Lifespan data on postural balance in multiple standing positions.

BACKGROUND: Maintaining balance is important throughout life. The Nintendo Wii Balance Board (WBB) can give reliable quantitative measures of postural balance, but reference data are lacking. Furthermore, one-leg standing balance across the adult lifespan is not fully described. The aim of the study was (1) to provide reference data on postural balance in multiple standing positions using a WBB, (2) to determine an age cut-off for the ability to stand on one-leg in men and women. METHODS: This was a cross-sectional study and data was collected in two cities in Denmark (Aalborg and Odense) and Norway (Oslo and Ålesund) during spring and summer of 2016. Postural balance was assessed in individuals across the adult lifespan in three different bases of support positions (hip-wide and narrow two-legged stance, and one-legged stance) using a WBB. Reference data were analyzed and presented in 10-year intervals. RESULTS: A total of 354 individuals aged 20-99 years were recruited. Reference data were presented in percentiles stratified by gender for the following age categories: 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80+. Data showed that the difference between men and women's balance was larger at older age with men performing worst. The cut-off ability to stand on one-leg was 72.5 years without statistical evidence of gender difference. CONCLUSION: This study reports reference data for postural balance across the entire adult lifespan using a WBB. More than half of the individuals over 72.5 years of age were unable to stand balanced on one-leg.

Reference data on hand grip and lower limb strength using the Nintendo Wii balance board: a cross-sectional study of 354 subjects from 20 to 99 years of age.

BACKGROUND: Accurate assessment of isometric hand grip strength (HGS) and isometric lower limb strength (LS) are often limited to specialized clinics due to high costs and need for specialized equipment and personnel. A mobile and user-friendly device would facilitate a wider use of these measures in the clinical setting. The Nintendo Wii Balance Board (WBB) is a novel and pragmatic tool that has been validated for measuring muscle strength and other clinically relevant physiological variables. However, reference data for HGS and LS are lacking. The purpose of the current study is to establish reference data for HGS and LS in individuals ≥20 years of age using the WBB method, and to characterize the effects of age in these measurements. METHOD: Healthy participants were recruited at various locations and their HGS and LS were tested by six assessors using the WBB. Reference data were analysed and presented in age-groups, while the age-related change in HGS and LS was tested and characterized with linear regression models. RESULTS: Three hundred and fifty-four participants between 20 and 99 years of age were tested. Data are presented separately according to gender and the following age categories: 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80+, and presented in absolute values as well as percentiles. The main findings were; (1) Significantly higher HGS and LS among males compared to females and for the dominant limb compared to the non-dominant limb, (2) a significant decline in strength with increasing age, and (3) the rate of decline increased significantly (i.e. it was non-linear) with age for HGS, but not for LS. CONCLUSION: This study reported reference data with percentiles for a novel method for assessing HGS and LS. Data were consistent with previously known effects of age and gender on HGS and LS. The presented data may supplement future trials using the WBB in research or in the clinical setting.

Allogeneic hematopoietic cell transplantation (HCT) in Hurler's syndrome using a reduced intensity preparative regimen.

Allogeneic hematopoietic cell transplantation (HCT) in patients with Hurler's syndrome can improve survival and ameliorate many aspects of Hurler's syndrome including neurologic decline and cardiac compromise. Unfortunately, the toxicity of traditional preparative regimens to organs affected by the syndrome may have deleterious effects. Additionally, despite the intensity of these regimens, achieving stable donor chimerism can be difficult. We report transplant outcomes following a reduced intensity, highly immunosuppressive preparative regimen consisting of alemtuzumab, fludarabine and melphalan prior to HCT in seven patients with Hurler's syndrome treated at two centers. Six patients received grafts from unrelated donors and one received a sibling donor graft. The preparative regimen was well tolerated. All patients had initial donor engraftment at 100 days; one patient had delayed loss of donor chimerism. There was no severe acute GVHD (no GI GVHD of grade II or more, no grade IV skin GVHD). Six of the seven children are surviving at a median of 1014 (726-2222) days post transplant. This reduced intensity preparative regimen has the potential to support engraftment and improve survival and outcome in patients with Hurler's syndrome undergoing HCT.

Effect of prior aspirin use on stroke severity in the trial of Org 10172 in acute stroke treatment (TOAST).

