Effect of expiratory muscle training on respiratory muscle fatigue in healthy adults: a randomized controlled trial.

[Purpose] This study examined the effects of expiratory muscle training on fatigue in individual respiratory muscles. [Participants and Methods] Healthy adult males (n=31) were randomly assigned to two groups: expiratory muscle training (n=15) and normal controls (n=16). In the expiratory muscle training group, training was performed once for 15 min at 50% load of the maximum expiratory mouth pressure twice daily for 4 weeks. Respiratory muscle fatigue indicators were measured using surface electromyography as the median power frequency of each respiratory muscle at the time of measuring the maximum inspiratory mouth pressure during 20 min of inspiratory muscle loading and maximum expiratory mouth pressure. [Results] In the expiratory muscle training group, the median power frequency values of the sternocleidomastoid, rectus abdominis, and internal oblique/external oblique before expiratory muscle training significantly decreased during inspiratory muscle loading. However, no difference was observed in the median power frequency values measured before and during inspiratory muscle loading after the expiratory muscle training. In the normal controls, the median power frequency values of the sternocleidomastoid and rectus abdominis significantly decreased during inspiratory muscle loading. [Conclusion] Expiratory muscle training increased fatigue tolerance of the sternocleidomastoid, rectus abdominis, and internal and external oblique muscles in healthy individuals.

Miglustat, a glucosylceramide synthase inhibitor, mitigates liver fibrosis through TGF-ß/Smad pathway suppression in hepatic stellate cells.

Transforming growth factor (TGF)-ß/Smad pathway is implicated in the pathogenesis of liver fibrosis, a condition characterized by excessive deposition of extracellular matrix (ECM) proteins such as collagen in response to chronic inflammation. It has been reported that ceramide regulates collagen production through TGF-ß/Smad pathway activation. In this study, we examined whether miglustat, an inhibitor of glucosylceramide synthase, can suppress liver fibrosis by reducing TGF-ß/Smad pathway activity. Human hepatic stellate cells (HHSteCs) were cultured with TGF-ß and multiple miglustat concentrations to examine dose-dependent effects on the expression levels of ECM-related genes and Smad proteins. To evaluate the efficacy of miglustat for fibrosis mitigation, C57BL/6 mice were treated with carbon tetrachloride (CCl4) for 4 weeks to induce liver fibrosis, followed by combined CCl4 plus miglustat for a further 2 weeks. To examine if miglustat can also prevent fibrosis, mice were treated with CCl4 for 2 weeks, followed by CCl4 plus miglustat for 2 weeks. Miglustat dose-dependently downregulated expression of α-smooth muscle actin and ECM components in TGF-ß-treated HHSteCs. Both phosphorylation and nuclear translocation of Smad2 and Smad3 were also suppressed by miglustat treatment. Sirius-Red staining and hydroxyproline assays of model mouse liver samples revealed that miglustat reduced fibrosis, an effect accompanied by decreased expression of ECM. Our findings suggest that miglustat can both prevent and reverse liver fibrosis by inhibiting TGF-ß/Smad pathway.

Effect of hip external rotator muscle contraction on pelvic floor muscle function and the piriformis.

INTRODUCTION AND HYPOTHESIS: There is a lack of in-depth understanding of the muscles surrounding the pelvic floor muscle (PFM). The study aimed to investigate the functional relationship between PFM and hip external rotator muscles by observing the piriformis muscle thickness and displacement of the bladder base under different contraction conditions of the hip external rotator and/or PFM. We hypothesized that PFM function would be the strongest when the hip external rotator and PFM contracted simultaneously and that during PFM contraction, the piriformis muscle would act as an auxiliary muscle and show coactivation. METHODS: The participants included 13 healthy adult women (mean age 23.8 ± 2.8 years). The three contraction conditions were PFM contraction, hip external rotator contraction, and simultaneous contraction of the hip external rotator and PFM. During the tasks, the piriformis muscle thickness and bladder base displacement were measured using ultrasonography and compared among the contraction conditions using one-way analysis of variance. RESULTS: Significant differences were noted in bladder base displacement among the three contraction conditions (P < 0.01), with PFM contraction having the highest value. The piriformis muscle thickness showed the greatest increase in simultaneous contraction. CONCLUSIONS: In our study, we showed PFM contraction positively influences piriformis contraction, while PFM function operationalized by bladder base displacement was highest during PFM contraction alone.

