The health-damaging potential of new types of flexible employment: a challenge for public health researchers.
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Economic Competition↗
Biomedical subjects
J Benach
Publications and source records attributed to J Benach.
The catalytic reaction and inhibition mechanism of Drosophila alcohol dehydrogenase: observation of an enzyme-bound NAD-ketone adduct at 1.4 A resolution by X-ray crystallography.
Drosophila alcohol dehydrogenase (DADH) is an NAD+-dependent enzyme that catalyzes the oxidation of alcohols to aldehydes/ketones. DADH is the member of the short-chain dehydrogenases/reductases family (SDR) for which the largest amount of biochemical data has been gathered during the last three decades. The crystal structures of one binary form (NAD+) and three ternary complexes with NAD+.acetone, NAD+.3-pentanone and NAD+.cyclohexanone were solved at 2.4, 2.2, 1. 4 and 1.6 A resolution, respectively. From the molecular interactions observed, the reaction mechanism could be inferred. The structure of DADH undergoes a conformational change in order to bind the coenzyme. Furthermore, upon binding of the ketone, a region that was disordered in the apo form (186-191) gets stabilized and closes the active site cavity by creating either a small helix (NAD+. acetone, NAD+.3-pentanone) or an ordered loop (NAD+.cyclohexanone). The active site pocket comprises a hydrophobic bifurcated cavity which explains why the enzyme is more efficient in oxidizing secondary aliphatic alcohols (preferably R form) than primary ones. Difference Fourier maps showed that the ketone inhibitor molecule has undergone a covalent reaction with the coenzyme in all three ternary complexes. Due to the presence of the positively charged ring of the coenzyme (NAD+) and the residue Lys155, the amino acid Tyr151 is in its deprotonated (tyrosinate) state at physiological pH. Tyr151 can subtract a proton from the enolic form of the ketone and catalyze a nucleophilic attack of the Calphaatom to the C4 position of the coenzyme creating an NAD-ketone adduct. The binding of these NAD-ketone adducts to DADH accounts for the inactivation of the enzyme. The catalytic reaction proceeds in a similar way, involving the same amino acids as in the formation of the NAD-ketone adduct. The p Kavalue of 9-9.5 obtained by kinetic measurements on apo DADH can be assigned to a protonated Tyr151 which is converted to an unprotonated tyrosinate (p Ka7.6) by the influence of the positively charged nicotinamide ring in the binary enzyme-NAD+form. pH independence during the release of NADH from the binary complex enzyme-NADH can be explained by either a lack of electrostatic interaction between the coenzyme and Tyr151 or an apparent p Kavalue for this residue higher than 10.0.
Alcohol Dehydrogenase↗
Infant and perinatal mortality in Spain 1981-1991: interprovincial variations in Autonomous Communities with extreme economic levels.
The aims of the present study were to describe and compare infant, neonatal, postneonatal and perinatal mortality in aggregates of Spanish Autonomous Communities (AC) with higher and lower income, as well as to describe and compare their respective inequalities among the provinces constituting AC with similar (high or low) and with extreme economic levels, over the period from 1981 to 1991. The coefficient of variation (weighted by the number of births) has been used as the measure of interprovincial inequalities in mortality within each aggregate of AC and time trends in the average mortality rates and in their coefficients of variation have been analyzed using simple linear regression. The results of the study confirmed that the four mortality rates were all higher in the aggregate of AC of lower income than in that of higher income, and have fallen in both in a similar manner. Thus the perinatal mortality rates for the lower and higher income aggregates of AC respectively were 17.3 and 12.5 per 1000 births in 1981, and 8.3 and 6.8 in 1991. The inequality in postneonatal mortality was dominant in the group of AC with a lower economic level whereas geographical inequalities in perinatal mortality predominated in the higher income group. The predominance of interprovincial inequalities in perinatal mortality when all the AC (with extreme economic levels) were considered suggest that economic factors are closely related to perinatal mortality.