BACKGROUND AND PURPOSE: Although the efficacy of aspirin in reducing stroke incidence is clear, its role in reducing stroke severity is disputed. This study compares stroke severity between patients who did or did not take aspirin in the week before stroke and enrollment in the Trial of Org 10172 in Acute Stroke Treatment (TOAST). METHODS: Of 1275 patients randomized, 509 reported aspirin use in the week before stroke; 766 did not. Clinical stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS) and the Supplementary Motor Examination (SME) at trial entry and at 3 months. Using these scales, we compared the categorization of stroke severity (mild, moderate, and severe) and mean scores between aspirin users and nonusers. RESULTS: The difference in distribution of baseline NIHSS scores was statistically significant between aspirin users and nonusers (P=0.006), with a greater percentage of milder strokes among aspirin users. The difference in mean baseline NIHSS scores was also significantly lower in aspirin users (8.2) and nonusers (9.3) (P=0.003). The distribution of baseline SME scores and mean SME scores also showed lower stroke severity in aspirin users than in nonusers (P=0.048 and P=0.004, respectively). At 3 months, differences in stroke severity measured by the SME but not the NIHSS remained statistically significant. Seven-day and 3-month mortality did not differ significantly. CONCLUSIONS: In this study aspirin use is associated with milder clinical deficits at stroke onset. These deficits may affect prognosis and influence response to treatment. Future clinical trials should ensure that prestroke aspirin use is comparable in study groups.

Ischemic stroke outcome: racial differences in the trial of danaparoid in acute stroke (TOAST).

OBJECTIVE: To determine racial differences in baseline stroke risk factors and other measures in the Trial of ORG 10172 in Acute Stroke Therapy (TOAST). Differences in these factors could influence response to acute stroke therapy and overall stroke outcome. METHODS: The authors compared baseline demographic, medical, stroke, physical examination, CT, laboratory, and neurologic factors among 292 African-American and 801 white patients who enrolled in the TOAST study. TOAST compared danaparoid (ORG 10172) with placebo among acute ischemic stroke patients who were treated within 24 hours of stroke onset. RESULTS: African-Americans were younger and more frequently had hypertension, diabetes mellitus, congestive heart failure, and prior strokes. In addition, African-Americans had higher mean diastolic blood pressure, more lacunar strokes, and more severe prestroke disability. There were no significant differences between African-Americans and white patients in outcomes at 7 days, overall number of adverse experiences, or occurrence of serious bleeds or hemorrhagic transformations. However, there was a trend toward a higher rate of favorable outcomes in white patients at 7 days. There was no significant difference in very favorable outcome at 3 months between African-American and white patients, but significantly more white patients had favorable outcome at 3 months. CONCLUSION: Although African-Americans possess a number of factors that should predict higher rates of poor stroke outcome after acute therapy, they have the capacity to respond similarly to white patients after acute stroke therapy. Perhaps younger age and presence of lacunar infarction are stronger predictors of good outcomes than was appreciated previously.

Differences between anterior and posterior circulation stroke in TOAST.

BACKGROUND AND PURPOSE: Clinicians have tended to view anterior circulation (AC) and posterior circulation (PC) strokes as separate entities, with different underlying pathogenesis, natural histories, and potential responsiveness to interventions such as anticoagulation. We sought to explore differences between AC and PC stroke in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). METHODS: For patients enrolled in TOAST, prospective clinical information was collected including outcome at 3 months. Data on vascular distribution were obtained from the clinical impression of the investigators. Group comparisons for categorical data were performed using Fisher's exact test. Independent sample t tests and analysis of covariance were used for all continuous data. RESULTS: The analysis included 1,039 patients with AC stroke and 180 patients with PC stroke. There were fewer women in the PC than in the AC groups, but otherwise there were no differences in demographics, risk factors or stroke subtypes between the two groups. Headache (AC 8.7%, PC 15%, p = 0.013) and vomiting (AC 3.5%, PC 17.8%, p < 0.001) were more common among PC patients. Mean baseline National Institutes of Health Stroke Scale (NIHSS) score was lower (less severe) among PC (6.1) than AC patients (9.5; p < 0.001). On univariate analysis, favorable outcome at 3 months was more common for PC patients in both the placebo group (PC 82%, AC 71%, p = 0.04) and heparinoid group (PC 87%, AC 73%, p = 0.005). However, multivariate analysis, controlling for gender, history of previous stroke and baseline NIHSS score, showed no difference in outcome between PC and AC stroke. For favorable outcome, there was no interaction between vascular distribution and treatment category, suggesting that the effect of heparinoid did not differ between PC and AC strokes. CONCLUSION: Patients with PC stroke seem to have a better long-term outcome than do AC patients, but this difference is no longer apparent when controlling for important prognostic variables. PC patients did not show any particular benefit from anticoagulation, and the efficacy of heparinoid did not vary between AC and PC stroke. While AC and PC patients do differ in some respects, it may be inappropriate to single out PC patients for anticoagulant treatment.

