During phase III, the gait length coefficient of variability was

During phase III, the gait length coefficient of variability was increased ∼30% at 10 months of age, and the time allotted for braking in each stride was shortened by 40% and the paw angle was increased by 50% at 11 months of age of Shh-nLZC/C/Dat-Cre mice relative to controls ( Figure 4C and Supplemental Results D; see Table S1for all indices of gait analyzed). We then

tested whether drugs efficacious in the management of PD would modify the locomotion abnormalities of Shh-nLZC/C/Dat-Cre mice. We systemically injected L-DOPA (dopamine precursor) trihexylphenidate (THP) (muscarinic antagonist), or vehicle 30 min prior to the analysis of locomotion in 12-month-old Shh-nLZC/C/Dat-Cre and control mice. The increased Lumacaftor in vitro variability in stride length was normalized by L-DOPA and THP, brake stride ratios were normalized by THP but not L-DOPA, and alterations in paw angles were normalized by L-DOPA, but not THP ( Figure 4D). Taken together, our behavioral studies revealed a dynamic and progressive locomotion phenotype whose pharmacological responsiveness Rucaparib suggests underlying alterations in the functional balance

of dopaminergic and cholinergic neurotransmission. Similarly to BDNF, which supports survival of cortical-striatal neurons (Baquet et al., 2004), Shh can also be transported anterogradely through axons (Thérond, 2012). Because of the lack of evidence for an autocrine mechanism for Shh dependent support of DA neurons we therefore hypothesized that Shh signaling from dopaminergic projections to striatal targets might be of relevance to the maintenance of DA neurons. We found that ∼25% of all Ptc1+ cells in the striatum are neurons (Figures 5A–5C) and that 6% of all striatal neurons coexpress Ptc1 (Figure 5F). Conversely, 100% of all ACh neurons and 98% of all FS interneurons express Ptc1 (Figures 5D–5F), consistent with the relative prevalence of ACh and FS neurons among all striatal neuronal subtypes (Bolam et al., 2006). Hence, our expression data suggested that mesencephalic DA neurons could communicate by Shh signaling selectively with all ACh

and FS neurons, and nonneuronal cells among their projection targets in the adult striatum. In Shh-nLZC/C/Dat-Cre mice compared to controls at 6 months of age, we observed a reduction in the number of ChAT+ neurons in the striatum that over was most pronounced in lateral/anterior aspects of the dorsal striatum ( Figures 5G and S4A–S4C). ACh and FS interneurons make up together only ∼6% of total striatal neurons ( Figure 5F) and are locally projecting. These attributes make it impossible to distinguish neuronal loss from downregulation of phenotypic marker expression by the quantitation of the total number of neurons or the exploitation of specific projection patterns. However, the main striatal cell populations can be identified based on cell type specific perinuclear staining patterns that can be visualized by the DNA intercalating dye ToPro3 ( Figures S5A–S5C).

Our previous

work showed that each of five distinct neuro

Our previous

work showed that each of five distinct neurodegenerative syndromes featured an atrophy pattern that mirrored the healthy functional ICN seeded by the cortical region most atrophied in patients with that syndrome (Seeley et al., 2009). The present study, in contrast, examined every brain region within the five disease-related atrophy selleck products maps to identify the regions whose connectivity pattern in health most resembled the atrophy map seen in each syndrome (see Figure 2 for a methods schematic). The resulting dataset fully specified the node pair connectivity strengths across all regions atrophied in any of the five diseases; collectively, these regions traversed most cerebral cortical and subcortical structures. With this information in hand, we used graph theoretical analyses to test model-based predictions of how network architecture in health relates to disease-associated tissue loss (Figure 1). Although previously described spatial atrophy patterns (Seeley et al., 2009) specified the brain regions interrogated for the current study, all network connectivity analyses were performed on an independent dataset of 16 healthy subjects aged 57 to 70 (8 females, all right-handed and psychoactive medication-free; see Experimental Procedures). The resulting connectivity patterns and graph metrics were used to relate each region’s healthy connectivity profile to that region’s disease-specific vulnerability,

defined as its atrophy severity in patients. In previous work (Seeley tuclazepam et al., 2009), we identified Tenofovir cost regional atrophy maxima for five neurodegenerative syndromes: Alzheimer’s disease (AD), behavioral variant frontotemporal dementia (bvFTD), semantic