Humans↗
Geographical patterns of excess mortality in Spain explained by two indices of deprivation.
STUDY OBJECTIVE: To analyse the geographical patterns and the magnitude of the association between deprivation and mortality in Spain. To estimate the excess of mortality in more deprived areas of the country by region. DESIGN: Cross sectional ecological study using 1991 census variables and mortality data for 1987-1992. SETTING: 2220 small areas in Spain. MAIN RESULTS: A geographical gradient from north east to south west was shown by both mortality and deprivation levels in Spain. Two dimensions of deprivation (that is, Index 1 and Index 2) obtained by exploratory factor analysis using four census indicators were found to predict mortality: mortality over 65 years of age was more associated with Index 1, while mortality under 65 years of age was more associated with Index 2. Excess mortality in the most deprived areas accounted for about 35,000 deaths. CONCLUSIONS: Two indices of deprivation strongly predict mortality in two age groups. Excess number of deaths in the most deprived geographical areas account for 10% of total number of deaths annually. In Spain there is great potential for reducing mortality if the excess risk in more deprived areas fell to the level of the most affluent areas.
Cities↗
The refined crystal structure of Drosophila lebanonensis alcohol dehydrogenase at 1.9 A resolution.
Drosophila alcohol dehydrogenase (DADH; EC 1.1.1.1) is a NAD(H)-dependent oxidoreductase belonging to the short-chain dehydrogenases/reductases (SDR) family. This homodimeric enzyme catalyzes the dehydrogenation of alcohols to their respective ketones or aldehydes in the fruit-fly Drosophila, both for metabolic assimilation and detoxification purposes. The crystal structure of the apo form of DADH, one of the first biochemically characterized member of the SDR family, was solved at 1.9 A resolution by Patterson methods. The initial model was improved by crystallographic refinement accompanied by electron density averaging, R-factor=20.5%, R-free=23.8%.DADH subunits show an alpha/beta single domain structure with a characteristic NAD(H) binding motif (Rossmann fold). The peptide chain of a subunit is folded into a central eight-stranded beta-sheet flanked on each side by three alpha-helices. The dimers have local 2-fold symmetry. Dimer association is dominated by a four-helix bundle motif as well as two C-terminal loops from each subunit, which represent a unique structural feature in SDR enzymes with known structure. Three structural features are characteristic for the active site architecture. (1) A deep cavity which is covered by a flexible loop (33 residues) and the C-terminal tail (11 residues) from the neighboring subunit. The hydrophobic surface of the cavity is likely to increase the specificity of this enzyme towards secondary aliphatic alcohols. (2) The residues of the catalytic triad (Ser138, Tyr151, Lys155) are known to be involved in enzymatic catalysis in the first line. The Tyr151 OH group is involved in an ionic bond with the Lys155 side-chain. Preliminary electrostatic calculations have provided evidence that the active form of Tyr151 is a tyrosinate ion at physiological pH. (3) Three well-ordered water molecules in hydrogen bond distance to side-chains of the catalytic triad may be significant for the proton release steps in DADH catalysis.A ternary structure-based sequence alignment with ten members of the SDR family with known three-dimensional structure has suggested to define a model consisting of four groups of residues, which relates the observed low degree of sequence identity to quite similar folding patterns and nearly identical distributions of residues involved in catalysis.
Alcohol Dehydrogenase↗
Drosophila alcohol dehydrogenase: evaluation of Ser139 site-directed mutants.
Drosophila alcohol dehydrogenase (DADH) belongs to the large and highly heterogeneous (15-30% residue identity) short-chain dehydrogenase/reductase family (SDR). It is the only reported member that oxidizes mainly ethanol and 2-propanol among other alcohols. To confirm the role of Ser139 we constructed two site-directed mutants, Ser139Ala and Ser139Cys, which show no enzymatic activity. Molecular replacement and data from crystallographically refined 3D structures confirm the position of Ser139, whose hydroxyl group faces the cleft of the presumed catalytic pocket, very close to Tyr152 and Lys156. Thus, consistent with the constitution of the catalytic triad of other SDR, our results suggest that Ser139 of DADH is directly involved in the catalytic reaction.
