Evaluating mice lacking serum carboxylesterase as a behavioral model for nerve agent intoxication

Mice and other rodents are typically utilized for chemical warfare nerve agent research. Rodents have large amounts of carboxylesterase in their blood, while humans do not. Carboxylesterase nonspecifically binds to and detoxifies nerve agent. The presence of this natural bioscavenger makes mice and other rodents poor models for studies identifying therapeutics to treat humans exposed to nerve agents. To obviate this problem, a serum carboxylesterase knockout (Es1 KO) mouse was created. In this study, Es1 KO and wild type (WT) mice were assessed for differences in gene expression, nerve agent (soman; GD) median lethal dose (MLD) values, and behavior prior to and following nerve agent exposure. No expression differences were detected between Es1 KO and WT mice in more than 34?000 mouse genes tested. There was a significant difference between Es1 KO and WT mice in MLD values, as the MLD for GD-exposed WT mice was significantly higher than the MLD for GD-exposed Es1 KO mice. Behavioral assessments of Es1 KO and WT mice included an open field test, a zero maze, a Barnes maze, and a sucrose preference test (SPT). While sex differences were observed in various measures of these tests, overall, Es1 KO mice behaved similarly to WT mice. The two genotypes also showed virtually identical neuropathological changes following GD exposure. Es1 KO mice appear to have an enhanced susceptibility to GD toxicity while retaining all other behavioral and physiological responses to this nerve agent, making the Es1 KO mouse a more human-like model for nerve agent research.     

A proposed framework for addressing supervisee-supervisor value conflict

Value conflicts between supervisees and supervisors can adversely affect supervisee development, service provision, and the supervision relationship. However, the role of value conflicts in supervision has been minimally considered. Building on the Farnsworth and Callahan (2013) model for addressing client-clinician value conflict, we propose a supervision-specific framework to help supervisors and supervisees navigate value conflicts that emerge during supervision. The proposed framework consists of three steps: (a) detection of value conflict in supervision; (b) identification and articulation of value conflicts; and (c) determination of appropriate recommendations for supervisees. Neither punitive nor corrective in purpose, the model is eminently exploratory and educational in nature.     

Extending conceptual frameworks: life course epidemiology for the study of back pain

Background  

Epidemiological studies have identified important causal and prognostic factors for back pain, but these frequently only identify a proportion of the variance, and new factors add little to these models. Recently, interest has increased in studying diseases over the life course, stimulated by the 1997 book by Kuh and Ben-Shlomo, a move accompanied by important conceptual and methodological developments. This has resulted in improvements in the understanding of other conditions like cardiovascular and respiratory disease. This paper aims to examine how conceptual frameworks from life course epidemiology could enhance back pain research.     

Angiotensin-converting enzyme gene polymorphism in a cohort of coronary angiography patients

An association between a polymorphism of the angiotensin-converting enzyme (ACE) gene and myocardial infarction (MI) in men has been previously reported. The present study examines the association between ACE genotype, atherosclerosis, MI, hypertension and other cardiovascular risk factors in Caucasian men (n=576) and women (n=124) who have undergone coronary angiography. Gene frequencies are also reported for African-American men (n=56). Genotype determination was based on the presence (allele I) or absence (allele D) of a 287 nucleotide Alu sequence in intron 16 of the ACE gene. Genotype frequencies for DD, ID and II were: 30.9, 47.7, 21.4% for Caucasian men; 28.2, 48.4, 23.4% for Caucasian women; and 30.4, 46.4, 23.2% for African-American men. There were no statistically significant associations between ACE genotype and number of plaques (> or =10% obstruction), lipid variables, or body mass index (BMI) for Caucasian men. Caucasian women with the DD genotype had on average fewer plaques, but this was accounted for by their younger ages. In Caucasian males, the DD genotype independently contributed to the presence of hypertension (odds ratio=1.8, 95% CI 1.1-2.9) after adjusting for age and BMI. In Caucasian males with total cholesterol levels less than 200 mg/dl (n=237), the DD (odds ratio=2.5, 95% CI 1.2-5.4) and ID genotypes (odds ratio=2.2, 95% CI 1.1-4.4) were associated with a history of MI.     

Eligibility for palivizumab prophylaxis in a cohort of children with severe bronchiolitis

In 2014, the American Academy of Pediatrics (AAP) updated their recommendations for palivizumab prophylaxis for children who are at high risk for severe respiratory syncytial virus (RSV) infection. To investigate the potential impact of the more restrictive 2014 criteria on the eligibility for palivizumab prophylaxis, we applied the 2012 and 2014 AAP recommendations for palivizumab prophylaxis to a multicenter cohort of 2207 US children hospitalized for bronchiolitis. According to the 2012 AAP recommendations, 215 children (9.7%) were eligible for palivizumab prophylaxis, while 140 children (6.3%) would have been eligible based on the 2014 updated recommendations (34.9% relative decrease; 95%CI: 28.5–41.7%). The decrease was largely driven by the restriction of eligibility to preterm infants with gestational age <29 weeks. Further development of and refinement of cost‐effective approaches for the prevention of severe RSV infection are needed.