Right Ventricular Outflow Tract Reconstructive Model in Adult Sheep

Patients born with congenital right ventricular outflow tract lesions are faced with invasive procedures to establish hemodynamic and physiological stability. Commonly, multiple subsequent surgical procedures are required due to deterioration of a previous repair. These procedures carry additive risks of mortality and morbidity. Less aggressive procedures with accompanying lower risk is ideal. Success in percutaneously placing a transcatheter valve has previously been reported; however, continued safety and efficacy of any technique needs continual assessment. We developed a model for preclinical evaluation of a percutaneous placement of a pulmonic transcatheter valve in adult sheep, including preoperative, surgical, and postoperative techniques for long-term evaluation. Adult sheep were assessed and determined to be acceptable for study enrollment. Perioperative antibiotics and analgesics were given prior to a left thoracotomy. A Medtronic, Hancock 1 valve conduit was inserted for reconstruction of the right ventricular outflow tract. The Hancock 1 valve conduit alone represented the control group and the test animals comprised the addition of a Melody? transcatheter pulmonary valve (TPV), within the Hancock 1 valve conduit. Fifteen adult sheep survived the surgical implant procedure with no perioperative mortality. There were four early postoperative deaths, three due to infection and one due to heart failure, secondary to intraoperative heart block. The remaining 11 animals remained healthy, gained weight, and survived to termination at 5 months. An initial definite-sized valve conduit was implanted, followed by inserting a single size TPV, which allowed a more accurate physiological assessment of any chosen valve. Our developed adult sheep model for percutaneous TPV implantation for right ventricular outflow tract lesions was successful for long-term assessment by utilizing our preoperative, surgical, and postoperative techniques.     

Validation of a clinical decision rule: chest X-ray in patients with chest pain and possible acute coronary syndrome

Current literature suggests that a large proportion of chest X-rays (CXRs) performed in emergency department (ED) patients with chest pain and suspected acute coronary syndrome (ACS) are unnecessary. The Canadian ACS Guidelines aim to guide clinicians in the appropriate use of CXR within this patient population. This study determined the prevalence of clinically significant CXR abnormalities and assessed the utility of the guidelines in a population of ED patients with chest pain and suspected ACS. Included in the study were participants over the age of 18 who presented to an Australian metropolitan ED, over a 1-year period, with a primary complaint of chest pain and who had a CXR and troponin level ordered in the ED (N?=?760). We retrospectively compared their radiographic findings with their recommendations for CXR according to the ACS Guidelines. We found that 12 % of the participants had a clinically significant chest X-ray. The guidelines had a sensitivity of 80 % (95 % CI 0.70–0.87) and specificity of 50 % (95 % CI 0.47–0.54). The positive predictive value was 18 % (95 % CI 0.15–0.22) with a 95 % negative predictive value (95 % CI 0.92–0.97). Had the ACS guidelines been applied to our patient population, the number of CXR performed would have been reduced by 47 %. This study suggests that the ACS Guidelines has the potential to reduce the numbers of unnecessary CXR performed in ED patients. However, this would come at the expense of missing a minority of significant CXR abnormalities.     

Longitudinal Determinants of Consistent Condom Use by Partner Type Among Young Injection Drug Users: The Role of Personal and Partner Characteristics

We investigated the longitudinal influence of individual-, relationship- and social-level factors on condom use by partner type among young injections drug users (IDUs) enrolled in the Collaborative Injection Drug Users Study-III/Drug Users Intervention Trial (CIDUS-III/DUIT) from 2002 to 2004. Based on longitudinal analysis using generalized estimating equations (GEE), consistent condom use with main partners was more commonly reported among males and those with greater self-efficacy for condom use; main partner’s desire for pregnancy and needle sharing were negatively associated with consistent condom use. Among those with casual partners, having fewer sex partners was associated with consistent condom use. Positive attitudes toward condom use and partner norms supporting condom use were associated with greater consistent condom use with both partner types. These findings suggest that intervention strategies targeting individual- and partner-level factors may provide avenues for intervening upon sexual risks among young IDUs.     

The Cognitive Behavior Survey: Testing for Factorial Validity and Time Invariance Across Two Years of Medical School

Background: The Cognitive Behavior Survey (CBS) assesses learner behavior in healthcare-related fields. Purpose: The study aims were to evaluate the factorial validity of the CBS, which purports to measure three dimensions of learner behavior—conceptualization, reflection, and memorization—and propose and test an alternative model including its time invariance. Methods: The CBS was administered to 3 cohorts of medical students upon matriculation and at the end of their 1st and 2nd year. Results: Confirmatory factor analysis (CFA) did not support the original CBS model. Exploratory factor analysis (EFA) with an independent sample provided a new model. Retesting the EFA model using CFA with the original sample yielded a model with improved fit and time invariance. Conclusions: This study provides evidence for the original CBS 3-factor structure but requires alternative scoring for a time-invariant model.     

Mouse Lung Structure and Function after Long-Term Exposure to an Atmospheric Carbon Dioxide Level Predicted by Climate Change Modeling

Background: Climate change models predict that atmospheric carbon dioxide [CO2] levels will be between 700 and 900 ppm within the next 80 y. Despite this, the direct physiological effects of exposure to slightly elevated atmospheric CO2 (as compared with ∼410 ppm experienced today), especially when exposures extend from preconception to adulthood, have not been thoroughly studied.Objectives: In this study we aimed to assess the respiratory structure and function effects of long-term exposure to 890 ppm CO2 from preconception to adulthood using a mouse model.Methods: We exposed mice to CO2 (∼890 ppm) from prepregnancy, through the in utero and early life periods, until 3 months of age, at which point we assessed respiratory function using the forced oscillation technique, and lung structure.Results: CO2 exposure resulted in a range of respiratory impairments, particularly in female mice, including higher tissue elastance, longer chord length, and lower lung compliance. Importantly, we also assessed the lung function of the dams that gave birth to our experimental subjects. Even though these mice had been exposed to the same level of increased CO2 for a similar amount of time (∼8wk), we measured no impairments in lung function. This suggests that the early life period, when lungs are undergoing rapid growth and development, is particularly sensitive to CO2.Discussion: To the best of our knowledge, this study, for the first time, shows that long-term exposure to environmentally relevant levels of CO2 can impact respiratory function in the mouse. https://doi.org/10.1289/EHP7305     

Etiology and Pathogenesis of Late-Onset Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative condition that occurs in two forms, an early-onset form that is genetically determined and a far more common late-onset form that is not. In both cases, the disease results in severe cognitive dysfunction, among other problems, and the late-onset form of the disease is now considered to be the most common cause of dementia among the elderly. While a good deal of research has been focused on elucidating the etiology of the late-onset form for more than two decades, results to date have been modest and have not yet engendered useful therapeutic strategies for cure of the disease. In this review, we discuss the prevalent ideas that have governed this research for several years, and we challenge these ideas with alternative findings suggesting a multifactorial etiology. We review promising newer ideas that may prove effective as therapeutic interventions for late-onset AD, as well as providing reliable means of earlier and more specific diagnosis of the disease process. In the discussions included here, we reference relevant clinical and basic science literature underlying research into disease etiology and pathogenesis, and we highlight current reviews on the various topics addressed.