The effect of altering a single component of a rehabilitation programme on the functional recovery of stroke patients: a systematic review and meta-analysis

OBJECTIVE: To evaluate the effect of altering a single component of a rehabilitation programme (e.g. adding bilateral practice alone) on functional recovery after stroke, defined using a measure of activity.

DATA SOURCES: A search was conducted of Medline/Pubmed, CINAHL and Web of Science.

REVIEW METHODS: Two reviewers independently assessed eligibility. Randomized controlled trials were included if all participants received the same base intervention, and the experimental group experienced alteration of a single component of the training programme. This could be manipulation of an intrinsic component of training (e.g. intensity) or the addition of a discretionary component (e.g. augmented feedback). One reviewer extracted the data and another independently checked a subsample (20%). Quality was appraised according to the PEDro scale.

RESULTS: Thirty-six studies (n = 1724 participants) were included. These evaluated nine training components: mechanical degrees of freedom, intensity of practice, load, practice schedule, augmented feedback, bilateral movements, constraint of the unimpaired limb, mental practice and mirrored-visual feedback. Manipulation of the mechanical degrees of freedom of the trunk during reaching and the addition of mental practice during upper limb training were the only single components found to independently enhance recovery of function after stroke.

CONCLUSION: This review provides limited evidence to support the supposition that altering a single component of a rehabilitation programme realises greater functional recovery for stroke survivors. Further investigations are required to determine the most effective single components of rehabilitation programmes, and the combinations that may enhance functional recovery.

Functional expression of thermo-sensitive TRP channels in human odontoblasts

Introduction: Accumulating evidence supports a role for odontoblasts in initiating tooth pain, however direct ionic mechanisms underlying dentine nociceptive function remain unclear. The transient receptor potential (TRP) ion channels are directly related to cellular mechanisms of nociception and thermo-sensitive function but their expression by human odontoblasts remains to be determined. Objectives: To investigate the expression and functionality of the thermo-sensitive TRP channels TRPV1, TRPV4, TRPM8 and TRPA1 in human odontoblasts. Methods: Human odontoblasts were derived from dental pulp of immature permanent third molars by explant method. Cell lysates of odontoblasts were subject to SDS- polyacrylamide gel electrophoresis and proteins were blotted onto nitrocellulose membranes. Blots were probed with primary antibodies to TRPA1, TRPM8, TRPV4 and TRPV1. Detection of bound primary antibodies was achieved using appropriate anti-species antibody conjugates and chemiluminescent substrates. Functionality of the channels was determined with Ca2+ microfluorimetry, where cells grown in cover slips and incubated with Fura 2AM prior to stimulation with capsaicin (TRPV1 agonist), 4 alpha-phorbol 12,13-didecanoate (4áPDD) (TRPV4 agonist), icilin (TRPA1 agonist) and menthol (TRPM8 agonist). Emitted fluorescence was measured and the fluorescence ratio (R) was calculated as F340/F380 to determine the level of [Ca2+]i. Results: Western blotting confirmed the molecular localisation of thermo-sensitive TRP channels in human odontoblasts. Functionality assays revealed increase in [Ca2+]i in response to capsacin, icillin, methanol and 4áPDD indicating functional expression of TRPV1, TRPA1, TRPM8 and TRPV4 respectively. Conclusions: Functional expression of thermo-sensitive TRP channels in human odontoblasts may indicate a crucial role for odontoblasts in thermally induced dental pain. (Supported by a Research Grant from the Royal College of Surgeons of Edinburgh)

Functional expression of TRPV4 in human periodontal ligament cells

Background: Periodontal ligament (PDL) cells are exposed to physical forces in vivo in response to mastication, parafunction, speech and orthodontic tooth movement. Although it has been shown that PDL cells perceive and respond directly to mechanical stimulation, the nature of the ion channels that mediate this mechanotransduction remain to be fully elucidated. The transient receptor potential (TRP) superfamily of ion channels is believed to play a critical role in sensory physiology, where they act as transducers for thermal, chemical and mechanical stimuli. Recent studies have shown that members of the vanilloid (TRPV) and ankyrin (TRPA) subfamilies encode mechanosensitive TRPs. The vanilloid family member TRPV4 is one such non selective calcium permeable cationic channel which has been shown to be activated by chemical ligands, hypotonicity, and mechanical stimuli. Objectives: The objective of the current study was to investigate functional expression of TRPV4 in cultured human PDL cells. Methods: Human PDL cells were grown in Dulbecco's Modified Eagle Medium with L-glutamine supplemented with 10% fetal bovine serum (FBS), 100UI/ml penicillin and 100μg/ml streptomycin. Cells in passage 4-6 were used in all experiments. TRPV4 functional expression was determined using ratiometric calcium imaging. Cultured cells were loaded with intracellular Ca2+ probe fura-2 and cells were then stimulated with the TRPV4 agonists, 4alpha-phorbol 12,13-didecanoate (4alpha-PDD), GSK1016790A or hypotonic solution. The TRPV4 antagonist RN 1734 was used to block the corresponding agonist responses. Results: PDL fibroblasts responded to application of TRPV4 agonists and hypotonic stimuli by an increase in intracellular calcium which was attenuated in the presence of the TRPV4 antagonist. Conclusions: We have shown for the first time the functional expression of the mechanosensitive TRPV4 channel in human PDL cells. The molecular identity and mechanisms of activation of mechanosensitive TRP channels in PDL cells merit further investigation.

Test-retest variability in structural and functional parameters of glaucoma damage in the glaucoma imaging longitudinal study.

PURPOSE:

To determine the test-retest variability in perimetric, optic disc, and macular thickness parameters in a cohort of treated patients with established glaucoma.

PATIENTS AND METHODS:

In this cohort study, the authors analyzed the imaging studies and visual field tests at the baseline and 6-month visits of 162 eyes of 162 participant in the Glaucoma Imaging Longitudinal Study (GILS). They assessed the difference, expressed as the standard error of measurement, of Humphrey field analyzer II (HFA) Swedish Interactive Threshold Algorithm fast, Heidelberg retinal tomograph (HRT) II, and retinal thickness analyzer (RTA) parameters between the two visits and assumed that this difference was due to measurement variability, not pathologic change. A statistically significant change was defined as twice the standard error of measurement.

RESULTS:

In this cohort of treated glaucoma patients, it was found that statistically significant changes were 3.2 dB for mean deviation (MD), 2.2 for pattern standard deviation (PSD), 0.12 for cup shape measure, 0.26 mm for rim area, and 32.8 microm and 31.8 microm for superior and inferior macular thickness, respectively. On the basis of these values, it was estimated that the number of potential progression events detectable in this cohort by the parameters of MD, PSD, cup shape measure, rim area, superior macular thickness, and inferior macular thickness was 7.5, 6.0, 2.3, 5.7, 3.1, and 3.4, respectively.

CONCLUSIONS:

The variability of the measurements of MD, PSD, and rim area, relative to the range of possible values, is less than the variability of cup shape measure or macular thickness measurements. Therefore, the former measurements may be more useful global measurements for assessing progressive glaucoma damage.