Myonuclear apoptosis via cleaved caspase-3 upregulation is related to macrophage accumulation underlying immobilization-induced muscle fibrosis.

INTRODUCTION/AIMS: Although macrophage accumulation plays a key role in the development of immobilization-induced muscle fibrosis, the underlying mechanisms remain unclear. Therefore, we focused on the alterations of myonuclear apoptosis via cleaved caspase-3, and investigated whether these changes may be related to macrophage accumulation. METHODS: Eight-week-old Wistar rats were divided into immobilization and control groups, and the soleus muscles were selected for analysis. RESULTS: The mRNA and protein expression of collagen and the number of CD11b-positive cells were significantly higher in the immobilized rats than in the control rats at 1 and 2 weeks. TdT-mediated dUTP nick end-labeling (TUNEL)-positive myonuclei counts in 1- and 2-week control rats were 0.2 ± 0.1 and 0.2 ± 0.5, whereas they were 1.0 ± 0.6 and 1.1 ± 0.5 in 1- and 2-week immobilized rats. The cleaved caspase-3 protein expressions in 1- and 2-week control rats were 0.2 ± 0.1 and 0.2 ± 0.1, whereas they were 0.5 ± 0.1 and 0.4 ± 0.2 in 1- and 2-week immobilized rats. TUNEL-positive myonuclei counts and cleaved caspase-3 protein expression were significantly higher in immobilized rats than in control rats at 1 and 2 weeks. The numbers of myonuclei in 1- and 2-week control rats were 2.8 ± 0.1 and 2.6 ± 0.4, whereas they were 2.2 ± 0.4 and 2.2 ± 0.2 in 1- and 2-week immobilized rats. The numbers of myonuclei were significantly lower in immobilized than in control rats at both time-points. DISCUSSION: Myonuclear apoptosis via the upregulation of cleaved caspase-3 might induce macrophage accumulation. These alterations are related to immobilization-induced muscle fibrosis.

Mechanisms underlying immobilization-induced muscle pain in rats.

INTRODUCTION: We investigated the mechanisms underlying immobilization-induced muscle pain in rats. METHODS: In rat skeletal muscle, pressure pain threshold (PPT) of the gastrocnemius muscle was measured, and nerve growth factor (NGF) level, peripheral nerve fiber density, macrophage number, and interleukin-1ß (IL-1ß) mRNA expression were examined. An NGF receptor inhibitor was injected intramuscularly to assess the relationship between PPT and NGF levels. RESULTS: Immobilization resulted in a decrease in PPT and increases in NGF level, C-fiber density, M1 macrophage number, and IL-1ß mRNA expression. Injection of NGF receptor inhibitor reversed the decrease in PPT. DISCUSSION: NGF upregulation may be a major contributor to immobilization-induced muscle pain. The increases in C-fiber density, M1 macrophage number, and IL-1ß mRNA expression may be related to immobilization-induced muscle pain.

Relationship between extensibility and collagen expression in immobilized rat skeletal muscle.

INTRODUCTION: This study investigated longitudinal changes in muscle extension and collagen expression in an immobilized rat soleus muscle, and assessed the relationship between both elements. METHODS: Soleus muscles of the control and immobilization groups (1, 2, 4, 8, and 12 weeks) were used for analysis of muscle extensibility and collagen expression. RESULTS: The slope value/physiological cross-sectional area (PCSA; a parameter for muscle extensibility) and hydroxyproline (a parameter for collagen expression) were significantly higher in the immobilization group than in the control group for all experimental time points. In the immobilization group, both factors were significantly higher at 4, 8, and 12 weeks than at 1 and 2 weeks after immobilization. A significant positive correlation was observed between the slope value/PCSA and hydroxyproline expression. DISCUSSION: The present study indicated that a decrease in muscle extensibility depended on collagen overexpression in immobilized rat soleus muscles. Muscle Nerve 57: 672-678, 2018.

Anatomical study of the articular branches innervated the hip and knee joint with reference to mechanism of referral pain in hip joint disease patients.

