Effect of wrist orthoses on upper limb function, activities of daily living, and stress response.

Introduction: This study examined the effects on upper limb function, activities of daily living, and stress responses when wearing a wrist orthosis made of padded fiberglass or thermoplastic and provided essential information for selecting an orthosis. Methods: Thirty-one healthy adults performed two tests while not wearing a wrist orthosis, wearing a padded fiberglass wrist orthosis, and wearing a thermoplastic wrist orthosis. The Purdue Pegboard Test examined upper limb control. In the second test, the actions indicated by the Hand20 questionnaire were performed while wearing a wrist orthosis. An electrocardiogram was obtained before and after each test to identify any changes in sympathetic nervous system activity. Results: The Purdue Pegboard Test scores were significantly higher when not wearing a wrist orthosis than when wearing wrist orthosis, and the Hand20 scores for all question were significantly lower. Thermoplastic wrist orthoses had fewer restrictions for upper limb function compared to padded fiberglass wrist orthoses, however activities of daily living were more limited. The low frequency/high frequency ratio and high frequency measures showed no significant differences. Conclusions: Pegboard test scores and the Hand 20 scores suggest that a wrist orthosis causes restriction of upper limb function.

Case Report: Virtual reality training for phantom limb pain after amputation.

Several reports have demonstrated the effectiveness of neurorehabilitation, such as mirror therapy or virtual reality, in treating phantom limb pain (PLP). This case study describes the effect of virtual reality training (VRT) on severe, long-term PLP and upper limb activity on the amputated side in a patient who underwent digit amputation 9 years prior. A woman in her 40 s underwent amputation of 2-5 fingers 9 years prior due to a workplace accident. She experienced persistent pain in the palms of her hand near the amputation sites. A single case design (ABA'B') was applied. Periods A and A' were set as periods without VRT intervention, and Periods B and B' were set as periods with VRT intervention. Periods A, B, A', and B' lasted 4, 10, 8, and 10 weeks, respectively. VRT was a task during which visual stimulation and upper limb movements were linked. The task consisted of catching a rolling ball in the display with a virtual hand, operated with both hands using a controller. VRT was performed once every 2-4 weeks for 30 min. Pain intensity was assessed using the short-form McGill Pain Questionnaire-2. Bilateral upper limb activity was measured continuously for 24 h using a triaxial accelerometer attached to the right and left wrist joints. The pain intensity was 147/220 points during Period A, 128 points during Period B, 93 points during Period A', and 100 points during Period B', showing a gradual decrease. Upper limb activity occurred mainly on the intact side during Periods A and B, whereas the activity on the amputated side increased 2-fold after Period A', and both upper extremities were used equally. Virtual reality training resulted in reduced pain intensity and increased activity in the upper limb. VRT may have induced reintegration of the sensory-motor loop, leading to a decrease in the PLP intensity. The upper limb activity on the amputated side may have also increased with the pain reduction. These results suggest that VRT may be valuable in reducing severe, long-term PLP.

Effectiveness of knee pad as an additional device for wheelchairs in improving upper-limb dexterity during seated tasks: a pilot study.

[Purpose] This study aimed to examine how supporting the knee from the front with a knee pad affected upper-limb dexterity while sitting. [Participants and Methods] A total of 14 healthy adult males were included in the study. As a measure of upper-limb dexterity, the number of pins was counted when the Purdue pegboard test was performed for 60 seconds. In addition, the ease of task performance was assessed using the visual analogue scale. There were two experimental conditions, with and without knee pad. The paired t-test was used to detect differences between the two conditions. A p-value of 0.05 was considered statistically significant. [Results] The Purdue pegboard test was 29.4 ± 2.5 and 27.9 ± 3.6 pins with and without knee pad, respectively. The VAS was 76.1 ± 10.3 and 62.9 ± 14.1 with and without knee pad, respectively. Both measured values were significantly higher with knee pad than without. [Conclusion] Supporting the knees from the front with knee pad improves upper-limb functionality while sitting, making it easier to perform seated tasks.

Correlation between kinesthetic motor imagery of an amputated limb and phantom limb pain.

