Validity of the Functional Classification of the Upper Extremities for Duchenne Muscular Dystrophy.

Objectives: Some upper-limb function assessments can evaluate treatments in the non-ambulatory stage of Duchenne muscular dystrophy (DMD). The Functional Classification of the Upper Extremities (FCUE) was developed for DMD in Japan. The FCUE is easier to use than the Performance of Upper Limb (PUL) and is more detailed than the Brooke Upper Extremity Scale. This study aimed to determine the concurrent validity of FCUE with other methods of assessment for DMD. Methods: This retrospective study reviewed the medical records of 39 boys with DMD from the National Center of Neurology and Psychiatry to evaluate the concurrent validity of the FCUE and PUL using non-parametric Spearman rank correlation (ρ). We also determined the concurrent validity of the Brooke Upper Extremity Scale and PUL for comparison. Results: The ρ value between the FCUE and PUL was -0.914 (P<0.001). The FCUE showed robust concurrent validity with the PUL. That correlation between the FCUE and Brooke Upper Extremity Scale gave a ρ value of -0.854 (P<0.001). Conclusions: The FCUE had a higher concurrent validity with the PUL than with the Brooke Upper Extremity Scale. The FCUE is considered a valid assessment tool of upper-limb function in boys with DMD. Selecting the best assessment method depends on the severity of the patient's condition and a balance between assessment accuracy and evaluation time.

A 10-Year Study of the Trend of Accidental Falls in the Elderly in a Japanese Hospital.

Elderly people are prone to falls. We established the Falls Prevention Working Group (FPWG) at our hospital in 2015 to reduce the number of falls during hospitalization. This study compared the trend of in-hospital falls in the elderly in two time periods (2008/9 and 2018/9) and determined the effects of FPWG-implemented measures. Using medical records, we counted the monthly number of falls suffered by patients during hospitalization in April 2008-March 2009 and April 2018-March 2019. We also categorized the falls according to the severity of fall-related complications.A total of 3609 hospital falls were recorded during the 2008-2019 period (2008/9: n = 433, 2018/9: n = 324). Falls were more common in patients aged 70-79 in 2008/9 but were noted in those aged ≥ 80 in 2018/9. The mean number of falls/month (27.3 ± 6.4, range: 12-45) was stable throughout the year. The incidence of falls in 2018/9 (1.90/1000 per persons per day) was significantly lower than in 2008/9 (2.30/1000, p = 0.006). Level ≥ 3b accidents, reflecting serious accidents with complications, were encountered in 12 of 433 accidents in 2008/9 compared with significantly fewer accidents (2 of the same severity among 324 accidents) in 2018/9 (p = 0.030).Our results showed a decrease in in-hospital falls in 2018/9 and that the sufferers were older relative to 10 years earlier. A multidisciplinary team should recommend measures to prevent falls and an environment "resilient" to falls, and encourage patients to be aware of possible falls.

Upper-Limb Functional Recovery in Chronic Stroke Patients after COVID-19-Interrupted Rehabilitation: An Observational Study.

Background/Objectives: Upper-limb function of chronic stroke patients declined when outpatient rehabilitation was interrupted and outings restricted, owing to the novel coronavirus infection (COVID-19) pandemic. We investigated whether these patients recovered upper-limb function post-resumption of outpatient rehabilitation. Methods: In this observational study, 43 chronic stroke hemiparesis patients with impaired upper extremity function were scored for limb function via the Fugl-Meyer assessment of the upper extremity (FMA-UE) and the Action Research Arm Test (ARAT) after a structured interview, evaluation, and intervention. Scores at 6 and 3 months pre- and 3 months post-rehabilitation interruption were examined retrospectively; scores immediately and at 3 and 6 months post-resumption of care were examined prospectively. The amount of change for each time period and an analysis of covariance were performed with time as a factor, changes in the FMA-UE and the ARAT scores as dependent variables, and statistical significance at 5%. Results: The time of evaluation significantly impacted the total score, as well as part C and part D of FMA-UE and total, pinch, and gross movement of the ARAT. Post-hoc tests showed that the magnitude of change in limb-function scores from immediately to 3 months post-resumption was significantly higher than the change from 3 months pre- to immediately post-interruption for the total score and part D of the FMA-UE, as well as grip and gross movement of the ARAT (p < 0.05). Conclusions: Upper-limb functional decline in chronic stroke patients, caused by the COVID-19 pandemic-related therapy interruption and outing restrictions, was resolved approximately 3 months post-resumption of rehabilitation therapy. Our data can serve as reference standards for planning and evaluating treatment for chronic stroke patients with inactivity-related impaired upper-limb function.

