accepted standard in estimating the stay prolongation attributable to surgical site infections is the matched-cohort study method (MCS), which is associated with selection bias. The ...Appropriateness Evaluation Protocol (AEP) has been used to estimate stay prolongation attributable to nosocomial infections but has not been validated specifically for surgical site infections.
To compare estimates of stay prolongation attributable to surgical site infections after digestive surgery, obtained by AEP and by MCS.
Sixty-five surgical site infections after digestive tract surgery were analyzed by AEP and MCS. AEP stay prolongation was the number of days judged specifically appropriate for the care of surgical site infections. MCS stay prolongation was the difference of stay duration in surgical site infection cases and two controls matched by age, sex, and diagnosis-related groups. Sensitivity and specificity of AEP, and agreement between both methods, were calculated.
The mean AEP stay prolongation was 3.5 days vs 7.2 days for MCS. The sensitivity of AEP was 58% and the specificity was 75%. The agreement between the two methods was poor.
Surgical site infections after digestive tract surgery increased the hospital stay. Accurate estimations of a prolongation of stay will vary according to the method selected.
We compared the effects of cycling and running exercise on hemorheological and hematological properties, as well as eryptosis markers. Seven endurance‐trained subjects randomly performed a ...progressive and maximal exercise test on a cycle ergometer and a treadmill. Blood was sampled at rest and at the end of the exercise to analyze hematological and blood rheological parameters including hematocrit (Hct), red blood cell (RBC) deformability, aggregation, and blood viscosity. Hemoglobin saturation (SpO2), blood lactate, and glucose levels were also monitored. Red blood cell oxidative stress, calcium content, and phosphatidylserine exposure were determined by flow cytometry to assess eryptosis level. Cycling exercise increased blood viscosity and RBC aggregation whereas it had no significant effect on RBC deformability. In contrast, blood viscosity remained unchanged and RBC deformability increased with running. The increase in Hct, lactate, and glucose concentrations and the loss of weight at the end of exercise were not different between running and cycling. Eryptosis markers were not affected by exercise. A significant drop in SpO2 was noted during running but not during cycling. Our study showed that a progressive and maximal exercise test conducted on a cycle ergometer increased blood viscosity while the same test conducted on a treadmill did not change this parameter because of different RBC rheological behavior between the 2 tests. We also demonstrated that a short maximal exercise does not alter RBC physiology in trained athletes. We suspect that exercise‐induced hypoxemia occurring during running could be at the origin of the RBC rheological behavior differences with cycling.
Purpose
– For the past 50 years, the research literature has shown that employment can contribute to an individual's personal development. Yet, it has also shown that it can become a life-threatening ...stressor. Reported occupational suicides increased by 22.2 percent between 1995 and 2010, becoming a leading cause of death in the USA. The purpose of this paper is to present the results of six US government reports on employee suicides between 1995 and 2012.
Design/methodology/approach
– Through an interpretive case study approach (Yin, 2003), this study undertook a document analysis of key US government reports examining occupational suicides. Specifically, an analysis of three US Bureau of Labor Statistics reports was undertaken along with other documents, identifying key themes and facts.
Findings
– The analysis of the US government reports reveals a dim legal recognition of employee suicide as an occupational accident. The paper presents the characteristics of suicides as an occupational accident as well as the profile of a typical US occupational suicide victim. Finally, the paper discusses the main causes of employee suicide.
Practical implications
– Organizations have a “duty of care” to their employees, both physical and psychological. Human resource (HR) professionals ought to create preventive policies to minimize work-related suicides and have clear crisis management systems in place, should an employee commit suicide or threaten to do so.
Originality/value
– Occupational distress is not typically apparent or obvious and is not the subject of many studies in the field of HRs. Yet, because of its rampant increase in today's organizations, its direct connection with employee suicide and its impact on organizational revenues, psychological distress in the workplace merits closer attention. This paper is unique as it provides insights for HR professionals based on the analysis of US government reports on work-related suicides.
Hereditary Protein S (PS) deficiency is a rare coagulation disorder associated with an increased risk of venous thrombosis (VT). The PS Heerlen (PSH) mutation is a rare S501P mutation that was ...initially considered to be a neutral polymorphism. However, it has been later shown that PSH has a reduced half-life in vivo which may explain the association of PSH heterozygosity with mildly reduced levels of plasma free PS (FPS). Whether the risk of VT is increased in PSH carriers remains unknown. We analyzed the association of PSH (rs121918472 A/G) with VT in 4,173 VT patients and 5,970 healthy individuals from four independent case-control studies. Quantitative determination of FPS levels was performed in a subsample of 1257 VT patients. In the investigated populations, the AG genotype was associated with an increased VT risk of 6.57 4.06-10.64 (p = 1.73 10
). In VT patients in whom PS deficiency was excluded, plasma FPS levels were significantly lower in individuals with PSH when compared to those without 72 + 13 vs 91 + 21 UI/dL; p = 1.86 10
, mean + SD for PSH carriers (n = 21) or controls (n = 1236) respectively. We provide strong evidence that the rare PSH variant is associated with VT in unselected individuals.
Cette étude s’inscrit dans l’optique de l’école inclusive en voulant relever de bonnes pratiques éducatives à mettre en place pour favoriser la réussite scolaire des élèves autistes en classe ...régulière, dans le cadre du passage entre l’ordre primaire et l’ordre secondaire. Les données recueillies s’appuient sur une recherche-action menée durant deux ans dans trois écoles de deux régions administratives du Québec. Des intervenants (n=25), des élèves autistes (n=11) et leurs parents (n=10) ont fait ressortir des aspects marquants relatifs à des pratiques à mettre en place pour favoriser l’éducation inclusive de tous. Les résultats indiquent qu’il s’avère impératif d’offrir des formations aux intervenants de classe ordinaire, sur la compréhension du schème de pensée de l’élève autiste. Les résultats soulignent également l’importance, pour les décideurs, d’assouplir les horaires de travail pour favoriser la mise en place d’une collaboration entre ressources des ordres d’enseignement primaire et secondaire et celles des réseaux communautaires et de réadaptation.
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