Genetic determinants of human hypertension.

Hypertension is a common trait of multifactorial determination imparting an increased risk of myocardial infarction, stroke, and end-stage renal disease. The primary determinants of hypertension, as well as the factors which determine specific morbid sequelae, remain unknown in the vast majority of subjects. Knowledge that a large fraction of the interindividual variation in this trait is genetically determined motivates the application of genetic approaches to the identification of these primary determinants. Success in this effort will afford insights into pathophysiology, permit preclinical identification of subjects with specific inherited susceptibility, and provide opportunities to tailor therapy to specific underlying abnormalities. To date, mutations in three genes have been implicated in the pathogenesis of human hypertension: mutations resulting in ectopic expression of aldosterone synthase enzymatic activity cause a mendelian form of hypertension known as glucocorticoid-remediable aldosteronism; mutations in the beta subunit of the amiloride-sensitive epithelial sodium channel cause constitutive activation of this channel and the mendelian form of hypertension known as Liddle syndrome; finally, common variants at the angiotensinogen locus have been implicated in the pathogenesis of essential hypertension in Caucasian subjects, although the nature of the functional variants and their mechanism of action remain uncertain. These early findings demonstrate the feasibility and utility of the application of genetic analysis to dissection of this trait.

Determinants of the phagocytic signal mediated by the type IIIA Fc gamma receptor, Fc gamma RIIIA: sequence requirements and interaction with protein-tyrosine kinases.

The Fc gamma receptor-associated gamma and zeta subunits contain a conserved cytoplasmic motif, termed the immunoglobulin gene tyrosine activation motif, which contains a pair of YXXL sequences. The tyrosine residues within these YXXL sequences have been shown to be required for transduction of a phagocytic signal. We have previously reported that the gamma subunit of the type IIIA Fc gamma receptor (Fc gamma RIIIA) is approximately 6 times more efficient in mediating phagocytosis than the zeta subunit of Fc gamma RIIIA. By exchanging regions of the cytoplasmic domains of the homologous gamma and zeta chains, we observed that the cytoplasmic area of the gamma chain bearing a pair of the conserved YXXL sequences is important in phagocytic signaling. Further specificity of phagocytic signaling is largely determined by the two internal XX amino acids in the YXXL sequences. In contrast, the flanking amino acids of the YXXL sequences including the seven intervening amino acids between the two YXXL sequences do not significantly affect the phagocytic signal. Furthermore, the protein-tyrosine kinase Syk, but not the related kinase ZAP-70, stimulated Fc gamma RIIIA-mediated phagocytosis. ZAP-70, however, increased phagocytosis when coexpressed with the Src family kinase Fyn. These data demonstrate the importance of the two specific amino acids within the gamma subunit YXXL cytoplasmic sequences in phagocytic signaling and explain the difference in phagocytic efficiency of the gamma and zeta chains. These results indicate the importance of Syk in Fc gamma RIIIA-mediated phagocytosis and demonstrate that ZAP-70 and syk differ in their requirement for a Src-related kinase in signal transduction.

Genetic and redox determinants of nitric oxide cytotoxicity in a Salmonella typhimurium model.

Paradoxically, nitric oxide (NO) has been found to exhibit cytotoxic, antiproliferative, or cytoprotective activity under different conditions. We have utilized Salmonella mutants deficient in antioxidant defenses or peptide transport to gain insights into NO actions. Comparison of three NO donor compounds reveals distinct and independent cellular responses associated with specific redox forms of NO. The peroxynitrite (OONO-) generator 3-morpholinosydnonimine hydrochloride mediates oxygen-dependent Salmonella killing, whereas S-nitrosoglutathione (GSNO) causes oxygen-independent cytostasis, and the NO. donor diethylenetriamine-nitric oxide adduct has no antibacterial activity. GSNO has the greatest activity for stationary cells, a characteristic relevant to latent or intracellular pathogens. Moreover, the cytostatic activity of GSNO may best correlate with antiproliferative or antimicrobial effects of NO, which are unassociated with overt cell injury. dpp mutants defective in active dipeptide transport are resistant to GSNO, implicating heterolytic NO+ transfer rather than homolytic NO. release in the mechanism of cytostasis. This transport system may provide a specific pathway for GSNO-mediated signaling in biological systems. The redox state and associated carrier molecules are critical determinants of NO activity.

Swapping structural determinants of ribonucleases: an energetic analysis of the hinge peptide 16-22.

Bovine seminal ribonuclease (BS-RNase) is a homodimeric enzyme strictly homologous to the pancreatic ribonuclease (RNase A). Native BS-RNase is an equilibrium mixture of two distinct dimers differing in the interchange of the N-terminal segments and in their biological properties. The loop 16-22 plays a fundamental role on the relative stability of the two isomers. Both the primary and tertiary structures of the RNase A differ substantially from those of the seminal ribonuclease in the loop region 16-22. To analyze the possible stable conformations of this loop in both enzymes, structure predictions have been attempted, according to a procedure described by Palmer and Scheraga [Palmer, K. A. & Scheraga, H. A. (1992) J. Comput. Chem. 13, 329-350]. Results compare well with experimental x-ray structures and clarify the structural determinants that are responsible for the swapping of the N-terminal domains and for the peculiar properties of BS-RNase. Minimal modifications of RNase A sequence needed to form a stable swapped dimer are also predicted.