Serum-activated assembly and membrane translocation of an endogenous Rac1:effector complex.

Rho family GTPases (Cdc42, Rac1, and RhoA) function downstream of Ras [1], and in a variety of cellular processes [2]. Studies to examine these functions have not directly linked endogenous protein interactions with specific in vivo functions of Rho GTPases. Here, we show that endogenous Rac1 and two known binding partners, Rho GDP dissociation inhibitor (RhoGDI) and p21-activated kinase (PAK), fractionate as distinct cytosolic complexes. A Rac1:PAK complex is translocated from the cytosol to ruffling membranes upon cell activation by serum. Overexpression of dominant-negative (T17N) Rac1 does not affect the assembly or distribution of this Rac1:PAK complex. This is the first direct evidence of how a specific function of Rac1 is selected by the assembly and membrane translocation of a distinct Rac1:effector complex.

ProFeel: low cost visual-haptic perceptualization of protein structure-structure alignments.

We describe ProFeel, an application for exploring molecular data from protein structure-structure alignments using a force-feedback joystick. Protein structure analysis is a useful application for multimodal information perceptualization because researchers in this area typically use several independent measures in assessment. A system that allows the user to simultaneously evaluate different criteria would therefore be quite useful. Four variables are assigned three different haptic effects each to allow the user to discern twelve separate data values. The haptic representation is coupled with a traditional molecular graphics visual display.

Cell polarity: Versatile scaffolds keep things in place.

Protein scaffolds organize transmembrane and cytoplasmic proteins and serve to integrate both structure and signaling at the apical junctional complex of polarized epithelial cells. These scaffolds are important in coordinating local and global changes in cell organization.

Antithrombotic treatment of ischemic stroke among patients with occlusion or severe stenosis of the internal carotid artery: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST).

OBJECTIVE: To examine the responses to early IV administration of an anticoagulant or placebo started within 24 hours of stroke among persons with an ipsilateral occlusion or severe stenosis of the internal carotid artery (ICA) identified by carotid duplex imaging. BACKGROUND: Patients with ischemic stroke of the cerebral hemisphere secondary to an ipsilateral occlusion or severe stenosis of the ICA generally have a poor prognosis. Early, accurate identification of these patients might permit improved treatment. METHODS: Exploratory analysis of outcomes at 7 days and 3 months was performed among patients enrolled in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) who had an ischemic stroke in the cerebral hemisphere ipsilateral to an occlusion or a stenosis >50% of the ICA identified by carotid duplex imaging. RESULTS: Regardless of treatment, patients with duplex evidence of an occlusion of the ICA had more severe strokes and poorer outcomes at 7 days and 3 months than patients who had a stenosis. Favorable outcomes at 7 days were noted in 64 of 119 patients given danaparoid (53.8%) and 41 of 108 patients treated with placebo (38.0%; p = 0.023). By 3 months, favorable outcomes were noted in 82 patients given danaparoid (68.3%) and 58 patients administered placebo (53.2%; p = 0.021). CONCLUSIONS: Early identification by duplex imaging of an occlusion or severe stenosis of the ICA ipsilateral to a hemispheric ischemic stroke might improve selection of patients who could be treated with emergent anticoagulation. Further testing of this approach is needed.

Baseline NIH Stroke Scale score strongly predicts outcome after stroke: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST).

OBJECTIVE: To compare the baseline National Institutes of Health Stroke Scale (NIHSS) score and the Trial of Org 10172 in Acute Stroke Treatment (TOAST) stroke subtype as predictors of outcomes at 7 days and 3 months after ischemic stroke. METHODS: Using data collected from 1,281 patients enrolled in a clinical trial, subtype of stroke was categorized using the TOAST classification, and neurologic impairment at baseline was quantified using the NIHSS. Outcomes were assessed at 7 days and 3 months using the Barthel Index (BI) and the Glasgow Outcome Scale (GOS). An outcome was rated as excellent if the GOS score was 1 and the BI was 19 or 20 (scale of 0 to 20). Analyses were adjusted for age, sex, race, and history of previous stroke. RESULTS: The baseline NIHSS score strongly predicted outcome, with one additional point on the NIHSS decreasing the likelihood of excellent outcomes at 7 days by 24% and at 3 months by 17%. At 3 months, excellent outcomes were noted in 46% of patients with NIHSS scores of 7 to 10 and in 23% of patients with scores of 11 to 15. After multivariate adjustment, lacunar stroke had an odds ratio of 3.1 (95% CI, 1.5 to 6.4) for an excellent outcome at 3 months. CONCLUSIONS: The NIHSS score strongly predicts the likelihood of a patient's recovery after stroke. A score of > or =16 forecasts a high probability of death or severe disability whereas a score of < or =6 forecasts a good recovery. Only the TOAST subtype of lacunar stroke predicts outcomes independent of the NIHSS score.

