Hearing impairment among adults: The impact of cardiovascular diseases and cardiovascular risk factors

Objective: To investigate the influence of cardiovascular diseases on hearing impairment (HI) among adults. Furthermore, to seek other potential risk factors for HI, such as smoking, obesity, and socioeconomic class. Design: A cross-sectional, unscreened, population-based, epidemiological study among adults. Study sample: The subjects (n = 850), aged 54–66 years, were randomly sampled from the population register. A questionnaire survey, an otological examination, and pure-tone audiometry were performed. Results: Cardiovascular diseases did not increase the risk for HI in a propensity-score adjusted logistic regression model: OR 1.24, 95% CI 0.79 to 1.96 for HI defined by better ear hearing level (BEHL), and OR 1.48, 95% CI 0.96 to 2.28 for HI defined by worse ear hearing level (WEHL), in the 0.5–4 kHz frequency range. Heavy smoking is a risk factor for HI among men (BEHL: OR 1.96, WEHL: OR 1.88) and women (WEHL: OR 2.4). Among men, obesity (BEHL, OR 1.85) and lower socioeconomic class (BEHL: OR 2.79, WEHL: OR 2.28) are also risk factors for HI. Conclusion: No significant association between cardiovascular disease and HI was found.     

Sex differences in cognition among persons with schizophrenia and healthy first-degree relatives

Previous research suggests differences between women and men in the clinical features of schizophrenia, but studies examining sex differences in neuropsychological functioning have reached inconsistent results. In the present study, sex differences in cognition and clinical features were investigated in population-based samples of participants with schizophrenia (n = 218), their healthy first-degree relatives (n = 438) and controls (n = 123). Sex differences in illness features were small; nevertheless, women with schizophrenia had less negative symptoms and lived independently more often than men. The schizophrenia group had impairments in all studied neuropsychological domains, and the relatives were impaired in processing speed and set-shifting. In all groups, women performed better than men in processing speed, set-shifting and verbal episodic memory, whereas men outperformed women in visual working memory. The group-by-sex interaction was significant in two variables: women outperformed men in the relatives group in immediate verbal reproduction and in the use of semantic clustering as a learning strategy, while there was no sex difference in the schizophrenia group. In conclusion, sex differences in cognition are mostly similar in schizophrenia to those among controls, despite sex differences in illness features. The preservation of sex differences also in first-degree relatives supports the conclusion.     

Founder population-specific HapMap panel increases power in GWA studies through improved imputation accuracy and CNV tagging

The combining of genome-wide association (GWA) data across populations represents a major challenge for massive global meta-analyses. Genotype imputation using densely genotyped reference samples facilitates the combination of data across different genotyping platforms. HapMap data is typically used as a reference for single nucleotide polymorphism (SNP) imputation and tagging copy number polymorphisms (CNPs). However, the advantage of having population-specific reference panels for founder populations has not been evaluated. We looked at the properties and impact of adding 81 individuals from a founder population to HapMap3 reference data on imputation quality, CNP tagging, and power to detect association in simulations and in an independent cohort of 2138 individuals. The gain in SNP imputation accuracy was highest among low-frequency markers (minor allele frequency [MAF] < 5%), for which adding the population-specific samples to the reference set increased the median R² between imputed and genotyped SNPs from 0.90 to 0.94. Accuracy also increased in regions with high recombination rates. Similarly, a reference set with population-specific extension facilitated the identification of better tag-SNPs for a subset of CNPs; for 4% of CNPs the R² between SNP genotypes and CNP intensity in the independent population cohort was at least twice as high as without the extension. We conclude that even a relatively small population-specific reference set yields considerable benefits in SNP imputation, CNP tagging accuracy, and the power to detect associations in founder populations and population isolates in particular.In the next generation of genome-wide association studies (GWAS), large consortia combine GWA results from platforms that have different single nucleotide polymorphism (SNP) marker resolutions and the capability for copy number polymorphism (CNP) discovery and genotyping (Cooper et al. 2008). The challenge of having data of different SNP resolutions across GWA studies can be overcome by genotype imputation: the inference of missing and unobserved data from the local linkage disequilibrium (LD) structure of a high-resolution reference sample (Li and Abecasis 2006; Marchini et al. 2007). Similarly, information on CNPs can be inferred from the variation of SNPs that correlate with CNP signal intensities in a reference set genotyped with a high-density array with good CNP coverage (Locke et al. 2006; McCarroll et al. 2006; Redon et al. 2006). The strategy of inferring CNPs from SNP data may assist future CNP studies by allowing for the determination of CNPs using a specific set of tagging SNPs instead of costly CNP detection and genotyping pipelines.In studies using samples of European origin, the SNP imputation and CNP-tagging reference panel has typically been the 60 CEPH (Utah residents with ancestry from Northern and Western Europe, abbreviation: CEU) samples from HapMap Phase 2 (The International HapMap Consortium 2003, 2007). Recently, additional HapMap populations were genotyped with two commercially available chips, the Illumina Infinium Human1M-single and Affymetrix Genome-Wide Human SNP Array 6.0 (The International HapMap 3 Consortium 2010). This new HapMap3 data set of 1184 samples offers better genomic information due to its increased sample size and the SNP and CNP data from the high-density genotyping arrays. The design of HapMap3 allows for the extension of the reference set into additional populations with different LD structures. Some of the most unique LD patterns in the world arise in founder populations (Service et al. 2006), many of which also display unique health risks (Peltonen et al. 1999; Orton et al. 2008). Given these characteristics, does it make sense for a founder population to have its own reference set and, if so, how would this impact our ability to detect disease variants? Here, we use a local reference set from the genetically distinct Finnish founder population (Supplemental Fig. 1; Service et al. 2006; Jakkula et al. 2008) to evaluate the accuracy, coverage, and power of SNP imputation and CNP tagging relative to that of the less-specific HapMap3 European samples CEU and TSI (from Tuscans in Italy).     

