Effects of augmented exercise therapy time after stroke: a meta-analysis

<p><b>Background and Purpose:</b> To present a systematic review of studies that addresses the effects of intensity of augmented exercise therapy time (AETT) on activities of daily living (ADL), walking, and dexterity in patients with stroke.</p> <p><b>Summary of Review:</b> A database of articles published from 1966 to November 2003 was compiled from MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, PEDro, DARE, and PiCarta using combinations of the following key words: stroke, cerebrovascular disorders, physical therapy, physiotherapy, occupational therapy, exercise therapy, rehabilitation, intensity, dose–response relationship, effectiveness, and randomized controlled trial. References presented in relevant publications were examined as well as abstracts in proceedings. Studies that satisfied the following selection criteria were included: (1) patients had a diagnosis of stroke; (2) effects of intensity of exercise training were investigated; and (3) design of the study was a randomized controlled trial (RCT). For each outcome measure, the estimated effect size (ES) and the summary effect size (SES) expressed in standard deviation units (SDU) were calculated for ADL, walking speed, and dexterity using fixed and random effect models. Correlation coefficients were calculated between observed individual effect sizes on ADL of each study, additional time spent on exercise training, and methodological quality. Cumulative meta-analyses (random effects model) adjusted for the difference in treatment intensity in each study was used for the trials evaluating the effects of AETT provided. Twenty of the 31 candidate studies, involving 2686 stroke patients, were included in the synthesis. The methodological quality ranged from 2 to 10 out of the maximum score of 14 points. The meta-analysis resulted in a small but statistically significant SES with regard to ADL measured at the end of the intervention phase. Further analysis showed a significant homogeneous SES for 17 studies that investigated effects of increased exercise intensity within the first 6 months after stroke. No significant SES was observed for the 3 studies conducted in the chronic phase. Cumulative meta-analysis strongly suggests that at least a 16-hour difference in treatment time between experimental and control groups provided in the first 6 months after stroke is needed to obtain significant differences in ADL. A significant SES supporting a higher intensity was also observed for instrumental ADL and walking speed, whereas no significant SES was found for dexterity.</p> <p><b>Conclusion:</b> The results of the present research synthesis support the hypothesis that augmented exercise therapy has a small but favorable effect on ADL, particularly if therapy input is augmented at least 16 hours within the first 6 months after stroke. This meta-analysis also suggests that clinically relevant treatment effects may be achieved on instrumental ADL and gait speed.</p&gt

Quality of life in Type 1 (insulin-dependent) diabetic patients prior to and after pancreas and kidney transplantation in relation to organ function

Improvement of the quality of life in Type 1 (insulin-dependent) diabetic patients with severe late complications is one of the main goals of pancreas and/or kidney grafting. To assess the influences of these treatment modalities on the different aspects of the quality of life a cross-sectional study in 157 patients was conducted. They were categorized into patients pre-transplant without dialysis (n=29; Group A), pre-transplant under dialysis (n=44; Group B), post-transplant with pancreas and kidney functioning (n=31; Group C), post-transplant with functioning kidney, but insulin therapy (n=29; Group D), post-transplant under dialysis and insulin therapy again (n=15; Group E) and patients after single pancreas transplantation and rejection, with good renal function, but insulin therapy (n=9; Group F). All patients answered a mailed, self-administered questionnaire (217 questions) consisting of a broad spectrum of rehabilitation criteria. The results indicate a better quality of life in Groups C and D as compared to the other groups. In general the scores are highest in C, but without any significant difference to D. Impressive significant differences between C or D and the other groups were found especially in their satisfaction with physical capacity, leisure-time activities or the overall quality of life. The satisfaction with the latter is highest in C (mean±SEM: 4.0±0.2 on a 1 to 5-rating scale; significantly different from A: 3.1±0.1, B: 2.7±0.2 and E: 2.6±0.3; p<0.01), followed by D (3.8±0.2; significantly different from B and E; p<0.01). Group F shows a mean of 3.1±0.4, which is not significantly different from C. The percentages of patients in each group, who are not working: A: 38 %, B: 64 %, C: 74 %, D: 66 %, E: 87 % and F: 78 % indicate that there is no marked improvement in the vocational situation after successful grafting

Apoptosis is not conserved in plants as revealed by critical examination of a model for plant apoptosis-like cell death

