Lipid peroxidation, occupational stress and aging in workers of a prehospital emergency service.

BACKGROUND: Stressful conditions lead to formation of excessive free radicals, and lipid peroxidation is one of the major outcomes of free radical-mediated injury that directly damages membranes and generates a number of secondary products. OBJECTIVES: To determine the levels of malondialdehyde, an end product of lipid peroxidation, according to demographic and occupational variables in workers of a prehospital emergency service and to analyse the relationship between malondialdehyde levels and burnout. MATERIAL AND METHODS: One hundred and eleven healthy workers of a prehospital emergency service and eighty aged-matched healthy individuals of both sexes as a control group were surveyed. Malondialdehyde levels were measured by the Bull and Marnett method. To measure burnout, the Maslach Burnout Inventory was used. RESULTS: Professional category is associated with lipid peroxidation and burnout levels (Malondialdehyde levels were: physicians 338.10+/-14.47, nurses 329.17+/-12.62 and technicians 296.74+/-14.28; burnout levels were: physicians 41.29+/-3.59, nurses 37.38+/-6.05 and technicians 35.33+/-5.87). Working at night and in the evening increased malondialdehyde and burnout levels. Malondialdehyde levels increase with age. No significant variations with respect to sex were detected. Significant variations in malondialdehyde levels were detected between singles (303.13+/-12.74) and married people (344.43+/-13.43) but not with respect to divorcees (326.44+/-11.74). Significant differences were detected in erythrocyte malondialdehyde levels between smokers (341.37+/-17.09) and nonsmokers (302.21+/-12.38), but not for alcohol consumption. CONCLUSIONS: These findings suggest a positive correlation between malondialdehyde, a biomarker of lipid peroxidation and occupational stress, as estimated by elements of the Maslach Burnout Inventory, and oxidative stress.     

Strategies to enhance transductional efficiency of adenoviral-based gene transfer to primary human fibroblasts and keratinocytes as a platform in dermal wounds

Genetically modified keratinocytes and fibroblasts are suitable for delivery of therapeutic genes capable of modifying the wound healing process. However, efficient gene delivery is a prerequisite for successful gene therapy of wounds. Whereas adenoviral vectors (Ads) exhibit superior levels of in vivo gene transfer, their transductional efficiency to cells resident within wounds may nonetheless be suboptimal, due to deficiency of the primary adenovirus receptor, coxsackie-adenovirus receptor (CAR). We explored CAR-independent transduction to fibroblasts and keratinocytes using a panel of CAR-independent fiber-modified Ads to determine enhancement of infectivity. These fiber-modified adenoviral vectors included Ad 3 knob (Ad5/3), canine Ad serotype 2 knob (Ad5CAV-2), RGD (Ad5.RGD), polylysine (Ad5.pK7), or both RGD and polylysine (Ad5.RGD.pK7). To evaluate whether transduction efficiencies of the fiber-modified adenoviral vectors correlated with the expression of their putative receptors on keratinocytes and fibroblasts, we analyzed the mRNA levels of CAR, alpha upsilon integrin, syndecan-1, and glypican-1 using quantitative polymerase chain reaction. Analysis of luciferase and green fluorescent protein transgene expression showed superior transduction efficiency of Ad5.pK7 in keratinocytes and Ad5.RGD.pK7 in fibroblasts. mRNA expression of alpha upsilon integrin, syndecan-1 and glypican-1 was significantly higher in primary fibroblasts than CAR. In keratinocytes, syndecan-1 expression was significantly higher than all the other receptors tested. Significant infectivity enhancement was achieved in keratinocytes and fibroblasts using fiber-modified adenoviral vectors. These strategies to enhance infectivity may help to achieve higher clinical efficacy of wound gene therapy.     

Falls and consequent injuries in hospitalized patients: effects of an interdisciplinary falls prevention program

Background  

Patient falls in hospitals are common and may lead to negative outcomes such as injuries, prolonged hospitalization and legal liability. Consequently, various hospital falls prevention programs have been implemented in the last decades. However, most of the programs had no sustained effects on falls reduction over extended periods of time.     

BMP-2 gene polymorphisms and osteoporosis: the Rotterdam Study.