INTRODUCTION: Referred pain in the anterior knee joint is the most common symptom in hip disease patients. The development of referred pain is considered to be related to dichotomizing peripheral sensory fibers. However, no gross anatomical findings identify any dichotomizing fibers innervating both the hip and knee joints. We dissected the femoral and obturator nerves in human cadavers to investigate the distribution of the articular branches in the hip and knee joints. Fourteen embalmed left lower limbs from 14 Japanese adult cadavers (five from females, nine from males, average age 73.8 ± 14.1 years) were observed macroscopically. The articular branches of the femoral and obturator nerves were dissected at the anterior margin of the groin toward the thigh region. After dissections of the articular nerves of the hip joints, the femoral and obturator nerves were exposed from proximally to distally to identify the articular nerves of the knee joints. The branching pattern of the articular branches in the hip and knee joints was recorded. In six of 14 limbs (42.9%), the femoral nerve supplied articular branches to the anteromedial aspect of both the hip and knee joints. These articular branches were derived from the same bundle of femoral nerve. These gross anatomical findings suggested that dichotomizing peripheral sensory fibers innervate the hip and knee joints and these could relate to the referred pain confirmed in the anterior knee joints of patients with hip disease. Clin. Anat. 31:705-709, 2018. © 2018 Wiley Periodicals, Inc.

Cyclic muscle twitch contraction inhibits immobilization-induced muscle contracture and fibrosis in rats.

We investigated the effects of cyclic muscle twitch contraction caused by neuromuscular electrical stimulation (NMES) on immobilization-induced muscle contracture and fibrosis in rats. Twenty-nine rats were divided into control, immobilization, and immobilization with muscle contraction groups. The ankle joints of the immobilization and muscle contraction rats were fixed in full plantar flexion with a plaster cast for 4 weeks. In the muscle contraction group, cyclic muscle twitch contraction of the soleus muscle was induced using a commercial device (1 Hz, 4 ± 2 mA, 60 min/day, 5 times/week) with the ankle joint immobilized. The dorsiflexion range of ankle joint motion in the muscle contraction group was significantly greater than that in the immobilization group. The expressions of fibrosis-related genes (i.e., hypoxia inducible factor-1α, transforming growth factor-ß1, α-smooth muscle actin, and types I and III collagen) were significantly decreased in the muscle contraction group compared to the immobilization group. The fluorescence intensities of type I and type III collagen in the perimysium and endomysium in the muscle contraction group were significantly decreased compared to the immobilization group. These results suggest that cyclic muscle twitch contraction induced by NMES might alleviate skeletal muscle fibrosis, reducing immobilization-induced muscle contracture.

Development and progression of immobilization-induced skin fibrosis through overexpression of transforming growth factor-ß1 and hypoxic conditions in a rat knee joint contracture model.

PURPOSE: The purpose of this study was to investigate the pathology and mechanism of immobilization-induced skin fibrosis in a rat joint contracture model. METHODS: Rats were randomly divided into control and immobilization groups. In the immobilization groups, knee joints of the rats were immobilized for 1, 2, and 4 weeks. After each immobilization, skin was dissected. To assess fibrosis in the skin, the thickness and area of adipocytes and connective tissue fibers were measured. Myofibroblasts were analyzed by immunohistochemistry by using anti-α-SMA as a marker. Gene expression levels of type I and III collagen, TGF-ß1, and HIF-1α were measured by using RT-PCR. RESULTS: One week after immobilization, there was a marked increase in the area of connective tissue fibers in the immobilization group. Type I and type III collagen were significantly increased with prolonged immobilization. Higher numbers of α-SMA-positive cells were noted in the immobilized group at 2 and 4 weeks after immobilization. The expression level of TGF-ß1 mRNA in the immobilization group increased after one week of immobilization. In contrast, the expression level of HIF1-α mRNA increased after 2 weeks of immobilization, and a greater increase was seen at 4 weeks after immobilization. CONCLUSIONS: These results suggest that immobilization induces skin fibrosis with accumulation of types I and III collagen. These fibrotic changes may be evoked by upregulation of TGF-ß1 after one week of immobilization. Additionally, upregulation of HIF-1α may relate to skin fibrosis by accelerating the differentiation of fibroblasts to myofibroblasts starting at 2 weeks after immobilization.

Prediction of prognosis of upper-extremity function following stroke-related paralysis using brain imaging.

