Molecular and metabolomic changes in the proximal colon of pigs infected with Trichuris suis.

The pig whipworm Trichuris suis is important in swine production because of its negative effects on pig performance and, notably, to some humans with inflammatory bowel disease as a therapeutic agent that modulates inflammation. The proximal colon of T. suis-infected pigs exhibited general inflammation around day 21 after inoculation with infective eggs that is transcriptionally characterized by markers of type-2 immune activation, inflammation, cellular infiltration, tissue repair enzymes, pathways of oxidative stress, and altered intestinal barrier function. Prominent gene pathways involved the Th2-response, de novo cholesterol synthesis, fructose and glucose metabolism, basic amino acid metabolism, and bile acid transport. Upstream regulatory factor analysis implicated the bile acid/farnesoid X receptor in some of these processes. Metabolic analysis indicated changes in fatty acids, antioxidant capacity, biochemicals related to methylation, protein glycosylation, extracellular matrix structure, sugars, Krebs cycle intermediates, microbe-derived metabolites and altered metabolite transport. Close to 1,200 differentially expressed genes were modulated in the proximal colon of pigs with a persistent adult worm infection that was nearly 90% lower in pigs that had expelled worms. The results support a model to test diets that favorably alter the microbiome and improve host intestinal health in both pigs and humans exposed to Trichuris.

Factors associated with participation and completion of a survey-based study.

PURPOSE: The Healthy Work Place (HWP) study investigated methods to improve clinicians' dissatisfaction and burnout. The purpose of this paper is to identify factors that influenced study enrollment and completion and assess effects of initial clinic site enrollment rates on clinician outcomes, including satisfaction, burnout, stress and intent to leave practice. DESIGN/METHODOLOGY/APPROACH: In total, 144 primary care clinicians (general internists, family physicians, nurse practitioners and physician assistants) at 14 primary care clinics were analyzed. FINDINGS: In total, 72 clinicians enrolled in the study and completed the first survey (50 percent enrollment rate). Of these, 10 did not complete the second survey (86 percent completion rate). Gender, type, burnout, stress and intervention did not significantly affect survey completion. Hence, widespread agreement about most moral/ethical issues (72 percent vs 22 percent; p=0.0060) and general agreement on treatment methods (81 percent vs 50 percent; p=0.0490) were reported by providers that completed both surveys as opposed to just the initial survey. Providers with high initial clinic site enrollment rates (=50 percent providers) obtained better outcomes, including improvements in or no worsening of satisfaction (odds ratio (OR)=19.16; p=0.0217) and burnout (OR=6.24; p=0.0418). SOCIAL IMPLICATIONS: More providers experiencing workplace agreement completed the initial and final surveys, and providers at sites with higher initial enrollment rates obtained better outcomes including a higher rate of improvement or no worsening of job satisfaction and burnout. ORIGINALITY/VALUE: There is limited research on clinicians' workplace and other factors that influence their participation in survey-based studies. The findings help us to understand how these factors may affect quality of data collecting and outcome. Thus, the study provides us insight for improvement of quality in primary care.

Effect of acute ozone exposure on the lung metabolomes of obese and lean mice.

Pulmonary responses to the air pollutant, ozone, are increased in obesity. Both obesity and ozone cause changes in systemic metabolism. Consequently, we examined the impact of ozone on the lung metabolomes of obese and lean mice. Lean wildtype and obese db/db mice were exposed to acute ozone (2 ppm for 3 h) or air. 24 hours later, the lungs were excised, flushed with PBS to remove blood and analyzed via liquid-chromatography or gas-chromatography coupled to mass spectrometry for metabolites. Both obesity and ozone caused changes in the lung metabolome. Of 321 compounds identified, 101 were significantly impacted by obesity in air-exposed mice. These included biochemicals related to carbohydrate and lipid metabolism, which were each increased in lungs of obese versus lean mice. These metabolite changes may be of functional importance given the signaling capacity of these moieties. Ozone differentially affected the lung metabolome in obese versus lean mice. For example, almost all phosphocholine-containing lysolipids were significantly reduced in lean mice, but this effect was attenuated in obese mice. Glutathione metabolism was also differentially affected by ozone in obese and lean mice. Finally, the lung metabolome indicated a role for the microbiome in the effects of both obesity and ozone: all measured bacterial/mammalian co-metabolites were significantly affected by obesity and/or ozone. Thus, metabolic derangements in obesity appear to impact the response to ozone.

Comparison of changes in the lipid profile of postmenopausal women with early stage breast cancer treated with exemestane or letrozole.

Effects of aromatase inhibitor (AI) therapy on the plasma lipid profile are not clear. Here the authors describe changes in fasting lipids (total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides) before and after 3 months of exemestane or letrozole treatment. HDL was reduced in the entire cohort (P < .001) and in the exemestane group (P < .001) but unchanged in the letrozole group (P = .169). LDL was increased in the entire cohort (P = .005) and in the letrozole group (P = .002) but unchanged in the exemestane group (P = .361). This effect was at least partially attributable to washout of tamoxifen as only patients with prior use of tamoxifen experienced a significant increase in LDL. Baseline HDL was an independent predictor of the change in HDL (r(2) = -0.128, P < .001), and prior tamoxifen use was associated with greater increases in LDL (r(2) = 0.057, P < .001). Use of lipid-altering medications did not protect against the exemestane-induced drop in HDL or the increase in LDL observed in women with prior use of tamoxifen taking letrozole. In conclusion, AI treatment and/or washout of tamoxifen induced detrimental changes in the lipid profile of postmenopausal women with breast cancer.