PRMT5-mediated methylation of STAT3 is required for lung cancer stem cell maintenance and tumour growth.

STAT3 is constitutively activated in many cancer types, including lung cancer, and can induce cancer cell proliferation and cancer stem cell (CSC) maintenance. STAT3 is activated by tyrosine kinases, such as JAK and SRC, but the mechanism by which STAT3 maintains its activated state in cancer cells remains unclear. Here, we show that PRMT5 directly methylates STAT3 and enhances its activated tyrosine phosphorylation in non-small cell lung cancer (NSCLC) cells. PRMT5 expression is also induced by STAT3, suggesting the presence of a positive feedback loop in cancer cells. Furthermore, methylation of STAT3 at arginine 609 by PRMT5 is important for its transcriptional activity and support of tumour growth and CSC maintenance. Indeed, NSCLC cells expressing the STAT3 mutant which R609 was replaced to alanine (R609K) show significantly impaired tumour growth in nude mice. Overall, our study reveals a mechanism by which STAT3 remains activated in NSCLC and provides a new target for cancer therapeutic approaches.

Validity of Spatio-Temporal Gait Parameters in Healthy Young Adults Using a Motion-Sensor-Based Gait Analysis System (ORPHE ANALYTICS) during Walking and Running.

Motion sensors are widely used for gait analysis. The validity of commercial gait analysis systems is of great interest because calculating position/angle-level gait parameters potentially produces an error in the integration process of the motion sensor data; moreover, the validity of ORPHE ANALYTICS, a motion-sensor-based gait analysis system, has not yet been examined. We examined the validity of the gait parameters calculated using ORPHE ANALYTICS relative to those calculated using conventional optical motion capture. Nine young adults performed gait tasks on a treadmill at speeds of 2−12 km/h. The three-dimensional position data and acceleration and angular velocity data of the feet were collected. The gait parameters were calculated from motion sensor data using ORPHE ANALYTICS, and optical motion capture data. Intraclass correlation coefficients [ICC(2,1)] were calculated for relative validities. Eight items, namely, stride duration, stride length, stride frequency, stride speed, vertical height, stance phase duration, swing phase duration, and sagittal angleIC exhibited excellent relative validities [ICC(2,1) > 0.9]. In contrast, sagittal angleTO and frontal angleIC demonstrated good [ICC(2,1) = 0.892−0.833] and moderate relative validity [ICC(2,1) = 0.566−0.627], respectively. ORPHE ANALYTICS was found to exhibit excellent relative validities for most gait parameters. These results suggest its feasibility for gait analysis outside the laboratory setting.

The Therapeutic Effects of Goreisan, a Traditional Japanese Herbal Medicine, on Lower-Limb Lymphedema after Lymphadenectomy in Gynecologic Malignancies: A Case Series Study.

BACKGROUND: Lower-limb lymphedema (LLL) is a chronic and progressive complication of gynecologic cancer treatment, including pelvic lymphadenectomy. This study aims to investigate the therapeutic effect of goreisan, a traditional Japanese medicine, which has been used for hydrostatic modulation on patients with LLL. METHODS: Patients diagnosed with LLL in our hospital in 2018 were included and principally treated with complex decongestive therapy (CDT), including elastic clothing and lymph drainage. The patients who received a combination therapy of CDT and goreisan (CDT-G group) were prescribed goreisan extract granules, with a dose of 7.5 g per os daily in three doses. Patients who were not prescribed goreisan received CDT alone (CDT group). The severity of lymphedema was evaluated by the estimated limb volume calculated by limb circumferences and the ratio of extracellular water (ECW) to total body water (TBW). RESULTS: Nineteen women with LLL after pelvic lymphadenectomy were included in the study. The number of patients in the CDT and CDT-G groups was 8 and 11, respectively. There were no statistically significant differences between the CDT and CDT-G groups in terms of patient characteristics and severity of LLL before treatment. Reduction in ECW/TBW in the CDT-G group (in the whole body and the affected lower limb) after the intervention was significantly more remarkable than that in the CDT group. CONCLUSIONS: Goreisan-based Japanese herbal therapy may be effective in patients with LLL after retroperitoneal lymphadenectomy.

Back muscle activity and sagittal spinal alignment during quadruped upper and lower extremity lift in young men with low back pain history.

BACKGROUND: Quadruped upper and lower extremity lift (QULEL) is performed for selective training of the lumbar multifidus muscle in patients with low back pain (LBP) or individuals with LBP history (LBPH). However, the activities of the back muscles and sagittal spinal alignment during QULEL are not clarified in individuals with LBPH. RESEARCH QUESTION: This study aimed to analyze the activities of the back muscles and sagittal spinal alignment during QULEL in young male with LBPH. METHODS: The study comprised 9 asymptomatic young men and 8 young men with LBPH. The activities of the lumbar multifidus, latissimus dorsi and thoracic erector spinae, and lumbar erector spinae muscles were measured using surface electromyography. The flexion angles of the upper and lower thoracic spine, and extension angle of the lumbar spine were measured using a 6-DF electromagnetic motion tracking system. The association with LBPH was investigated using multiple logistic regression analysis with a forward selection method, with the activities of the back muscles, sagittal spinal alignment, age, body height, and body weight as independent variables. RESULTS: Multiple logistic regression analysis (p = 0.0002) showed that the activity of the latissimus dorsi and thoracic erector spinae muscles in the side on which the lower extremity was lifted and body height were significant and independent determinants of LBPH, but other factors were not. SIGNIFICANCE: The results of this study suggest that the activity of the latissimus dorsi and thoracic erector spinae muscles increases while there are no decrease in activity of the lumbar multifidus muscle and excessive extension of the lumbar spine during QULEL in young men with LBPH.