dementia (SD), progressive nonfluent aphasia (PNFA), and corticobasal syndrome (CBS). Then, using healthy subjects scanned with task-free fMRI, we used these five atrophy maxima as “seed” regions to derive five ICNs, representing regions whose blood-oxygen level-dependent (BOLD) signal time-series significantly correlated with that of the seed. The atrophy maxima seeded ICNs that resembled the parent atrophy maps, supporting the view that neurodegenerative disease patterns are network based. By studying only one seed region per atrophy pattern, however, this approach could not determine which regions featured maximal connectivity to the other vulnerable regions. We anticipated that each disease-associated pattern would harbor focal “epicenters,” regions whose connectivity patterns—in the healthy brain—most closely mirrored the disease vulnerability pattern. To seek out these epicenters, here we took a more comprehensive, data-driven approach by studying all regions within each of the five atrophy patterns. For example (Figure 2), we created 1,128 4 mm radius spherical regions of interest (ROIs) covering the entire bvFTD atrophy pattern and built 1,128 functional ICN maps, one seeded by each ROI, for each of our 16 healthy subjects.

Neurofilament compaction is an early event caused by calpain-medi

Neurofilament compaction is an early event caused by calpain-mediated proteolysis of neurofilament side arms or phosphorylation. Calcium influx triggers microtubule disassembly (Giza and Hovda, 2001; Barkhoudarian et al., 2011). Cytoskeletal pathology may have several mediators. In animal trauma models of axonal pathology,

calcium homeostasis disruption results in calpain-mediated Ku-0059436 concentration proteolytic degradation of essential cytoskeletal proteins, such as neurofilament proteins. Calcium homeostasis is the primary regulator of calpain activation; disruption leads to increased intracellular-free calcium (McCracken et al., 1999; McGinn et al., 2009; Saatman et al., 2010). Microtubule disorganization may be a direct effect of dynamic axon stretching. Ultrastructural analysis of axons displays immediate

breakage and buckling of microtubules postinjury, which triggers progressive microtubule disassembly (Tang-Schomer et al., 2010). This results in accumulation of organelles that are transported in the axon, and axonal swelling called axonal retraction balls, with eventual disconnection and axotomy (Giza and Hovda, 2001; Barkhoudarian et al., 2011). Neuronal damage with axonal bulbs and swellings is most commonly located in the cortical sulci at the interface between gray and white matter (Chen et al., 2004). MRI studies that use DTI show that the extent of DAI after mild TBI is related to postconcussion cognitive problems (Lipton et al., 2008; Niogi et al., 2008; Wilde et al., 2008). Protein Tyrosine Kinase inhibitor As early as the 1970s, Corsellis et al. (1973) reported neurofibrillary tangles in neocortical areas in boxers with CTE. Several studies have since confirmed these findings of extensive tangle pathology in postmortem studies (Dale et al., 1991; Tokuda et al., 1991; Schmidt et al., 2001; Hof et al., 1992; Geddes et al., 1996). In addition to neurofibrillary tangles, neuropil treads and glial tangles are also elements of CTE (McKee et al., 2009). Cortical tangles also constitute a key component of Alzheimer’s disease. But because they are found in many

only chronic neurological diseases (Wisniewski et al., 1979) with different etiology, it is possible that they represent a more general response to neurodegenerative pathology. Indeed, their abundance in CTE, which is caused by repeated brain trauma episodes, further supports that they may represent a response to brain damage. Tangles are found intracellularly in the cytoplasm of neurons and consist of thread-like aggregates of hyperphosphorylated tau protein (Grundke-Iqbal et al., 1986). Tau is a normal axonal protein that binds to microtubules via its microtubule-binding domains, thus promoting microtubule assembly and stability. There are six different isoforms of tau, each containing several serine or threonine residues that can be phosphorylated. In AD, tau is frequently found in a hyperphosphorylated form (Figure 2).