The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells.

Previous RNA immunoprecipitation followed by proteomic approaches successfully demonstrated that Embryonic Lethal, Abnormal Vision, Drosophila-Like 1 (ELAVL1) interacts with hepatitis B virus (HBV)-derived RNAs. Although ELAVL family proteins stabilize AU-rich element (ARE)-containing mRNAs, their role in HBV transcription remains unclear. This study conducted loss-of-function assays of ELAVL1 for inducible HBV-replicating HepAD38 cells and HBx-overexpressed HepG2 cells. In addition, clinicopathological analyses in primary hepatocellular carcinoma (HCC) surgical samples were also conducted. Lentivirus-mediated short hairpin RNA knockdown of ELAVL1 resulted in a decrease in both viral RNA transcription and production of viral proteins, including HBs and HBx, probably due to RNA stabilization by ELAVL1. Cell growth of HepAD38 cells was more significantly impaired in ELAVL1-knockdown than those in the control group, with or without HBV replication, indicating that ELAVL1 is involved in proliferation by factors other than HBV-derived RNAs. Immunohistochemical analyses of 77 paired HCC surgical specimens demonstrated that diffuse ELAVL1 expression was detected more frequently in HCC tissues (61.0%) than in non-tumor tissues (27.3%). In addition, the abundant expression of ELAVL1 tended to affect postoperative recurrence in HBV-related HCC patients. In conclusion, ELAVL1 contributes not only to HBV replication but also to HCC cell growth. It may be a potent therapeutic target for HBV-related HCC treatment.

The reliability and effectiveness of shoulder joint evaluation by ultrasonography in stroke patients: deltoid muscle thickness, acromion-humeral distance, acromion-lesser tuberosity distance.

[Purpose] This study aimed to evaluate the reliability of the intraclass correlation coefficient (ICC) in measuring deltoid muscle thickness (DMT) at different angles, acromion-humeral distance (AHD), and acromion nodule tuberosity (ALT) distance in a resting position in stroke patients using ultrasonography. [Participants and Methods] We included 40 stroke patients. During the measurement of parameters by ultrasonography, we measured the deltoid muscle thickness on both sides at three test angles (0°, 30°, and 60° abduction) and AHD and ALT on both sides at 0° angle. The ICC was used to assess intra- and interrater reliability. The relationship between the hemiplegic and non-hemiplegic sides and each angle were analyzed using a two-way repeated-measure analysis of variance (ANOVA). [Results] When the shoulders were at three testing angles (0°, 30°, and 60° abduction), the deltoid muscle thickness of the hemiplegic and non-hemiplegic sides showed good reliability; the AHD and ALT of the shoulder joint at 0° angle equally showed good reliability. There was a significant difference in each abduction angle of the shoulder joint between the thickness of the hemiplegic and non-hemiplegic deltoid. [Conclusion] Measuring deltoid muscle thickness by ultrasonography showed excellent reliability and can be used in stroke patients.

Evaluation of supraspinatus muscle changes in the shoulder joint of stroke patients with hemiplegic and shoulder subluxation using ultrasonography: comparison between affected and unaffected sides.

[Purpose] The shoulder joint has a very unstable structure yet a significantly wide range of motion. Weakness of the muscles around the shoulder joint may cause shoulder joint subluxation. This study aimed to determine changes in supraspinatus muscle thickness between different shoulder abduction angles using ultrasonography and to compare differences in supraspinatus muscle thickness changes between the affected and unaffected sides depending on shoulder joint subluxation. [Participants and Methods] Forty hemiplegic patients with stroke were recruited (20 patients with and 20 without shoulder subluxation). Using ultrasonography, we measured supraspinatus muscle thickness at three shoulder joint abduction angles and calculated the differences in supraspinatus muscle thickness. Depending on subluxation, we separately analyzed the thickness and variations in the supraspinatus muscle on both the affected and unaffected sides. [Results] In stroke patients with shoulder subluxation, the difference in supraspinatus muscle thickness was significantly less in the affected side than in the unaffected side. [Conclusion] The thickness and rate of supraspinatus muscle thickness change was significantly less in the affected side than in the unaffected side in stroke patients with shoulder subluxation.

