Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation

Activation of CD4⁺ T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4⁺ effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T cell populations are uncertain. Here, we evaluated CD4⁺ T cell populations in murine models and determined that inflammatory Teffs maintain high expression of glycolytic genes and rely on high glycolytic rates, while Tregs are oxidative and require mitochondrial electron transport to proliferate, differentiate, and survive. Metabolic profiling revealed that pyruvate dehydrogenase (PDH) is a key bifurcation point between T cell glycolytic and oxidative metabolism. PDH function is inhibited by PDH kinases (PDHKs). PDHK1 was expressed in Th17 cells, but not Th1 cells, and at low levels in Tregs, and inhibition or knockdown of PDHK1 selectively suppressed Th17 cells and increased Tregs. This alteration in the CD4⁺ T cell populations was mediated in part through ROS, as N-acetyl cysteine (NAC) treatment restored Th17 cell generation. Moreover, inhibition of PDHK1 modulated immunity and protected animals against experimental autoimmune encephalomyelitis, decreasing Th17 cells and increasing Tregs. Together, these data show that CD4⁺ subsets utilize and require distinct metabolic programs that can be targeted to control specific T cell populations in autoimmune and inflammatory diseases.     

Prophylaxis with Teicoplanin and Cefuroxime Reduces the Rate of Prosthetic Joint Infection after Primary Arthroplasty

The aim of this study was to compare the prosthetic joint infection (PJI) rate after total joint arthroplasty in two consecutive periods of treatment with different antibiotic prophylaxes: cefuroxime versus cefuroxime plus teicoplanin. We retrospectively reviewed 1,896 patients who underwent total hip arthroplasty or total knee arthroplasty between March 2010 and February 2013. From March 2010 to August 2011, patients received 1.5 g of cefuroxime during induction of anesthesia and another 1.5 g 2 h later (the C group). From September 2011, 800 mg of teicoplanin was added to cefuroxime (the CT group). Throughout the period studied, there were no variations in pre- or postoperative protocols. Univariate and multivariate analyses were performed to evaluate independent predictors of PJI. There were 995 (55.7%) patients in the C group and 791 (44.3%) in the CT group. Patients in the CT group had a significantly lower PJI rate than patients in the C group (1.26% versus 3.51%, P = 0.002). There were no infections due to Staphylococcus aureus in the CT group (0% versus 1.6% in the C group, P < 0.001). A stepwise forward Cox regression model identified male sex (hazard ratio [HR], 3.85; 95% confidence interval [CI], 2.09 to 7.18), a body mass index of ≥35 kg/m² (HR, 2.93; 95% CI, 1.37 to 6.27), the presence of lung disease (HR, 2.46; 95% CI, 1.17 to 5.15), and red blood cell transfusion (HR, 3.70; 95% CI, 1.89 to 7.23) to be independent variables associated with a higher risk of PJI. The addition of teicoplanin was associated with a lower risk of infection (HR, 0.35; 95% CI, 0.17 to 0.74). In conclusion, the addition of teicoplanin to cefuroxime during primary arthroplasty was associated with a significant reduction in the global PJI rate due to a reduction of infections caused by Gram-positive bacteria.     

Differences in participation based on self-esteem in power and manual wheelchair users on a university campus: a pilot study

Objectives: To examine the relationship of self-esteem and wheelchair type with participation of young adult manual and power wheelchair users with diverse physical disabilities. Design: Cross-sectional survey study. Setting: Large University Campus. Participants: A convenience sample of college students (N?=?39) with self-reported physical disabilities who are full time wheelchair users (>40 per week) and are two or more years post illness or injury. Interventions: Not applicable. Main outcome measures: The Rosenberg Self-Esteem Scale was used to measure self-esteem, and the Craig Handicap Assessment and Reporting Technique was used to measure participation. Results: Self-esteem correlated highly with cognitive independence (CI) (r?=?0.58), mobility (r?=?0.67) and social integration (SI) (r?=?0.52). Use of manual wheelchair was significantly related to higher levels of CI and mobility while longer use of any wheelchair (power or manual) was significantly associated with higher levels of mobility and SI. In addition higher self-esteem independently predicted a significant proportion of the variance in CI, mobility and SI, while type of wheelchair predicted a significant proportion of the variance in CI (p?Conclusions: High self-esteem was found to be the strongest predictor of participation in a population of young adults with mobility limitations. Better understanding of the factors influencing participation may help to facilitate new interventions to minimize the disparities between persons with disabilities and their able bodied peers.

• Implication for Rehabilitation

• A total of 46.8% of wheelchair users report the desire for increased community participant but face significant barriers.

• The type of wheelchair has been identified as having a large impact on participation.

• This study found self-esteem to be the strongest predictor of participation, which is notable because self-esteem is a characteristic that is potentially modifiable with treatment.

     

Trypanosoma cruzi infection in Triatoma sordida before and after community-wide residual insecticide spraying in the Argentinean Chaco

Triatoma sordida is a secondary vector of Trypanosoma cruzi in the Gran Chaco and Cerrado eco-regions where it frequently infests peridomestic and domestic habitats. In a well-defined area of the humid Argentine Chaco, very few T. sordida were found infected when examined by optical microscopic examination (OM). In order to further assess the role of T. sordida and the relative magnitude of subpatent bug infections, we examined the insects for T. cruzi infection, parasite Discrete Typing Units (DTUs) and bloodmeal sources using various molecular techniques. Among 205 bugs with a negative or no OM-based diagnosis, the prevalence of infection determined by kDNA-PCR was nearly the same in bugs captured before (6.3%) and 4 months after insecticide spraying (6.4%). On average, these estimates were sixfold higher than the prevalence of infection based on OM (1.1%). Only TcI was identified, a DTU typically associated with opossums and rodents. Chickens and turkeys were the only bloodmeal sources identified in the infected specimens and the main local hosts at the bugs’ capture sites. As birds are refractory to T. cruzi infection, further studies are needed to identify the infectious bloodmeal hosts. The persistent finding of infected T. sordida after community-wide insecticide spraying highlights the need of sustained vector surveillance to effectively prevent T. cruzi transmission in the domestic and peridomestic habitats.     

Preliminary Data from Community Aging in Place,Advancing Better Living for Elders,a Patient‐Directed,Team‐Based Intervention to Improve Physical Function and Decrease Nursing Home Utilization: The First 100 Individuals to Complete a Centers for Medicare and Medicaid Services Innovation Project

Current medical models frequently overlook functional limitations and the home environment even though they partially determine healthcare usage and quality of life. The Centers for Medicare and Medicaid Services (CMS) Innovation Center funds projects that have potential to affect the “triple aim,” a framework for decreasing costs while improving health and quality of life. This article presents preliminary data from Community Aging in Place, Advancing Better Living for Elders (CAPABLE), a model funded by the CMS Innovation Center and designed to overcome the functional and home environmental barriers of older adults. CAPABLE is a patient‐directed, team‐based intervention comprising an occupational therapist, a registered nurse, and a handyman to decrease hospitalization and nursing home usage of community‐dwelling older adults with functional limitations who are dually eligible for Medicare and Medicaid. Activity of daily living limitations improved in 79% of the first 100 people who completed the intervention. Preliminary findings of this novel intervention may have implications for other older adults with functional limitations.