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Research Objectives This study aims to examine the safety and feasibility of implementing an additional hour of time-on-task upper limb training using video game technology (VGT) or conventional Occupational Therapy (COT) in the early phase post-stroke. Design This is a randomized controlled, single-site trial. After a rollup period, sixty participants will be randomized to either a therapy group (VGT or COT) versus standard of care. Patients receive an additional hour of time-on-task upper limb training 5 days a week for the duration of their hospital stay. Setting Hospital acute stroke unit or acute rehabilitation unit. Participants Patients are eligible if they had stroke within the previous four weeks and have upper extremity weakness. Interventions VGT therapy includes the MindPod Dolphin, immersive gaming software that promotes motor recovery and bimanual arm trainer. COT includes Graded Repetitive Arm Supplementary Program. Main Outcome Measures Primary outcomes are safety and feasibility of adding an additional hour of VGT or COT into acute stroke units as measured by successful completion of the extra session. Secondary outcomes include time on task and session duration. Results In the rollup period, 14 patients were enrolled. They had an average age of 57 years. Initially, patients spent an average of 15 minutes time-on-task during 23 minute session; after protocol iteration they achieved 43 minutes during 80 minutes sessions. There have been no safety issues and motor endpoints and perceived exertion are measured. Study is ongoing. Conclusions This study is examining the safety and feasibility of integrating VGT for an additional hour of upper limb training in the early phase of post-stroke care. Author(s) Disclosures Authors have no disclosures.

BackgroundEvidence from animal studies suggests that greater reductions in post-stroke motor impairment can be attained with significantly higher doses and intensities of therapy focused on movement quality. These studies also indicate a dose-timing interaction, with more pronounced effects if high-intensity therapy is delivered in the acute/subacute, rather than chronic, post-stroke period.ObjectiveTo compare two approaches of delivering high-intensity, high-dose upper limb therapy in patients with subacute stroke: a novel exploratory neuro-animation therapy (NAT), and modified conventional occupational therapy (COT).MethodsTwenty-four patients were randomized to NAT or COT and underwent 30 sessions of 60 minutes time-on-task in addition to standard care. The primary outcome was the Fugl-Meyer Upper Extremity motor score (FM-UE). Secondary outcomes included: Action Research Arm Test (ARAT), grip strength, Stroke Impact Scale (SIS) hand domain, and upper-limb kinematics. Outcomes were assessed at baseline, and days 3, 90, and 180 post-training. Both groups were compared to a matched historical cohort (HC), which received only 30 minutes of upper limb therapy per day.ResultsThere were no significant between-group differences in FM-UE change or any of the secondary outcomes at any timepoint. Both high-dose groups showed greater recovery on the ARAT (7.3 ±2.9 pts, p=0.011), but not the FM-UE (1.4 ±2.6 pts, p =0.564) when compared to the HC.ConclusionsTwo forms of high-dose intensive upper limb therapy produced greater activity but not impairment improvements compared with regular care. Neuroanimation may offer a new enjoyable, efficient and scalable way to deliver increased upper limb therapy.Clinicaltrials.gov registration NCT02292251

Objective Symptomatic knee osteoarthritis (OA) and meniscal tear are often treated with weight-bearing exercises and without ordering advanced imaging (e.g. MRI). This may lead to missed diagnoses of subchondral insufficiency fracture of the knee (SIFK). Failure to diagnose SIFK has treatment implications, as patients with SIFK are typically managed with a period of reduced weight-bearing. The primary objective of this study is to determine the prevalence of undiagnosed SIFK among persons treated non-operatively for knee pain and suspected meniscal tear(s). Methods The randomized controlled trial, TeMPO (Treatment of Meniscal Problems and Osteoarthritis), enrolls subjects whose clinicians suspect concomitant meniscal tear and knee OA. TeMPO participants undergo MRI ordered by the study to confirm meniscal tear. All study-ordered MRIs revealing a fracture were reviewed by two study radiologists who noted features of the fracture and joint. We report prevalence of SIFK and clinical and imaging features on these subjects with 95% confidence intervals. Results Ten of the 340 study-ordered MRIs had SIFK, resulting in an estimated prevalence of 2.94% (95% CI: 1.15%, 4.71%). Eight of the ten participants with SIFK had fractures located medially. The femur was involved in five of these participants, tibia in four, and both in one. Five of the ten participants did not have meniscal tears. Conclusions This is the only reported estimate of undiagnosed SIFK in adults with knee pain, to our knowledge. Approximately 3% of patients managed with weight-bearing exercise for suspected meniscal tear may have SIFK, a diagnosis typically treated with reduced weight-bearing approaches.

