Mutant huntingtin impairs immune cell migration in Huntington disease

In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed.     

Efficiency of neuromuscular electrical stimulation: A comparison of elicited force and subject tolerance using three electrical waveforms

Objective: Efficacy of neuromuscular electrical stimulation (NMES) is limited by the discomfort of electrically elicited contractions. Most studies of tolerance to NMES have examined stimulation to maximal tolerance. NMES efficiency is the amount of elicited force at a specific level of tolerance. This study is the first to describe and examine such. Design: A repeated measures design was used. Electrically elicited force (EEF) was measured using three waveforms: burst-modulated alternating current (BMAC), pulsed current (PC), and burst-modulated pulsed current (BMPC). EEF at a tolerance rating of 5/10 on a visual analog scale (VAS) was recorded. The dependent variables were EEF up to 5/10 VAS, current amplitude at 5/10, and percent maximal isometric force at 5/10. Results: EEF and percent maximal voluntary isometric force were significantly greater with BMPC versus BMAC (p = 0.001 and 0.004). No differences were noted between PC and BMAC or BMPC and PC. Amplitude was significantly greater with BMAC compared to BMPC and PC (p = 0.003 and 0.015). No difference in amplitude was noted between PC and BMPC. Conclusion: For the same level of discomfort, BMPC yielded one-third greater muscle force than BMAC and at a lesser current amplitude. These data evidence a greater efficiency for BMPC than BMAC.     

Increasing dietary EPA and DHA influence estimated fatty acid desaturase activity in systemic organs which is reflected in the red blood cell in mice

Delta-5 (D5D) and delta-6 (D6D) desaturase are key enzymes in fatty acid (FA) metabolism. Dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may alter tissue FA composition via D5D and D6D. The purpose was to determine the relationship between dietary EPA?+?DHA, estimated desaturase activities of various tissues and the reflection of desaturase activity in the red blood cell (RBC). Mice were fed diets with increasing percent of energy from EPA?+?DHA. Phospholipid FA composition of heart, muscle, spleen, lung, adipose tissues and RBC were analysed. D5D and D6D enzyme activity estimates (EAE) were calculated as the ratio of 20:4/20:3 and 20:3/18:2, respectively. D5D EAE decreased in all tissues, except muscle, with increasing dietary EPA?+?DHA. RBC D5D EAE positively correlated with D5D EAE in all tissues. RBC D6D EAE positively correlated with muscle and inversely correlated with adipose D6D EAE. Our findings suggest differential influence of dietary EPA?+?DHA upon tissue desaturase activities.     

Antidepressant Use is Associated with Increased Energy Intake and Similar Levels of Physical Activity

Antidepressants have been associated with weight gain, but the causes are unclear. The aims of this study were to assess the association of antidepressant use with energy intake, macronutrient diet composition, and physical activity. We used data on medication use, energy intake, diet composition, and physical activity for 3073 eligible adults from the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Potential confounding variables, including depression symptoms, were included in the models assessing energy intake, physical activity, and sedentary behavior. Antidepressant users reported consuming an additional (mean ± S.E.) 215 ± 73 kcal/day compared to non-users (p = 0.01). There were no differences in percent calories from sugar, fat, or alcohol between the two groups. Antidepressant users had similar frequencies of walking or biking, engaging in muscle-strengthening activities, and engaging in moderate or vigorous physical activity. Antidepressant users were more likely to use a computer for ≥2 h/day (OR 1.77; 95% CI: 1.09–2.90), but TV watching was similar between the two groups. These results suggest increased energy intake and sedentary behavior may contribute to weight gain associated with antidepressant use. Focusing on limiting food intake and sedentary behaviors may be important in mitigating the weight gain associated with antidepressant use.     

The National Institute of Nursing Research Graduate Partnerships Program (NINR-GPP): An opportunity for PhD students

The Institutional Graduate Partnerships Program (GPP) offered by the National Institute of Nursing Research (NINR) provides an exceptional opportunity for students who are enrolled in any PhD program in nursing across the nation to complete dissertation research on the premier research campus of the National Institutes of Health, Bethesda, MD. The goal of this doctoral fellowship program, which is up to 3 years in length, is to train promising doctoral students in basic and clinical research. This knowledge and skill set is necessary for the next generation of nurse scientists to ultimately conduct translational research. In this article, the authors describe the program, eligibility requirements, application procedures, and selection criteria for NINR-supported GPP nursing students. Also provided are tips for interested students and outcomes of current and former NINR-supported GPP students (NINR-GPP).     

Microscopy with ultraviolet surface excitation (MUSE): A novel approach to real‐time inexpensive slide‐free dermatopathology

Traditional histology relies on processing and physically sectioning either frozen or formalin‐fixed paraffin‐embedded (FFPE) tissue into thin slices (typically 4‐6 μm) prior to staining and viewing on a standard wide‐field microscope. Microscopy using ultraviolet (UV) surface excitation (MUSE) represents a novel alternative microscopy method that works with UV excitation using oblique cis‐illumination, which can generate high‐quality images from the cut surface of fresh or fixed tissue after brief staining, with no requirement for fixation, embedding and histological sectioning of tissue specimens. We examined its potential utility in dermatopathology. Concordance between MUSE images and hematoxylin and eosin (H&E) slides was assessed by the scoring of MUSE images on their suitability for identifying 10 selected epidermal and dermal structures obtained from minimally fixed tissue, including stratum corneum, stratum granulosum, stratum spinosum, stratum basale, nerve, vasculature, collagen and elastin, sweat glands, adipose tissue and inflammatory cells, as well as 4 cases of basal cell carcinoma and 1 case of pseudoxanthoma elasticum deparaffinized out of histology blocks. Our results indicate that MUSE can identify nearly all normal skin structures seen on routine H&E as well as some histopathologic features, and appears promising as a fast, reliable and cost‐effective diagnostic approach in dermatopathology.