[Purpose] Diffusion tensor imaging (DTI) has attracted attention as a method for determining prognosis following paralysis after stroke. However, DTI can assess the degree of damage to the corticospinal tract but cannot evaluate other brain regions. In this study, we examined in detail the prognosis of upper-limb function of the paralyzed side following stroke, using DTI and voxel-based morphometry (VBM). [Subjects and Methods] We studied 17 consecutive patients diagnosed with stroke, including hemorrhagic and ischemic types, who exhibited hemiparesis and were treated in our hospital. DTI and VBM were performed 14 days after admission. Outcome measurements that assessed upper limb function were Fugl-Meyer Assessment (FMA) and Motor Activity Log (MAL), which were applied after 3 months. [Results] The fractional anisotropy ratio of the bilateral cerebral peduncles (rFA) was significantly correlated with FMA, amount of use, and quality of movement 3 months after stroke. The precentral gyrus significantly degenerated as compared with the control group for a case with notable motor paralysis, for which rFA was high. [Conclusion] We suggest it may be possible to predict recovery of upper limb function following stroke by combining DTI and VBM visualization methods.

Upregulation of interleukin-1ß/transforming growth factor-ß1 and hypoxia relate to molecular mechanisms underlying immobilization-induced muscle contracture.

INTRODUCTION: In this study we investigated the molecular mechanism underlying muscle contracture in rats. METHODS: The rats were divided into immobilization and control groups, and soleus muscles of the right and left sides were selected for analyses. RESULTS: The levels of CD11b and α-SMA protein, IL-1ß, and TGF-ß1 mRNA, and type I and III collagen protein and mRNA were significantly greater in the immobilization group than in the control group at all time-points. HIF-1α mRNA levels were significantly higher in the immobilization group at 4 weeks. Moreover, HIF-1α, α-SMA, and type I collagen levels were significantly higher at 4 weeks than at 1 and 2 weeks in the immobilization group. CONCLUSIONS: In the early stages of immobilization, upregulation of IL-1ß/TGF-ß1 via macrophages may promote fibroblast differentiation that could affect muscle contracture. The soleus muscle became hypoxic in the later stages of immobilization, suggesting that hypoxia influences the progression of muscle contracture.

Effects of Isometric Quadriceps Muscle Exercise with Visual and Auditory Feedback at 1 Year after Total Knee Arthroplasty.

OBJECTIVE: To examine the effect of isometric quadriceps exercises with visual and auditory feedback after total knee arthroplasty (TKA). METHODS: The sample included 41 patients from our previous study who could be followed up for 1 year after TKA. Patients in the intervention group performed isometric quadriceps exercises with visual and auditory feedback using the quadriceps training machine from the 2nd to the 14th day after TKA, whereas those in the control group underwent standard postoperative rehabilitation (without visual or auditory feedback during isometric quadriceps exercises) in the hospital. Patients were evaluated for pain intensity, timed up and go test (TUG) score, 10-m gait speed, 6-minute walking distance (6MWD), and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score 1 year after TKA. Additionally, exercise habits and responses to the International Physical Activity Questionnaire (IPAQ) were investigated. RESULTS: Pain intensity was significantly lower in the intervention group than in the control group. Greater improvements in the TUG test scores, 10-m gait speed, 6MWD, and WOMAC scores were observed in the intervention group. Walking activity, as recorded by the IPAQ, and the proportion of patients with exercise habits were significantly higher in the intervention group than in the control group. CONCLUSIONS: These results suggest that performing isometric quadriceps exercise with visual and auditory feedback using the quadriceps training machine has good effects, such as pain reduction, physical function improvement, exercise tolerance, and increased physical activity at 1 year after TKA.

Low-intensity pulsed ultrasound phonophoresis with diclofenac alleviated inflammation and pain via downregulation of M1 macrophages in rats with carrageenan-induced knee joint arthritis.