Immediate effects of neuromuscular joint-facilitation bridging exercises on walking ability and balance function in stroke patients.

[Purpose] This study aimed to examine the immediate effects of a pelvic neuromuscular joint-facilitation intervention on the walking and balance ability of patients with hemiplegia caused by cerebrovascular accidents. [Participants and Methods] A total of 15 patients with hemiplegia caused by cerebrovascular accidents underwent a neuromuscular joint-facilitation lumbar-pattern intervention (intervention group), a bridge exercise (bridge intervention group), or a neuromuscular joint-facilitation bridge intervention (neuromuscular joint-facilitation bridge group). Each intervention was randomly administered at 7-day intervals. Measurement items included the timed up-and-go test, functional reach test, 10-m maximum walking speed test, and load in the standing position. Measurements were taken before and after the intervention in each group. [Results] The timed up-and-go test result was significantly shorter in the neuromuscular joint-facilitation intervention group. Timed up-and-go test results, functional reach, 10-m walking time, and standing load (non-paralyzed side) significantly improved in the neuromuscular joint-facilitation bridge group. [Conclusion] The neuromuscular joint-facilitation bridge intervention was immediately effective in patients with hemiplegia caused by cerebrovascular accidents and improved their walking and balance ability.

Acquisition of mesenchymal-like phenotypes and overproduction of angiogenic factors in lenvatinib-resistant hepatocellular carcinoma cells.

Lenvatinib is one of the first-line drugs for patients with advanced hepatocellular carcinoma (HCC) and widely used around the world. However, the mechanisms underlying resistance to lenvatinib remain unclear. In this study, we conducted characteristic analyses of lenvatinib-resistant HCC cells. Lenvatinib-resistant HCC cell lines were established by exposure to serially escalated doses of lenvatinib over 2 months. The biological characteristics of these cells were examined by in vitro assays. To investigate the cytokine profile of lenvatinib-resistant HCC cells, the supernatant derived from lenvatinib-resistant Huh7 cells was subjected to nitrocellulose membrane-based sandwich immunoassay. Both activation of the MAPK/MEK/ERK signaling pathway and upregulation of epithelial mesenchymal transition markers were observed in lenvatinib-resistant cells. Concordant with these findings, proliferation and invasion abilities were enhanced in these cells compared with control cells. Screening of a cytokine array spotted with 105 different antibodies to human cytokines enabled us to identify 16 upregulated cytokines in lenvatinib-resistant cells. Among them, 3 angiogenic cytokines: vascular endothelial growth factor (VEGF), platelet-derived growth factor-AA (PDGF-AA), and angiogenin, were increased significantly. Conditioned medium from lenvatinib-resistant cells accelerated tube formation of human umbilical vein cells. In conclusion, lenvatinib-resistant HCC cells were characterized by enhanced proliferation and invasion abilities. These findings might contribute to the establishment of new combination therapies with lenvatinib.

Minimal detectable change in handgrip strength and usual and maximum gait speed scores in community-dwelling Japanese older adults requiring long-term care/support.

Aging is an important issue in Japan that has led to a large number of older adults requiring long-term care/support. Therefore, we determined the range of measurement error in the measurement of handgrip strength and gait speed which are representative tests. This cross-sectional study included 111 community-dwelling Japanese older adults aged ≥65 years who required long-term care/support and underwent ambulatory rehabilitation. Handgrip strength and usual and maximum gait speed were measured on two days in one single week. Minimal detectable change (MDC) was calculated. The MDC in handgrip strength was 2.9 kg for the overall population, 3.2 kg for the male participants, and 2.4 kg for the female participants. For the overall population, the MDC in usual gait speed was 0.18 m/s and that in maximum gait speed was 0.23 m/s. These MDCs are expected to be suitable for judging clinical changes because this study considered gender and typical tests.

