Many studies report that people with temporomandibular disorders (TMD) are more sensitive to experimental pain stimuli than TMD-free controls. Such differences in sensitivity are observed in remote body sites as well as in the orofacial region, suggesting a generalized upregulation of nociceptive processing in TMD cases. This large case-control study of 185 adults with TMD and 1,633 TMD-free controls measured sensitivity to painful pressure, mechanical cutaneous, and heat stimuli, using multiple testing protocols. Based on an unprecedented 36 experimental pain measures, 28 showed statistically significantly greater pain sensitivity in TMD cases than controls. The largest effects were seen for pressure pain thresholds at multiple body sites and cutaneous mechanical pain threshold. The other mechanical cutaneous pain measures and many of the heat pain measures showed significant differences, but with lesser effect sizes. Principal component analysis (PCA) of the pain measures derived from 1,633 controls identified five components labeled: (1) heat pain ratings, (2) heat pain aftersensations and tolerance, (3) mechanical cutaneous pain sensitivity, (4) pressure pain thresholds, and (5) heat pain temporal summation. These results demonstrate that, compared to TMD-free controls, chronic TMD cases are more sensitive to many experimental noxious stimuli at extra-cranial body sites, and provides for the first time the ability to directly compare the case-control effect sizes of a wide range of pain sensitivity measures.

This paper describes methods used in the project “Orofacial Pain Prospective Evaluation and Risk Assessment” (OPPERA) and evaluates socio-demographic characteristics associated with temporomandibular disorders (TMD) in the OPPERA case-control study. Representativeness was investigated by comparing socio-demographic profiles of OPPERA participants with population census profiles of counties near study sites and by comparing age- and gender-associations with TMD in OPPERA and the 2007-09 US National Health Interview Survey. Volunteers aged 18-44 years were recruited at four US study sites: 3,263 people without TMD were enrolled into the prospective cohort study; 1,633 of them were selected as controls for the baseline case-control study. Cases were 185 volunteers with examiner-classified TMD. Distributions of some demographic characteristics among OPPERA participants differed from census profiles, although there was less difference in socio-economic profiles. Odds of TMD was associated with greater age in this 18-44 year range; females had three times the odds of TMD as males; and relative to non-Hispanic-Whites, other racial groups had one-fifth the odds of TMD. Age- and gender-associations with chronic TMD were strikingly similar to associations observed in the US population. Assessments of representativeness in this demographically diverse group of community volunteers suggest that OPPERA case-control findings have good internal validity.

Although previous studies have documented a bottleneck in the transmission of mtDNA genomes from mothers to offspring, several aspects remain unclear, including the size and nature of the bottleneck. Here, we analyze the dynamics of mtDNA heteroplasmy transmission in the Genomes of the Netherlands (GoNL) data, which consists of complete mtDNA genome sequences from 228 trios, eight dizygotic (DZ) twin quartets, and 10 monozygotic (MZ) twin quartets. Using a minor allele frequency (MAF) threshold of 2%, we identified 189 heteroplasmies in the trio mothers, of which 59% were transmitted to offspring, and 159 heteroplasmies in the trio offspring, of which 70% were inherited from the mothers. MZ twin pairs exhibited greater similarity in MAF at heteroplasmic sites than DZ twin pairs, suggesting that the heteroplasmy MAF in the oocyte is the major determinant of the heteroplasmy MAF in the offspring. We used a likelihood method to estimate the effective number of mtDNA genomes transmitted to offspring under different bottleneck models; a variable bottleneck size model provided the best fit to the data, with an estimated mean of nine individual mtDNA genomes transmitted. We also found evidence for negative selection during transmission against novel heteroplasmies (in which the minor allele has never been observed in polymorphism data). These novel heteroplasmies are enhanced for tRNA and rRNA genes, and mutations associated with mtDNA diseases frequently occur in these genes. Our results thus suggest that the female germ line is able to recognize and select against deleterious heteroplasmies.

In a two-year study of asthma mortality in New Zealand conducted between August 1981 and July 1983, the certified cause of death and its subsequent statistical coding was compared with the opinion of a panel of respiratory physicians who had made detailed enquiry into the medical history and circumstances surrounding the death of each patient. When the panel's opinion was taken as the reference standard, the national health statistics overestimated asthma mortality for all age groups by 26.0%. For patients aged 15-64 years, the net overestimate was 12.9%, no greater than that found in a similar study in this age group in the United Kingdom. Failure of certifying doctors and coroners to follow appropriate procedures for identification of the primary condition leading to death, or misdiagnosis of other lung disease as asthma, accounted for most inaccuracies in certification. In patients under age 35 years, certification and statistical coding of asthma death was considered accurate in 97.8% of all cases, but accuracy declined with increasing age. The high New Zealand asthma mortality rate, especially in young people, could not be explained by inaccuracies in death certification or statistical coding.

No abstract