Effects of electromagnetic stimuli on bone and bone cells in vitro: Inhibition of responses to parathyroid hormone by low-energy low-frequency fields

Low-energy electromagnetic fields pulsed at frequencies of 10-90 Hz significantly increase healing of chronic fracture nonunions in man. These fields are effective at tissue current levels several orders of magnitude lower than those required for transmembrane depolarization of normal cells. We have examined the effects of two clinically used pulsed electromagnetic fields on cultures of the osteoblast-like mouse bone cell line MMB-1. Both fields significantly reduced cellular production of cAMP in response to parathyroid hormone and osteoclast activating factor. Neither basal nor fluoride-activated levels of adenylate cyclase were altered in membranes from cells cultured in the fields; however, the same membrane preparations exhibited markedly inhibited responses to parathyroid hormone. The fields blocked the inhibitory effects of the hormone on collagen synthesis by MMB-1 cells. However, there was no effect on the inhibition of collagen synthesis by 1,25-dihydroxyvitamin D(3), which is believed to act primarily by a nuclear, rather than by a membrane-dependent, mechanism. No significant differences were noted between effects of the two fields, one generating continuous pulse trains (72 Hz) and the other generating recurrent bursts (15 Hz) of shorter pulses. We hypothesize that these field effects are mediated primarily at the plasma membrane of osteoblasts, either by interference with hormone-receptor interactions or by blocking of receptor-cyclase coupling in the membrane. These responses occurred with induced extracellular fields of 1 mV/cm or less, even though transmembrane potential gradients are typically 10(5) V/cm.     

Prospective cohort study of hostility and the risk of cardiovascular disease mortality

BACKGROUND: Recent literature reviews have questioned hostility as a risk factor for heart disease. However, controversy persists due to the rarity of large-scale prospective cohort studies of initially healthy populations. METHODS: We prospectively investigated the association between hostility and cardiovascular (and all-cause) mortality among 20,550 men and women, 41-80 years of age, participating in the European Prospective Investigation into Cancer and Nutrition in Norfolk (EPIC-Norfolk), United Kingdom study. Participants were recruited by post from general practice age-sex registers and subsequently attended health checks that included the assessment of coronary disease risk factors. Hostility assessment was completed by postal questionnaire. RESULTS: During mean follow-up of 6 years, 1284 deaths were recorded including 481 from cardiovascular disease (CVD). Hostility was not associated with CVD mortality, after adjustment for age and prevalent disease, in either men (rate ratio for a 1 SD decrease in hostility score, representing increased hostility, 1.09; 95% confidence interval 0.98-1.22) or in women (rate ratio 1.00; 95% confidence interval 0.86-1.26). Subgroup analysis suggested hostility may be associated with CVD mortality (independent of age, prevalent disease and cigarette smoking) for participants reporting very high hostility and for those aged less than 60 years. CONCLUSIONS: Hostility was not associated with an increased risk of cardiovascular mortality in this population study of older adults.     

Initial thyroid status and cardiovascular risk factors: The EPIC‐Norfolk prospective population study

Context Thyroid status affects several aspects of cardiovascular risk profile, including lipid levels and blood pressure. Whether thyroid status affects the risk of coronary heart disease (CHD) and all‐cause mortality remains controversial. Design The EPIC‐Norfolk prospective population study. Mean follow‐up was 10·6 years. Patients Study participants were 11 554 men and women aged 45–79 years, who were living in Norfolk, UK. Measurements Baseline cardiovascular risk factors were recorded and concentrations of thyroid‐stimulating hormone (TSH) and free thyroxine (FT4) were measured in baseline samples. Regression analyses were performed to assess the association between thyroid hormone levels and cardiovascular risk factors. A proportional hazards model was used to estimate the risk of CHD and all‐cause mortality by baseline thyroid status. No information was available on thyroid treatment during follow‐up. Results Thyroid abnormalities were common, particularly among women. Thyroid abnormalities were associated with an altered cardiovascular risk profile. Even within the normal range, thyroid hormone levels, TSH more strongly than FT4, were associated with lipid levels and blood pressure among both men and women. We did not observe a significant association between subclinical thyroid abnormalities and risk of CHD or all‐cause mortality. Conclusions Despite the association between thyroid hormone levels and cardiovascular risk factors, thyroid status was not statistically significantly associated with the risk of future CHD or all‐cause mortality in this large cohort.     