Social determinants and health effects of low and high severity intimate partner violence

PURPOSE: We sought to analyze whether the sociodemographic profile of battered women varies according to the level of severity of intimate partner violence (IPV), and to identify possible associations between IPV and different health problems taking into account the severity of these acts. METHODS: A cross-sectional study of 8,974 women (18-70 years) attending primary healthcare centers in Spain (2006-2007) was performed. A compound index was calculated based on frequency, types (physical, psychological, or both), and duration of IPV. Descriptive and multivariate procedures using logistic regression models were fitted. RESULTS: Women affected by low severity IPV and those affected by high severity IPV were found to have a similar sociodemographic profile. However, divorced women (odds ratio [OR], 8.1; 95% confidence interval [CI], 3.2-20.3), those without tangible support (OR, 6.6; 95% CI, 3.3-13.2), and retired women (OR, 2.7; 95% CI, 1.2-6.0) were more likely to report high severity IPV. Women experiencing high severity IPV were also more likely to suffer from poor health than were those who experienced low severity IPV. CONCLUSIONS: The distribution of low and high severity IPV seems to be influenced by the social characteristics of the women involved and may be an important indicator for estimating health effects. This evidence may contribute to the design of more effective interventions.

A metasynthesis of qualitative studies regarding opinions and perceptions about barriers and determinants of health services’ accessibility in economic migrants

Background: Access to health services is an important health determinant. New research in health equity is required, especially amongst economic migrants from developing countries. Studies conducted on the use of health services by migrant populations highlight existing gaps in understanding which factors affect access to these services from a qualitative perspective. We aim to describe the views of the migrants regarding barriers and determinants of access to health services in the international literature (1997–2011). Methods: A systematic review was conducted for Qualitative research papers (English/Spanish) published in 13 electronic databases. A selection of articles that accomplished the inclusion criteria and a quality evaluation of the studies were carried out. The findings of the selected studies were synthesised by means of metasynthesis using different analysis categories according to Andersen’s conceptual framework of access and use of health services and by incorporating other emergent categories. Results: We located 3,025 titles, 36 studies achieved the inclusion criteria. After quality evaluation, 28 articles were definitively synthesised. 12 studies (46.2%) were carried out in the U.S and 11 studies (42.3%) dealt with primary care services. The participating population varied depending mainly on type of host country. Barriers were described, such as the lack of communication between health services providers and migrants, due to idiomatic difficulties and cultural differences. Other barriers were linked to the economic system, the health service characteristics and the legislation in each country. This situation has consequences for the lack of health control by migrants and their social vulnerability. Conclusions: Economic migrants faced individual and structural barriers to the health services in host countries, especially those with undocumented situation and those experimented idiomatic difficulties. Strategies to improve the structures of health systems and social policies are needed.

Social determinants of self-perceived discrimination in Spain

Objectives: To analyse the association between self-perceived discrimination and social determinants (social class, gender, country of origin) in Spain, and further to describe contextual factors which contribute to self-perceived discrimination. Methods: Cross-sectional design using data from the Spanish National Health Survey (2006). The dependent variable was self-perceived discrimination, and independent and stratifying variables were sociodemographic characteristics (e.g. sex, social class, country of origin, educational level). Logistic regression was used. Results: The prevalence of self-perceived discrimination was 4.2% for men and 6.3% for women. The likelihood of self-perceived discrimination was higher in people who originated from low-income countries: men, odds ratio (OR) 5.59 [95% confidence interval (CI) 4.55–6.87]; women, OR 4.06 (95% CI 3.42–4.83). Women were more likely to report self-perceived discrimination by their partner at home than men [OR 8.35 (95% CI 4.70–14.84)]. The likelihood of self-perceived discrimination when seeking work was higher among people who originated from low-income countries than their Spanish counterparts: men, OR 13.65 (95% CI 9.62–19.35); women, OR 10.64 (95% CI 8.31–13.62). In comparison with Spaniards, male white-collar workers who originated from low-income countries [OR 11.93 (95% CI 8.26–17.23)] and female blue-collar workers who originated from low-income countries (OR 1.6 (95% CI 1.08–2.39)] reported higher levels of self-perceived discrimination. Conclusions: Self-perceived discrimination is distributed unevenly in Spain and interacts with social inequalities. This particularly affects women and immigrants.

Social determinants of sexual satisfaction in Spain considered from the gender perspective

Aims: To describe gender- and social class-related inequalities in sexual satisfaction and analyze their relationship with self-perceived health status. Methods: This population-based, cross-sectional study included 7384 sexually active people aged 16 years and over residing in Spain in 2009 (3951 men and 3433 women). The explanatory variables were gender, age, social class, share in performing domestic tasks, spend time looking after oneself, collaborate economically in supporting the family, caring for children, self-perceived health status, and the desire to increase or decrease frequency of having sexual relations. Bivariate and multivariate logistic regression models were fitted. Results: Among women, sexual satisfaction declines progressively after age 45. Sexual satisfaction is 1.7 times higher among women who look after themselves and who feel good compared with those who do not. The odds of wanting to increase sex is 3.3 times higher for women who are satisfied compared with women who desire a lower frequency of sexual intercourses; and good perceived health was associated with sexual satisfaction. In satisfied men, the corresponding odds is 1.9 times that of men desiring to reduce their frequency of sex. Conclusions: Gender and social class inequalities are found in sexual satisfaction. This is associated with perceived health status, adding evidence in support of the World Health Organization definition of sexual health.

[ Māāṟajil nabẖûvat] : manuscript, 1900?

Story of Prophet Abraham translated from a Persian text (possibly Muʻīn ad-Dīn Farāhi's "Maʻārij an-nubūwwah fī madārij al-futuwwah"), story of Prophet Zakariya from a text entitled Māālamil tanzīl (possibly Abū Muḥammad Ḥusain bin Masʻūd Baǵavī's "Maʻālim at-tanzīl") and two stories from the Sakhāvat nāma (possibly Sakhāvat nāma-i Ḥaẓrat ʻĀlī, the popular versified account of the miracles attributed to Ḥaẓrat ʻAlī).