BACKGROUND AND AIMS: Positron emission tomography (PET) with the radioligand [(11)C]-D-deprenyl has shown increased signal at location of pain in patients with rheumatoid arthritis and chronic whiplash injury. The binding site of [(11)C]-D-deprenyl in peripheral tissues is suggested to be mitochondrial monoamine oxidase in cells engaged in post-traumatic inflammation and tissue repair processes. The association between [(11)C]-D-deprenyl uptake and the transition from acute to chronic pain remain unknown. Further imaging studies of musculoskeletal pain at the molecular level would benefit from establishing a clinical model in a common and well-defined injury in otherwise healthy and drug-naïve subjects. The aim of this study was to investigate if [(11)C]-D-deprenyl uptake would be acutely elevated in unilateral ankle sprain and if tracer uptake would be reduced as a function of healing, and correlated with pain localizations and pain experience.

METHODS: Eight otherwise healthy patients with unilateral ankle sprain were recruited at the emergency department. All underwent [(11)C]-D-deprenyl PET/CT in the acute phase, at one month and 6-14 months after injury.

RESULTS: Acute [(11)C]-D-deprenyl uptake at the injury site was a factor of 10.7 (range 2.9-37.3) higher than the intact ankle. During healing, [(11)C]-D-deprenyl uptake decreased, but did not normalize until after 11 months. Patients experiencing persistent pain had prolonged [(11)C]-D-deprenyl uptake in painful locations.

CONCLUSIONS AND IMPLICATIONS: The data provide further support that [(11)C]-D-deprenyl PET can visualize, quantify and follow processes in peripheral tissue that may relate to soft tissue injuries, inflammation and associated nociceptive signaling. Such an objective correlate would represent a progress in pain research, as well as in clinical pain diagnostics and management.

BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).

MATERIALS AND METHODS: The case-control portion of the study was conducted in nine UK centres with men aged 50-69 years who underwent prostate-specific antigen (PSA) screening for prostate cancer within the Prostate testing for cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.

RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (p <0.0014, multiple-testing threshold). These fell into four classes: i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); ii) fatty acids and ratios; iii) amino acids; iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.

CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.

IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

Studying gene-environment interactions requires that the amount and quality of the lifestyle data is comparable to what is available for the corresponding genomic data. Sweden has several crucial prerequisites for comprehensive longitudinal biomedical research, such as the personal identity number, the universally available national health care system, continuously updated population and health registries and a scientifically motivated population. LifeGene builds on these strengths to bridge the gap between basic research and clinical applications with particular attention to populations, through a unique design in a research-friendly setting. LifeGene is designed both as a prospective cohort study and an infrastructure with repeated contacts of study participants approximately every 5 years. Index persons aged 18-45 years old will be recruited and invited to include their household members (partner and any children). A comprehensive questionnaire addressing cutting-edge research questions will be administered through the web with short follow-ups annually. Biosamples and physical measurements will also be collected at baseline, and re-administered every 5 years thereafter. Event-based sampling will be a key feature of LifeGene. The household-based design will give the opportunity to involve young couples prior to and during pregnancy, allowing for the first study of children born into cohort with complete pre-and perinatal data from both the mother and father. Questions and sampling schemes will be tailored to the participants' age and life events. The target of LifeGene is to enrol 500,000 Swedes and follow them longitudinally for at least 20 years.

AIMS:

We aimed to investigate the association of number of completed races and finishing time with risk of arrhythmias among participants of Vasaloppet, a 90 km cross-country skiing event.