The effects of neuromuscular joint facilitation treatment using neck patterns on the acoustic analysis of swallowing sounds in healthy adults.

[Purpose] We aimed to investigate the changes in the swallowing sounds of healthy adults during neuromuscular joint facilitation treatment using neck patterns. [Participants and Methods] A total of 20 healthy adults (10 males and 10 females; mean age, 29.2 ± 6.3 years) swallowed 10 mL of water four times under three conditions (after the neuromuscular joint facilitation neck-flexion resistance pattern, after the Shaker-type exercise, and during relaxed sitting without prior exercise [control]), randomly ordered with an interval greater than 3 days. Swallowing sounds for each water swallow were recorded using cervical auscultation. [Results] The mean amplitude of swallowing sound intensity and the mean spectral frequency were significantly higher after the neuromuscular joint facilitation neck-flexion resistance pattern and the Shaker-type exercise, in comparison with those in the control group. [Conclusion] Neuromuscular joint facilitation training with the neck-flexion resistance pattern influenced swallowing sounds to the same degree as the Shaker-type exercise, implying that this resistance pattern may enhance suprahyoid muscle contraction.

Differences in the total hip rotation range of motion between sides in healthy young Japanese adults.

[Purpose] To investigate the difference by degrees in total hip rotation range of motion (ROM) between sides and with regard to gender in healthy young Japanese adults. [Participants and Methods] Data from previously published studies were used. We utilized the left and right hip rotation ROM of 205 Japanese participants aged 18 to 25 years, who satisfied the inclusion criteria and were randomly measured three times in the prone position by the double-blind method. The average value of the three measurements was used to calculate the left-right difference of the hip total rotation ROM in the hip joints, which is the sum of the hip internal and external rotation ROM. We investigated the distribution of the total hip rotation considering the flexibility factor and its relationship with gender. [Results] We confirmed that there were seven participants with 2 SD or more and two with 3 SD or more. No significant difference was found in the left-right difference in the total hip rotation ROM, regardless of gender. [Conclusion] The distribution of left-right differences in the total hip rotation ROM in healthy young adults showed the existence of a significant left-right difference of 2 SD or more.

The immediate effects of neuromuscular joint facilitation on chronic low back pain in young and elderly people.

[Purpose] This study aimed to investigate the changes in the pain severity and muscle hardness of the multifidus and longissimus muscles of young and elderly patients with low back pain after neuromuscular joint facilitation treatment. [Participants and Methods] The participants were 13 young patients and 11 elderly patients with chronic low back pain. The neuromuscular joint facilitation lumbar approach was used in all participants. The muscle hardness of the multifidus and longissimus muscles was assessed at the L4 and L5 levels of the lumbar spine. The changes in pain severity of low back pain were assessed using a visual analogue scale before and after treatment. [Results] Visual analogue scale scores significantly decreased in both groups after treatment. The young group showed significant differences in muscle hardness pre- and post-intervention. In addition, except for the muscle hardness of the multifidus muscle before intervention, on the side with pain at the L5 level, longissimus muscle hardness was higher in the elderly, as compared to the young patient group. [Conclusion] Interventions with neuromuscular joint facilitation have an immediate effect on pain relief in young and elderly people with chronic low back pain and on muscle spasms in young people with chronic low back pain.

Immediate effects of neuromuscular joint facilitation treatment on vertebral artery blood flow.

[Purpose] The purpose of this study was to investigate the changes in blood flow velocity and the vascular diameter of vertebral arteries before and after neuromuscular joint facilitation interventions via the cervical spine approach in healthy adults. [Participants and Methods] We included 16 healthy adults (9 males and 7 females). The interventions were performed successively, separated by a one-week interval. The order of interventions was randomized. The blood-flow velocity and diameter of the vertebral artery were measured before and after the intervention. The neuromuscular joint facilitation group underwent neuromuscular joint facilitation neck flexion pattern and extension pattern training on the right side of the cervical spine, while the control group was asked to rest for 5 min. [Results] The neuromuscular joint facilitation group showed a significant increase in systolic blood flow velocity and mean blood flow velocity of the right vertebral artery after the intervention. In contrast, the control group showed no significant differences for any of the measured parameters after the intervention. [Conclusion] Neuromuscular joint facilitation intervention via the cervical spine approach may be recommended to improve vertebral artery function.