(Two additional neurons showed significant firing after the NS bu

(Two additional neurons showed significant firing after the NS but not after the DS, and these were not analyzed.) The difference in DS- and NS-evoked firing was not due to differences in ongoing locomotor behavior during cue excitation because firing also differed in trials in which the locomotor onset

latency was >500 ms; average post-DS firing was 16.1 ± 1.7 spikes/s and post-NS firing was 8.3 ± 1.2 spikes/s (p < 0.001, Wilcoxon test). Consistent with this observation, the onset and peak of the DS-evoked excitation preceded locomotor onset in the vast majority of trials (Figures 2D and S2). To determine whether post-DS firing GSK J4 was time locked to cue onset or to the onset of locomotion, we focused on a subset of correct DS trials with >200 ms separation between cue onset, locomotion, and lever press (median of 21 trials selected per neuron; see Supplemental Experimental Procedures). Aligned ERK activity to cue onset, the greatest change in average firing rate was immediately after the cue (Figure 2D). In contrast,

these same data show little change in firing rate at the time of locomotion onset (Figure 2E) or in relation to lever press or receptacle entry (Figure S2). Consistent with previous reports (Nicola et al., 2004), DS-evoked firing was greater on trials in which an operant response was made (16.8 ± 1.8 spikes/s) compared to when it was absent (12.5 ± 1.7 spikes/s; p < 0.001, Wilcoxon test; n = 54 neurons recorded in sessions with at least one missed DS trial). Thus, because cue-evoked firing consistently preceded locomotor onset and was greater when a reward-seeking response was subsequently made, cue-evoked excitation could influence the initiation or maintenance of cued reward-seeking behavior. We next determined the relationship between cue-evoked firing and the subsequent

reward-seeking movement using a generalized linear model (GLM). We analyzed only the DS trials in which a lever press response was made so that the cue value and the Phosphatidylinositol diacylglycerol-lyase ultimate outcome were identical in every trial. First, we determined which aspects of locomotor behavior to test for a relationship with neural activity. Because the locomotor responses in this task can begin at any point in the behavioral chamber, these movements can be described by many different variables. To select an appropriate set of locomotor features, we first calculated a large and redundant set of locomotor variables for each trial ( Table S1). We then used principal components analysis and factor analysis (PCA/FA) to identify a small number of underlying factors that accounted for the majority (74.2%) of cross-trial variability among all of the locomotor variables ( Table S2; Supplemental Experimental Procedures).

, 2005, Schuske et al , 2003 and Verstreken et al , 2003) To ass

, 2005, Schuske et al., 2003 and Verstreken et al., 2003). To assess the potential occurrence of an endocytic

delay, as expected if endophilin was involved in CCP fission, we performed dynamic assays of endocytosis using a synaptopHluorin-based strategy (Sankaranarayanan and Ryan, 2000). In TKO cells, the time constant of endocytic recovery following a 10 Hz stimulus for 30 s was approximately 2.5-fold slower in TKO (71.4 ± 15.8 s) than in WT (29.3 ± 5.2 s) (Figure 4A). Given sufficient time, however, the signal recovered and synapses could sustain multiple rounds of exo/endocytosis. Similar results were obtained with vGLUT1-pHluorin, this website a chimera of the vesicular glutamate transporter vGLUT1 with pHluorin (Voglmaier et al., 2006) (26.6.5 ± 6.7 s in WT and 82.2 ± 12 s in TKO) (Figure 4B). Thus, although the SH3 domains of endophilin 1 and 3 interact with vGLUT1 (Voglmaier et al., 2006), the defect in the compensatory endocytic recapture of this protein in endophilin TKO cells is not significantly more severe that the defect in the reinternalization of synaptobrevin. In principle, the delayed poststimulus

recovery could be due to a delay in the acidification of the newly formed vesicles. However, a brief exposure to acid medium during the recovery (Sankaranarayanan and Ryan, 2000) demonstrated that the pHluorin responsible for the increased signal remained buy EPZ5676 cell-surface exposed, thus suggesting a bona fide endocytic delay (Figure 4F). The slower kinetics of endocytosis in TKO neurons could be fully rescued by transfection with endophilin

1 (Figures 4B–4E). In contrast, a mutant endophilin 1 construct that contains the BAR domain but that lacks the SH3 domain produced a limited rescue of the endocytic defect, and primarily during the late phase of the recovery (Figures 4B–4E). Because the BAR domain of endophilin for alone is recruited to the CCP neck, a possible interpretation of this partial rescue of endocytosis is a facilitatory and/or stabilizing effect of the overexpressed BAR domain on the vesicle neck. To gain direct insight into whether the endocytic delay observed in TKO cultures was due to a block in fission, we performed electron microscopy (EM). TKO synapses revealed a strikingly different phenotype relative to controls: a reduced number of SVs and a strong accumulation of clathrin-coated vesicular profiles (Figures 5A–5C). Surprisingly, no accumulation of CCPs was observed. In sections of some nerve terminals, nearly the entire pool of SVs had been replaced by clathrin-coated profiles (Figure 5B). Quantification of EM micrographs showed that the mean number of SVs per synapse was substantially lower (39.8%) in TKO than in controls, whereas the number of CCVs had increased more than 31 times (Figures 5F–5I). Similar, but less severe, changes were observed at synapses of DKO neurons (Figures 5F–5I).