METHODS AND RESULTS:

All the participants without cardiovascular disease who completed Vasaloppet during 1989-98 were followed through national registries until December 2005. Primary outcome was hospitalization for any arrhythmia and secondary outcomes were atrial fibrillation/flutter (AF), bradyarrhythmias, other supraventricular tachycardias (SVT), and ventricular tachycardia/ventricular fibrillation/cardiac arrest (VT/VF/CA). Among 52 755 participants, 919 experienced arrhythmia during follow-up. Adjusting for age, education, and occupational status, those who completed the highest number of races during the period had higher risk of any arrhythmias [hazard ratio (HR)1.30; 95% CI 1.08-1.58; for ≥5 vs. 1 completed race], AF (HR 1.29; 95% CI 1.04-1.61), and bradyarrhythmias (HR 2.10; 95% CI 1.28-3.47). Those who had the fastest relative finishing time also had higher risk of any arrhythmias (HR 1.30; 95% CI 1.04-1.62; for 100-160% vs. >240% of winning time), AF (1.20; 95% CI 0.93-1.55), and bradyarrhythmias (HR 1.85; 95% CI 0.97-3.54). SVT or VT/VF/CA was not associated with finishing time or number of completed races.

CONCLUSIONS:

Among male participants of a 90 km cross-country skiing event, a faster finishing time and a high number of completed races were associated with higher risk of arrhythmias. This was mainly driven by a higher incidence of AF and bradyarrhythmias. No association with SVT or VT/VF/CA was found.

BACKGROUND:

While it is well known that physical inactivity is a major risk factor for cardiovascular disease, there is still a search for the mechanisms by which exercise exerts its positive effect. Skeletal muscle fibre type can be affected to some extent by exercise, and different fibre types possess different anti-inflammatory and glucometabolic properties that may influence cardiovascular disease risk.

DESIGN:

Population-based cohort study.

METHODS:

We investigated relations of skeletal muscle morphology to risk of cardiovascular events in a sample of 466 71-year-old men without cardiovascular disease, of which 295 were physically active (strenuous physical activity at least 3 h/week).

RESULTS:

During a median of 13.1 years of follow up, 173 major cardiovascular events occurred. Among physically active men, 10% higher proportion of type-I (slow-twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95% confidence interval 0.74-0.95) for cardiovascular events, and 10% higher proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several sets of multivariable-adjusted models. No association of muscle fibre type with risk of cardiovascular events was observed among physically inactive men.

CONCLUSIONS:

Higher skeletal muscle proportion of type-I fibres was associated with lower risk of cardiovascular events and a higher proportion of type-IIx fibres was associated with higher risk of cardiovascular events. These relations were only observed in physically active men. Skeletal muscle fibre composition may be a mediator of the protective effects of exercise against cardiovascular disease.

BACKGROUND: Prenatal life exposures, potentially manifested as altered birth size, may influence the later risk of major chronic diseases through direct biologic effects on disease processes, but also by modifying adult behaviors such as physical activity that may influence later disease risk. METHODS/PRINCIPAL FINDINGS: We investigated the association between birth weight and leisure time physical activity (LTPA) in 43,482 adolescents and adults from 13 Nordic cohorts. Random effects meta-analyses were performed on categorical estimates from cohort-, age-, sex- and birth weight specific analyses. Birth weight showed a reverse U-shaped association with later LTPA; within the range of normal weight the association was negligible but weights below and above this range were associated with a lower probability of undertaking LTPA. Compared with the reference category (3.26-3.75 kg), the birth weight categories of 1.26-1.75, 1.76-2.25, 2.26-2.75, and 4.76-5.25 kg, had odds ratios of 0.67 (95% confidence interval: 0.47, 0.94), 0.72 (0.59, 0.88), 0.89 (0.79, 0.99), and 0.65 (0.50, 0.86), respectively. The shape and strength of the birth weight-LTPA association was virtually independent of sex, age, gestational age, educational level, concurrent body mass index, and smoking. CONCLUSIONS/SIGNIFICANCE: The association between birth weight and undertaking LTPA is very weak within the normal birth weight range, but both low and high birth weights are associated with a lower probability of undertaking LTPA, which hence may be a mediator between prenatal influences and later disease risk.