Changes in Structural Neural Networks in the Recovery Process of Motor Paralysis after Stroke.

In recent years, neurorehabilitation has been actively used to treat motor paralysis after stroke. However, the impacts of rehabilitation on neural networks in the brain remain largely unknown. Therefore, we investigated changes in structural neural networks after rehabilitation therapy in patients who received a combination of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) and intensive occupational therapy (intensive-OT) as neurorehabilitation. Fugl-Meyer assessment (FMA) for upper extremity (FMA-UE) and Action Research Arm Test (ARAT), both of which reflected upper limb motor function, were conducted before and after rehabilitation therapy. At the same time, diffusion tensor imaging (DTI) and three-dimensional T1-weighted imaging (3D T1WI) were performed. After analyzing the structural connectome based on DTI data, measures related to connectivity in neural networks were calculated using graph theory. Rehabilitation therapy prompted a significant increase in connectivity with the isthmus of the cingulate gyrus in the ipsilesional hemisphere (p < 0.05) in patients with left-sided paralysis, as well as a significant decrease in connectivity with the ipsilesional postcentral gyrus (p < 0.05). These results indicate that LF-rTMS combined with intensive-OT may facilitate motor function recovery by enhancing the functional roles of networks in motor-related areas of the ipsilesional cerebral hemisphere.

Multimodal treatment, including extracorporeal shock wave therapy, for refractory chronic tension-type headache: a case report.

BACKGROUND: Few reports have described multidisciplinary treatment, including extracorporeal shock wave therapy, for patients with refractory chronic tension-type headache. In this study, we conducted multidisciplinary treatment for a patient with chronic tension-type headache who suffered from chronic headache refractory to treatment. CASE PRESENTATION: The patient was a 45-year-old Japanese male suffering from 20 years of headache. As his headache had worsened recently, he visited a local clinic. With the diagnosis of suspected tension-type headache, its treatment was unsuccessful and he was referred to our hospital. The neurology department confirmed the tension-type headache and prescribed another medication, but he showed no improvement. Then, the patient was referred to the rehabilitation medicine department for consultation. At the initial visit, we identified multiple myofascial trigger points in his bilateral posterior neck and upper back regions. At the initial visit, he was prescribed 10 mL of 1% lidocaine injected into the muscles in these areas. In addition, he received 2000 extracorporeal shock wave therapy into bilateral trapezius muscles, and was instructed to take oral Kakkonto extract granules, benfotiamine, pyridoxine hydrochloride, and cyanocobalamin. Cervical muscle and shoulder girdle stretches and exercises were also recommended. At follow-up treatment visits, we used extracorporeal shock wave therapy to bilateral trapezius muscles, which led to immediate pain relief. After 11 weeks, he was not taking any medication and his headache was subjectively improved and his medical treatment ended. CONCLUSION: A patient with chronic tension-type headache refractory to regular treatment was successfully treated with a multimodal approach including extracorporeal shock wave therapy in addition to standard treatment. For patients with tension-type headache accompanied by myofascial trigger points, it may be recommended to promptly consider aggressive multimodal treatment that includes extracorporeal shock wave therapy.

Small-Molecule Drug Repurposing for Counteracting Phototoxic A2E Aggregation.