A response was deemed a failure if the integrated response area a

A response was deemed a failure if the integrated response area after the flash was less than 64% greater than the integral of the absolute value of the baseline-corrected trace before the flash; the time window for integration was 400 and 600 ms in wild-type and GCAPs−/− rods, respectively. This 64% difference criterion was selected for its empirical robustness: in one test rod, the difference in failure count between using a 50% criterion and a 90% criterion corresponded

to a difference in 38 versus 42 failures out of 155 total responses. The 64% criterion counted 41. The failure count provided an estimate of the number of singletons (ns), using Poisson statistics. We then assumed our singleton population to be the set of ns Nintedanib order nonfailure responses having the smallest amplitudes. The mean singleton and the amplitude c.v. did not vary greatly when the singleton population was altered by the

inclusion of 1–2 additional responses or the exclusion of 1–2 of the largest responses. In addition, the average singleton determined from the set of ns was indistinguishable from that average single click here photon response calculated from variance-to-mean analysis. Likewise, the average of the responses that were deemed failures showed no time-dependent changes in current ( Figures 6A–6B). We elected not to use matched-filter analysis to identify singletons, as this approach assumes that all SPRs have an effectively identical shape combined with broadband noise—an

assumption that begs the question of how the SPR shape would change with variation in R∗ lifetime. Nonetheless, we compared the method used here to the traditional matched filter analysis-histogram method (e.g., Field and Rieke, 2002). We found that the matched filter method had a tendency to produce lower coefficients of variation for both WT and GCAPs−/− singletons, though this difference was not significant (GCAPs−/− c.v.: 0.40 ± 0.02 using matched filter analysis versus 0.42 ± 0.02 using smallest oxyclozanide nonfailures; WT: 0.31 ± 0.03 using matched filter analysis versus 0.34 ± 0.01 using smallest nonfailures). The matched filter analysis identified 246 total wild-type singletons from 5 rods, while the number of singletons expected from the number of identified failures is 263. The corresponding numbers for 4 GCAPs−/− rods are 142 and 152. In sum, matched filter analysis tended to identify fewer responses as singletons, in particular excluding more of the large amplitude responses on the fringe that would escape the boundaries imposed on the singles peak. When these responses are included in the statistical expectation method employed in the paper, they tend to increase the standard deviation. For each rod used for measuring reproducibility, the identified singletons were used to generate the time-dependent average.

, 2011) Nevertheless, known marker genes (Lein et al , 2007) for

, 2011). Nevertheless, known marker genes (Lein et al., 2007) for layers 2/3, 4, 5, 6, and 6b demonstrated high concordance between individual samples and specific layers

(Figure 1B, Belgard et al., 2011). We compared our RNA-seq results with those previously obtained using microarrays for layer 6 and 6b from anterior cortex (putative S1) of postnatal day 8 mice (Hoerder-Suabedissen et al., 2009). RNA-seq levels for samples E and F were highly and significantly concordant with microarray expression levels for layers 6 and 6b despite methodological differences and the difference in age (Supplemental Experimental Procedures): 85% (147 of 173) of genes whose expression click here was found, with microarrays, to be significantly lower in layer 6 versus 6b also showed lower expression in sample E versus F; significant concordance was also found for 87% (385 of 441) of genes significantly lower in layer 6b versus 6, compared with sample F versus E (each test, p < 2 × 10−16, two-tailed binomial test relative to a probability of 0.5). We next predicted 6,734 “patterned” genes that are preferentially expressed in one or more layers and 5,689 “unpatterned” genes that were expressed more uniformly across all layers. For this, layer expression for 2,200 genes annotated from in situ hybridization images (see also Belgard

et al., 2011) was used for training a naive Bayes classifier for each layer 2–6b. (Annotated marker genes were insufficient to permit training of a reliable classifier for layer 1.) whatever These curations are generally consistent

