Feasibility of integrative games and novel therapeutic game controller for telerehabilitation of individuals chronic post-stroke living in the community.

BACKGROUND: Intensive, adaptable and engaging telerehabilitation is needed to enhance recovery and maximize outcomes. Such services may be provided under early supported discharge, or later for chronic populations. A novel virtual reality game-based telerehabilitation system was designed for individuals post-stroke to enhance their bimanual upper extremity motor function, cognition, and wellbeing. OBJECTIVES: To evaluate the feasibility of novel therapeutic game controller and telerehabilitation system for home use. METHODS: Individuals chronic post-stroke and their caregivers were recruited (n = 8 + 8) for this feasibility study. One was a screen failure and seven completed 4 weeks (20 sessions) of home-based therapy with or without remote monitoring. Standardized clinical outcome measures were taken pre- and post-therapy. Game performance outcomes were sampled at every session, while participant and caregiver subjective evaluations were done weekly. RESULTS: There was a 96% rate of compliance to protocol, resulting in an average of 13,000 total arm repetitions/week/participant. Group analysis showed significant (p <.05) improvements in grasp strength (effect size [ES] = 0.15), depression (Beck Depression Inventory II, ES = 0.75), and cognition (Neuropsychological Assessment Battery for Executive Function, ES = 0.46). Among the 49 outcome variables, 36 variables (73.5%) improved significantly (p = .001, binomial sign test). Technology acceptance was very good with system rating by participants at 3.7/5 and by caregivers at 3.5/5. CONCLUSIONS: These findings indicate the feasibility and efficacy of the system in providing home-based telerehabilitation. The BrightBrainer system needs to be further evaluated in randomized control trials and with individuals early post-stroke.

Vitamin d and serum cytokines in a randomized clinical trial.

Background. The role of vitamin D in the body's ability to fight influenza and URI's may be dependent on regulation of specific cytokines that participate in the host inflammatory response. The aim of this study was to test the hypothesis that vitamin D can influence intracellular signaling to regulate the production of cytokines. Subjects and Methods. This study was a 3-month prospective placebo-controlled trial of vitamin D3 supplementation in ambulatory adults [Li-Ng et al., 2009]. 162 volunteers were randomized to receive either 50 µg/d (2000 IU) of vitamin D3 or matching placebo. 25(OH)D and the levels of 10 different cytokines (IL-2, 4, 5, 6, 8, 10, 13, GM-CSF, IFN-γ, TNF-α) were measured in the serum of participants at baseline and the final visit. There were 6 drop-outs from the active vitamin D group and 8 from the placebo group. Results. In the active vitamin D group, we found a significant median percent decline in levels of GM-CSF (-62.9%, P < .0001), IFN-γ (-38.9%, P < .0001), IL-4 (-50.8%, P = .001), IL-8 (-48.4%, P < .0001), and IL-10 (-70.4%, P < .0001). In the placebo group, there were significant declines for GM-CSF (-53.2%, P = .0007) and IFN-γ (-34.4%, P = .0011). For each cytokine, there was no significant difference in the rate of decline between the two groups. 25(OH)D levels increased in the active vitamin D group from a mean of 64.3 ± 25.4 nmol/L to 88.5 ± 23.2 nmol/L. Conclusions. The present study did not show that vitamin D3 supplementation changed circulating cytokine levels among healthy adults.

The relative influence of calcium intake and vitamin D status on serum parathyroid hormone and bone turnover biomarkers in a double-blind, placebo-controlled parallel group, longitudinal factorial design.

BACKGROUND: Adequate calcium and vitamin D are needed to maintain calcium balance. OBJECTIVE: Our objective was to examine the influence of calcium intake and vitamin D exposure separately and their interaction on biomarkers of calcium sufficiency. DESIGN: Healthy men and women, age 20-80 yr, were randomly allocated to four groups: 1) double placebo, 2) calcium (1200 mg daily) plus placebo, 3) vitamin D(3) (100 microg) plus placebo, and 4) vitamin D(3) and calcium. Fasting serum and urine as well as serum and urine 2 h after a calcium load (600 mg of calcium carbonate) were obtained at baseline and 3 months. RESULTS: Ninety-nine participants were randomized; 78 completed the study. Baseline demographics, protein intake and laboratory studies did not differ among the four groups. Study medication compliance was 90%. Fasting bone turnover markers declined after 3 months only in the two groups given calcium supplements and increased in the vitamin D(3) plus placebo calcium group. The calcium load resulted in a decrease in PTH and in bone turnover markers that did not differ among groups. Urinary calcium excretion increased in the combined group. Mean serum 25-hydroxyvitamin D increased from a baseline of 67 (18 sd) nmol/liter to 111 (30 sd) nmol/liter after vitamin D supplementation. CONCLUSION: Increased habitual calcium intake lowered markers of bone turnover. Acute ingestion of a calcium load lowered PTH and bone turnover markers. Additional intake of 100 microg/d vitamin D(3) did not lower PTH or markers of bone turnover.

Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration.

BACKGROUND: Indirect evidence suggests that optimal vitamin D status is achieved with a serum 25-hydroxyvitamin D [25(OH)D] concentration >75 nmol/L. OBJECTIVE: We aimed to determine the intake of vitamin D(3) needed to raise serum 25(OH)D to >75 nmol/L. DESIGN: The design was a 6-mo, prospective, randomized, double-blinded, double-dummy, placebo-controlled study of vitamin D(3) supplementation. Serum 25(OH)D was measured by radioimmunoassay. Vitamin D(3) intake was adjusted every 2 mo by use of an algorithm based on serum 25(OH)D concentration. RESULTS: A total of 138 subjects entered the study. After 2 dose adjustments, almost all active subjects attained concentrations of 25(OH)D >75 nmol/L, and no subjects exceeded 220 nmol/L. The mean (+/-SD) slope at 9 wk [defined as 25(OH)D change/baseline dose] was 0.66 +/- 0.35 (nmol/L)/(microg/d) and did not differ statistically between blacks and whites. The mean daily dose was 86 microg (3440 IU). The use of computer simulations to obtain the most participants within the range of 75-220 nmol/L predicted an optimal daily dose of 115 microg/d (4600 IU). No hypercalcemia or hypercalciuria was observed. CONCLUSIONS: Determination of the intake required to attain serum 25(OH)D concentrations >75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations. Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey suggests a dose of 95 microg/d (3800 IU) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 microg/d (5000 IU) for those below that threshold.

Dose response to vitamin D supplementation among postmenopausal African American women.

BACKGROUND: Reports on the dose response to vitamin D are conflicting, and most data were derived from white men and women. OBJECTIVE: The objective was to determine the response of serum 25-hydroxyvitamin D [25(OH)D] to oral vitamin D(3) supplementation in an African American population. DESIGN: Healthy black postmenopausal women (n = 208) participated in a vitamin D(3) supplementation trial for a period of 3 y. Analyses were done in the vitamin D supplementation arm (n = 104) to quantify the response in serum 25-hydroxyvitamin D concentrations at a steady state vitamin D input. The participants received 20 microg/d (800 IU) oral vitamin D(3) for the initial 2 y and 50 microg/d (2000 IU) for the third year. RESULTS: Supplementation with 20 microg/d (800 IU/d) vitamin D(3) raised the mean serum 25(OH)D concentration from a baseline of 46.9 +/- 20.6 nmol/L to 71.4 +/- 21.5 nmol/L at 3 mo. The mean (+/-SD) concentration of serum 25(OH)D was 87.3 +/- 27.0 nmol/L 3 mo after supplementation increased to 50 microg/d (2000 IU/d). All participants achieved a serum 25(OH)D concentration >35 nmol/L, 95% achieved a concentration >50 nmol/L, but only 60% achieved a concentration >75 nmol/L. All patients had concentrations <153 nmol/L. On the basis of our findings, an algorithm for prescribing vitamin D so that patients reach optimal serum concentrations was developed. The algorithm suggests a dose of 70 microg (2800 IU/d) for those with a concentration >45 nmol/L and a dose of 100 microg (4000 IU/d) for those with a concentration <45 nmol/L. CONCLUSIONS: Supplementation with 50 microg/d (2000 IU/d) oral vitamin D(3) is sufficient to raise serum 25-hydroxyvitamin D concentrations to >50 nmol/L in almost all postmenopausal African American women. However, higher doses were needed to achieve concentrations >75 nmol/L in many women in this population.

Optimal vitamin D status and serum parathyroid hormone concentrations in African American women.

BACKGROUND: Optimal vitamin D status for the prevention of osteoporosis has been inferred from examinations of the serum 25-hydroxyvitamin D [25(OH)D] concentration below which there is an increase in serum parathyroid hormone (PTH). OBJECTIVE: The objectives of the study were to ascertain whether a threshold for serum 25(OH)D exists below which serum PTH increases and whether persons with 25(OH)D above this threshold have lower rates of bone loss than do persons with 25(OH)D below the threshold. DESIGN: The relation of serum 25(OH)D to serum PTH was analyzed in 208 African American women studied longitudinally for 3 y. These healthy women in midlife were randomly assigned to receive placebo or 800 IU vitamin D3/d; after 2 y, the vitamin D3 supplementation was increased to 2000 IU/d. Both groups received calcium supplements to ensure an adequate calcium intake. A systematic literature review found a wide range of threshold values in part due to varied calcium intake. RESULTS: A Loess plot suggested a breakpoint between 40 and 50 nmol/L for serum 25(OH)D. A line-line model was fitted to the data, and it showed a spline knot at 44 nmol/L. A heuristic approach verified that PTH does not decline as rapidly when the serum concentration of 25(OH)D is >40 nmol/L as when it is <40 nmol/L. We found no significant difference in rates of bone loss between persons with 25(OH)D concentrations above and below 40 nmol/L. CONCLUSION: Although a threshold for 25(OH)D can be identified, we suggest that it should not be used to recommend optimal vitamin D status.