Despite the well-established role of oxidative stress in the pathogenesis of age-related macular degeneration (AMD), the mechanism underlying phototoxicity remains unclear. Herein, we used a drug repurposing approach to isolate an FDA-approved drug that blocks the aggregation of the photoinducible major fluorophore of lipofuscin, the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). Our fluorescence-based screening combined with dynamic light scattering (DLS) analysis led to the identification of entacapone as a potent inhibitor of A2E fluorescence and aggregation. The entacapone-mediated inhibition of A2E aggregation blocks its photodegradation and offers photoprotection in A2E-loaded retinal pigment epithelial (RPE) cells exposed to blue light. In-depth mechanistic analysis suggests that entacapone prevents the conversion of toxic aggregates by redirecting A2E into off-pathway oligomers. These findings provide evidence that aggregation contributes to the phototoxicity of A2E.

Physical Therapy Combined with Transcranial Magnetic Stimulation Therapy: Treatment Practice Considering the Effect of Reducing Upper Limb Spasticity on Gait.

We perform physical therapy combined with repetitive transcranial magnetic stimulation (rTMS) in stroke patients with hemiplegia in the maintenance phase with the intent of improving the support of paralyzed leg. In gait evaluation in patients with hemiplegia, it is important to assess elements related to coordination carefully. rTMS therapy is effective in alleviating the tension of upper limbs. As rTMS helps upper-limb swing to become evident during gait, it makes trunk rotation necessary for left-right coordination appear more easily. As a result, rTMS has potential for improved upper-limb swing or trunk rotation. Post-rTMS therapy may prepare for the environment suitable for hip extending the stance phase of the paralyzed side. In physical therapy, it is advisable to practice standing up, maintaining standing posture or walking by making good use of these effects. We conduct practices in combination with the following: standing up focusing on load evenly distributed on both sides, standing on slant-board training, which enables forward shift of center of mass, walking by fixating upper limbs to the back of the body with the intent of extending the stance phase of the paralyzed side, and increasing trunk rotation. It is also necessary to discuss the combination with injection with botulinum toxin, which suppresses spasticity of ankle plantar flexors with the physician. Gait is associated with a variety of factors and has significant intrapatient and interpatient variations. In this regard, physiotherapists are required to develop a treatment program based on a quantitative evaluation, especially, in patients with hemiplegia.

Improved language function for post-stroke aphasia in the long term following repeated repetitive transcranial magnetic stimulation and intensive speech-language-hearing therapy: a case report.

BACKGROUND: There have been no papers reporting improvement in language function and changes in cerebral blood flow following repeated use of repetitive transcranial magnetic stimulation in combination with intensive speech-language-hearing therapy. This case report concerns the efficacy of repeated use of repetitive transcranial magnetic stimulation and intensive speech-language-hearing therapy for a certain patient suffering from aphasia following stroke, plus the findings of the cerebral blood flow measurements. CASE PRESENTATION: The patient was a 71-year-old right-handed Japanese male who developed fluent aphasia following a left middle cerebral artery stroke. He underwent repetitive transcranial magnetic stimulation and intensive speech-language-hearing therapy five times in total. The repetitive transcranial magnetic stimulation was applied to right inferior frontal gyrus at the frequency of 1 Hz plus 2 hours per day of intensive speech-language-hearing therapy. The patient's language function was evaluated in the short term and long term. Cerebral blood flow was measured with single photon emission computed tomography scan. As a result, in the short term, the patient's language function improved especially during the initial hospitalization. In the long term, it improved gradually and stabilized.Cerebral blood flow was increased in the right hemisphere. CONCLUSIONS: The findings of the study indicate that the repeated use of repetitive transcranial magnetic stimulation and intensive speech-language-hearing therapy may be effective in improving and preserving language function and increasing cerebral blood flow for aphasia following stroke.

Repetitive Transcranial Magnetic Stimulation and Rehabilitation Therapy for Upper Limb Hemiparesis in Stroke Patients: A Narrative Review.