Alcohol Dehydrogenase↗
Active site directed mutagenesis of 3 beta/17 beta-hydroxysteroid dehydrogenase establishes differential effects on short-chain dehydrogenase/reductase reactions.
Mutagenetic replacements of conserved residues within the active site of the short-chain dehydrogenase/reductase (SDR) superfamily were studied using prokaryotic 3 beta/17 beta-hydroxysteroid dehydrogenase (3 beta/17 beta-HSD) from Comamonas testosteroni as a model system. The results provide novel data to establish Ser 138 as a member of a catalytically important "triad" of residues also involving Tyr151 and Lys155. A Ser-->Ala exchange at position 138 results in an almost complete (> 99.9%) loss of enzymatic activity, which is not observed with a Ser-->Thr replacement. This indicates that an essential factor for catalysis is the ability of side chain 138 to form hydrogen bond interactions. Mutations in the NAD(H) binding region, in strands beta A, beta D, and adjacent turns, reveal two additional residues, Thr12 and Asn87, which are important for correct binding of the coenzyme and with a differential effect on the reactions catalyzed. Thus, mutation of Thr12 to Ala results in a complete loss of the 3 beta-dehydrogenase activity, whereas the 3-oxoreductase activity remains unchanged. On the other hand, a T12S substitution yields a protein with unaltered catalytic constants for both reactions, revealing that a specific hydrogen bond is critical for the dehydrogenase activity. Our interpretation of the available crystal structure of 3 alpha/20 beta-HSD from Streptomyces hydrogenans suggests a hydrogen bond in that enzyme between the Thr12 side chain and the backbone NH of Asn87 rather than the coenzyme, indicating that this hydrogen bond to the beta D strand might determine a crucial difference between the reductive and the oxidative reaction types. Similarly, mutation of Asn87 to Ala results in an 80% reduction of kcat/Km in the dehydrogenase direction but also unchanged 3-oxoreductase properties. It appears that the binding of NAD+ to the protein is influenced by local structural changes involving strand beta D and turn beta A to alpha B.
17-Hydroxysteroid Dehydrogenases↗
Crystallization and crystal packing of recombinant 3 (or 17) beta-hydroxysteroid dehydrogenase from Comamonas testosteroni ATTC 11996.
The enzyme 3 (or 17) beta-hydroxysteroid dehydrogenase from Comamonas testosteroni was crystallized. Crystals, of up to 0.6 mm in their longest dimension and suitable for a crystallographic analysis have been obtained by the vapour diffusion method. They belong to the orthorhombic lattice type and diffract to a maximum resolution of 0.23 nm. A final data set obtained by merging data from three crystals resulted in a completeness of 90% with an Rmerge of 6%. A molecular replacement search carried out by using 3 alpha (or 20 beta)-hydroxysteroid dehydrogenase from Streptomyces hydrogenans as a search model allowed us to assign I222 as the correct space group and to propose a model for the crystal packing, with one monomer per asymmetric unit. Thus, the whole unit cell contains two tetramers. The R-factor after rigid body refinement is 48.1%.
17-Hydroxysteroid Dehydrogenases↗
Should policy recommendations be excluded from epidemiologic research papers?
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Epidemiology↗
Detection of Borrelia burgdorferi antigens in cerebrospinal fluid.
