Molecular Analysis of a Multistep Lung Cancer Model Induced by Chronic Inflammation Reveals Epigenetic Regulation of p16 and Activation of the DNA Damage Response Pathway

The molecular hallmarks of inflammation-mediated lung carcinogenesis have not been fully clarified, mainly due to the scarcity of appropriate animal models. We have used a silica-induced multistep lung carcinogenesis model driven by chronic inflammation to study the evolution of molecular markers and genetic alterations. We analyzed markers of DNA damage response (DDR), proliferative stress, and telomeric stress: γ-H2AX, p16, p53, and TERT. Lung cancer-related epigenetic and genetic alterations, including promoter hypermethylation status of p16(CDKN2A), APC, CDH13, Rassf1, and Nore1A, as well as mutations of Tp53, epidermal growth factor receptor, K-ras, N-ras, and c-H-ras, have been also studied. Our results showed DDR pathway activation in preneoplastic lesions, in association with inducible nitric oxide synthase and p53 induction. p16 was also induced in early tumorigenic progression and was inactivated in bronchiolar dysplasias and tumors. Remarkably, lack of mutations of Ras and epidermal growth factor receptor, and a very low frequency of Tp53 mutations suggest that they are not required for tumorigenesis in this model. In contrast, epigenetic alterations in p16(CDKN2A), CDH13, and APC, but not in Rassf1 and Nore1A, were clearly observed. These data suggest the existence of a specific molecular signature of inflammation-driven lung carcinogenesis that shares some, but not all, of the molecular landmarks of chemically induced lung cancer.     

Predictors of patient satisfaction with hospital health care

Background  

We used a validated inpatient satisfaction questionnaire to evaluate the health care received by patients admitted to several hospitals. This questionnaire was factored into distinct domains, creating a score for each to assist in the analysis.     

Health-related quality of life and appropriateness of cholecystectomy

OBJECTIVE: To evaluate the relationship among appropriateness of the use of cholecystectomy and outcomes. SUMMARY BACKGROUND DATA: The use of cholecystectomy varies widely across regions and countries. Explicit appropriateness criteria may help identify suitable candidates for this commonly performed procedure. This study evaluates the relationship among appropriateness of the use of cholecystectomy and outcomes. METHODS: Prospective observational study in 6 public hospitals in Spain of all consecutive patients on waiting lists to undergo cholecystectomy for nonmalignant disease. Explicit appropriateness criteria for the use of cholecystectomy were developed by a panel of experts using the RAND appropriateness methodology and applied to recruited patients. Patients were asked to complete 2 questionnaires that measure health-related quality of life-the Short Form 36 (SF-36) and the Gastrointestinal Quality of Life Index (GIQLI)-before the intervention and 3 months after it. RESULTS: Patients judged as being appropriate candidates for cholecystectomy, using the panel's explicit appropriateness criteria, had greater improvements in the bodily pain, vitality, and social function domains of the SF-36 than those judged to be inappropriate candidates. They also demonstrated improvements in the GIQLI's physical impairment domain. Interventions judged as inappropriate were performed primarily among patients without symptoms of cholelithiasis. Those asymptomatic had a lower improvement in the bodily pain, social functioning, and physical summary scale of the SF-36 and in the symptomatology, physical impairment, and total score domains of the GIQLI. CONCLUSIONS: These results suggest a direct relationship between the application of explicit appropriateness criteria and better outcomes, as measured by health-related quality of life. They also indicate that patients without symptoms are not good candidates for cholecystectomy.     

Mucosal immunization of sheep with a Maedi-Visna virus (MVV) env DNA vaccine protects against early MVV productive infection

Gene gun mucosal DNA immunization of sheep with a plasmid expressing the env gene of Maedi-Visna virus (MVV) was used to examine the protection against MVV infection in sheep from a naturally infected flock. For immunization, sheep were primed with a pcDNA plasmid (pcDNA-env) encoding the Env glycoproteins of MVV and boosted with combined pcDNA-env and pCR3.1-IFN-gamma plasmid inoculations. The pcDNA plasmid used in the control group contained the lacZ coding sequences instead of the env gene. Within a month post-challenge, the viral load in the vaccinated group was lower (p < or = 0.05) and virus was only detected transiently compared with the control group. Furthermore, 2 months later, neutralizing antibodies (NtAb) were detected in all the control animals and none of the vaccinated animals (p < or = 0.01). These results demonstrated a significant early protective effect of this immunization strategy against MVV infection that restricts the virus replication following challenge in the absence of NtAb production. This vaccine protective effect against MVV infection disappeared after two years post-challenge, when active replication of MVV challenge strain was observed. Protection conferred by the vaccine could not be explained by OLA DRB1 allele or genotype differences. Most of the individuals were DRB1 heterozygous and none was totally resistant to infection.     

Adult health

The objective of this study is to analyse the social inequalities in health status, health related behaviours and mortality among the 25-64 years Spanish population. Data come from the 1997 Spanish National Health Survey, the 1999 Spanish National Survey on Working Conditions, the 2001 Yearbook of Labour and Social Affairs Statistics and the 1998 Mortality Statistics. Most health-related behaviours are more unfavourable for men (smoking, alcohol consumption and overweight) and for less privileged social classes. Among women, entrance into the labour market is associated with more unhealthy behaviours except for overweight. Low weight, however, is more frequent among employed females. Self-perceived health status is better among men, more privileged social class persons and among workers. Whereas classical physical job hazards and work injuries mostly affect men, the impact of psychosocial job hazards and of exposures derived from the domestic work is higher for women. As in other developed countries, the paradox exists that whereas women have a poorer self-perceived health status, mortality is higher among men. The male excess in mortality is related to health-related behaviours that to a great extent are determined by traditional values assigned to masculinity, with higher consumption of tobacco (lung cancer), alcohol (cirrhosis), drugs (HIV and AIDS) and risky behaviours related to injuries. Health policies should take into account social inequalities in health determined by gender, social class and employment status. For doing so, it is important to increase the development of research on social inequalities and of health information systems sensitive to social inequalities.     

Women, family demands and health: the importance of employment status and socio-economic position

Although it is generally assumed that women engaged in paid work have better health than full-time homemakers, little is known about the situation in Southern European countries like Spain or about differences in the impact of family demands by employment status or the potential interaction with educational level. The objectives of this study are to analyse whether inequalities in health exist among housewives and employed women, and to assess whether the relationship between family demands and health differs by employment status. Additionally, for both objectives we examine the potential different patterns by educational level. The data have been taken from the 1994 Catalonian Health Survey (Spain). The sample was drawn from all women aged 25-64 years who were employed or full-time homemakers and married or cohabiting. Four health indicators (self-perceived health status, limiting long-standing illness, chronic conditions and mental health) and two health related behaviours (hours of sleeping and leisure-time physical activity) were analysed. Family demands were measured through household size, living with children under 15 and living with elderly. Overall, female workers had a better health status than housewives, although this pattern was more consistent for women of low educational level. Conversely, the health related behaviours analysed were less favourable for workers, mainly for those of low educational level. Among workers of low educational level, family demands showed a negative effect in most health indicators and health related behaviours, but had little or no negative association at all in workers of high educational level or in full-time homemakers. Moreover, among women of low educational level, both workers and housewives, living with elderly had showed a negative association with poor health status and health related behaviours. These results emphasise the need of considering the interaction between family demands, employment status and educational level in analysing the impact of family demands on women's health as well as in designing family policies and programmes of women's health promotion.