with the literature and other SAHA HDAC in vivo expression data sets (Allen Institute for Brain Science, Top 1,000 Genes Analysis: Validation of Frequently Accessed Genes in the Allen Mouse Brain Atlas, http://mouse.brain-map.org/pdf/Top1000GenesAnalysis.pdf, 2010). A classifier was also constructed to separate patterned from unpatterned genes. Classifier generalization accuracies were assessed with 10-fold cross-validation (Figure 1C; Table 1; Figure S1), and smoothed calibration curves were constructed for the resulting predicted probabilities to arrive at accurate estimates of enrichment likelihood (Figure S2). Finally, these classifiers were applied to both known and previously unknown genes and transcripts (Table S2; Belgard et al., 2011). A total of 11,410 known genes (10,261 protein-coding) were expressed at sufficiently high levels for their layer patterning to be classifiable. Predicted layer expression patterns typically recapitulated both the literature (Figure 2A) and the results of the high-throughput curation-based approach (Table 1). Upon correcting for false positives and false negatives, we found that an estimated 5,835 of these 11,410 classifiable known genes (51%) were expressed preferentially in one or more layers (Table 1, Supplemental Experimental Procedures).

monocytogenes but no significant differences in attachment effici

monocytogenes but no significant differences in attachment efficiency were found and for this reason, these results are not given in Table 1. For the frequency effect between the given range for high power ultrasound, it was suggested that the different frequencies of ultrasound treatment had no significant effect on the decontamination efficiency of S. typhimurium (P > 0.05) in the washing of iceberg lettuce,

the average reductions learn more for 25, 32–40, and 62–70 kHz treatments were 1.4, 1.3, and 1.3 log10 CFU/g respectively (not shown in Table 1). The ultrasound application in water significantly reduced the numbers of S. typhimurium (approx. 1.5 log10 CFU/g reduction, 97.9% reduction). These reductions were significantly different (P < 0.05) from the water control in the decontamination of fresh produce. Simple water washings allowed microbial log reductions of 1.43 ± 0.04 CFU/g red bell peppers. Among the technologies applied ozone in aqueous solution, ultrasounds and ultraviolet

C radiation, NVP-BGJ398 datasheet ultrasound was found one of the most effective process. On average, 1.98 ± 0.21 log CFU/g reductions on Listeria innocua occurred when red bell pepper samples had been washed with aqueous ultrasounds ( Alexandre et al., 2013). There are some studies designed to investigate the single and combined effects of ultrasound with some chemicals such as organic acids, acidified sodium chloride, ethanol, chlorine dioxide, and peracetic acid on the microbial inactivation of some fruits and vegetables (Huang et al., 2006, Zhou et al., 2009, Sagong et al., 2011, Rivera et al., 2011 and São José and Vanetti, 2012). Sagong et al. (2011) compared the effectiveness of combining treatments of ultrasound (30 W/L, 40 kHz, 5–10 min) with different organic acid (malic, GBA3 citric and lactic

acids) concentrations (0, 0.3, 0.5, 0.7, 1, and 2), and treatment times (5, 10, 20, 30, and 60 min) with mild agitation at 20 °C against E. coli O157:H7, S. typhimurium, and L. monocytogenes. The maximum reductions of E. coli O157:H7, S. typhimurium and L. monocytogenes were determined as 2.7 (lactic acid), 3.2 (citric acid), and 2.9 (malic acid) log10 CFU/g after a combined treatment with ultrasound and 2% organic acid for 5 min., respectively (P < 0.05). The reduction effect of ultrasound on S. typhimurium, E. coli O157:H7, and L. monocytogenes counts between the 5 and 10 min treatments were not significantly (P > 0.05) different on fresh lettuce in an ultrasound treatment with organic acid applications. The similar data obtained from different studies suggest that the reduction effect of ultrasound occurred primarily during the first 5 min and did not significantly increased even after a 10 min treatment in different samples such as parsley, lettuce, cabbage, carrot, cucumber, strawberry, onion, and pepper (mentioned in Seymour et al., 2002; Sagong et al., 2011). Alegria et al.