Objective: This study aimed to investigate the effects of low-intensity pulsed ultrasound (LIPUS) phonophoresis with diclofenac on inflammation and pain in the acute phase of carrageenan-induced arthritis in rats. Design: 60 male Wistar rats were randomly divided into the arthritis, diclofenac, LIPUS, phonophoresis, and sham-arthritis control groups. LIPUS and transdermal diclofenac gel were applied to the lateral side of the inflamed knee for 7 days, initiated postinjection day 1. In the phonophoresis group, diclofenac gel was rubbed onto the skin, followed by LIPUS application over the medication. Knee joint transverse diameters, pressure pain thresholds (PPTs), and paw withdrawal thresholds (PWT) were evaluated. The number of CD68-, CD11c-, and CD206-positive cells, and IL-1ß and COX-2 mRNA expression were analyzed 8 days after injection. Results: In the phonophoresis group, the transverse diameter, PPT, PWT significantly recovered at the day 8 compared to those in the LIPUS and diclofenac groups. The number of CD68- and CD11c-positive cells in the phonophoresis group was significantly lower than that in the LIPUS and diclofenac groups, but no significant differences were observed among three groups in CD206-positive cells. IL-1ß and COX-2 mRNA levels were lower in the phonophoresis group than in the arthritis group, although there were no differences among the LIPUS, diclofenac, and phonophoresis groups. Conclusion: LIPUS phonophoresis with diclofenac is more effective to ameliorate inflammation and pain compared to diclofenac or LIPUS alone, and the mechanism involves the decrease of M1 macrophages.

Effects of a Rehabilitation Program Combined with Pain Management That Targets Pain Perception and Activity Avoidance in Older Patients with Acute Vertebral Compression Fracture: a Randomised Controlled Trial.

This study aimed to investigate the effect of a rehabilitation program combined with pain management targeting pain perception and activity avoidance on multifaceted outcomes in older patients with acute vertebral compression fractures (VCFs). We randomised 65 older adults with acute VCFs to either an intervention group (n = 32), involving usual rehabilitation combined with pain management that targeted pain perception and activity avoidance, or a control group (n = 33), involving only usual rehabilitation. The usual rehabilitation was initiated immediately after admission. All patients were treated conservatively. Pain management aimed to improve the patients' daily behaviour by increasing their daily activities despite pain, rather than by focusing on eliminating the pain. Pain intensity and psychological statuses such as depression, pain catastrophising, and physical activity levels were assessed on admission. Two weeks postadmission and at discharge, physical performance measures were assessed along with the above-given measurements. A significant main effect of the group was observed for the intensity of lower back pain, favouring the intervention group (F = 5.135, p = 0.027). At discharge, it was significantly better in the intervention group than in the control group (p = 0.011). A time-by-group interaction emerged for magnification of the pain catastrophising scale (p = 0.012), physical activity levels (p < 0.001), and six-minute walking distance (p = 0.006), all favouring the intervention group. Rehabilitation programs combined with pain management targeting pain perception and activity avoidance could be an effective conservative treatment for older patients with acute VCFs.

The Relationship Between Physical Activity and Limited Range of Motion in the Older Bedridden Patients.

Background: The purpose of this study is to examine the association between physical activity and contracture in older patients confined to bed in long-term care (LTC) facilities. Methods: Patients wore ActiGraph GT3X+ for 8 hours on their wrists, and vector magnitude (VM) counts were obtained as the amount of activity. The passive range of motion (ROM) of joints was measured. The severity of ROM restriction classified, as the tertile value of the reference ROM of each joint, was scored 1-3 points. Spearman's rank correlation coefficients (Rs) were used to measure the association between the VM counts per day and ROM restrictions. Results: The sample comprised 128 patients with a mean (SD) age of 84.8 (8.8) years. The mean (SD) of VM was 84574.6 (115195.2) per day. ROM restriction was observed in most joints and movement directions. ROMs in all joints and movement directions, except wrist flexion and hip abduction, were significantly correlated with VM. Furthermore, the VM and ROM severity scores showed a significant negative correlation (Rs = -0.582, p < .0001). Conclusions: A significant correlation between the physical activity and ROM restrictions indicates that a decrease in the amount of physical activity could be one of the causes of contracture.

Short-Term Effects of Isometric Quadriceps Muscle Exercise with Auditory and Visual Feedback on Pain, Physical Function, and Performance after Total Knee Arthroplasty: A Randomized Controlled Trial.