The tendency to claim more knowledge than one actually has is common and well documented; however, little research has focused on the neural mechanisms that underlie this phenomenon. The goal of the present study was to investigate the cortical correlates of overclaiming. Transcranial magnetic stimulation (TMS) was delivered to the medial prefrontal cortex (MPFC), supplementary motor area, and precuneus during the presentation of a series of words that participants were told made up a cultural IQ test. However, participants were not informed that 50% of the words were actually fabricated. False claiming was reduced following MPFC TMS. Furthermore, reaction time decreases following MPFC TMS indicated that participants engaged in less reflection during the task, suggesting a potential reduction in social monitoring of behavior.

Ingested protein results in an increase in circulating insulin and glucagon concentrations and no change, or a slight decrease, in circulating glucose. In subjects with type 2 diabetes, when protein is ingested with glucose, insulin is further increased and the glucose rise is less than when glucose is ingested alone. Presumably these effects are due to the amino acids present in the proteins. The effects of individual amino acids, ingested in physiologic amounts, with or without glucose, have not been determined. Therefore, we have begun a systematic study of the response to ingested amino acids. Eight young, non-obese, subjects (4 men, 4 women) ingested 1 mmol proline/kg lean body mass, 25 g glucose, 25 g glucose + 1 mmol proline/kg lean body mass or water only on 4 separate occasions at 8 am. Blood was obtained before and after ingestion of the test meal over the following 150 minutes. Proline ingestion resulted in a 13-fold increase in the plasma proline concentration. This was decreased by 50% when glucose was ingested with proline. Proline alone had little effect on glucose, insulin, or glucagon concentrations. However, ingestion of proline with glucose resulted in a 23% attenuation of the glucose area response and no change in insulin response compared with the response to that of glucose alone. A glucose-stimulated decrease in glucagon was further facilitated by proline. Ingested proline is readily absorbed. It reduces the glucose-induced increase in glucose concentration in the presence of an unchanged insulin and a decreased glucagon response.

In a randomized, crossover 5-wk study design, we recently reported that a weight-maintaining diet in which the percentage of total food energy as protein was increased from 15-30% resulted in a decrease in postprandial glucose and glycohemoglobin in people with untreated type 2 diabetes without a significant change in insulin. Protein was substituted for carbohydrate in the diet. The fat content remained unchanged. In this publication, we present data on other hormones and metabolites that were considered to potentially be affected by substitution of protein for carbohydrate in the diet. The mean fasting plasma GH and total IGF-I concentrations were elevated on the 30% protein diet. The urinary free cortisol also was increased. However, the urinary aldosterone was unchanged. Although urinary pH was decreased, calcium excretion was not significantly increased. The plasma postprandial alpha-amino nitrogen concentrations were increased, but the 24-h integrated concentration was unchanged, indicating an accelerated amino acid removal rate. The plasma urea nitrogen was increased as expected. The urea production rate also was increased such that a new steady-state fasting value was present. The calculated urea production rate accounted for 97% of the protein ingested on the 15% protein diet, but only 80% on the 30% protein diet, suggesting net nitrogen retention on the high-protein diet. In conclusion, an increase in dietary protein results in a number of metabolic adaptations in addition to reducing the circulating glucose concentration. Serum TSH, total T(3), free T(4), B(12), folate, homocysteine, uric acid, and creatinine concentrations were unchanged.

Study Objective. To determine if milk thistle (silymarin) alters the pharmacokinetics of indinavir. Design. Sequential crossover trial. Setting. General clinical research center. Subjects. Ten healthy subjects. Intervention. Indinavir 800 mg 3 times/day was given for four doses on days 1 and 2. Silymarin 160 mg 3 times/day was given on days 3–15. On day 16 and for one dose on day 17, both drugs were given at the same dosages. Measurements and Main Results. Indinavir's pharmacokinetic parameters were evaluated at steady state both before and after administration of 14 days of silymarin. Blood samples were collected −0.25, 0.5, 1, 2, 3, 4, and 5 hours after indinavir dosing and assayed by high-performance liquid chromatography. The final pharmacokinetic model had first-order absorption after a lag time, and two compartments with first-order elimination from the central compartment. When given alone and combined with silymarin, respectively, the geometric mean (95% confidence interval [CI]) steady-state indinavir area under the plasma concentration-time curve was 20.7 hr·mg/L (15.3–28.2 hr·mg/L) and 19.4 hr·mg/L (15.8–23.6 hr·mg/L) and the trough plasma concentration was 0.340 mg/L (0.232–0.497 mg/L) and 0.232 mg/L (0.129–0.419 mg/L). Conclusion. Silymarin has no apparent effect on indinavir plasma concentrations.