We examined CSF for Borrelia burgdorferi antigens using antigen-capture ELISA and Western (immuno) blot. Antigen-capture ELISA was positive in 38 of 77 (49%) CSF samples obtained from neurologic patients with presumed B burgdorferi infection, compared with one of 34 (3%) CSF samples obtained from other neurologic disease controls who came from a region endemic for Lyme disease. Western immunoblot was positive for B burgdorferi antigens in 12 of 22 (55%) CSF samples from the B burgdorferi infected groups, compared with none of 11 CSF samples from the control group. CSF antigen detection should prove helpful in evaluating patients for suspected neurologic Lyme disease.
Adolescent↗
[Primary aseptic osteonecrosis of the femur head in adults].
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Adolescent↗
An empirical evaluation of various priors in the empirical Bayes estimation of small area disease risks.
Empirical and fully Bayes estimation of small area disease risks places a prior distribution on area-specific risks. Several forms of priors have been used for this purpose including gamma, log-normal and non-parametric priors. Spatial correlation among area-specific risks can be incorporated in log-normal priors using Gaussian Markov random fields or other models of spatial dependence. However, the criterion for choosing one prior over others has been mostly logical reasoning. In this paper, we evaluate empirically the various priors used in the empirical Bayes estimation of small area disease risks. We utilize a Spanish mortality data set of a 12-year period to give the underlying true risks, and estimate the true risks using only a 3-year portion of the data set. Empirical Bayes estimates are shown to have substantially smaller mean squared errors than Poisson likelihood-based estimates. However, relative performances of various priors differ across a variety of mortality outcomes considered. In general, the non-parametric prior provides good estimates for lower-risk areas, while spatial priors provide good estimates for higher-risk areas. Ad hoc composite estimates averaging the estimates from the non-parametric prior and those from a spatial log-normal prior appear to perform well overall. This suggests that an empirical Bayes prior that strikes a balance between these two priors, if one can construct such a prior, may prove to be useful for the estimation of small area disease risks.
Adult↗
[Social self-positioning as indicator of socioeconomic status].
OBJECTIVE: Self-perceived class results from directly questioning subjects about his or her social class. The aim of this investigation was to analyse self-perceived class in relation to other indicator variables of socioeconomic level. METHODS: Data from the 1994 Catalan Health Interview Survey, a cross-sectional survey of a representative sample of the non-institutionalised population of Catalonia was used. We conducted a discriminant analysis to compute the degree of right classification when different socioeconomic variables potentially related to self-perceived class were considered. All subjects who directly answered the questionnaire were included (N = 12,245). With the aim of obtaining the discriminant functions in a group of subjects and to validate it in another one, the subjects were divided into two random samples, containing approximately 75% and 25% of subjects (analysis sample, n = 9,248; and validation sample, n = 2,997). RESULTS: The final function for men and women included level of education, social class (based in occupation) and equivalent income. This function correctly classified 40.9% of the subjects in the analysis sample and 39.2% in the validation sample. Two other functions were selected for men and women separately. In men, the function included level of education, professional category, and family income (39.2% of classification in analysis sample and 37.2% in validation sample). In women, the function (level of education, working status, and equivalent income) correctly classified 40.3% of women in analysis sample whereas the percentage was 38.9% in validation sample. The percentages of right classification were higher for the highest and lowest classes. CONCLUSION: These results show the utility of a simple variable to self-position within the social scale. Self-perceived class is related to education, income, and working determinants.
Adolescent↗
[Employment precariousness: an emerging public health problem?].
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Economics↗
[Description of psychosocial risk factors in four companies].
OBJECTIVE: To describe the distribution of work-related psychosocial risk factor scores in four companies according to the personal and occupational characteristics of the workers. METHODS: Cross-sectional study of a sample of 890 workers in four companies who participated in this study voluntarily. The overall response rate was 34.5%. A self-administrated questionnaire was used to measure the presence of demand, control and social support according to the workers' perceptions. Statistical analyses were performed using median and dispersion measures of psychosocial risk factors for each company separately, as well as description of their distribution according to personal and occupational variables. RESULTS: The median score for social support was almost always equal to 5 for all four companies. However, there was greater variability in psychological demand (between 13 and 16), and for control (between 20 and 26). Comparison of the scores for social and occupational variables revealed similar values for social support but not for control and demand, which showed greater variation according to sex (men), age group (less than 40 years) and occupation (clerks). CONCLUSIONS: Although the low response rate could limit the validity of our results, this is the first study to value the distribution of work-related psychosocial risk factor scores in four companies in Spain. Variability among companies for different groups of workers was found. This study could be useful for future studies exploring the feasibility of defining reference values for use in preventive measures.