Severe acute pain after total knee arthroplasty (TKA) may cause delay in muscle strength and functional recovery, and it is a risk factor for chronic postoperative pain. Although pharmacological approaches are the typical firstline to treat acute pain; recently, nonpharmacological approaches such as exercise have been increasingly applied. The purpose of this investigation was to evaluate the effects of a rehabilitation program involving isometric quadriceps exercise with auditory and visual feedback to improve the short-term outcome after TKA. Sixty-two patients, planning a primary unilateral TKA, were randomly assigned to either an intervention group (n = 31) involving isometric quadriceps exercise with auditory and visual feedback in usual rehabilitation after TKA or a control group (n = 31) involving a standardized program for TKA. Patients in the intervention group performed the isometric quadriceps muscle exercise using the Quadriceps Training Machine from 2 to 14 days after TKA instead of the traditional quadriceps sets. Pain intensity, isometric knee extension strength, range of motion, timed up and go test (TUG), 10-m gait speed, 6-minute walking distance, the Western Ontario and McMaster University Osteoarthritis index (WOMAC), the hospital anxiety and depression scale, and the pain catastrophizing scale were assessed before TKA (baseline) and 1 to 3 weeks after TKA. Pain intensity significantly decreased in the intervention group than in the control group at 1 (p = 0.005), 2 (p = 0.002), and 3 (p = 0.010) weeks after TKA. Greater improvements in TUG (p = 0.036), 10-m gait speed (p = 0.047), WOMAC total score (p = 0.017), pain (p = 0.010), and function (p = 0.028) 3 weeks after TKA were observed in the intervention group. These results suggest that isometric quadriceps exercises with auditory and visual feedback provided early knee pain relief, possibly leading to better improvements in physical performance, and patient's perception of physical function in the early stages of postoperative TKA. Further studies should investigate whether this short-term effect is sustainable.

Relationship Between Muscle Quality or Stiffness Measured by Ultrasonography and Range of Motion in Hospitalized Older Adults.

Older adults who require nursing care have joint contractures characterized by limited range of motion (ROM). The present study investigated age-related muscle changes using ultrasonography and the relationship between ROM and muscle changes in older adults. Twenty-two healthy young adults (mean age: 23.3 y) and 60 hospitalized older adults (mean age: 86.1 y) participated. ROM of hip abduction was measured using a goniometer. Echo intensity (EI), reflecting interstitial fibrous tissue or fat within adductor longus (ADDl) was measured using B-mode ultrasonography, and strain ratio (SR), reflecting ADDl stiffness, was measured by strain elastography. The Mann-Whitney U-test and Spearman's correlation test were used for analysis. The ROM and SR of older adults were significantly lower than those of young adults (both p values <0.001). The EI was significantly higher in older adults than in young adults (p < 0.001). In older adults, the SR was moderately correlated with ROM (ρ = 0.49, p < 0.001). In conclusion, limited ROM and increase in interstitial fibrous tissue or fat and stiffness occur with aging, and the SR measured by strain elastography is useful for investigating the effect of muscle stiffness on the ROM of hospitalized older adults.

Depression, catastrophizing, and poor performance in women with persistent acute low back pain from vertebral compression fractures: A prospective study.

BACKGROUND: Research on the multi-faceted characteristics of persistent severe acute lower back pain (LBP) resulting from acute vertebral compression fractures (VCFs) is lacking. OBJECTIVE: To investigate the psychological and functional status of older patients with persistent severe acute LBP after conservative treatment of VCFs. METHODS: This prospective study included women aged 50 years and older who had acute VCFs and were admitted to the hospital. Pain intensity, depression, pain catastrophizing, activities of daily living (ADL), muscle strength, and vertebral deformity were assessed on admission. At 2 and 4 weeks post-admission, physical performance tests were performed along with the above measures. RESULTS: We divided 131 participants into severe (n= 64) and mild (n= 67) groups according to their pain intensity at 4 weeks. Compared to the mild group, the severe group showed significantly higher levels of depression and catastrophizing, with significantly poorer muscle strength and endurance. There were no significant differences in ADL and vertebral deformities between the two groups. CONCLUSIONS: Our results suggest that older patients with persistent severe acute LBP resulting from VCFs tend to be depressed and pain catastrophizing. Furthermore, persistent severe acute LBP negatively impacts endurance and muscle strength but not ADL.