Recent technological advances in non-invasive brain stimulation (NIBS) have led to the development of therapies for post-stroke upper extremity paralysis. Repetitive transcranial magnetic stimulation (rTMS), a NIBS technique, controls regional activity by non-invasively stimulating selected areas of the cerebral cortex. The therapeutic principle by which rTMS is thought to work is the correction of interhemispheric inhibition imbalances. The guidelines for rTMS for post-stroke upper limb paralysis have graded it as a highly effective treatment, and, based on functional brain imaging and neurophysiological testing, it has been shown to result in progress toward normalization. Our research group has published many reports showing improvement in upper limb function after administration of the NovEl Intervention Using Repetitive TMS and intensive one-to-one therapy (NEURO), demonstrating its safety and efficacy. Based on the findings to date, rTMS should be considered as a treatment strategy based on a functional assessment of the severity of upper extremity paralysis (Fugl-Meyer Assessment), and NEURO should be combined with pharmacotherapy, botulinum treatment, and extracorporeal shockwave therapy to maximize therapeutic effects. In the future, it will be important to establish tailormade treatments in which stimulation frequency and sites are adjusted according to the pathological conditions of interhemispheric imbalance, as revealed by functional brain imaging.

The impact of preoperative muscle strength on postoperative walking ability in patients undergoing total knee arthroplasty.

Although knee extensor muscle strength is strongly associated with postoperative walking ability (PWA) in patients undergoing total knee arthroplasty (TKA), few studies have considered the impact of both knee extensor and flexor muscle strength. This study aimed to determine whether operative side knee flexor and extensor muscle strength before surgery affects the PWA of patients who undergo TKA while accounting for potential covariates. This multicenter retrospective cohort study involved four university hospitals, and patients who underwent unilateral primary TKA were included. The outcome measure was the 5-m maximum walking speed test (MWS), which was completed 12 weeks postoperatively. Muscle strength was measured as the maximum isometric muscle strength required for knee flexor and extensor. Three multiple regression models with a progressively larger number of variables were developed to determine the predictors of 5-m MWS at 12 weeks post-TKA surgery. One hundred thirty-one patients who underwent TKA were enrolled in the study (men, 23.7%; mean age, 73.4 ± 6.9 years). Age, sex, operative side knee flexor muscle strength before surgery, Japanese Orthopaedic Association knee score, and preoperative walking ability were significantly associated with PWA in the final model of the multiple regression analysis ( R2 = 0.35). The current findings suggest that the operative side knee flexor muscle strength before surgery is a robust modifiable predictor of improved PWA. We believe that further validation is needed to determine the causal relationship between preoperative muscle strength and PWA.

Impact of the quantity and quality of the skeletal muscle on survival among patients undergoing allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Poor skeletal muscle function is relatively high in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), leading to various negative health outcomes. This study aimed to investigate the relationship between the quantity and quality of skeletal muscle before transplantation and the short-to long-term survival after transplantation in patients undergoing allo-HSCT. METHODS: This retrospective cohort study included 156 patients undergoing allo-HSCT (men, 67.3 %; median age, 53 years; interquartile range, 42-61 years). The quantity and quality of the skeletal muscle were measured at the psoas major at the level of the third lumbar vertebrae using a computed tomography (CT) and were defined as psoas muscle index (PMI) and CT values (CTV), respectively. The outcome measure of this study was overall survival (OS) after allo-HSCT, and we examined the relationship between survival at three time points (6, 12, and 24 months) after transplantation, PMI, and CTV. RESULTS: PMI was significantly associated with survival at all time points in the crude model (P < 0.001), and a significant association was observed in the fully adjusted model (P < 0.01). CTV was significantly associated with survival at all time points in the crude model (P < 0.05), but not in the fully adjusted model (P > 0.05). CONCLUSIONS: We found that the quantity and quality of the skeletal muscle before transplantation were significantly associated with OS at 6, 12, and 24 months after transplantation, showing a particularly robust association with quantity.

