Individual patient data meta-analysis of randomized controlled trials of community occupational therapy for stroke patients

<p><b>Background and Purpose:</b> Trials of occupational therapy for stroke patients living in the community have varied in their findings. It is unclear why these discrepancies have occurred.</p> <p><b>Methods:</b> Trials were identified from searches of the Cochrane Library and other sources. The primary outcome measure was the Nottingham Extended Activities of Daily Living (NEADL) score at the end of intervention. Secondary outcome measures included the Barthel Index or the Rivermead ADL (Personal ADL), General Health Questionnaire (GHQ), Nottingham Leisure Questionnaire (NLQ), and death. Data were analyzed using linear or logistic regression with a random effect for trial and adjustment for age, gender, baseline dependency, and method of follow-up. Subgroup analyses compared any occupational therapy intervention with control.</p> <p><b>Results:</b> We included 8 single-blind randomized controlled trials incorporating 1143 patients. Occupational therapy was associated with higher NEADL scores at the end of intervention (weighted mean difference [WMD], 1.30 points, 95% confidence intervals [CI], 0.47 to 2.13) and higher leisure scores at the end of intervention (WMD, 1.51 points; 95% CI, 0.24 to 2.79). Occupational therapy emphasizing activities of daily living (ADL) was associated with improved end of intervention NEADL (WMD, 1.61 points; 95% CI, 0.72 to 2.49) and personal activities of daily living (odds ratio [OR], 0.65; 95% CI, 0.46 to 0.91), but not NLQ. Leisure-based occupational therapy improved end of intervention NLQ (WMD, 1.96 points; 95% CI, 0.27 to 3.66) but not NEADL or PADL.</p> <p><b>Conclusions:</b> Community occupational therapy significantly improved personal and extended activities of daily living and leisure activity in patients with stroke. Better outcomes were found with targeted interventions.</p&gt

Forest Composition Change and Biophysical Climate Feedbacks Across Boreal North America

Deciduous tree cover is expected to increase in North American boreal forests with climate warming and wildfire. This shift in composition has the potential to generate biophysical cooling via increased land surface albedo. Here we use Landsat-derived maps of continuous tree canopy cover and deciduous fractional composition to assess albedo change over recent decades. We find, on average, a small net decrease in deciduous fraction from 2000 to 2015 across boreal North America and from 1992 to 2015 across Canada, despite extensive fire disturbance that locally increased deciduous vegetation. We further find near-neutral net biophysical change in radiative forcing associated with albedo when aggregated across the domain. Thus, while there have been widespread changes in forest composition over the past several decades, the net changes in composition and associated post-fire radiative forcing have not induced systematic negative feedbacks to climate warming over the spatial and temporal scope of our study

Impacts of Climate and Insect Herbivory on Productivity and Physiology of Trembling Aspen (Populus tremuloides) in Alaskan Boreal Forests

Climate change is impacting forested ecosystems worldwide, particularly in the Northern Hemisphere where warming has increased at a faster rate than the rest of the globe. As climate warms, trembling aspen (Populus tremuloides) is expected to become more successful in northern boreal forests because of its current presence in drier areas of North America. However, large-scale productivity decline of aspen has recently been documented throughout the United States and Canada as a result of drought and insect outbreaks. We used tree ring measurements (basal area increment (BAI) and stable carbon isotopes (δ 13C)) and remote sensing indices of vegetation productivity (NDVI) to study the impact of climate and damage by the aspen epidermal leaf miner (Phyllocnistis populiella) on aspen productivity and physiology in interior Alaska. We found that productivity decreased with greater leaf mining and was not sensitive to growing season (GS) moisture availability. Although productivity decreased during high leaf mining years, it recovered to pre-outbreak levels during years of low insect damage, suggesting a degree of resilience to P. populiella mining. Climate and leaf mining interacted to influence tree ring δ 13C, with greater leaf mining resulting in decreased δ 13C when GS moisture availability was low. We also found that NDVI was negatively associated with leaf mining, and positively correlated with BAI and the δ 13C decrease corresponding to mining. This suggests that NDVI is capturing not only variations in productivity, but also changes in physiology associated with P. populiella. Overall, these findings indicate that the indirect effects of P. populiella mining have a larger impact on aspen productivity and physiology than climate under current conditions, and is essential to consider when assessing growth, physiology and NDVI trends in interior Alaska

Resident immune cells of the avascular lens: Mediators of the injury and fibrotic response of the lens.

