High platelet content can increase storage lesion rates following Intercept pathogen inactivation primarily in platelet concentrates prepared by apheresis

Background: Pathogen inactivation methods for platelet concentrates are increasingly being used in blood banks worldwide. In vitro studies have demonstrated its effects on storage lesion, but little routine quality control data on blood banking outcomes have been reported. Materials and Methods: Swirling of distributed products was monitored before and after implementation of Intercept pathogen inactivation. Metabolic parameters pH, glucose and lactic acid were determined in a random cohort of expired pathogen-inactivated products. Storage lesion indicators in apheresis concentrates with premature low swirling were compared to concentrates with normal swirling. Results: During validation for implementing Intercept pathogen inactivation, pH and glucose levels decreased faster in apheresis platelet concentrates with high platelet content than with low platelet content or than in pathogen-inactivated pooled buffy coat-derived products. In routine products, glucose exhaustion was more often found in apheresis compared to buffy coat-derived platelet concentrates despite 3-7% more plasma carryover in the former. Annual incidence of premature low swirling increased significantly by 50% following implementation of pathogen inactivation implementation for apheresis but not for pooled buffy coat platelet concentrates. In addition, apheresis concentrates with premature low swirling had a significantly higher median platelet count (50 x 10(11)) than unaffected products (35 x 10(11)). Conclusion: The risk of increased storage lesion rates following Intercept pathogen inactivation is higher for apheresis than for buffy coat-derived platelet concentrates, especially when platelet contents are higher than 50 x 10(11)

Exercise dosage to facilitate the recovery of balance, walking, and quality of life after stroke

Background: Although aerobic training (AT) and resistance training (RT) are recommended after stroke, the optimal dosage of these interventions and their effectiveness on balance, walking capacity, and quality of life (QoL) remain conflicting. Objective: Our study aimed to quantify the effects of different modes, dosages and settings of exercise therapy on balance, walking capacity, and QoL in stroke survivors. Methods: PubMed, CINHAL, and Hinari databases were searched for randomised controlled trials (RCTs) evaluating the effects of AT and RT on balance, walking, and QoL in stroke survivors. The treatment effect was computed by the standard mean differences (SMDs). Results: Twenty-eight trials (n = 1571 participants) were included. Aerobic training and RT interventions were ineffective on balance. Aerobic training interventions were the most effective in improving walking capacity (SMD = 0.37 [0.02, 0.71], p = 0.04). For walking, capacity, a higher dosage (duration ≥ 120 min/week; intensity ≥ 60% heart rate reserve) of AT interventions demonstrated a significantly greater effect (SMD = 0.58 [0.12, 1.04], p = 0.01). Combined AT and RT improved QoL (SMD = 0.56 [0.12, 0.98], p = 0.01). Hospital located rehabilitation setting was effective for improving walking capacity (SMD = 0.57 [0.06, 1.09], p = 0.03) compared with home and/or community and laboratory settings. Conclusions: Our findings showed that neither AT nor RT have a significant effect on balance. However, AT executed in hospital-located settings with a higher dose is a more effective strategy to facilitate walking capacity in chronic stroke. In contrast, combined AT and RT is beneficial for improving QoL. Clinical implications: A high dosage of aerobic exercise, duration ≥ 120 min/week; intensity ≥ 60% heart rate reserve is beneficial for improving walking capacity

The senotherapeutic nicotinamide riboside raises platelet nicotinamide adenine dinucleotide levels but cannot prevent storage lesion

BACKGROUND Supplementation of the adenine nicotinamide dinucleotide (NAD) precursor nicotineamide riboside (NR) has recently been shown to increase life-span of cells, tissues, and entire organisms. The impact of NR on platelet longevity has not been tested. STUDY DESIGN AND METHODS A pool-and-split design of buffy coat derived platelet concentrates (PCs) was used. One arm was treated with cumulative doses of NR-triflate, the control arm with sodium triflate. Storage lesion was monitored for 23 days. Platelet metabolic and functional parameters were tested. Clearance of human platelets was measured in a mouse model of transfusion. RESULTS Total intracellular NAD levels in platelets decreased two-fold from 4.8 +/- 0.5 fmol (mean +/- SD, n = 6) to 2.1 +/- 1.8 fmol per 10(3) control cells, but increased almost 10-fold to 41.5 +/- 4.1 fmol per 10(3) NR treated platelets. This high intracellular NAD level had no significant impact on platelet count, mean platelet volume, swirling, nor on lactate and glucose levels. Platelet aggregation and integrin alpha(IIb)beta(3) activation declined steadily and comparably in both conditions. GPIb alpha levels were slightly lower in NR-treated platelets compared to control, but this was not caused by reduced receptor shedding because glycocalicin increased similarly. Apoptotic markers cytochrome c, Bcl-xL, cleaved caspase-3, and Bak were not different throughout storage for both conditions. Platelet survival in a mouse model of transfusion was not different between NR-treated and control platelets. CONCLUSION Platelets carry the cellular machinery to metabolize NR into NAD at rates comparable to other eukaryotic cells. Unlike those cells, platelet life-span cannot be prolonged using this strategy