Administrative Personnel↗
[Analysis of the mechanisms of minor occupational injuries in the construction industry in Spain].
OBJECTIVES: The construction industry produces the highest number of occupational injuries in Spain (25.6%). Of these, 98.5% were minor injuries with 5 million workdays lost in 2000. This occurred even after the recent introduction of numerous health and occupational safety regulations. The objective of the present study was to identify the specific mechanisms of minor occupational injuries in the construction sector. METHODS: In 2000, there were 235,853 minor occupational injuries in the construction industry. From these, injuries in general construction and civil engineering were selected (n = 155,044). These injuries affected both the total number of workers in the sector as well as bricklayers and unskilled construction workers. Insurance and financial activities (n = 2,019) were selected as a reference economic sector. Minor occupational injuries due to nontraumatic processes (heart attack, etc.) were taken as a control group (n = 167), assuming that the risk of nontraumatic processes was independent of economic activities. Odds ratios (OR) were adjusted by age, sex, years of work experience, type of employment and company size through nonconditional logistic regression models. RESULTS: The mechanisms with the highest risk of minor occupational lesions in construction workers as a group compared with employees in the financial sector were projection of fragments (OR = 33.0; 95% CI, 15.3-70.8) and being struck by objects (OR = 18.2; CI 95%, 9.7-34.1). These were also the most specific mechanisms of injury in the subgroup of bricklayers and unskilled construction workers. CONCLUSIONS: Activities aimed at preventing minor occupational injuries in the construction sector should be orientated towards these mechanisms, especially projection of fragments despite the low frequency of this mechanism compared with that of other mechanisms. Case-control design is a useful alternative approach for research into occupational injuries.
Accidental Falls↗
[Social inequality seriously compromises health].
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Health Services Accessibility↗
[Types of employment and health: analysis of the Second European Survey on Working Conditions].
OBJECTIVES: To investigate the relationships among types of employment and several health self-perceived outcomes in a sample of active workers from the 15 state members of the European Union. METHODS: Cross-sectional study with data drawn from the Second European Survey on Working Conditions (n = 15,146 individuals). The predictive variable was the types of employment aggregated in: permanent workers, sole traders, small employers (less than 10 employees) and temporary workers (full-and part-time). Unconditional logistic regression models were adjusted by age, gender and several indications of working conditions. Permanent workers was used as the baseline category. RESULTS: Employees with permanent (69,3%) and temporary (12,5%) contracts notified the highest level of a job absenteeism while temporary employees reported the highest level of job dissatisfaction. On the other hand, sole traders (12,2%) and small employees (6.1%) notified the most frequent level of overall fatigue, backache and muscular pains. Having permanent workers as baseline category, temporary employees was associated with high dissatisfaction (OR = 1.68), and and overall fatigue (OR = 1.16), but with lower frequency of stress (OR = 0.74) and job absenteeism (OR = 0.87). Small employers showed a low frequency of absenteeism (OR = 0.68), but a high stress (OR = 1.77) and overall fatigue (OR = 1.27). Finally, sole traders reported more frequently overall fatigue (OR = 1.40), and stress (OR = 1.33), but less job absenteeism (OR = 0.58). CONCLUSIONS: These findings suggest that types of employment may have an independent effect on several health self-perceive outcomes. Further research is necessary to overcome various shortcoming of this study, and to assess the role either job security or level of income and social protection.
Absenteeism↗