BACKGROUND: Phantom limb pain (PLP) is a frequent painful sensation in amputees, and motor imagery (MI) is a useful approach for the treatment of this type of pain. However, it is not clear regarding the best MI modality for PLP. OBJECTIVES: The purpose of this study was to investigate the relationship between the PLP and MI modality in upper limb amputees. STUDY DESIGN: Observational study. METHODS: Eleven patients who underwent unilateral upper limb amputation participated in this study. The MI modality (kinesthetic and visual) and PLP intensity were evaluated using the Kinesthetic and Visual Imagery Questionnaire (KVIQ)-20 and a visual analog scale. MI ability was also assessed during the hand mental rotation task. We examined the correlation between MI modalities, ability, and pain intensity. RESULTS: The total KVIQ kinesthetic score was negatively correlated with pain intensity (r = -0.71, P < 0.01): the more vivid the kinesthetic imagery, the weaker the pain. In particular, the reduction in pain intensity was associated with strong kinesthetic imagery of opposing movements of the deficient thumb (r = -0.81, P < 0.01). The KVIQ visual score and MI ability were not associated with pain intensity. CONCLUSIONS: Our data showed that the reduction of PLP could be associated with the kinesthetic modality of MI but not with visual modality or MI ability. In other words, it was suggested that the more vivid the sensation of moving muscles and joints in the defect area, the lower the PLP intensity. To reduce PLP, clinicians may prefer interventions using the kinesthetic modality.

Relationship between pain intensity, pain catastrophizing, and self-efficacy in patients with frozen shoulder: a cross-sectional study.

BACKGROUND: Pain catastrophizing and self-efficacy are useful for predicting pain; these are associated with pain intensity and facilitate evaluation of psychological factors. However, it remains unclear whether the effects are direct or indirect in patients with frozen shoulder; the impact on each variable has also not been clarified. Thus, this study aimed to examine the structural relationship between pain catastrophizing, self-efficacy, and pain intensity in patients with frozen shoulder. METHODS: Participants who were diagnosed with frozen shoulder between January 2016 and March 2017 were recruited from a single orthopedic clinic. Patients aged 18 years or older, who had been symptomatic for < 1 year and reported localized pain in one shoulder, experienced night pain, and had restricted active and passive shoulder motions were included. Pain intensity (Numerical Rating Scale (NRS)), pain catastrophizing (Pain Catastrophizing Scale (PCS)), and self-efficacy (Pain Self-Efficacy Questionnaire (PSEQ)) were measured at the first examination, and the relationship was examined using the Bayesian estimation method. The model was modified repeatedly based on the posterior prediction p value, deviance information criterion (DIC), and Bayesian information criterion (BIC); the model with the highest explanatory power was adopted as the final model. RESULTS: Ninety-three patients diagnosed with frozen shoulder were included in this study. On path analysis, the model in which pain intensity affected psychological factors had the most explanation. The convergence index potential scale reduction was below 1.1, and the convergence of the estimate was confirmed. The posterior prediction p value was 0.25, DIC = 1328.705, and BIC = 1356.872; the validity of the fit of the model was confirmed. The path coefficients from the NRS to the PSEQ, from the NRS to the PCS, and from the PSEQ to the PCS scores were - 0.232 (95% confidence interval (CI), - 0.406 to - 0.033), 0.259 (95% CI, 0.083-0.419), and - 0.504 (95% CI, - 0.646 to - 0.334), respectively; these values were statistically significant (p < 0.05). CONCLUSION: Our results show that pain intensity increases the risk of chronic pain including pain catastrophizing and self-efficacy and that pain catastrophizing increases by decreasing self-efficacy in patients with frozen shoulder.

Time of Evaluation of Pain Catastrophizing after Surgery for Upper Extremity Motor Disorders.