Tissues typically harbor subpopulations of resident immune cells that function as rapid responders to injury and whose activation leads to induction of an adaptive immune response, playing important roles in repair and protection. Since the lens is an avascular tissue, it was presumed that it was absent of resident immune cells. Our studies now show that resident immune cells are a shared feature of the human, mouse, and chicken lens epithelium. These resident immune cells function as immediate responders to injury and rapidly populate the wound edge following mock cataract surgery to function as leader cells. Many of these resident immune cells also express MHCII providing them with antigen presenting ability to engage an adaptive immune response. We provide evidence that during development immune cells migrate on the ciliary zonules and localize among the equatorial epithelial cells of the lens adjacent to where the ciliary zonules associate with the lens capsule. These findings suggest that the vasculature-rich ciliary body is a source of lens resident immune cells. We identified a major role for these cells as rapid responders to wounding, quickly populating each wound were they can function as leaders of lens tissue repair. Our findings also show that lens resident immune cells are progenitors of myofibroblasts, which characteristically appear in response to lens cataract surgery injury, and therefore, are likely agents of lens pathologies to impair vision like fibrosis

High-throughput screen using a single-cell tyrosine phosphatase assay reveals biologically active inhibitors of tyrosine phosphatase CD45

Many cellular signaling events are regulated by tyrosine phosphorylation and mediated by the opposing actions of protein tyrosine kinases and phosphatases. Protein tyrosine phosphatases are emerging as drug targets, but poor cell permeability of inhibitors has limited the development of drugs targeting these enzymes [Tautz L, et al. (2006) Expert Opin Ther Targets 10:157–177]. Here we developed a method to monitor tyrosine phosphatase activity at the single-cell level and applied it to the identification of cell-permeable inhibitors. The method takes advantage of the fluorogenic properties of phosphorylated coumaryl amino propionic acid (pCAP), an analog of phosphotyrosine, which can be incorporated into peptides. Once delivered into cells, pCAP peptides were dephosphorylated by protein tyrosine phosphatases, and the resulting cell fluorescence could be monitored by flow cytometry and high-content imaging. The robustness and sensitivity of the assay was validated using peptides preferentially dephosphorylated by CD45 and T-cell tyrosine phosphatase and available inhibitors of these two enzymes. The assay was applied to high-throughput screening for inhibitors of CD45, an important target for autoimmunity and infectious diseases [Hermiston ML, et al. (2003) Annu Rev Immunol 21:107–137]. We identified four CD45 inhibitors that showed activity in T cells and macrophages. These results indicate that our assay can be applied to primary screening for inhibitors of CD45 and of other protein tyrosine phosphatases to increase the yield of biologically active inhibitors

The DRESS trial: a feasibility randomized controlled trial of a neuropsychological approach to dressing therapy for stroke inpatients

Objective: To investigate two approaches to treating patients with persistent dressing problems and cognitive difficulties following stroke. Design: Pilot randomized controlled trial. Setting: Inpatient stroke rehabilitation service. Subjects: Seventy consecutive stroke patients with persistent dressing problems and accompanying cognitive difficulties at two weeks after their stroke. Interventions: Patients were randomly allocated to six weeks of either a systematic neuropsychological approach, based on analysis of dressing problems and further cognitive testing, or to the control group who received conventional (functional) dressing practice. Both groups received treatment three times a week in accordance with two separately prepared manuals. Main measures: Nottingham Stroke Dressing Assessment (NSDA), Line Cancellation, 10-hole peg transfer test, Object Decision, Gesture Imitation. Patients were assessed at six weeks after randomization by an independent assessor masked to group allocation. Results: Both neuropsychological and functional groups improved performance on the NSDA over the treatment period (31% and 22%, respectively) but there was no significant difference between groups at six weeks. However, the neuropsychological group showed a significantly greater improvement on a line cancellation test of visual neglect (t(62) = 2.1, P < 0.05) and a planned subanalysis for those with right hemisphere damage showed a trend towards better dressing outcome (P = 0.07, one-tailed). Conclusions: Results demonstrate the potential benefits of a systematic neuropsychological approach to dressing therapy, particularly for patients with right hemisphere damage. This study suggests the need for a phase III study evaluating the efficacy of a systematic neuropsychological approach in treating dressing difficulties, targeting patients with right hemisphere stroke and visuospatial impairments

Cardiac xenotransplantation: Recent preclinical progress with 3-month median survival

ObjectivesTransplantation is limited by a lack of human organ donors. Organs derived from animals, most likely the pig, represent a potential solution to this problem. For the heart, 90-day median graft survival of life-supporting pig hearts transplanted to nonhuman primates has been considered a reasonable standard for entry into the clinical arena. Overcoming the immune barrier to successful cardiac xenotransplantation is most appropriately first explored with the non–life-supporting heterotopic model.MethodsWe performed a series of 7 heterotopic heart transplantations from CD46 transgenic pigs to baboons using a combination of therapeutic agents largely targeted at controlling the synthesis of anti-pig antibodies. Rituximab (anti-CD20) and Thymoglobulin (rabbit antithymocyte globulin [ATG]; SangStat Medical Corp, Fremont, Calif) were used as induction therapy. Baseline immunosuppression consisted of splenectomy, tacrolimus, sirolimus, steroids, and TPC (an anti-Gal antibody therapeutic). Rejection events were not treated.ResultsBy using Kaplan-Meier analysis, median graft survival was 96 days (range, 15–137 days; 95% confidence interval, 38–99 days). Only 2 grafts were lost as a result of rejection, as defined by cessation of graft palpation. There was no evidence of a consumptive coagulopathy, infectious complications were treatable, and no posttransplantation lymphoproliferative disorders occurred. No cellular infiltration was observed.ConclusionsThis study reports the longest median survival to date (96 days) of pig hearts transplanted heterotopically into baboons. Duplication of these results in the orthotopic life-supporting position could bring cardiac xenotransplantation to the threshold of clinical application