The results provide evidence for competitive encoding of alternat

The results provide evidence for competitive encoding of alternative potential reach plans in PRR and PMd, reflecting the monkeys’ average choice preferences, but being independent of the immediate behavioral choice of the monkey. This is consistent with the idea that the brain utilizes probabilistic representations throughout all stages of the decision process until an action is finally required (Knill and Pouget, 2004). Importantly, our results suggest that in situations of uncertain choice of which transformation rule to apply, the sensorimotor

system can www.selleckchem.com/products/Fasudil-HCl(HA-1077).html construct all potential motor goal alternatives, and then select among these alternatives, once enough evidence for a proper choice is available, rather than preliminarily betting on one of the transformation rules and computing only the single corresponding motor plan. This strategy could denote a valuable and general principle in decision making, allowing a more comprehensive cost-benefit

analysis that includes the consequential costs of the movements associated with each Abiraterone molecular weight choice. In PMG-CI trials (Figure 2), one spatial and one contextual visual cue were presented to the subjects at different times during the trial (ViewSonic VX922 LCD screen; 5 ms off-on-off response time). The peripheral spatial cue was located at one of four possible positions (0°, 90°, 180°, and 270°) with an eccentricity Cell press of 9 cm (14.5° visual angle, VA) relative to the fixation point. The contextual cue consisted of a green (direct-cued) or blue (inferred-cued) frame around the central eye and hand fixation

points. It instructed the subject to reach toward (direct, proreach) or to the position diametrically opposite of the spatial cue (inferred, antireach). A trial was initiated by the monkey by fixating a small red square in the center of the screen (eye fixation tolerance: 2.0-3.0° VA; 224 Hz CCD camera, ET-49B, Thomas Recording, Giessen, Germany) and touching an adjacent white square of the same size (hand fixation tolerance: 4.0° VA, touch screen mounted directly in front of the video screen; IntelliTouch, ELO Systems, Menlo Park, CA). After a random period of 500–1000 ms (fixation period) the spatial cue was shown briefly for 200 ms. During the following 800–2000 ms (memory period) only the fixation squares were visible. The contextual cue was shown for 170 ms at the end of the memory period and the hand fixation square disappeared (GO signal). The monkey had to make a reach toward the instructed goal within a maximum of 700–1000 ms (movement period, 4.9° VA reach tolerance) and hold the goal position for 300–400 ms (feedback period). The monkey received visual feedback about the correct movement goal (filled circle of the same color as the contextual cue at the goal location) at the end of a correct trial. Eye fixation had to be kept throughout the trial.

Participants from both groups had the tape reapplied twice per we

Participants from both groups had the tape reapplied twice per week for four weeks, making a total of eight applications. They were instructed not to change any medication prescribed by their physician and not to seek other treatment for their low back pain during the course of the study. Regular physical activities were allowed, which were also monitored during the treatment sessions. Four outcomes were measured: the intensity of pain, which was determined by a numerical rating scale; disability associated with back pain, which was Epigenetic pathway inhibitors assessed

by completion of the Roland Morris Disability Questionnaire21; global impression of recovery, which was evaluated by a Global Perceived Modulators Effect scale22 and adverse events. The numerical rating scale, the Roland Morris Disability Questionnaire and the Global Perceived Effect scale were professionally translated, cross-culturally adapted into Brazilian Portuguese, and tested for their measurement properties for people with low back pain in Brazil.23, 24 and 25 The primary outcomes were pain intensity

and disability associated with low back pain, which were measured immediately after treatments (four weeks). The secondary outcomes were pain intensity and disability associated with GSK1120212 solubility dmso low back pain, which were measured 12 weeks after randomisation, and global impression of recovery, which was measured immediately after treatments (four weeks) and 12 weeks after randomisation. The numerical rating scale for pain26 evaluates the perceived intensity of pain, using an 11-point scale from 0, representing ‘no pain’, to 10, which is the ‘worst possible pain’. Participants were asked to report the level of pain intensity based on the previous seven days. The Roland Morris Disability Questionnaire21 is used to assess disability associated with back pain. It consists of 24 items, which

describe common activities that people have difficulty performing due to back pain. The greater the number of activities checked, the greater the level of disability. Participants were asked to fill in the items that applied whatever on the day the questionnaire was completed. The Global Perceived Effect Scale22 is an 11-point scale ranging from -5, representing ‘much worse’, to +5, which is ‘completely recovered’, with 0 representing ‘no change’. For all measures of global perceived effect (at baseline and at all follow ups), participants were asked, ‘Compared with the beginning of the first episode, how would you describe your lower back today?’ This scale has good measurement properties.22 and 27 Any type of adverse effects, such as allergic reactions or skin problems, were also recorded by asking the participants if they had felt any itching or irritation on the skin where the tape was applied. The study was designed to detect a between-group difference of 1 point in pain intensity measured by the numerical rating scale, with an estimated standard deviation of 1.