Dendritic Cells Transduced to Express Interleukin 4 Reduce Diabetes Onset in Both Normoglycemic and Prediabetic Nonobese Diabetic Mice

Background: We and others have previously demonstrated that treatment with bone marrow derived DC genetically modified to express IL-4 reduce disease pathology in mouse models of collagen-induced arthritis and delayed-type hypersensitivity. Moreover, treatment of normoglycemic NOD mice with bone marrow derived DC, genetically modified to express interleukin 4 (IL-4), reduces the onset of hyperglycemia in a significant number of animals. However, the mechanism(s) through which DC expressing IL-4 function to prevent autoimmune diabetes and whether this treatment can reverse disease in pre-diabetic NOD mice are unknown. Methodology/Principal Findings: DC were generated from the bone marrow of NOD mice and transduced with adenoviral vectors encoding soluble murine IL-4 (DC/sIL-4), a membrane-bound IL-4 construct, or empty vector control. Female NOD mice were segregated into normoglycemic (<150mg/dL) and prediabetic groups (between 150 and 250 mg/dL) on the basis of blood glucose measurements, and randomized for adoptive transfer of 106 DC via a single i.v. injection. A single injection of DC/sIL-4, when administered to normoglycemic 12-week old NOD mice, significantly reduced the number of mice that developed diabetes. Furthermore, DC/sIL-4, but not control DC, decreased the number of mice progressing to diabetes when given to prediabetic NOD mice 12-16 weeks of age. DC/sIL-4 treatment also significantly reduced islet mononuclear infiltration and increased the expression of FoxP3 in the pancreatic lymph nodes of a subset of treated animals. Furthermore, DC/sIL-4 treatment altered the antigen-specific Th2:Th1 cytokine profiles as determined by ELISPOT of splenocytes in treated animals. Conclusions: Adoptive transfer of DC transduced to express IL-4 into both normoglycemic and prediabetic NOD mice is an effective treatment for T1D. © 2010 Ruffner, Robbins

A whey protein-based multi-ingredient nutritional supplement stimulates gains in lean body mass and strength in healthy older men: A randomized controlled trial

Protein and other compounds can exert anabolic effects on skeletal muscle, particularly in conjunction with exercise. The objective of this study was to evaluate the efficacy of twice daily consumption of a protein-based, multi-ingredient nutritional supplement to increase strength and lean mass independent of, and in combination with, exercise in healthy older men. Forty-nine healthy older men (age: 73 ± 1 years [mean ± SEM]; BMI: 28.5 ± 1.5 kg/m2) were randomly allocated to 20 weeks of twice daily consumption of either a nutritional supplement (SUPP; n = 25; 30 g whey protein, 2.5 g creatine, 500 IU vitamin D, 400 mg calcium, and 1500 mg n-3 PUFA with 700 mg as eicosapentanoic acid and 445 mg as docosahexanoic acid); or a control (n = 24; CON; 22 g of maltodextrin). The study had two phases. Phase 1 was 6 weeks of SUPP or CON alone. Phase 2 was a 12 week continuation of the SUPP/CON but in combination with exercise: SUPP + EX or CON + EX. Isotonic strength (one repetition maximum [1RM]) and lean body mass (LBM) were the primary outcomes. In Phase 1 only the SUPP group gained strength (Σ1RM, SUPP: +14 ± 4 kg, CON: +3 ± 2 kg, P < 0.001) and lean mass (LBM, +1.2 ± 0.3 kg, CON: -0.1 ± 0.2 kg, P < 0.001). Although both groups gained strength during Phase 2, upon completion of the study upper body strength was greater in the SUPP group compared to the CON group (Σ upper body 1RM: 119 ± 4 vs. 109 ± 5 kg, P = 0.039). We conclude that twice daily consumption of a multi-ingredient nutritional supplement increased muscle strength and lean mass in older men. Increases in strength were enhanced further with exercise training

Excessive daytime sleepiness is associated with an increased frequency of falls and sarcopenia

Background: This cross-sectional study aimed to examine associations between excessive daytime sleepiness (EDS) with falls and falls related conditions in older adults. Methods: To assess EDS, the Epworth Sleepiness Scale was used, with a score of ≥11/24 points indicating EDS. Number of falls and fall history (at least one) in the last year were recorded. Timed Up and Go test (TUG) was used to assess fall risk. Sarcopenia was defined by SARC-F tool. A grip strength score of the dominant hand, measured with a hand-grip dynamometer, less than 16 kg in females and 27 kg in males was accepted as dynapenia. Frailty status was defined by five dimensions including shrinking, exhaustion, low levels of activity, weakness, and slowness with those scoring positive on ≥3 dimensions being categorized as frail. The relationship between EDS with outcomes including fall, number of falls, falls risk, dynapenia, sarcopenia and frailty was investigated. Results: Of the 575 outpatients (mean age 78.7 ± 7.5 years, female:70.4%), the prevalence of EDS was 19.8%. In the multivariable model adjusted for age, sex, living status, marital status, polypharmacy, osteoarthritis, Parkinson disease, depression and dementia; EDS was significantly associated with the number of falls last year (IRR = 1.94, 95% CI: 1.42–2.65) and sarcopenia (OR = 2.41, 95% CI: 1.41–4.12). EDS was not significantly associated with TUG based fall risk, frailty and dynapenia. Conclusions: EDS was observed in approximately one in every five older adults. EDS should be evaluated as part of geriatric assessment. Moreover, older patients with EDS should be further assessed for falls and sarcopenia

The effects of upper limb loading on spinal shrinkage during treadmill walking

Everyday activities such as walking either loaded or unloaded may elicit spinal shrinkage in an order of magnitude that has been related to lower back pain. The present study aims to compare the effects of unloaded treadmill walking with walking carrying loads representing everyday shopping tasks. Walking tasks were performed on 7 healthy males, consisting of unloaded walking and walking carrying 7.5% and 15% of body weight. Motion analysis was used to track four reflective markers at 100Hz, dividing the spine into three segments and static data was collected in 5 minute intervals over a 30 minute period. Total spine and segment length changes were compared to original length in the sagittal plane and the effects of load, time and their interaction were analysed using ANOVA. Total spinal length and lumbar segment decreased with respect to time (p < 0.001). Load affected the percentage length change at each spinal segment (p < 0.005), with the lumbar segment showing greatest height loss at the highest load. Inter-segmental variations in length resulted in the non-significant effect of load on the percentage length change of the total spine (P = 0.263). The upper and lower thoracic segments showed greater anterior lean with the heavier loads (p = 0.000) and the lumbar segment showed the opposite trend (p = 0.000). Results suggest that the body adopts less anterior lean with an immediate load bearing demand, to decrease the flexion moment arm of the load about the lumbar spine and thus decrease the necessary extension moment generated by the spinal extensors for spinal stability. Further postural alteration in the same direction is observed with prolonged loading. In combination with lumbar spinal shrinkage, such postural changes are likely to increase the loading on the facet joints with potential deleterious consequences for low back pai