Background-Given the indications of increased risk for fatal myocardial infarction (MI) in people who use snus, a moist smokeless tobacco product, we hypothesized that discontinuation of snus use after an MI would reduce mortality risk. Methods and Results-All patients who were admitted to coronary care units for an MI in Sweden between 2005 and 2009 and were <75 years of age underwent a structured examination 2 months after discharge (the baseline of the present study). We investigated the risk of mortality in post-MI snus quitters (n=675) relative to post-MI continuing snus users (n=1799) using Cox proportional hazards analyses. During follow-up (mean 2.1 years), 83 participants died. The mortality rate was 9.7 (95% confidence interval, 5.7-16.3) per 1000 person-years at risk in post-MI snus quitters and 18.7 (14.8-23.6) per 1000 person-years at risk in post-MI continuing snus users. After adjustment for age and sex, post-MI snus quitters had half the mortality risk of post-MI continuing snus users (hazard ratio, 0.51; 95% confidence interval, 0.29-0.91). In a multivariable-adjusted model, the hazard ratio was 0.57 (95% confidence interval, 0.32-1.02). The corresponding estimate for people who quit smoking after MI versus post-MI continuing smokers was 0.54 (95% confidence interval, 0.42-0.69). Conclusions-In this study, discontinuation of snus use after an MI was associated with a nearly halved mortality risk, similar to the benefit associated with smoking cessation. These observations suggest that the use of snus after MI should be discouraged.

Background:

Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure.

Design:

Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers.

Methods:

Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure.

Results:

In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use.

Conclusion:

Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.

“Spinal Cord Injury without Radiographic Abnormality” (SCIWORA) is a term that denotes objective clinical signs of posttraumatic spinal cord injury without evidence of fracture or malalignment on plain radiographs and computed tomography (CT) of the spine. SCIWORA is most commonly seen in children with a predilection for the cervical spinal cord due to the increased mobility of the cervical spine, the inherent ligamentous laxity, and the large head-to-body ratio during childhood. However, SCIWORA can also be seen in adults and, in rare cases, the thoracolumbar spinal cord can be affected too. Magnetic resonance imaging (MRI) has become a valuable diagnostic tool in patients with SCIWORA because of its superior ability to identify soft tissue lesions such as cord edema, hematomas and transections, and discoligamentous injuries that may not be visualized in plain radiographs and CT. The mainstay of treatment in patients with SCIWORA is nonoperative management including steroid therapy, immobilization, and avoidance of activities that may increase the risk of exacerbation or recurrent injury. Although the role of operative treatment in SCIWORA can be controversial, surgical alternatives such as decompression and fusion should be considered in selected patients with clinical and MRI evidence of persistent spinal cord compression and instability.

Objective: We sought to study the anatomic variations of the cochlear aqueduct and its accessory canals in human temporal bones using micro-CT and a 3D reconstruction paradigm. More knowledge about the anatomic variations of these structures, particularly at the basal turn of the cochlea and round window niche, may be important to better preserve residual hearing as well as the neural supply during cochlear implant surgery.

Methods: An archival collection of 30 human temporal bones underwent micro-CT and 3D reconstruction. A surface enhancement paradigm was applied. The application displays reconstructed slices as a 3D object with realistic 3D visualization of scanned objects. Virtual sectioning or cropping of the petrous bone presented subsequent areas. Thereby, the bony canals could be followed from inside the basal turn of cochlea and middle ear to the jugular foramen.

Results: The cochlear aqueduct was always paralleled by an accessory canal containing the inferior cochlear vein. It ran from the basal turn of the cochlea and exited laterally in the jugular foramen. In 70% of the cases, a secondary accessory canal was observed and it derived mostly from a depression or infundibulum located in the floor of the round window niche. This canal also exited in the jugular foramen. The secondary accessory canal occasionally anastomosed with the primary accessory canal suggesting that it contains a vein that drains middle ear blood to the cranial sinus.

Conclusion: Micro-CT with 3D surface reconstruction paradigm offers new possibilities to study the topographic anatomy of minor details in the human inner ear. The technique creates simulated transparent castings of the labyrinth with a coinciding surface view through enhancement of contrast between boundaries. Accessory canals that drain blood from the cochlea, spiral ganglion, and middle ear could be characterized three-dimensionally.