Effect of the COVID-19 lockdown period on the physical condition, living habits, and physical activity of citizens in Beijing, China.

[Purpose] We aimed to explore the effects of the COVID-19-induced lockdown in Beijing. [Participants and Methods] We distributed a web-based questionnaire survey among 1,029 Beijing citizens to inquire about their physical condition, living habits, and physical activity before and during home isolation. [Results] In the context of forced home isolation due to COVID-19, both males and females reported reductions in daily steps and weekly exercise time and significant increases in daily physical activity time and daily sitting time. The proportions of smokers, patients with metabolic syndrome, and patients with internal diseases were higher in males than in females; females had lower daily step counts and spent more time sitting. [Conclusion] The COVID-19 lockdown affected the physical condition, living habits, and physical activity of both males and females; females were more affected than males. People should be cognizant of the various effects of COVID-19 lockdowns on the body. We recommend a reasonable diet and appropriate home exercise. There is a need to develop training methods and evaluation tools for home exercises in COVID-19 lockdowns.

Effects of inner muscle resistance exercise on stress urinary incontinence: a randomized clinical controlled trial.

[Purpose] This study investigated the effects of co-contraction resistance exercises of the transverse abdominal and pelvic floor muscles in middle-aged females with stress urinary incontinence. [Participants and Methods] We included 32 females with stress urinary incontinence and divided them into two groups: the inner muscle training group and the pelvic floor muscle group. The thickness of the transverse abdominal muscle was measured during four tasks: (1) rest, (2) maximum contraction of the transverse abdominal muscle, (3) maximum contraction of the pelvic floor muscle, and (4) maximum co-contraction of the transverse abdominal and pelvic floor muscles. In the latter three tasks, measurements were obtained while the participants performed resistance movements using a Thera-band®. A home program was conducted in both groups, and the intervention lasted for 8 weeks. [Results] The cure rates for SUI were 87.5% and 68.8% in the inner muscle training and pelvic floor muscle groups, respectively. After the intervention, the thickness of the transverse abdominal muscle significantly increased in the inner muscle training groups performing maximum co-contraction of the transverse abdominal and pelvic floor muscles and maximum contraction of the transverse abdominal muscle. [Conclusion] Inner muscle training exercises are more effective than pelvic floor muscle exercises in improving inner muscle function and urinary incontinence in middle-aged females.

Curative effect of long-term intervention using a new device in patients with chronic low back pain.

[Purpose] This study aimed to observe the changes in the thickness of the transverse abdominis muscle after long-term training with a new device using ultrasound imaging and to determine the impact of these changes on chronic low back pain (CLBP). [Participants and Methods] This study included 60 participants with CLBP, who were divided into groups that adopted different positions during the training regimen: new device intervention group (NDG), sitting training group (STG), and supine training group (SPTG). Patients in the NDG used the new device during training. We measured the thickness of the transverse abdominis muscle and determined the pain level using the visual analog scale (VAS). [Results] After 8 weeks of training, the thickness of the transverse abdominis muscle changed in all the three groups, with the change being significantly greater in the NDG than in the other groups. Additionally, the VAS results indicated that the pain relief was highest when the new device was used. [Conclusion] The thickness of the transverse abdominis muscle increased the most in patients who were trained with the new interventional device, and the CLBP was significantly relieved in them.

Analysis of the relationship between the transversus abdominis and lower back pain using an ultrasound.