Background: Animals and plants diverged over one billion years ago and evolved unique mechanisms for many cellular processes, including cell death. One of the most well-studied cell death programmes in animals, apoptosis, involves gradual cell dismantling and engulfment of cellular fragments, apoptotic bodies, through phagocytosis. However, rigid cell walls prevent plant cell fragmentation and thus apoptosis is not applicable for executing cell death in plants. Furthermore, plants are devoid of the key components of apoptotic machinery, including phagocytosis as well as caspases and Bcl-2 family proteins. Nevertheless, the concept of plant "apoptosis-like programmed cell death" (AL-PCD) is widespread. This is largely due to superficial morphological resemblances between plant cell death and apoptosis, and in particular between protoplast shrinkage in plant cells killed by various stimuli and animal cell volume decrease preceding fragmentation into apoptotic bodies.Results: Here, we provide a comprehensive spatio-temporal analysis of cytological and biochemical events occurring in plant cells subjected to heat shock at 40-55 degrees C and 85 degrees C, the experimental conditions typically used to trigger AL-PCD and necrotic cell death, respectively. We show that cell death under both conditions was not accompanied by membrane blebbing or formation of apoptotic bodies, as would be expected during apoptosis. Instead, we observed instant and irreversible permeabilization of the plasma membrane and ATP depletion. These processes did not depend on mitochondrial functionality or the presence of Ca2+ and could not be prevented by an inhibitor of ferroptosis. We further reveal that the lack of protoplast shrinkage at 85 degrees C, the only striking morphological difference between cell deaths induced by 40-55 degrees C or 85 degrees C heat shock, is a consequence of the fixative effect of the high temperature on intracellular contents.Conclusions: We conclude that heat shock-induced cell death is an energy-independent process best matching definition of necrosis. Although the initial steps of this necrotic cell death could be genetically regulated, classifying it as apoptosis or AL-PCD is a terminological misnomer. Our work supports the viewpoint that apoptosis is not conserved across animal and plant kingdoms and demonstrates the importance of focusing on plant-specific aspects of cell death pathways

SPIRO- the automated Petri plate imaging platform designed by biologists, for biologists

Phenotyping of model organisms grown on Petri plates is often carried out manually, despite the procedures being time-consuming and laborious. The main reason for this is the limited availability of automated phenotyping facilities, whereas constructing a custom automated solution can be a daunting task for biologists. Here, we describe SPIRO, the Smart Plate Imaging Robot, an automated platform that acquires time-lapse photographs of up to four vertically oriented Petri plates in a single experiment, corresponding to 192 seedlings for a typical root growth assay and up to 2500 seeds for a germination assay. SPIRO is catered specifically to biologists' needs, requiring no engineering or programming expertise for assembly and operation. Its small footprint is optimized for standard incubators, the inbuilt green LED enables imaging under dark conditions, and remote control provides access to the data without interfering with sample growth. SPIRO's excellent image quality is suitable for automated image processing, which we demonstrate on the example of seed germination and root growth assays. Furthermore, the robot can be easily customized for specific uses, as all information about SPIRO is released under open-source licenses. Importantly, uninterrupted imaging allows considerably more precise assessment of seed germination parameters and root growth rates compared with manual assays. Moreover, SPIRO enables previously technically challenging assays such as phenotyping in the dark. We illustrate the benefits of SPIRO in proof-of-concept experiments which yielded a novel insight on the interplay between autophagy, nitrogen sensing, and photoblastic response

Filling in the gaps: a road map to establish a model system to study developmental programmed cell death

Only a handful of model systems for studying programmed cell death (PCD) exist. The model Arabidopsis thaliana has generated a plethora of knowledge, but it is essential to introduce new models to broaden our understanding of the commonalities of PCD. This review focuses on Aponogeton madagascariensis (the lace plant) as a choice model to study PCD in vivo. PCD plays a key role in plant development and defence. Thus, identifying key regulators across plants is a priority in the field. The formation of perforations in lace plant leaves in areas called areoles is a striking example of PCD. Cells undergoing PCD within areoles can be easily identified from a loss of their anthocyanin pigmentation. In contrast, cells adjacent to veins, non-PCD cells, retain anthocyanins, creating a gradient of cell death. The spatiotemporal pattern of perforation formation, a gradient of cell death within areoles, and the availability of axenic cultures provide an excellent in vivo system to study mechanisms of developmental PCD. The priorities to further develop this model involve sequencing the genome, establishing transformation protocols, and identifying anthocyanin species to determine their medicinal properties. We discuss practical methodologies and challenges associated with developing the lace plant as a model to study PCD

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally

Global Transcriptomic Profiling Using Small Volumes of Whole Blood: A Cost-Effective Method for Translational Genomic Biomarker Identification in Small Animals

