Relationship of lipid oxidation with subclinical atherosclerosis and 10-year coronary events in general population

Objectives

To assess 1) the association of lipid oxidation biomarkers with 10-year coronary artery disease (CAD) events and subclinical atherosclerosis, and 2) the reclassification capacity of these biomarkers over Framingham-derived CAD risk functions, in a general population.

Methods

Within the framework of the REGICOR study, 4782 individuals aged between 25 and 74 years were recruited in a population-based cohort study. Follow-up of the 4042 who met the eligibility criteria was carried out. Plasma, circulating oxidized low-density lipoprotein (oxLDL) and oxLDL antibodies (OLAB) were measured in a random sample of 2793 participants.End-points included fatal and non-fatal acute myocardial infarction (AMI) and angina. Carotid intima-media thickness (IMT) in the highest quintile and ankle-brachial index <0.9 were considered indicators of subclinical atherosclerosis.

Results

Mean age was 50.0 (13.4) years, and 52.4% were women. There were 103 CAD events (34 myocardial infarction, 43 angina, 26 coronary deaths), and 306 subclinical atherosclerosis cases. Oxidized LDL was independently associated with higher incidence of CAD events (HR = 1.70; 95% Confidence Interval: 1.02–2.84), but not with subclinical atherosclerosis. The net classification index of the Framingham-derived CAD risk function was significantly improved when ox-LDL was included (NRI = 14.67% [4.90; 24.45], P = 0.003). No associations were found between OLAB and clinical or subclinical events. The reference values for oxLDL and OLAB are also provided (percentiles).

Conclusions

OxLDL was independently associated with 10-year CAD events but not subclinical atherosclerosis in a general population, and improved the reclassification capacity of Framingham-derived CAD risk functions.     

Experiencia de colaboración entre atención primaria y salud mental en el Departamento de Salud La Ribera, 7 años después

Despite the high prevalence of mental health problems among patients attending primary care, diagnosis and treatment of these disorders remain inadequate. Sound training of primary care physicians in how to manage mental health problems is needed to reduce the health, economic and social impact associated with these disorders. Among other elements, there is a need for cooperation between primary care physicians and mental health services. Distinct models are available for such collaboration. In 2006, our health department started a collaboration between these two levels of heath care, using a liaison model. Delays until the first specialist visit were reduced and satisfaction among health professionals increased, although these results should be interpreted with caution. Evidence has recently accumulated on the usefulness of the collaborative model, but evaluation of this model and extrapolation of its results are complex. We intend to evaluate our model more thoroughly, similar to other projects in our environment.     

Chronic fatigue syndrome and personality: A case-control study using the alternative five factor model

Neuroticism is the personality dimension most frequently associated with chronic fatigue syndrome (CFS). Most studies have also shown that CFS patients are less extraverted than non-CFS patients, but results have been inconsistent, possibly because the facets of the extraversion dimension have not been separately analyzed. This study has the following aims: to assess the personality profile of adults with CFS using the Alternative Five-Factor Model (AFFM), which considers Activity and Sociability as two separate factors of Extraversion, and to test the discriminant validity of a measure of the AFFM, the Zuckerman–Kuhlman Personality Questionnaire, in differentiating CFS subjects from normal-range matched controls. The CFS sample consisted of 132 consecutive patients referred for persistent fatigue or pain to the Department of Medicine of a university hospital. These were compared with 132 matched normal population controls. Significantly lower levels of Activity and significantly higher levels of Neuroticism-Anxiety best discriminated CFS patients from controls. The results are consistent with existing data on the relationship between Neuroticism and CFS, and clarify the relationship between Extraversion and CFS by providing new data on the relationship of Activity to CFS.     

Impact of in vitro evolution on antigenic diversity of Mycobacterium bovis bacillus Calmette-Guerin (BCG)

Mycobacterium bovis bacillus Calmette-Guerin (BCG), the only vaccine currently used against tuberculosis, is an attenuated derivative of M. bovis that has been propagated in vitro for more than 40 years. We have previously reported that the experimentally-verified human T cell epitopes of the M. tuberculosis complex (MTBC) are the most conserved elements of the genome; whether immune recognition is the force driving the conservation of epitopes in the MTBC is unknown. Therefore, we sequenced the genomes of 12 BCG strains to determine whether T cell epitopes were under selection pressure during BCG in vitro evolution. We constructed a genome-wide phylogeny and refined the previously-determined BCG phylogeny. Notably, we identified a new cluster between BCG Japan and BCG Russia, and repositioned the relationships of several strains within the lineage. We also compared the sequence diversity of 1530 experimentally verified human T cell epitopes in the BCG vaccines with those in the MTBC. We found 23% of the known T cell epitopes are absent, and that the majority (82%) of the absent epitopes in BCG are contained in 6 proteins encoded in 2 regions of difference (RD) unique to BCG strains. We also found that T cell epitope sequences in BCG are more conserved than non-epitope sequences in the same gene. Finally, we find evidence that epitope sequence variation in BCG potentially affects human T cell recognition. These findings provide new insight into sequence variation in a slow-growing bacterium closely related to the MTBC that has been subjected to prolonged passage outside of a mammalian host, and indicate little difference in the extent of variation in vivo and in vitro.     