[Purpose] This study aimed to observe the thickness of the transverse abdominis muscle in different contraction states using ultrasound, and to investigate the diagnostic capability of transverse abdominal muscle thickness for nonspecific lower back pain. [Participants and Methods] This study included 108 healthy adults (30-50 years old), consisting of 33 participants with low back pain (13 males, 20 females; defined as those who had experienced low back pain for more than six months) and 75 participants without low back pain (22 males, 53 females). The body mass index, body trunk muscle mass, and transverse abdominal muscle thickness, measured at a static state, during the end of inspiration, end of expiration, transverse abdominis contraction, and simultaneous pelvic floor and transverse abdominis muscle contraction, were measured. [Results] Chronic low back pain was correlated with the transverse abdominis muscle thickness during simultaneous transverse abdominis and pelvic floor muscle contraction. [Conclusion] The thickness of the transverse abdominis muscle during simultaneous transverse abdominis and pelvic floor muscle contraction was a viable diagnostic index for evaluating the degree of chronic lower back pain.

Reliability of the infrared motion-time acquisition system for each motion segment in the timed up-and-go test.

[Purpose] This study aimed to investigate the reliability of an infrared motion-time acquisition system by measuring the time taken for five motion segments (sit-to-stand, forward gait, mid-turn, return gait, and turn-stand-to-sit) in the timed up-and-go test. [Participants and Methods] In total, 30 healthy adults (25.1 ± 4.6 years, 19 males and 11 females) were included in this study. Tester A and Tester B measured the time taken in the timed up-and-go test and its five motion segments with an infrared motion-time acquisition system, and two measurements were made by Tester A and one by Tester B. [Results] Intraclass correlation coefficients of the time taken for the five motion segments in the timed up-and-go test and the intra- and inter-rater intraclass correlation coefficients were greater than 0.9. [Conclusion] Infrared motion-time acquisition systems and its five motion segments are reliable and provide accurate measurements during the timed up-and-go test.

Measurement reliability and cooperative movement of the pelvic floor and transverse abdominal muscles.

[Purpose] This study examined the measurement reliability and cooperative movement of the pelvic floor and transverse abdominal muscles. [Participants and Methods] The participants were seven healthy adult females. Transverse abdominal muscle thickness and bladder floor elevation were measured under the following conditions during active exercise and during resistance exercise: the resting state, maximum contraction of the transverse abdominal muscle, maximum contraction of the pelvic floor muscle, and maximum co-contraction of the transverse abdominal and pelvic floor muscles. Measurements were taken at rest and under each exercise condition. [Results] The intraclass correlation coefficients of transverse abdominal muscle thickness and bladder floor elevation showed high reproducibility under all conditions. The maximum contraction of the pelvic floor muscle showed a high correlation with the maximum co-contraction of the transverse abdominal muscle and pelvic floor muscle during resistance exercise. A significant regression line was found between transverse abdominal muscle thickness and bladder floor elevation under all conditions. The regression equation was as follows: transverse abdominal muscle thickness=0.113 bladder floor elevation+0.377 (r2=0.21). [Conclusion] This study demonstrated that the measurement reliability of the transverse abdominal and pelvic floor muscles is high, and that both muscles exhibit cooperative movement.

Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan.

Background Conversion from sorafenib to regorafenib is primarily an evidence-based treatment strategy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the safety and efficacy of sequential therapy with sorafenib and regorafenib in patients with advanced HCC by analysis of outcomes in clinical practice with the aim to complement phase III findings. Methods The medical records of patients with advanced HCC receiving regorafenib were retrieved to collect data on sorafenib administration at seven Japanese institutions. Radiological responses and adverse events were evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Common Terminology Criteria for Adverse Events version 4.0, respectively. Results Before March 2018, 44 patients were administered regorafenib for advanced HCC. The median sorafenib treatment duration was 8.4 months. The most common adverse events were similar to those reported by the RESORCE trial. The median overall survival (OS) was 17.3 months (95% confidence interval [CI] 11.4-22.9), and 17 of 37 patients (45.9%) discontinued regorafenib and received sequential systemic therapy after regorafenib. These patients had significantly longer OS than those who were treated by the best supportive care or sub-optimal therapy (not reached versus 8.7 months [95% CI 5.8-11.7]; P < 0.001). Conclusion The results based on Japanese clinical practices verified the tolerability of regorafenib in advanced HCC. Major regorafenib-associated adverse events were similar to those related to sorafenib. OS was significantly longer than expected, which might be associated with the sequential systemic therapies after regorafenib, mainly lenvatinib.