Background: The evaluation of pain catastrophizing, which is a negative emotion associated with pain, is useful for predicting pain after surgery and is also associated with upper extremity disability. Therefore, it is important to evaluate pain catastrophizing after surgery for upper limb musculoskeletal disorders. This study examined the appropriate time to evaluate pain catastrophizing after surgery for upper extremity motor disorders. Methods: A total of 32 patients underwent surgery. Pain catastrophizing (Pain Catastrophizing Scale: PCS) and pain intensity (Numerical Rating Scale: NRS) were measured at the start of rehabilitation and 2, 4, and 8 weeks postoperatively. The subjective ability of the upper extremity was measured 8 weeks postoperatively using the Hand20 questionnaire. The variation in the postoperative PCS and NRS were investigated. Results: The PCS and NRS values were significantly lower 2 weeks postoperatively than at the time rehabilitation started. Pain catastrophizing was a significant predictor of pain, with the greatest degree of prediction at 2 weeks. Pain catastrophizing was also a significant predictor of the Hand20 result at 8 weeks postoperatively. Conclusions: Our data shows that pain catastrophizing should be evaluated 2 weeks postoperatively for the prediction of continuing pain.

Virtual reality-based action observation facilitates the acquisition of body-powered prosthetic control skills.

BACKGROUND: Regular body-powered (BP) prosthesis training facilitates the acquisition of skills through repeated practice but requires adequate time and motivation. Therefore, auxiliary tools such as indirect training may improve the training experience and speed of skill acquisition. In this study, we examined the effects of action observation (AO) using virtual reality (VR) as an auxiliary tool. We used two modalities during AO: three-dimensional (3D) VR and two-dimensional (2D) computer tablet devices (Tablet). Each modality was tested from first- and third-person perspectives. METHODS: We studied 40 healthy right-handed participants wearing a BP prosthesis simulator on their non-dominant hands. The participants were divided into five groups based on combinations of the different modalities and perspectives: first-person perspective on VR (VR1), third-person perspective on VR (VR3), first-person perspective on a tablet (Tablet1), third-person perspective on a tablet (Tablet3), and a control group (Control). The intervention groups observed and imitated the video image of prosthesis operation for 10 min in each of two sessions. We evaluated the level of immersion during AO using the visual analogue scale. Prosthetic control skills were evaluated using the Box and Block Test (BBT) and a bowknot task (BKT). RESULTS: In the BBT, there were no significant differences in the amount of change in the skills between the five groups. In contrast, the relative changes in the BKT prosthetic control skills in VR1 (p < 0.001, d = 3.09) and VR3 (p < 0.001, d = 2.16) were significantly higher than those in the control group. Additionally, the immersion scores of VR1 (p < 0.05, d = 1.45) and VR3 (p < 0.05, d = 1.18) were higher than those of Tablet3. There was a significant negative correlation between the immersion scores and the relative change in the BKT scores (Spearman's rs = - 0.47, p < 0.01). CONCLUSIONS: Using the BKT of bilateral manual dexterity, VR-based AO significantly improved short-term prosthetic control acquisition. Additionally, it appeared that the higher the immersion score was, the shorter the execution time of the BKT task. Our findings suggest that VR-based AO training may be effective in acquiring bilateral BP prosthetic control, which requires more 3D-based operation.

Repeated inversions within a pannier intron drive diversification of intraspecific colour patterns of ladybird beetles.

How genetic information is modified to generate phenotypic variation within a species is one of the central questions in evolutionary biology. Here we focus on the striking intraspecific diversity of >200 aposematic elytral (forewing) colour patterns of the multicoloured Asian ladybird beetle, Harmonia axyridis, which is regulated by a tightly linked genetic locus h. Our loss-of-function analyses, genetic association studies, de novo genome assemblies, and gene expression data reveal that the GATA transcription factor gene pannier is the major regulatory gene located at the h locus, and suggest that repeated inversions and cis-regulatory modifications at pannier led to the expansion of colour pattern variation in H. axyridis. Moreover, we show that the colour-patterning function of pannier is conserved in the seven-spotted ladybird beetle, Coccinella septempunctata, suggesting that H. axyridis' extraordinary intraspecific variation may have arisen from ancient modifications in conserved elytral colour-patterning mechanisms in ladybird beetles.

Indoxyl glucuronide, a protein-bound uremic toxin, inhibits hypoxia-inducible factor‒dependent erythropoietin expression through activation of aryl hydrocarbon receptor.

