Assessing the Temporality Between Transitions onto Opioid Agonist Therapy and Engagement with Antiretroviral Therapy in a Cohort of HIV-Positive People Who Use Opioids Daily

AIDS and Behavior - A robust evidence-base describes the beneficial association between opioid agonist therapy (OAT) and HIV-related outcomes among people living with HIV and opioid use disorder....     

Production of reflex cough by brainstem respiratory networks

Delineation of neural mechanisms involved in reflex cough is essential for understanding its many physiological and clinical complexities, and the development of more desirable antitussive agents. Brainstem networks that generate and modulate the breathing pattern are also involved in producing the motor patterns during reflex cough. Neurones of the ventrolateral medulla respiratory pattern generator mutually interact with neural networks in the pons, medulla and cerebellum to form a larger dynamic network. This paper discusses evidence from our laboratory and others supporting the involvement of the nucleus tractus solitarii, midline raphe nuclei and lateral tegmental field in the medulla, and the pontine respiratory group and cerebellum in the production of reflex cough. Gaps in our knowledge are identified to stimulate further research on this complicated issue.     

Health related quality of life in women with elderly onset rheumatoid arthritis

OBJECTIVE: To examine the association of elderly onset rheumatoid arthritis (RA) with health related quality of life in a population based cohort of older women. METHODS: A nested case-control study of elderly onset RA within the Iowa Women's Health Study (IWHS), a prospective cohort established in 1986 of 41,000 women aged 55 to 69 years. A supplemental questionnaire was mailed to 122 RA cases and 1132 frequency matched controls from the cohort. We used unconditional logistic regression and linear regression to examine the association of elderly onset RA with self-reported measures of functional disability and quality of life. RESULTS: Elderly onset RA was associated with a 6-fold risk (OR 6.0, 95% CI 3.6-10.1) of significant functional disability (Health Assessment Questionnaire score (3) 1). Similarly, elderly onset RA was significantly associated with lower physical component scores of the Medical Outcome Study Short Form-12 (37.2 +/- 10.9 vs 43.6 +/- 11.6; p < 0.001). CONCLUSION: Among a community based cohort, elderly onset RA was strongly associated with functional disability and reduced quality of life. These associations were independent of other age associated factors including depression, recent fracture, and multiple comorbidities.     

Early clinical results of long coronary arteriotomy, endarterectomy and reconstruction combined with multiple bypass grafting for severe coronary artery disease

Within a 2.5-year period between 1985 and 1988, long coronary arteriotomy, endarterectomy and reconstruction (principally left anterior descending artery) and multiple bypass grafting (mean graft rate was 9) were performed in 130 of 329 patients (40%) with severe diffuse coronary artery disease to ensure complete myocardial revascularization. Ninety-two percent of the patients who underwent exercise testing had abnormal (greater than 1 mm ST) depression and/or positive results on scintigraphy. Long coronary arteriotomy (5 to 12 cm), endarterectomy and reconstruction of the left anterior descending artery and its branches, were performed in 121 patients; of the left circumflex artery and its branches in 13 patients; and of the right coronary artery and its branches beyond the crux in 18 patients. Single endarterectomy and reconstruction was performed in 109 patients, double in 20 and triple in 1. The operative mortality was 2.3% and the perioperative infarction was 1.5%. Twenty-four patients (among them 38% who had undergone greater than 1 previous bypass operation) were randomly selected and studied within 20 days after surgery. This group comprised a total of 69 coronary conduits of which 68 (99%) were patent, and a total of 206 coronary anastomoses of which 202 (98%) were patent. Thirty-two of 33 conduits (97%) to endarterectomized and reconstructed arteries were patent. One hundred and twenty-six of 127 patients were followed up for a mean of 20 months; 120 of the 121 patients (99%) were in angina class I by Canadian Cardiovascular Society classification, and 63 of 71 patients (89%) had a normal treadmill exercise stress test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interactions between chromosomal and nonchromosomal elements reveal missing heritability

The measurement of any nonchromosomal genetic contribution to the heritability of a trait is often confounded by the inability to control both the chromosomal and nonchromosomal information in a population. We have designed a unique system in yeast where we can control both sources of information so that the phenotype of a single chromosomal polymorphism can be measured in the presence of different cytoplasmic elements. With this system, we have shown that both the source of the mitochondrial genome and the presence or absence of a dsRNA virus influence the phenotype of chromosomal variants that affect the growth of yeast. Moreover, by considering this nonchromosomal information that is passed from parent to offspring and by allowing chromosomal and nonchromosomal information to exhibit nonadditive interactions, we are able to account for much of the heritability of growth traits. Taken together, our results highlight the importance of including all sources of heritable information in genetic studies and suggest a possible avenue of attack for finding additional missing heritability.A fundamental problem in genetics is unraveling the link between genotype and phenotype. Ascertaining the heritability of a trait is a key step toward harnessing the predictive capacity of genetic information for human disease risk assessment and therapy (1). Knowledge of all of the elements contributing to heritability would facilitate the establishment of a causal relationship between the information that is passed down from generation to generation and the resulting phenotype. Genome-wide association studies (GWASs) have successfully identified many human polymorphisms that are associated with traits such as height, eye color, or susceptibility to common diseases, but these variants typically explain only a small proportion of the observed heritability of a trait (2, 3).A number of explanations for missing heritability have been suggested (2), including the existence of many weak variants with effects too small to achieve statistical significance (4), interactions between variants that cannot be identified with current studies (5), rare variants that were not identified by GWAS, and epigenetic effects (6–8). The contribution of nonchromosomal information to the missing heritability is rarely considered, despite the fact that there is a long history documenting the effect in many organisms of diverse cytoplasmic elements on phenotype. Recent work on a mouse model of Crohn disease supports a combinatorial model of complex disease traits in which the pathology requires the interaction between a specific mutation in the mouse and a specific strain of virus (9). Another recent study showed strong effects on the plant metabolome stemming from variation in mitochondrial and chloroplast genomes (10). In humans, the importance of nonchromosomal information has been supported by targeted analyses, but these studies have not analyzed its impact on heritability in a well-controlled context (11–13). Such nonchromosomal interactions might help explain why shared mutations in humans do not always produce the same phenotype, thus reducing the apparent heritability of a trait (14, 15).We sought to characterize explicitly how nonchromosomal modifiers collectively influence the heritability of a trait, colony size, in a system unique to yeast where we use a defined chromosomal genotype and vary the cytoplasmic genetic information. Yeast has at least four well-studied sources of inherited, nonchromosomal information: mitochondrial DNA, an endogenous dsRNA virus (16, 17), prions (18, 19), and a 2µ plasmid (20, 21).Our results show that the nonchromosomal contribution to heritability can be large, adding another dimension to the estimation of heritability in wild populations. Nonchromosomal information is not under the usual constraints of the nuclear genome. These nonchromosomal elements are extremely unstable: they mutate at higher frequencies than the DNA of the chromosomal genome, may be lost at high frequencies without loss of viability, and can vary in copy number from cell to cell. Thus, careful controls and measurements are necessary to characterize the effects of nonchromosomal modifiers.