Recovery of Patients With Upper Limb Paralysis Due to Stroke Who Underwent Intervention Using Low-Frequency Repetitive Transcranial Magnetic Stimulation Combined With Occupational Therapy: A Retrospective Cohort Study.

OBJECTIVES: The combination of repetitive transcranial magnetic stimulation (rTMS) and motor practice is based on the theory of neuromodulation and use-dependent plasticity. Predictive planning of occupational therapy (OT) is important for patients with rTMS conditioning. Recovery characteristics based on the severity of pretreatment upper extremity paralysis can guide the patient's practice plan for using the paretic hand. Therefore, we evaluated the recovery of patients with upper limb paralysis due to stroke who underwent a novel intervention of rTMS combined with OT (NEURO) according to the severity of upper limb paralysis based on the scores of the Fugl-Meyer assessment for upper extremity (FMA-UE) with recovery in proximal upper extremity, wrist, hand, and coordination. MATERIALS AND METHODS: In this multicenter retrospective cohort study, the recovery of 1397 patients with upper limb paralysis was analyzed by severity at six hospitals that were accredited by the Japanese Stimulation Therapy Society for treatment. The delta values of the FMA-UE scores before and after NEURO were compared among the groups with severe, moderate, and mild paralysis using the generalized linear model. RESULTS: NEURO significantly improved the FMA-UE total score according to the severity of paralysis (severe = 5.3, moderate = 6.0, and mild = 2.9). However, when the FMA-UE subscores were analyzed separately, the results indicated specific improvements in shoulder/elbow, wrist, fingers, and coordination movements, depending on the severity. CONCLUSIONS: This study had enough patients who were divided according to severity and stratified by lesion location and handedness parameters. Our results suggest that independently of these factors, the extent of recovery of upper limb motor parts after NEURO varies according to the severity of paralysis.

Upper Limb Function Recovery by Combined Repetitive Transcranial Magnetic Stimulation and Occupational Therapy in Patients with Chronic Stroke According to Paralysis Severity.

Repetitive transcranial magnetic stimulation (rTMS) with intensive occupational therapy improves upper limb motor paralysis and activities of daily living after stroke; however, the degree of improvement according to paralysis severity remains unverified. Target activities of daily living using upper limb functions can be established by predicting the amount of change after treatment for each paralysis severity level to further aid practice planning. We estimated post-treatment score changes for each severity level of motor paralysis (no, poor, limited, notable, and full), stratified according to Action Research Arm Test (ARAT) scores before combined rTMS and intensive occupational therapy. Motor paralysis severity was the fixed factor for the analysis of covariance; the delta (post-pre) of the scores was the dependent variable. Ordinal logistic regression analysis was used to compare changes in ARAT subscores according to paralysis severity before treatment. We implemented a longitudinal, prospective, interventional, uncontrolled, and multicenter cohort design and analyzed a dataset of 907 patients with stroke hemiplegia. The largest treatment-related changes were observed in the Limited recovery group for upper limb motor paralysis and the Full recovery group for quality-of-life activities using the paralyzed upper limb. These results will help predict treatment effects and determine exercises and goal movements for occupational therapy after rTMS.

Treatment outcome of local injection of botulinum toxin for claw toe: Differences between cerebral hemorrhage and infarction.