Blood is an ideal tissue for the identification of novel genomic biomarkers for toxicity or efficacy. However, using blood for transcriptomic profiling presents significant technical challenges due to the transcriptomic changes induced by ex vivo handling and the interference of highly abundant globin mRNA. Most whole blood RNA stabilization and isolation methods also require significant volumes of blood, limiting their effective use in small animal species, such as rodents. To overcome these challenges, a QIAzol-based RNA stabilization and isolation method (QSI) was developed to isolate sufficient amounts of high quality total RNA from 25 to 500 μL of rat whole blood. The method was compared to the standard PAXgene Blood RNA System using blood collected from rats exposed to saline or lipopolysaccharide (LPS). The QSI method yielded an average of 54 ng total RNA per μL of rat whole blood with an average RNA Integrity Number (RIN) of 9, a performance comparable with the standard PAXgene method. Total RNA samples were further processed using the NuGEN Ovation Whole Blood Solution system and cDNA was hybridized to Affymetrix Rat Genome 230 2.0 Arrays. The microarray QC parameters using RNA isolated with the QSI method were within the acceptable range for microarray analysis. The transcriptomic profiles were highly correlated with those using RNA isolated with the PAXgene method and were consistent with expected LPS-induced inflammatory responses. The present study demonstrated that the QSI method coupled with NuGEN Ovation Whole Blood Solution system is cost-effective and particularly suitable for transcriptomic profiling of minimal volumes of whole blood, typical of those obtained with small animal species

The Role of Quantitative Pharmacology in an Academic Translational Research Environment

Translational research is generally described as the application of basic science discoveries to the treatment or prevention of disease or injury. Its value is usually determined based on the likelihood that exploratory or developmental research can yield effective therapies. While the pharmaceutical industry has evolved into a highly specialized sector engaged in translational research, the academic medical research community has similarly embraced this paradigm largely through the motivation of the National Institute of Health (NIH) via its Roadmap initiative. The Clinical and Translational Science Award (CTSA) has created opportunities for institutions which can provide the multidisciplinary environment required to engage such research. A key component of the CTSA and an element of both the NIH Roadmap and the FDA Critical Path is the bridging of bench and bedside science via quantitative pharmacologic relationships. The infrastructure of the University of Pennsylvania/Children’s Hospital of Philadelphia CTSA is highlighted relative to both research and educational objectives reliant upon quantitative pharmacology. A case study, NIH-sponsored research program exploring NK1r antagonism for the treatment NeuroAIDS is used to illustrate the application of quantitative pharmacology in a translational research paradigm

Reflectivity, Reflexivity, Reflexivism: IR's 'Reflexive Turn' - and Beyond

The notion of ‘reflexivity’ has been so intimately tied to the critique of positivism and empiricism in International Relations (IR) that the emergence of post-positivism has naturally produced the anticipation of a ‘reflexive turn’ in IR theory. Three decades after the launch of the post-positivist critique, however, reflexive IR has failed to impose itself as either a clear or serious contender to mainstream scholarship. Reasons for this failure include: the proliferation of different understandings of ‘reflexivity’ in IR theory that entail significantly different projects and concerns for IR scholarship; the equation of ‘reflexive theory’ with ‘critical’ and ‘emancipatory theory’ and the consequent confusion of ethical/normative issues with strictly epistemic/theoretical ones; and the refusal to consider reflexive IR as a ‘research programme’ concerned with empirical knowledge, not just meta-explanation. The development of reflexivity in IR theory as a sustainable cognitive and praxeological effort is nonetheless possible — and still needed. This article suggests what taking the ‘reflexive turn’ would really entail for IR.</jats:p

Re-visualising international relations:Audio-visual projects and direct encounters with the political in security studies tla

In this paper we discuss how an innovative audio-visual project was adopted to foster active, rather than declarative learning, in critical International Relations (IR). First, we explore the aesthetic turn in IR, to contrast this with forms of representation that have dominated IR scholarship. Second, we describe how students were asked to record short audio or video projects to explore their own insights through aesthetic and non-written formats. Third, we explain how these projects are understood to be deeply embedded in social science methodologies. We cite our inspiration from applying a personal sociological imagination, as a way to counterbalance a ‘marketised’ slant in higher education, in a global economy where students are often encouraged to consume, rather than produce knowledge. Finally, we draw conclusions in terms of deeper forms of student engagement leading to new ways of thinking and presenting new skills and new connections between theory and practice