Bax and Bcl-2 are focally overexpressed in the normal epithelium of cancerous prostates

OBJECTIVE: Development of prostate cancer is connected with a disturbance of apoptosis. Prostate cancer is multifocal, suggesting that the control of apoptosis is impaired at multiple foci. We wanted to know whether apoptosis is generally disturbed in cancerous prostates and if changes in apoptotic control could be detected even in the absence of any morphologically visible changes. Therefore, we compared expression of two common apoptotic markers, Bax and Bcl-2, in normal epithelium of cancerous prostates and controls. We also evaluated the expression of these proteins in hyperplasia, prostatic intraepithelial neoplasia (PIN), carcinomas of different Gleason grades and capsular perineural invasion. MATERIAL AND METHODS: The tissue material was obtained from radical prostatectomies, transurethral resection chips and autopsies. Individual tissue arrays were done for each patient. The intensity of Bax and Bcl-2 immunostaining was estimated semiquantitatively. The data were analyzed using a linear mixed-models analysis as well as dichotomized staining indices. RESULTS: Normal epithelium of cancerous prostates contained foci with high expression of Bax and Bcl-2. The expression of Bax in Gleason grades 3-5 carcinoma was significantly higher than that in Gleason grade 2, and was highest in foci with perineural invasion. The expression of Bcl-2 was strongest in PIN foci. CONCLUSIONS: Expression of Bax and Bcl-2 in normal epithelium of cancerous prostates suggests that increases in these indirect markers may reflect altered apoptotic control in these foci. Further studies are needed to show whether these changes represent the earliest step of the multifocal carcinogenetic process. Control of apoptosis seems to be involved and modulated during local progression of prostate cancer.     

Physicians' Ethics Forum: a Web-based ethics consultation service

To meet all physicians' needs for ethics consultation in Finland, a novel form of service, the Physicians' Ethics Forum, was founded in 2003. The Forum is a cost-efficient service based on electronic communication. In this paper, experiences throughout its first 6 years are described.     

Muscle injuries: optimising recovery

Muscle injuries are one of the most common traumas occurring in sports. Despite their clinical importance, there are only a few clinical studies on the treatment of muscle injuries. Lack of clinical studies is most probably attributable to the fact that there is not only a high heterogeneity in the severity of injuries, but also the injuries take place in different muscles, making it very demanding to carry out clinical trials. Accordingly, the current treatment principles of muscle injuries have either been derived from experimental studies or been tested empirically only. Clinically, first aid for muscle injuries follows the RICE (Rest, Ice, Compression and Elevation) principle. The objective of RICE is to stop the injury-induced bleeding into the muscle tissue and thereby minimise the extent of the injury. Clinical examination should be carried out immediately after the injury and 5-7 days after the initial trauma, at which point the severity of the injury can be assessed more reliably. At that time, a more detailed characterisation of the injury can be made using imaging diagnostic modalities (ultrasound or MRI) if desired. The treatment of injured skeletal muscle should be carried out by immediate immobilisation of the injured muscle (clinically, relative immobility/avoidance of muscle contractions). However, the duration of immobilisation should be limited to a period sufficient to produce a scar of sufficient strength to bear the forces induced by remobilisation without re-rupture and the return to activity (mobilisation) should then be started gradually within the limits of pain. Early return to activity is needed to optimise the regeneration of healing muscle and recovery of the flexibility and strength of the injured skeletal muscle to pre-injury levels. The rehabilitation programme should be built around progressive agility and trunk stabilisation exercises, as these exercises seem to yield better outcome for injured skeletal muscle than programmes based exclusively on stretching and strengthening of the injured muscle.