BACKGROUND: Some patients with post-stroke claw toe respond well to botulinum toxin (BoNT) treatment while others do not. This study was designed to assess the impact of stroke type (cerebral hemorrhage and cerebral infarction) on the outcome of BoNT treatment for claw toe. METHODS: We retrospectively examined the medical records of patients who received local BoNT (onabotulinumtoxin A) injections into the flexor hallucis longus (FHL) and flexor digitorum longus (FDL) muscles. All patients suffered stroke-related leg paralysis and spasticity. RESULTS: The study participants were 58 patients (mean age, 61.4 ± 10.3 years, ± SD) with time since stroke of 6.7 ± 4.4 years. The stroke type was cerebral hemorrhage (n = 38) and cerebral infarction (n = 20). After a total of 124 BoNT administrations with medical records entries on the subjective symptoms, the odds for symptomatic improvement was approximately 5.8 times higher in patients of the infarction group compared with the hemorrhage group (OR = 5.787, 95% CI = 2.369-14.134, p = 0. 000). Fifty-one patients (32 with cerebral hemorrhage, 19 with cerebral infarction) received the first local BoNT injection and had available medical records, analysis of which showed a significantly higher rate of symptomatic improvement in patients of the infarction group than those of the hemorrhage group (p = 0.006). After adjustment by factors known to influence treatment outcome (degree of spasticity and paralysis, BoNT dosage, and extent of FDL muscle control of toe movements), the treatment effect was predominantly higher in patients with cerebral infarction. CONCLUSION: The BoNT treatment response was better for claw toes in cerebral infarction patients than in hemorrhage patients, possibly suggesting that claw toe is associated with more severe spasticity in this group of patients.

Study Protocol for a Multicenter, Randomized Controlled Trial to Improve Upper Extremity Hemiparesis in Chronic Stroke Patients by One-to-One Training (NEURO®) with Repetitive Transcranial Magnetic Stimulation.

During recovery from upper limb motor paralysis after stroke, it is important to (1) set the exercise difficulty level according to the motor paralysis severity, (2) provide adequate exercises, and (3) motivate the patient to achieve the goal. However, these factors have not been well-formulated. This multicenter, randomized controlled trial study aims to examine the therapeutic effects of these three factors on patients undergoing a novel intervention using repetitive transcranial magnetic stimulation and intensive one-to-one training (NEURO®) and to formulate a corresponding research protocol. The control group will receive conventional NEURO® occupational therapy. In the intervention group, four practice plans will be selected according to the Fugl-Meyer assessment (FMA-UE) scores of the upper extremity. The goal is to predict the post-treatment outcomes based on the pre-treatment FMA-UE scores. Based on the degree of difficulty and amount of practice required, we can formulate a practice plan to promote upper limb motor recovery. This occupational therapy plan will be less influenced by the therapist's skill, facilitating effective rehabilitation. The study findings may be utilized to promote upper limb motor paralysis recovery and provide a basis for proposing activities of daily living adapted to upper limb function.

Effects and safety of high-frequency rTMS in acute intracerebral hemorrhage patients: A pilot study.

OBJECTIVE: Although high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) in chronic intracerebral hemorrhage (ICH) is beneficial, it has been poorly investigated in rTMS for acute ICH. Our aim is to investigate the effects and safety of rTMS in acute spontaneous ICH. METHODS: We prospectively performed HF-rTMS on consecutive patients with ICH within 24 h from onset between April 2019 and August 2021. The inclusion criterion was (1) persistent paralysis, with an NIHSS scale of 1 or higher for at least 3 days after onset. The exclusion criteria were (1) cortical, subcortical, and cerebellar ICH, (2) disturbance of consciousness, and (3) over 80 years of age. For the purpose of comparison, we used a conventional rehabilitation group whose patients met the same criteria between April 2016 and March 2019. We evaluated incidence of epilepsy and exacerbation of the NIHSS score in the rTMS group. We also compared the two groups regarding clinical background and outcome. RESULTS: Enrolled in the study were a total of 44 patients. Of the patients, 22 (50%) were in the rTMS group. The median (IQR) time from onset to the start of rTMS was 9 (6-12) days. There were no cases of epilepsy or exacerbation of NIHSS after the start of rTMS. Favorable outcome (modified Rankin Scale score of between 0 and 2) at 3 months was frequently observed in the rTMS group (73% vs 27%, p = 0.006). HF-rTMS was independently associated with favorable outcome at 3 months (OR = 11.5, 95% CI = 2.194-60.447, p = 0.004). CONCLUSIONS: HF-rTMS may be safe and effective in acute ICH patients.