Effect of exercise and/or educational interventions on physical activity and pain in patients with hip/knee osteoarthritis: A systematic review with meta-analysis.

OBJECTIVE: To investigate the effectiveness of exercise and/or educational intervention on physical activity and pain in patients with hip/knee osteoarthritis (OA) using systematic review and meta-analysis. METHODS: We searched randomized controlled trials that investigated physical activity and pain and compared exercise and/or educational intervention with usual care in patients with hip/knee OA in MEDLINE (PubMed), ProQuest, Scopus, and the Physiotherapy Evidence Database (PEDro), including all those published by April 30, 2022 and written in English. Studies that newly applied analgesics after onset of the intervention were excluded. The revised Cochrane risk-of-bias tool for randomized trials was used to assess the methodological qualities. The random-effects model was used for meta-analysis with standard mean differences using RevMan version 5.4. The body of evidence for each study was synthesized using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Twenty studies including 2,350 patients were included (7 exercise studies, 8 educational intervention studies and 5 combination studies). The meta-analysis demonstrated that there is very low evidence that combination therapy of exercise and educational intervention improve the physical activity level at the endpoint (4 articles; SMD 0.33, 95% CI 0.04 to 0.51, P = 0.03). Low evidence was observed for combination therapy reducing pain (4 articles; SMD -0.15, 95% CI -0.29 to -0.02, P = 0.03). DISCUSSION: The current evidence indicated that combination therapy of exercise and educational intervention leads to improved physical activity and pain reduction in hip/knee OA patients, but the risk of bias in each study, especially in allocation concealment, downgraded the evidence level. These findings support the use of a combination therapy of exercise and educational intervention to promote physical activity levels in patients with hip/knee OA. TRAIL REGISTRATION: There was no financial support for this research. The protocol was registered at the International Prospective Register of Systematic Reviews (registration code: CRD42020205804).

[Differences in the bone mineral density in patients with Kanemi Yusho treated before and after the age of 18 years].

This study examined patients with Kanemi Yusho. The patients' height, weight, and bone mineral density were measured. The density of the distal end of the radius was measured using dual energy X-ray absorptiometry and the calcaneum was measured with ultrasound. We also measured urine levels of cross-linked N-telopeptides of type I collagen, serum tartrate-resistant acid phosphatase 5b, serum bone-specific alkaline phosphatase, serum Ca, serum P and blood PCB level. The patient group that took PCBs when they were 0 to 18 years old (such patients were 42 to 60 years old at the time of the study) showed no correlation between the bone density of the radius and calcaneum in spite of treatment received when they were over 18 years of age (> 60 years of age at the time of the study). The bone mineral density in Kanemi Yusho was not different from the control group. The levels of only serum bone-specific alkaline phosphatase were correlated with the bone mineral density of the radius and calcaneum in patients treated when they were over 18 years of age (currently over 60 years old). PCBs might have had an effect on bone density and bone metabolism.

Voluntary Forelimbs Exercise Reduces Immobilization-Induced Mechanical Hyperalgesia in the Rat Hind Paw.

Voluntary exercise is sufficient to protect against neuropathic pain. However, it is unclear whether voluntary exercise reduces immobilization-induced hyperalgesia. We examined the effect of voluntary forelimb exercise on immobilized-induced hyperalgesia in hind paws of rats. Wistar rats were randomly divided into the (1) both hind limbs immobilized group (IM group), (2) immobilization and exercise with nonimmobilized fore limbs group (EX group), and (3) control group. In the IM and EX groups, the bilateral ankle joints of each rat were immobilized in full plantar flexion with a plaster cast for eight weeks. In the EX group, voluntary exercise using nonimmobilized forelimbs in the running wheel was administered during the immobilization period, while hind limbs were kept immobilized (60 min/day, 5 days/week). Mechanical hyperalgesia in the hind paw was measured using a digital von Frey device every week. To investigate the abnormality of primary sensory neurons and central sensitization, the number of calcitonin gene-related peptide-positive cells in the dorsal root ganglion and the expression level of calcitonin gene-related peptide in the spinal dorsal horn were analyzed by immunohistochemical staining. Immobilization-induced mechanical hyperalgesia was inhibited in the EX group compared to the IM group at three weeks after immobilization. In the EX group, the number of calcitonin gene-related peptide-positive cells in the dorsal root ganglion and the expression level of calcitonin gene-related peptide were significantly decreased compared to those in the IM group. Our results therefore suggest that voluntary forelimb exercise during hind limb immobilization partially reduces immobilization-induced hyperalgesia by suppressing that the plastic changes of the primary sensory nerves that excessively transmit pain and increased responsiveness of nociceptive neurons in the spinal dorsal horn.