Protalign: a 3-dimensional protein alignment assessment tool.

Protein fold recognition (sometimes called threading) is the prediction of a protein's 3-dimensional shape based on its similarity to a protein of known structure. Fold predictions are low resolution; that is, no effort is made to rotate the protein's component amino acid side chains into their correct spatial orientations. The goal is simply to recognize the protein family member that most closely resembles the target sequence of unknown structure and to create a sensible alignment of the target to the known structure (i.e., a structure-sequence alignment). To facilitate this type of structure prediction, we have designed a low resolution molecular graphics tool. ProtAlign introduces the ability to interact with and edit alignments directly in the 3-dimensional structure as well as in the usual 2-dimensional layout. It also contains several functions and features to help the user assess areas within the alignment. ProtAlign implements an open pipe architecture to allow other programs to access its molecular graphics capabilities. In addition, it is capable of "driving" other programs. Because amino acid side chain orientation is not relevant in fold recognition, we represent amino acid residues as abstract shapes or glyphs much like Lego (tm) blocks and we borrow techniques from comparative flow visualization using streamlines to provide clean depictions of the entire protein model. By creating a low resolution representation of protein structure, we are able to at least double the amount of information on the screen. At the same time, we create a view that is not as busy as the corresponding representations using traditional high resolution visualization methods which show detailed atomic structure. This eliminates distracting and possibly misleading visual clutter resulting from the mapping of protein alignment information onto a high resolution display of the known structure. This molecular graphics program is implemented in Open GL to facilitate porting to other platforms.

PROMUSE: a system for multi-media data presentation of protein structural alignments.

We present and evaluate PROMUSE: an integrated visualization/sonification system for analyzing pairwise protein structural alignments (superpositions of two protein structures in three-dimensional space). We also explore how the use of sound can enhance the perception and recognition of specific aspects of the local environment at given positions in the represented molecular structure. Sonification presents several opportunities to researchers. For those with visual impairment, data sonification can be a useful alternative to visualization. Sonification can further serve to improve understanding of information in several ways. One use for data sonification is in tasks such as background monitoring, in which case sounds can be used to indicate thresholding events. With PROMUSE, data represented visually may be enhanced or disambiguated by adding sound to the presentation. This aspect of data representation is particularly important for showing features that are difficult to represent visually, due to occlusion or other factors. Another feature of our system is that by representing some variables through sound and others visually, the amount of information that may be represented simultaneously is extended. Our tool aims to augment the power of data visualization rather than replace it. To maximize the utility of our sonifications to represent data, we employed musical voices and melodic components with unique characteristics. We also used sound effects such as panning a voice to the left or right speaker and changing its volume to maximize the individuality of the sonification elements. By making the sonification parameters distinct, we allow the user to focus on those portions of the sonification necessary to resolve possible ambiguities in the visual display. Sonifications of low level data such as raw protein or DNA sequences tend to sound random, and not very musical. We chose instead to sonify an analysis of data features, and thereby present a higher level view of the data. We also used brief melodic phrases rather than single notes in order to generate sounds that were more pleasing and musically idiomatic. To validate the utility of our system, we present the results of an experiment in which PROMUSE was used to test the use of sound as an aid for clarifying visual information. We also compare the overall effectiveness of visual versus aural information delivery.

Acute blood glucose level and outcome from ischemic stroke. Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators.