The Spanish version of the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) is valid for use in the general population

Purpose

Mental well-being has aroused interest in Europe as an indicator of population health. The Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) was developed in the United Kingdom showing good face validity and has been previously adapted into Spanish. The aim of this study is to assess the validity and reliability of the Spanish version of WEMWBS in the general population.

Methods

Cross-sectional home face-to-face interview survey with computer-assisted personal interviewing was administered with the 2011 Catalan Health Interview Survey Wave 3, which is representative of the non-institutionalized general population of Catalonia, Spain. A total of 1,900 participants 15+ years of age were interviewed. The Spanish version of WEMWBS was administered together with socioeconomic and health-related variables, with a hypothesized level of association.

Results

Similar to the original, confirmatory factor analysis fits a one-factor model adequately (CFI = 0.974; TLI = 0.970; RMSEA = 0.059; χ ² = 584.82; df = 77; p < .001) and has a high internal consistency (Cronbach’s alpha = 0.930; Guttman’s lambda 2 = 0.932). The WEMWBS discriminated between population groups in all health-related and socioeconomic variables, except in gender (p = 0.119), with a magnitude similar to that hypothesized. Overall, mental well-being was higher for the general population of Catalonia (average and whole distribution) than that for Scotland general population.

Conclusions

The Spanish version of WEMWBS showed good psychometric properties similar to the UK original scale. Whether better mental well-being in Catalonia is due to methodological or substantive cultural, social, or environmental factors should be further researched.     

The Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) Questionnaire: item reduction and further validation

Purpose

The Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) Questionnaire is a patient and parent-completed disease-specific instrument used in Hunter syndrome (mucopolysaccharidosis II), a rare paediatric progressive multi-systemic lysosomal storage disease. The objective of this study was to shorten the number of items of the Questionnaire to reduce response burden while maintaining its content validity.

Methods

Data collected in a clinical trial were used. An iterative process helped identifying redundant or low performing items based on content validity and psychometric properties. Validation on the retained items was assessed using patients and parent’s responses in terms of reliability, validity and responsiveness.

Results

The HS-FOCUS was completed by 49 patients and 84 parents. Items were mainly removed owing to high floor effects, high inter-item correlations (>0.80) or inadequate content. The shortened patient and parent versions (18 and 21 items) each contained five function domains. Internal consistency and test–retest reliability were >0.70 for most domains, except Breathing and School/work. Concurrent validity was demonstrated by significant correlations (>0.30) with similar concepts of previously validated measures. Significant differences were found in all domain scores across levels of disability.

Conclusions

The shortened HS-FOCUS is a reliable, valid and responsive measure, where burden in answering the Questionnaire was reduced without compromising its validity.     

Immunofluorescence analysis of sensory nerve endings in the interosseous membrane of the forearm

The human interosseous membrane (IOM) is a fundamental stabilizer during forearm rotation. To investigate the dynamic aspects of forearm stability, we analyzed sensory nerve endings in the IOM. The distal oblique bundle (DOB), the distal accessory band (DAB), the central band (CB), the proximal accessory band (PAB), the dorsal oblique accessory cord (DOAC) and the proximal oblique cord (POC) were dissected from 11 human cadaver forearms. Sensory nerve endings were analyzed at two levels per specimen as total cell amount/mm² after immunofluorescence staining with low-affinity neurotrophin receptor p75, protein gene product 9.5, S-100 protein and 4′,6-diamidino-2-phenylindole on an Apotome microscope, according to Freeman and Wyke’s classification. Sensory nerve endings were significantly more commonly found to be equally distributed throughout the structures, rather than being epifascicular, interstitial, or close to the insertion into bone (P ≤ 0.001, respectively). Free nerve endings were the predominant mechanoreceptor in all six structures, with highest density in the DOB, followed by the POC (P ≤ 0.0001, respectively). The DOB had the highest density of Pacini corpuscles. The DOAC and CB had the lowest amounts of sensory innervation. The high density of sensory corpuscles in the DOB, PAB and POC indicate that proprioceptive control of the compressive and directional muscular forces acting on the distal and proximal radioulnar joints is monitored by the DOB, PAB and POC, respectively, due to their closed proximity to both joints, whereas the central parts of the IOM act as structures of passive restraint.