Renal anemia is common among chronic kidney disease (CKD) patients, and is mainly caused by inadequate erythropoietin (EPO) production from kidneys due to dysfunction of intracellular hypoxia-inducible factor (HIF) signaling in renal EPO-producing cells. We have previously shown that indoxyl sulfate (IS), a representative protein-bound uremic toxin accumulated in the blood of CKD patients, inhibits hypoxia-induced HIF activation and subsequent EPO production through activation of aryl hydrocarbon receptor (AHR). In this study, we further investigated the effects of other protein-bound uremic toxins on HIF-dependent EPO expression using EPO-producing HepG2 cells. We found that indoxyl glucuronide (IG) and IS, but not p-cresyl sulfate, phenyl sulfate, 3-indoleacetic acid or hippuric acid, inhibited hypoxia mimetic cobalt chloride-induced EPO mRNA expression. Furthermore, IG at concentrations similar to the blood levels in CKD patients inhibited the transcriptional activation of HIF induced by both cobalt chloride treatment and hypoxic culture. IG also induced CYP1A1 mRNA expression and nuclear translocation of AHR protein, indicating that IG activates AHR signaling. Blockade of AHR by a pharmacological antagonist CH-223191 abolished the IG-induced inhibition of HIF activation. Collectively, this study is the first to elucidate the biological effects of IG to inhibit HIF-dependent EPO production through activation of AHR. Our data suggests that not only IS but also IG contributes to the impairment of HIF signaling in renal anemia.

Molecular Characterization of Eye Pigmentation-Related ABC Transporter Genes in the Ladybird Beetle Harmonia axyridis Reveals Striking Gene Duplication of the white Gene.

Many species of ladybird beetles (Coccinellidae) possess vivid body colors. These colors and patterns show diversity between coccinellid species, or even within species. However, the molecular underpinnings of these striking body colors are scarcely understood. One of the candidate pigmentation molecules responsible for ladybird body color is ommochrome pigment, which is well known as the red pigment molecule responsible for the red eyes of Drosophila. Various insects also use ommochrome in body coloration. It is known that ommochrome pigment precursors are imported into appropriate cells by the ATP binding cassette (ABC) transporter proteins White and Scarlet. Thus, these ABC transporter genes are potentially involved in various color and pattern expressions seen in ladybird beetle species. In this study, in order to identify the repertory of ABC transporter genes responsible for such body colors, we performed molecular characterization of pigment-related ABC transporter genes, especially white and scarlet, in the coccinellid Harmonia axyridis. By using whole genome data for H. axyridis and subsequent RACE-PCR, six white orthologs and one scarlet ortholog were successfully identified. According to the results of functional analyses via RNA interference (RNAi), only one of these genes had a major function in eye pigmentation. Specific effects on body color and pattern were not detected by our RNAi experiments of any of these genes. This is the first report of this striking duplication of white genes and their functional analyses in insects.

Indoxyl sulfate, a uremic toxin in chronic kidney disease, suppresses both bone formation and bone resorption.

Abnormalities of bone turnover are commonly observed in patients with chronic kidney disease (CKD), and the low-turnover bone disease is considered to be associated with low serum parathyroid hormone (PTH) levels and skeletal resistance to PTH. Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood of patients with CKD. Recently, we have reported that IS exacerbates low bone turnover induced by parathyroidectomy (PTX) in adult rats, and suggested that IS directly induces low bone turnover through the inhibition of bone formation by mechanisms unrelated to skeletal resistance to PTH. To define the direct action of IS in bone turnover, we examined the effects of IS on bone formation and bone resorption in vitro. In cultures of mouse primary osteoblasts, IS suppressed the expression of osterix, osteocalcin, and bone morphogenetic protein 2 (BMP2) mRNA and clearly inhibited the formation of mineralized bone nodules. Therefore, IS directly acts on osteoblastic cells to suppress bone formation. On the other hand, IS suppressed interleukin (IL)-1-induced osteoclast formation in cocultures of bone marrow cells and osteoblasts, and IL-1-induced bone resorption in calvarial organ cultures. In cultures of osteoblasts, IS suppressed the mRNA expression of RANKL, the receptor activator of NF-κB ligand, which is a pivotal factor for osteoclast differentiation. Moreover, IS acted on osteoclast precursor, bone marrow-derived macrophages and RAW264.7 cells, and suppressed RANKL-dependent differentiation into mature osteoclasts. IS may induce low-turnover bone disease in patients with CKD by its direct action on both osteoblasts and osteoclast precursors to suppress bone formation and bone resorption.