Early walking time is associated with recovery of activities of daily living during hospitalization in older patients with community-acquired pneumonia: A single-center prospective study.

AIM: Pneumonia is a common disease with a high mortality rate among older adults that is associated with a decline in activities of daily living (ADL) during hospitalization. The aims of this study were to investigate the following: (i) early physical activity time among older patients hospitalized with community-acquired pneumonia; and (ii) the association of physical activity time with the recovery of ADL. METHODS: A prospective observational study was carried out in patients aged ≥65 years hospitalized with community acquired pneumonia. We measured the time spent standing and walking as physical activity time using the activPAL accelerometer from the third to the ninth day of admission. Patients underwent rehabilitation during their hospitalization, and rehabilitation effectiveness was calculated using the motor Functional Independence Measure on admission and at day 10. We used stepwise multiple regression to examine the relationship between physical activity time and rehabilitation effectiveness. RESULTS: A total of 87 patients were included in the analysis. Median (interquartile range) physical activity time was 69 min/day (43-103 min/day). In the multiple regression model, a greater daily walking time, higher cognitive and physical function, and ADL at admission were independently associated with rehabilitation effectiveness (adjusted R2  = 0.32, P < 0.0001). For every increase of 10 min/day of walking time, ADL improved by 7.8% (B = 7.8, 95% CI 1.3-14.2, P = 0.02). CONCLUSIONS: Older patients hospitalized with community-acquired pneumonia have low levels of physical activity, and increasing early walking time might be an effective strategy to accelerate the recovery of ADL. Geriatr Gerontol Int 2021; 21: 1099-1104.

Effect of belt electrode-skeletal muscle electrical stimulation on immobilization-induced muscle fibrosis.

PURPOSE: Macrophage accumulation in response to decreasing myonuclei may be the major mechanism underlying immobilization-induced muscle fibrosis in muscle contracture, an intervention strategy suppressing these lesions is necessary. Therefore, this research investigated the effect of belt electrode-skeletal muscle electrical stimulation (B-SES), a new electrical stimulation device, to the macrophage accumulation via myonuclei decrease in immobilization-induced muscle fibrosis. MATERIALS AND METHODS: 18 Wistar male rats were divided into the control group, immobilization group (with plaster cast fixation to immobilize the soleus muscles in a shortened position for 2 weeks), and B-SES group (with muscle contractile exercise through B-SES during the immobilization period). B-SES stimulation was performed at a frequency of 50 Hz and an intensity of 4.7 mA, muscle contractile exercise by B-SES was applied to the lower limb muscles for 20 minutes/session (twice a day) for 2 weeks (6 times/week). The bilateral soleus muscles were used for histological, immunohistochemical, biochemical, and molecular biological analyses. RESULTS: The number of myonuclei was significantly higher in the B-SES group than in the immobilization group, and there was no significant difference between the B-SES and control groups. The cross-sectional area of type I and II myofibers in the immobilization and B-SES groups was significantly lower than that in the control group, and the cross-sectional area of type I myofibers in the B-SES group was higher than that in the immobilization group. However, Atrogin-1 and MuRF-1 mRNA expression in the immobilization and B-SES groups was significantly higher than those in the control group. Additionally, the number of macrophages, IL-1ß, TGF-ß1, and α-SMA mRNA expression, and hydroxyproline expression was significantly lower in the control and B-SES groups than those in the immobilization group. CONCLUSION: This research surmised that muscle contractile exercise through B-SES prevented immobilization-induced muscle fibrosis, and this alteration suppressed the development of muscle contracture.