Aspirin in the aetiology of Crohn's disease and ulcerative colitis: a European prospective cohort study

Aliment Pharmacol Ther 2011; 34: 649–655

Summary

Background Aspirin has detrimental effects on the gastrointestinal tract mucosa and may play a role in the aetiology of inflammatory bowel disease. Aim To investigate if the regular use of aspirin is associated with the development of Crohn’s disease (CD) and ulcerative colitis (UC) using, for the first time, a prospective cohort study design. Methods A total of 135 780 men and women in Europe, aged 30–74 years, were recruited into the European Prospective Investigation into Cancer and Nutrition study. Participants completed questionnaires at baseline detailing their regular aspirin use and were then followed up to identify those who developed either incident CD or UC. Each case was matched with four controls and odds ratios (OR) were calculated, adjusting for cigarette smoking. Potential interactions between aspirin and smoking were assessed. Results A total of 35 participants developed CD and a further 84 were diagnosed with UC. Regular aspirin intake was positively associated with the risk of developing CD (OR = 6.14, 95% CI = 1.76–21.35). In those who took aspirin and smoked there was no detectable increased risk of CD (OR = 0.30, 95% CI = 0.03–3.08). No association was found between regular aspirin use and UC (OR = 1.29, 95% CI = 0.67–2.46). Conclusions A strong positive association between regular aspirin use and CD, but not UC, was observed. The data suggest that regular aspirin use should be measured in epidemiological work on CD. If such findings are consistent in other work then aspirin may affect the development of CD in a middle‐aged to elderly population.     

Rat Mcs5a is a compound quantitative trait locus with orthologous human loci that associate with breast cancer risk

Breast cancer risk is a polygenic trait. To identify breast cancer modifier alleles that have a high population frequency and low penetrance we used a comparative genomics approach. Quantitative trait loci (QTL) were initially identified by linkage analysis in a rat mammary carcinogenesis model followed by verification in congenic rats carrying the specific QTL allele under study. The Mcs5a locus was identified by fine-mapping Mcs5 in a congenic model. Here we characterize the Mcs5a locus, which when homozygous for the Wky allele, reduces mammary cancer risk by 50%. The Mcs5a locus is a compound QTL with at least two noncoding interacting elements: Mcs5a1 and Mcs5a2. The resistance phenotype is only observed in rats carrying at least one copy of the Wky allele of each element on the same chromosome. Mcs5a1 is located within the ubiquitin ligase Fbxo10, whereas Mcs5a2 includes the 5' portion of Frmpd1. Resistant congenic rats show a down-regulation of Fbxo10 in the thymus and an up-regulation of Frmpd1 in the spleen. The association of the Mcs5a1 and Mcs5a2 human orthologs with breast cancer was tested in two population-based breast cancer case-control studies (approximately 12,000 women). The minor alleles of rs6476643 (MCS5A1) and rs2182317 (MCS5A2) were independently associated with breast cancer risk. The minor allele of rs6476643 increases risk, whereas the rs2182317 minor allele decreases risk. Both alleles have a high population frequency and a low penetrance toward breast cancer risk.     

Contemporary issues in dental education in Australia

Australia has witnessed a proliferation of dental workforce training opportunities over the last 15 years, including dentists, dental therapists, dental hygienists and prosthetists. The reasons for this have not been examined critically. Universities have welcomed the opportunities to increase the student base but do not seem to have examined the advisability of continued expansion or its impact on the delivery and costs of health services. Nor have they enquired expressly whether they have any responsibility in these matters. Public health benefits should constitute a significant element of curriculum design. There seems to have been a general acceptance of the premise that more is necessarily better. Ironically, these developments have occurred in the face of significant recurrent cost increments and serious academic staff shortages. The schools have responded with alterations to curriculum content. Student cohort composition, course structures, educational focus, postgraduate training and research have been affected. The primary purpose of this review is to highlight the issues which currently drive workforce training and curriculum content and to suggest that some current practices should be re-examined as a starting point for setting defined common objectives within the Australian dental educational spectrum. Salient issues which require examination include course standards and accreditation, workforce mix, dental health demands, public service obligations and staffing profiles.     

Evaluation of two methods of interpolating quarterly trihalomethane levels between sampling dates

Epidemiological studies of the relationship between disinfection byproducts (DBPs) and adverse birth outcomes often use a single quarterly sample result to characterize an exposure period during a pregnancy. Concentrations of trihalomethanes (THMs), a frequently studied class of DBPs, can fluctuate considerably between sampling periods so that a single point measurement in time may not adequately characterize levels over an exposure period. In addition to obtaining compliance samples that are required quarterly at a limited number of sampling sites, the New York City water supply system takes monthly THM samples at a large number of sites. We used these monthly data to investigate two methods for interpolating between quarterly measurements: cubic splines and linear interpolation. We based interpolations on 1 month in each calendar quarter and checked the interpolated values against the actual data values from the other 2 months of the quarter. Both methods produced generally acceptable fits: 90% of the observed discrepancies between fitted and actual values were less than 14 microg/l and over half were less than 5 microg/l for total trihalomethanes (THM4). These numbers are about half the change in THM4 level from one quarter to the next and compare favorably with the range of 0-80 microg/l or more used in many studies. Comparable results were obtained for chloroform and bromodichloromethane, the two THMs with levels high enough to analyze. Linear interpolation generally performed better than the spline fit, producing lower average discrepancies and fewer large discrepancies. Linear interpolation can be a useful and easily applied method for developing improved exposure estimates using quarterly sampling data.     

Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees

Background  

Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence- and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date. The aim of the Balance@Work project is to develop, evaluate, and implement an occupational health guideline aimed at the prevention of weight gain among employees.