Activation of aryl hydrocarbon receptor mediates suppression of hypoxia-inducible factor-dependent erythropoietin expression by indoxyl sulfate.

Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood of patients with chronic kidney disease (CKD). In addition to the involvement in the progression of CKD, a recent report indicates that IS suppresses hypoxia-inducible factor (HIF)-dependent erythropoietin (EPO) production, suggesting that IS may also contribute to the progression of renal anemia. In this report, we provide evidence that aryl hydrocarbon receptor (AhR) mediates IS-induced suppression of HIF activation and subsequent EPO production. In HepG2 cells, IS at concentrations similar to the blood levels in CKD patients suppressed hypoxia- or cobalt chloride-induced EPO mRNA expression and transcriptional activation of HIF. IS also induced AhR activation, and AhR blockade resulted in abolishment of IS-induced suppression of HIF activation. The HIF transcription factor is a heterodimeric complex composed of HIF-α subunits (HIF-1α and HIF-2α) and AhR nuclear translocator (ARNT). IS suppressed nuclear accumulation of the HIF-α-ARNT complex accompanied by an increase of the AhR-ARNT complex in the nucleus, implying the involvement of interactions among AhR, HIF-α, and ARNT in the suppression mechanism. In rats, oral administration of indole, a metabolic precursor of IS, inhibited bleeding-induced elevation of renal EPO mRNA expression and plasma EPO concentration and strongly induced AhR activation in the liver and renal cortex tissues. Collectively, this study is the first to elucidate the detailed mechanism by which AhR plays an indispensable role in the suppression of HIF activation by IS. Hence, IS-induced activation of AhR may be a potential therapeutic target for treating renal anemia.

Indoxyl sulfate exacerbates low bone turnover induced by parathyroidectomy in young adult rats.

Low-turnover bone disease is one of the bone abnormalities observed in patients with chronic kidney disease (CKD) and is recognized to be associated with low serum parathyroid hormone (PTH) level and skeletal resistance to PTH. Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood as renal dysfunction progresses in CKD patients. A recent in vitro study using an osteoblastic cell culture system suggests that IS has an important role in the pathogenesis of low bone turnover through induction of skeletal resistance to PTH. However, the effects of IS on the progression of low bone turnover have not been elucidated. In the present study, we produced rats with low bone turnover by performing parathyroidectomy (PTX) and fed these rats a diet containing indole, a precursor of IS, to elevate blood IS level from indole metabolism. Bone metabolism was evaluated by measuring histomorphometric parameters of secondary spongiosa of the femur. Histomorphometric analyses revealed significant decreases in both bone formation-related parameters and bone resorption-related parameters in PTX rats. In indole-treated PTX rats, further decreases in bone formation-related parameters were observed. In addition, serum alkaline phosphatase activity, a bone formation marker, and bone mineral density of the tibia tended to decrease in indole-treated PTX rats. These findings strongly suggest that IS exacerbates low bone turnover through inhibition of bone formation by mechanisms unrelated to skeletal resistance to PTH.

A visible dominant marker for insect transgenesis.

Transgenesis of most insects currently relies on fluorescence markers. Here we establish a transformation marker system causing phenotypes visible to the naked eye due to changes in the color of melanin pigments, which are widespread in animals. Ubiquitous overexpression of arylalkylamine-N-acetyl transferase in the silkworm, Bombyx mori, changes the color of newly hatched first-instar larvae from black to a distinctive light brown color, and can be used as a molecular marker by directly connecting to baculovirus immediate early 1 gene promoter. Suppression of black pigmentation by Bm-arylalkylamine-N-acetyl transferase can be observed throughout the larval stages and in adult animals. Alternatively, overexpression in another gene, B. mori ß-alanyl-dopamine synthetase (Bm-ebony), changes the larval body color of older instars, although first-instar larvae had normal dark coloration. We further show that ectopic Bm-arylalkylamine-N-acetyl transferase expression lightens coloration in ladybird beetle Harmonia axyridis and fruit fly Drosophila melanogaster, highlighting the potential usefulness of this marker for transgenesis in diverse insect taxa.