Water-based therapeutic exercise in stroke: a scoping review.

PURPOSE: To (1) describe the state of the literature on water-based therapeutic exercise (WBTE) for people living with stroke, (2) describe the content and structure of interventions, (3) summarize the effects of interventions described in the literature, and (4) identify gaps in the literature limiting application and implementation. MATERIALS AND METHODS: Scoping review methodology described by Arksey and O'Malley (2005) and Levac et al. (2010). Electronic databases were searched for articles with eligibility criteria including: (1) adult stroke survivors (18 years or older) of any type (ischemic/hemorrhagic) or stage (acute/chronic) in any setting, and (2) the study intervention involved WBTE to address a post-stroke deficit. RESULTS: 40 articles were included in this review. Five trials had a treatment control, 20 had an active comparison. Calculated intervention effect sizes demonstrated a strong effect of WBTE on balance and gait related outcomes in 80% of controlled and comparison trials. CONCLUSIONS: This scoping review highlights common parameters of WBTE interventions and provides an inventory of the differences in the treatment approaches utilized in this population. Opportunities for future work include the development of a standardized treatment protocol, qualitative or mixed methodology research, and greater inclusion of more individuals with more severe stroke-related impairments. IMPLICATIONS FOR REHABILITATIONWater-based therapeutic exercise is an approach that may allow stroke survivors to carry out challenging activities in a safe and accessible environment.Water-based interventions for stroke survivors appear to have a beneficial impact on walking and balance.Given that an aquatic environment offers an opportunity for individuals with more significant physical impairments to carry out early practice of walking and balance related tasks, clinicians should explore the feasibility and effectiveness for this subset of stroke survivors.

Regulation of the strypsin-related proteinase ISP2 by progesterone in endometrial gland epithelium during implantation in mice.

Hormones prepare the uterus for the arrival and subsequent invasion of the embryo during pregnancy. Extracellular matrix-degrading proteinases and their inhibitors are involved in this integration process. Recent genetic evidence indicates that there is redundancy within the implantation proteinase cascade, indicating that additional proteinases may be involved. Recently, we described a novel implantation serine proteinase (ISP1) gene that encodes the embryo-derived enzyme strypsin, which is necessary for blastocyst hatching in vitro and the initiation of invasion. The evidence presented in the present study indicates that a second proteinase secreted from the uterus also participates in lysis of the zona pellucida. A second implantation serine proteinase gene (ISP2) was isolated, which encodes a related secreted tryptase expressed specifically within uterine endometrial glands. In pseudopregnancy, ISP2 gene expression is dependent on progesterone priming and is inhibited by the antiprogestin RU486. On the basis of similarities between ISP2 gene expression and that of a progesterone-regulated luminal proteinase associated with lysis of the zona pellucida, it is possible that the strypsin-related protein, ISP2, may encode a zona lysin proteinase.

A novel murine tryptase involved in blastocyst hatching and outgrowth.

Before implantation the blastocyst is maintained within a proteinaceous coat, the zona pellucida, which prevents polyspermy and ectopic pregnancy. An extracellular trypsin-like activity, which is necessary for hatching from the zona pellucida in vitro, is localized to the abembryonic pole of the blastocyst. Upon hatching, the extracellular matrix-degrading proteinases urokinase plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP-9) are thought to promote blastocyst invasion. However, gene disruption experiments have demonstrated that uPA and MMP-9 are dispensable and, thus, that other key enzymes are involved in implantation. In this study, a novel implantation serine proteinase (ISP1) gene, which is distantly related to haematopoietic tryptases and represents a novel branch of the S1 proteinase family, was cloned. ISP1 is expressed throughout morulae and blastocysts during hatching and outgrowth. Abrogation of ISP1 mRNA accumulation using antisense oligodeoxynucleotides disrupts blastocyst hatching and outgrowth in vitro. The results of this study indicate that the ISP1 gene probably encodes the long sought after 'hatching enzyme' that is localized to the abembryonic pole during hatching in vitro. ISP1 is the earliest embryo-specific proteinase to be expressed in implantation and may play a critical role in connecting embryo hatching to the establishment of implantation competence at the abembryonic pole of the blastocyst.

ES cell neural differentiation reveals a substantial number of novel ESTs.