Effects of Flexor Digitorum Longus Muscle Anatomical Structure on the Response to Botulinum Toxin Treatment in Patients with Post-Stroke Claw Foot Deformity.

(1) Background: The purpose of this retrospective case-control study was to determine the relationship between the control of toe movements by flexor hallucis longus (FHL) and flexor digitorum longus (FDL) muscles and the response to treatment with botulinum toxin (BoNT) in post-stroke patients with claw toe. (2) Methods: Subjects with stroke-related leg paralysis/spasticity and claw toes received multiple injections of BoNT (onabotulinumtoxin A) into the FHL or FDL muscles. We investigated the relationship between the mode of transmission of FHL and FDL muscle tension to each toe (MCT) and treatment outcome using the data of 53 patients who received 124 injections with clinically recorded treatment outcome. We also dissected the potential variables that could determine the treatment outcome. (3) Results: The effectiveness of BoNT treatment was significantly altered by FDL-MCT (OR = 0.400, 95% CI = 0.162-0.987, p = 0.047). Analysis of the response to the first BoNT injection showed an odds ratio of FDL-MCT of approximately 6.0 times (OR = 0.168, 95% CI = 0.033-0.857, p = 0.032). The more tibial the influence of the FDL muscle on each toe, the better the treatment outcome on the claw toe. (4) Conclusions: The anatomic relation between FDL muscle and each toe seems to affect the response to treatment with BoNT in post-stroke patients with claw toes.

Chemoproteomic Identification of Blue-Light-Damaged Proteins.

Visible light, particularly in the blue region of the spectrum, can cause cell dysfunction through the generation of singlet oxygen, contributing to cellular aging and age-related pathologies. Although photooxidation of nucleic acids, lipids, and amino acids has been extensively studied, the magnitude and span of blue-light-induced protein damages within proteome remain largely unknown. Herein we present a chemoproteomic approach to mapping blue-light-damaged proteins in live mammalian cells by exploiting a nucleophilic alkyne chemical probe. A gene ontology enrichment analysis revealed that cell surface proteins are more readily oxidized than other susceptible sets of proteins, including mitochondrial proteins. In particular, the integrin family of cell surface receptors (ITGs) was highly ranked in the mammalian cells tested, including human corneal endothelial cells. The blue-light-oxidized ITGB1 protein was functionally inactive in promoting cell adhesion and proliferation, suggesting that the photodamage of integrins contributes to the blue-light-induced cell dysfunction. Further application of our method to various cells and tissues should lead to a comprehensive analysis of light-sensitive proteins.

Rehabilitation therapy for a severe case of coronavirus disease 2019: a case report.

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) infection require a long period of time to return to work and society due to significant physical weakness even after recovery. Here we report a patient with a history of nephrectomy who developed severe COVID-19 infection associated with muscle weakness but was able to return to society after rehabilitation therapy. CASE PRESENTATION: A Japanese man in his 40s was admitted to the hospital with PCR-based COVID-19 diagnosis. The respiratory condition worsened rapidly and was treated with extracorporeal membrane-assisted ventilation in the intensive case unit. On admission to the Rehabilitation Department on day T + 30 [T: day patient became febrile (38 °C)], he was unable to stand for a long time and used a walker. Rehabilitation therapy was postponed to prevent COVID-19 spread, but the patient was encouraged to exercise during isolation to improve trunk and lower extremity muscle strength. Physical therapy commenced on day T + 49 to improve gait and trunk and lower limb muscle strength. He was able to walk independently and later returned to work following discharge on day T + 53. A computed tomography scan showed an increase in psoas muscle volume from 276 before to 316 cm3 after physical therapy, together with a decrease in whole-body extracellular water:total body weight ratio from 0.394 to 0.389. CONCLUSIONS: We have described the beneficial effects of rehabilitation therapy in a patient with severe COVID-19 infection. In addition to exercise, we believe that nutrition is even more important in increasing skeletal muscle mass. Rehabilitation therapy is recommended to enhance the return of severely ill COVID-19 patients to routine daily activity.