Combinatorial synthesis of (YxGd1-x)Ba2Cu3Ox superconducting thin films

Environmentally friendly water-based YBa2Cu3Ox (YBCO) and GdBa2Cu3Ox (GdBCO) precursor solutions were synthesized to realize thin films by chemical solution deposition. Pure YBCO and GdBCO precursor solutions were used for ink plotting on SrTiO3 substrates and subsequent thermal treatment at the corresponding crystallization temperature. Phase formation of Gd123 requires a higher crystallization temperature of 840 °C compared to the Y123 phase. The critical temperature of YBCO films is about 92 K with a sharp transition into the superconducting state. Micro liter sized ink volumes of YBCO and GdBCO were successfully mixed for two-dimensional ink plotting of a (YxGd1-x)Ba2Cu3Ox film library. A homogeneous surface and no indication of a-axis growth were found in all mixed films

State of the Art on Prediction of Concrete Pumping

Large scale constructions needs to estimate a possibility for pumping concrete. In this paper, the state of the art on prediction of concrete pumping including analytical and experimental works is presented. The existing methods to measure the rheological properties of slip layer (or called lubricating layer) are first introduced. Second, based on the rheological properties of slip layer and parent concrete, models to predict concrete pumping (flow rate, pumping pressure, and pumpable distance) are explained. Third, influencing factors on concrete pumping are discussed with the test results of various concrete mixes. Finally, future need for research on concrete pumping is suggested.ope

Control intervention design for preclinical and clinical trials: consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was ranked easy to address and very important, "variability in usual care" was ranked hard to address and of low importance, and "understanding the content of the control and how it differs from the experimental intervention" was ranked very important but not easy to address. The CONtrol DeSIGN (CONSIGN) decision support tool was developed to address the identified challenges and enhance comparator selection, description, and reporting. CONSIGN is a web-based tool inclusive of seven steps that guide the user through control comparator design. The tool was refined through multiple rounds of pilot testing that included more than 130 people working in neurorehabilitation research. Four hypothetical exemplar trials, which span preclinical, mood, aphasia, and motor recovery, demonstrate how the tool can be applied in practice. Six consensus recommendations are defined that span research domains, professional disciplines, and international borders.</p

The Armeo Spring as training tool to improve upper limb functionality in multiple sclerosis: a pilot study

<p>Abstract</p> <p>Background</p> <p>Few research in multiple sclerosis (MS) has focused on physical rehabilitation of upper limb dysfunction, though the latter strongly influences independent performance of activities of daily living. Upper limb rehabilitation technology could hold promise for complementing traditional MS therapy. Consequently, this pilot study aimed to examine the feasibility of an 8-week mechanical-assisted training program for improving upper limb muscle strength and functional capacity in MS patients with evident paresis.</p> <p>Methods</p> <p>A case series was applied, with provision of a training program (3×/week, 30 minutes/session), supplementary on the customary maintaining care, by employing a gravity-supporting exoskeleton apparatus (Armeo Spring). Ten high-level disability MS patients (Expanded Disability Status Scale 7.0-8.5) actively performed task-oriented movements in a virtual real-life-like learning environment with the affected upper limb. Tests were administered before and after training, and at 2-month follow-up. Muscle strength was determined through the Motricity Index and Jamar hand-held dynamometer. Functional capacity was assessed using the TEMPA, Action Research Arm Test (ARAT) and 9-Hole Peg Test (9HPT).</p> <p>Results</p> <p>Muscle strength did not change significantly. Significant gains were particularly found in functional capacity tests. After training completion, TEMPA scores improved (<it>p </it>= 0.02), while a trend towards significance was found for the 9HPT (<it>p </it>= 0.05). At follow-up, the TEMPA as well as ARAT showed greater improvement relative to baseline than after the 8-week intervention period (<it>p </it>= 0.01, <it>p </it>= 0.02 respectively).</p> <p>Conclusions</p> <p>The results of present pilot study suggest that upper limb functionality of high-level disability MS patients can be positively influenced by means of a technology-enhanced physical rehabilitation program.</p

Improving the efficiency of clinical trials in multiple sclerosis

BACKGROUND: Phase 3 clinical trials for disease-modifying therapies in relapsing-remitting multiple sclerosis (RRMS) have utilized a limited number of conventional designs with a high degree of success. However, these designs limit the types of questions that can be addressed, and the time and cost required. Moreover, trials involving people with progressive multiple sclerosis (MS) have been less successful. OBJECTIVE: The objective of this paper is to discuss complex innovative trial designs, intermediate and composite outcomes and to improve the efficiency of trial design in MS and broaden questions that can be addressed, particularly as applied to progressive MS. METHODS: We held an international workshop with experts in clinical trial design. RESULTS: Recommendations include increasing the use of complex innovative designs, developing biomarkers to enrich progressive MS trial populations, prioritize intermediate outcomes for further development that target therapeutic mechanisms of action other than peripherally mediated inflammation, investigate acceptability to people with MS of data linkage for studying long-term outcomes of clinical trials, use Bayesian designs to potentially reduce sample sizes required for pediatric trials, and provide sustained funding for platform trials and registries that can support pragmatic trials. CONCLUSION: Novel trial designs and further development of intermediate outcomes may improve clinical trial efficiency in MS and address novel therapeutic questions