We have used a method for synchronously differentiating murine embryonic stem (ES) cells into functional neurons and glia in culture. Using subtractive hybridization we isolated approximately 1200 cDNA clones from ES cell cultures at the neural precursor stage of neural differentiation. Pilot studies indicated that this library is a good source of novel neuro-embryonic cDNA clones. We therefore screened the entire library by single-pass sequencing. Characterization of 604 non-redundant cDNA clones by BLAST revealed 96 novel expressed sequence tags (ESTs) and an additional 197 matching uncharacterized ESTs or genomic clones derived from genome sequencing projects. With the exception of a handful of genes, whose functions are still unclear, most of the 311 known genes identified in this screen are expressed in embryonic development and/or the nervous system. At least 80 of these genes are implicated in disorders of differentiation, neural development and/or neural function. This study provides an initial snapshot of gene expression during early neural differentiation of ES cell cultures. Given the recent identification of human ES cells, further characterization of these novel and uncharacterized ESTs has the potential to identify genes that may be important in nervous system development, physiology and disease.

Murine subtilisin-like proteinase SPC6 is expressed during embryonic implantation, somitogenesis, and skeletal formation.

During mammalian embryogenesis, proteinases are important for both matrix remodeling and the activation of latent growth factors. As subtilisin-like prohormone convertases (SPCs) have recently been found to activate members of the matrix metalloproteinase and transforming growth factor-beta (TGF-beta) families, we sought to investigate the role of this gene family in murine implantation and embryogenesis. Using active site polymerase chain reaction (PCR) cloning, four members of the SPC family were identified at embryonic day 6.5: SPC1, SPC2, SPC3, and SPC6. In situ hybridization analysis of sectioned E6.5 embryos in utero demonstrated strong SPC6 expression in differentiated decidua, overlapping and extending beyond the region previously described for the metalloproteinase inhibitor TIMP-2. Lower levels of SPC6 expression were observed in trophoblasts and in the ectoplacental cone, suggesting multiple roles for this enzyme in implantation. Northern analysis showed that SPC6 mRNA in embryos is represented by two distinct sizes of message--the isoform SPC6-1 (3.0 kb) is most abundant at all stages, but significant levels of SPC6-b (6.0 kb) occur in E12.5 embryos. Whole mount in situ hybridization to E8.5 embryos demonstrated strong SPC6 expression in the most posterior somite. This somitic staining moved caudally with the developing embryo and by E10.5 became localized to the posterior of the tail, indicating that SPC6 is involved in somitogenesis. SPC6 was expressed at low levels throughout the embryo, except in the developing nervous system, and strong expression was observed in the first branchial arch and in skeletal regions of the developing vertebrae, limbs, and craniofacium, suggesting additional roles for SPC6 in skeletogenesis.

Kinetic characterization of dihydrofolate reductase from Drosophila melanogaster.

The kinetic characteristics of a purified insect dihydrofolate reductase (DHFR) have been described. The Km values for the substrate dihydrofolate and the cofactor NADPH have been estimated by primary and secondary Hanes plots to be 0.3 and 5.2 microM, respectively. Drosophila melanogaster DHFR can use folate and NADH at acidic pH values, but at a much lower rate than the preferred substrate and cofactor. Folic acid is a partial competitive inhibitor of Drosophila DHFR (Ki = 0.4 microM) and trimethoprim is a complete competitive inhibitor (Ki = 5.4 microM). Methotrexate binds less tightly to the Drosophila enzyme than to many other DHFRs (Kd = 0.9 nM). Drosophila DHFR is inhibited by KCl and organic mercurials and is slightly activated by urea. These data indicate that Drosophila DHFR has some characteristics which are typical of vertebrate DHFRs and others which are typical of prokaryotic DHFRs. The study of this enzyme, therefore, should aid in the definition of the structural features that are responsible for the kinetic characteristics in different DHFRs.

The purification of dihydrofolate reductase from Drosophila melanogaster.

Dihydrofolate reductase (DHFR) has been purified over 30,000-fold from Drosophila adults with a yield of 35%, using a combination of low pH extraction, (NH4)2SO4 precipitation, Sephadex gel filtration, Affi-Gel blue affinity chromatography, ion exchange and gel filtration FPLC. The Drosophila enzyme is a soluble, 17-22 kDa monomeric protein displaying the two pH optima characteristic of eukaryotic DHFRs. The sequence of the first 23 amino acids from the amino-terminal end of the protein shows that Drosophila DHFR is more homologous to the mosquito and vertebrate DHFRs than to the prokaryotic enzymes. However, the percent similarity between the two insect enzymes is not as close as expected when compared to the virtually identical initial sequence conservation of mammalian DHFRs.