A randomized controlled trial of vitamin D3 supplementation in African American women.

BACKGROUND: We conducted a randomized, placebo-controlled, double-blind trial to test the hypothesis that vitamin D(3) supplementation would prevent bone loss in calcium-replete, African American postmenopausal women. METHODS: Two hundred eight healthy black postmenopausal women, 50 to 75 years of age, were assigned to receive either placebo or 20 microg/d (800 IU) of vitamin D(3). Calcium supplements were provided to ensure a total calcium intake of 1200 to 1500 mg/d. After 2 years, the vitamin D(3) dose was increased to 50 microg/d (2000 IU) in the active group, and the study continued for an additional year. Bone mineral density (BMD) was measured every 6 months. Markers of bone turnover, vitamin D metabolites, and parathyroid hormone (PTH) levels were measured in serum. RESULTS: There were no significant differences in BMD between the active and control groups throughout the study. There was also no relationship between serum 25-hydroxyvitamin D levels attained and rates of bone loss. There was an increase in BMD of the total body, hip, and radius at 1 year in both groups. Over the 3 years, BMD declined at these sites by 0.26% to 0.55% per year. The BMD of the lumbar spine increased slightly in the placebo and active groups. There were no persistent changes in serum PTH levels or the markers of bone turnover, although there was a transient decline in PTH in both groups at 3 months. No significant adverse events were attributed to vitamin D supplementation. CONCLUSIONS: There was no observed effect of vitamin D(3) supplementation on bone loss or bone turnover markers in calcium-replete, postmenopausal African American women. Further studies are needed to determine if these findings are applicable to women of other ethnic groups.

Effects of transgene expression of superoxide dismutase and glutathione peroxidase on pulmonary epithelial cell growth in hyperoxia.

Prolonged exposure to supraphysiological oxygen concentrations results in the generation of reactive oxygen species, which can cause significant lung injury in critically ill patients. Supplementation with human recombinant antioxidant enzymes (AOE) may mitigate hyperoxic lung injury, but it is unclear which combination and concentration will optimally protect pulmonary epithelial cells. First, stable cell lines were generated in alveolar epithelial cells (MLE12) overexpressing one or more of the following AOE: Mn superoxide dismutase (MnSOD), CuZnSOD, or glutathione peroxidase 1. Next, A549 cells were transduced with 50-300 particles/cell of recombinant adenovirus containing either LacZ or each of the three AOE (alone or in combination). Cells were then exposed to 95% O(2) for up to 3 days, with cell number and viability determined daily. Overexpression of either MnSOD (primarily mitochondrial) or CuZnSOD (primarily cytosolic) reversed the growth inhibitory effects of hyperoxia within the first 48 h of exposure, resulting in a significant increase in viable cells (P < 0.05), with 1.5- to 3-fold increases in activity providing optimal protection. Protection from mitochondrial oxidation was confirmed by assessing aconitase activity, which was significantly improved in cells overexpressing MnSOD (P < 0.05). Data indicate that optimal protection from hyperoxic injury occurs in cells coexpressing MnSOD and glutathione peroxidase 1, with prevention of mitochondrial oxidation being a critical factor. This has important implications for clinical trials in preterm infants receiving SOD supplementation to prevent acute and chronic lung injury.

Body fat content and 25-hydroxyvitamin D levels in healthy women.

Obesity is associated with alterations in the vitamin D endocrine system. Lower levels of serum 25-hydroxyvitamin D (25-OHD) in morbidly obese individuals may be secondary to an alteration in tissue distribution resulting from an increase in adipose mass. Therefore, morbidly obese individuals are expected to need higher doses of vitamin D supplementation than the general population. However, it is still unknown whether adiposity (or percentage body fat) should be taken into consideration while assessing vitamin D requirements in the general population. To study the relationship between 25-OHD levels and percentage body fat content in healthy women, we studied 410 healthy women between 20 and 80 yr of age with body mass index ranging from 17 to 30 kg/m2. We analyzed the correlation between serum 25-OHD level and percentage body fat measured by dual energy x-ray absorptiometry. We also analyzed the influence of season, dietary vitamin D intake, age, and race on this relationship. The levels of serum 25-OHD inversely correlated with percentage body fat. The correlation was -0.13 (P = 0.013) after adjusting for race, age, season, and dietary vitamin D intake. In a multiple stepwise regression, race and season were found to have a major influence on serum 25-OHD (cumulative R2 = 0.34), and percentage body fat, although modest (additional R2 = 0.02), also had an independent statistically significant influence on serum 25-OHD levels. We conclude, percentage body fat content is inversely related to the serum 25-OHD levels in healthy women.