OBJECTIVE: To study the relation between acute blood glucose level and outcome from ischemic stroke. BACKGROUND: Hyperglycemia may augment acute ischemic brain injury and increase the risk of hemorrhagic transformation of the infarct. METHODS: The authors analyzed the relation between admission blood glucose level (within 24 hours from ischemic stroke onset) and clinical outcome in 1,259 patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST)-a placebo-controlled, randomized, double-blind trial to test the efficacy of a low-molecular weight heparinoid in acute ischemic stroke. Very favorable outcome was defined as a Glasgow Outcome Scale score of 1 and a modified Barthel index of 19 or 20. Neurologic improvement at 3 months was defined as a decrease by > or =4 points on the NIH Stroke Scale compared with baseline or a final score of 0. Hemorrhagic transformation of infarct was assessed within 10 days after onset of stroke with repeat cerebral CT. Stroke subtype as lacunar or nonlacunar (atherothromboembolic, cardioembolic, and other or undetermined etiology) was classified by one investigator after completion of stroke evaluation according to study protocol. RESULTS: In all strokes combined (p = 0.03) and in nonlacunar strokes (p = 0.02), higher admission blood glucose levels were associated with worse outcome at 3 months according to multivariate logistic regression analysis adjusted for stroke severity, diabetes mellitus, and other vascular risks. In lacunar strokes, the relationship between acute blood glucose level and outcome was related to treatment. In the placebo group, higher admission blood glucose levels were associated with better outcome at 3 months. However, in the active drug group, as the glucose level increased from 50 to 150 mg/dL, the probability of a very favorable outcome decreased sharply and remained relatively unchanged as the glucose level increased further (p = 0.002, for overall effect of glucose on outcome). Acute blood glucose level was not associated with symptomatic hemorrhagic transformation of infarcts or with neurologic improvement at 3 months. CONCLUSIONS: During acute ischemic stroke hyperglycemia may worsen the clinical outcome in nonlacunar stroke, but not in lacunar stroke, and is not associated with an increased risk of hemorrhagic transformation of the infarct.

Nicotine polacrilex dose effects: serum nicotine levels and sensory characteristics.

This study evaluated serum nicotine and sensory differences of five different doses of nicotine polacrilex (0.0, 0.5, 1.0, 2.0 and 4.0 mg nicotine), three of which have been used as placebo doses in clinical trials (0.0, 0.5, and 1.0 mg) and two of which are currently available as pharmacologic treatments for smoking cessation (2.0 or 4.0 mg nicotine). Twenty-one smokers received, on different days and in random order, five pieces of each of the five doses of polacrilex. The objective of the study was to evaluate whether consistent serum nicotine and sensory differences would be observed between the doses. After 5 h use, the 0.0, 0.5, 1.0, 2.0, and 4.0 mg doses produced the following results: (1) there was a linear trend across the placebo doses of nicotine polacrilex in serum nicotine and nicotine flavor, although pairwise dose comparisons were not significant, (2) the 0.0 and 0.5 mg placebo doses resulted in serum nicotine and sensory ratings that were significantly different from the 2.0 mg dose, and even more so from the 4.0 mg dose, (3) the 1.0 mg dose was not different from the 2.0 mg dose on serum nicotine level and several sensory characteristics, though it was different from the 4.0 mg dose on both, and (4) the 4.0 mg dose resulted in significantly higher serum nicotine and usually higher sensory ratings than the 2.0 mg dose. Since the 0.0 mg placebo achieves sensory effects that are comparable to the nicotine-containing placebo doses, it is recommended over the 0.5 and 1.0 mg doses as the nicotine polacrilex placebo of choice in most clinical trials.

Effects of differing nicotine-replacement doses on weight gain after smoking cessation.

OBJECTIVE: To prospectively assess effects of doses of a nicotine-replacement agent on weight gain in men and women after smoking cessation. DESIGN: Four-week, randomized, double-blind clinical trial. SETTING: Outpatient medical clinic. STUDY PARTICIPANTS: Healthy volunteers who smoked at least 10 cigarettes per day. INTERVENTION: Pharmacologic: Random assignment to 0, 2, or 4 mg of nicotine polacrilex on a fixed-dose schedule (one piece per hour while awake). Behavioral: Brief, medical/behavioral counseling regarding smoking cessation. MAIN OUTCOME MEASURE: Weight change as a function of dose and gender only in participants abstinent for all 4 week. (Self-reported abstinence verified by breath carbon monoxide levels). RESULTS: Weight change in women abstinent for 4 weeks (n = 16) was +1.69, +0.33, and -0.26 kg in the placebo, 2-mg, and 4-mg groups, respectively, compared with +1.60, +1.45, and +1.18 kg for the men who were abstinent for 4 weeks (n = 19). Medication use did not differ as a function of dose or gender. CONCLUSIONS: Nicotine polacrilex suppressed, in a dose-related fashion, weight gain after smoking cessation in successfully treated women. Weight gain was not shown to be suppressed in men, possibly because of small sample size.