After reported associations of variations in the BMP-2 gene with osteoporosis in small populations, we studied the association of the BMP-2 gene polymorphisms Ser37Ala and Arg190Ser with osteoporosis in 6353 men and women from the Rotterdam Study. We did not observe an association of these variants with BMD, bone loss, hip structural analysis parameters, and fracture risk. INTRODUCTION: Bone morphogenetic protein 2 (BMP-2) plays a role in osteoblast differentiation. BMP-2 gene variation has previously been associated with osteoporosis in various small populations, but current evidence remains inconclusive about the exact association with osteoporosis. Therefore, we studied the association of two polymorphisms located in the BMP-2 gene (Ser37Ala and Arg190Ser) and haplotypes defined by these polymorphisms with BMD, rates of bone loss, parameters of hip structural analysis (HSA), and fractures in the Rotterdam Study, a large prospective cohort study of diseases in the elderly. MATERIALS AND METHODS: Databases were searched for polymorphisms and haplotype blocks in the BMP-2 gene region. Allele frequencies for Ser37Ala and Arg190Ser were determined in 60 blacks and 110 Chinese from Coriell panels. Genotype data on Ser37Ala and Arg190Ser were available for 6353 individuals from the Rotterdam Study population. Haplotype alleles defined by Ser37Ala and Arg190Ser were inferred using PHASE software. Genotype and haplotype analyses for BMD (measured at the lumbar spine and femoral neck), bone loss per year (measured at the femoral neck), and HSA were performed using AN(C)OVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All outcomes were adjusted for age, height, and weight. RESULTS: Allele frequencies were 2.5% for Ala37 and 40.2% for Ser190, whereas haplotype allele frequencies were 57.28% (Ser37Arg190), 40.19% (Ser37Ser190), 2.50% (Ala37Arg190), and 0.02% (Ala37Ser190). For BMD, bone loss, HSA outcomes, and (incident) fractures, no differences could be seen between genotype and haplotype groups. Conclusions: In this large population-based cohort of Dutch whites, we conclude that the BMP-2 Ser37Ala and Arg190Ser polymorphisms or haplotypes thereof are not associated with parameters of osteoporosis.     

Repetitive transcranial magnetic stimulation (rTMS): a new therapeutic approach in subjective tinnitus?

Subjective (non-recordable) tinnitus is the conscious perception of a phantom sound, and a very frequent, sometimes disabling, condition. Even if subjective tinnitus is often related to peripheral hearing loss, neurophysiological and functional imaging studies provide increasing evidence for an involvement both auditory and non-auditory central nervous pathways in the generation of tinnitus and related distress. Repetitive transcranial magnetic stimulation (rTMS) has been proposed to relieve tinnitus by reducing auditory cortex hyperexcitability associated with this condition. This paper will review the first clinical results reported in auditory cortex rTMS studies, with special reference to the pathophysiology of tinnitus processing and the mechanisms of action of rTMS. Although rTMS appears to be a very promising tool for the diagnosis and the treatment of tinnitus patients, available knowledge is still very limited at the moment. Further basic research and clinical studies are needed in order to optimize the parameters of stimulation (stimulus frequency, cortical target definition) and to validate the application of this technique in the management of patients with disabling tinnitus.     

Incidence of asthma and net change in symptoms in relation to changes in obesity.

The incidence of asthma has been reported to be associated with obesity. An alternative analysis, of net change in prevalence, does not require exclusion of those with asthma at baseline. Follow-up data were obtained from 9,552 participants in the European Community Respiratory Health Survey and the Swiss cohort Study on Air Pollution and Lung Disease in Adults. Incidence of asthma was analysed by proportional hazards regression, and net changes in symptoms and asthma status by generalised estimating equations, by obesity group. Incidence and net change in ever having had asthma were greater in females than in males, and in participants who remained obese compared with those who were never obese (hazard ratio 2.00, 95% confidence interval 1.25-3.20; excess net change 2.8%, 0.4-5.3% per 10 yrs). The effect of being obese on net change in diagnosed asthma was greater in females than in males, but for net change in wheeze without a cold it was greater in males. The present results are consistent with asthma being more frequently diagnosed in females, especially obese females. These findings may help to explain the reports of a stronger association between asthma and obesity in females than in males.     

Complete maternal uniparental isodisomy of chromosome 4 in a subject with major depressive disorder detected by high density SNP genotyping arrays.

Uniparental isodisomy (iUPD) is a rare genetic condition caused by non-disjunction during meiosis that ultimately leads to a duplication of either the maternal or paternal chromosome in the affected individual. Two types of disorders can result, those due to imprinted genes and those due to homozygosity of recessive disease-causing mutations. Here, we describe the third known case of complete chromosome 4 iUPD of maternal origin. This condition became apparent during whole genome linkage studies of psychiatric disorders in the Portuguese population. The proband is an adult female with normal fertility and no major medical complaints, but a history of major depressive disorder and multiple suicide attempts. The proband's siblings and parents had normal chromosome 4 genotypes and no history of mood disturbance. A brief review of other studies lends support for the possibility that genes on chromosome 4 might confer risk for mood disorders. We conclude that chromosome 4 maternal uniparental disomy (UPD) is a rare disorder that may present with a major depressive phenotype. The lack of a common disease phenotype between this and two other cases of chromosome 4 iUPD [Lindenbaum et al. [1991] Am J Med Genet 49(Suppl 285):1582; Spena et al. [2004] Eur J Hum Genet 12:891-898) would suggest that there is no vital maternal gene imprinting on chromosome 4. However, since there is no reported case of paternal chromosome 4 UPD, paternal gene imprinting on chromosome 4 cannot be excluded.