[Hypotonic Versus Isotonic Electrolyte Solution for Perioperative Fluid Therapy in Infants].

BACKGROUND: This study was designed to evaluate the effects of perioperative administration of an isotonic electrolyte solution with 1% glucose (IT) on blood sodium (Na+) and blood glucose (BG) concentrations in pediatric patients < 1-year-old undergoing plastic surgery in comparison with a conventional hypotonic electrolyte solution with 2.6% glucose (HT). METHODS: Fifty Patients were randomly allocated to HT group and IT group. Na+ and BG were measured at induction of anesthesia (Tind), the end of surgery (Tend), and 4 hours after surgery (T4h). RESULTS: Patient characteristics were similar for the 2 groups. In the HT group, Na+ at Tend insignificantly dropped compared with that at Tind, whereas in the IT group Na+ was significantly elevated. Na+ at T4h significantly increased compared with that at Tend in each group. No cases developed new dysnatremia or dysglycemia in IT group. The incidence of hyponatremia at Tend was significantly lower in the IT group. A positive correlation between intraoperative Na+ concentration changes and the infusion duration was observed in the IT group. CONCLUSIONS: Isotonic solution with 1% glucose is suggested to be safe in infants during and after surgery.

Immediate effect of Masai Barefoot Technology shoes on knee joint moments in women with knee osteoarthritis.

Footwear modification can beneficially alter knee loading in patients with knee osteoarthritis. This study evaluated the effect of Masai Barefoot Technology shoes on reductions in external knee moments in patients with knee osteoarthritis. Three-dimensional motion analysis was used to examine the effect of Masai Barefoot Technology versus control shoes on the knee adduction and flexion moments in 17 women (mean age, 63.6 years) with radiographically confirmed knee osteoarthritis. The lateral and anterior trunk lean values, knee flexion and adduction angles, and ground reaction force were also evaluated. The influence of the original walking pattern on the changes in knee moments with Masai Barefoot Technology shoes was evaluated. The knee flexion moment in early stance was significantly reduced while walking with the Masai Barefoot Technology shoes (0.25±0.14Nm/kgm) as compared with walking with control shoes (0.30±0.19 Nm/kgm); whereas the knee adduction moment showed no changes. Masai Barefoot Technology shoes did not increase compensatory lateral and anterior trunk lean. The degree of knee flexion moment in the original walking pattern with control shoes was correlated directly with its reduction when wearing Masai Barefoot Technology shoes by multiple linear regression analysis (adjusted R2=0.44, P<0.01). Masai Barefoot Technology shoes reduced the knee flexion moment during walking without increasing the compensatory trunk lean and may therefore reduce external knee loading in women with knee osteoarthritis.

Kinematic characteristics of the scapula and clavicle during military press exercise and shoulder flexion.

BACKGROUND: The military press is an exercise frequently prescribed for scapular and shoulder rehabilitation. Although this exercise has previously been analyzed by electromyography, its kinematic features remain poorly understood. In this study, we aimed to clarify these features of the military press and suggest relevant clinical applications. METHODS: Sixteen healthy men participated in this study. The participants performed the military press while holding 2 kg weights, as well as shoulder flexion with and without 2 kg weights, and an electromagnetic motion capture system was used to analyze the kinematic features of the scapula, clavicle, and humerus during these exercises. The motions of the scapula and clavicle were analyzed at 10° increments of shoulder flexion from 30° to 120°. RESULTS: The military press involved less scapular internal rotation, greater upward rotation, and greater posterior tilt than shoulder flexion with or without weights, especially in the starting to middle range of shoulder flexion. Greater clavicular retraction and elevation were also seen during the military press. DISCUSSION: The movements of the scapula and clavicle during the military press differ significantly from those during shoulder flexion with and without weights. The kinematic features of the military press, which involved less scapular internal rotation, greater upward rotation, and greater posterior tilt than did shoulder flexion, may make it a useful re-education exercise (if pain allows) for patients with decreased scapular external rotation, upward rotation, and posterior tilting. The results of this study might provide a kinematic basis for the use of this widely performed shoulder exercise.

[A case of sarcoidosis with superior vena cava syndrome diagnosed by mediastinoscopy].

A bilateral hilar lymphadenopathy on the chest radiograph of a 30-year-old man was pointed out in a medical examination. Four months later, he was admitted to our hospital because of exacerbation of a bilateral hilar lymphadenopathy on the chest radiograph with high fever. Physical examination revealed a marked swelling of the face and upper arms as well as a dilated jugular vein. The fever, which was his chief complaint, responded to antibiotic therapy. A CT scan of the chest confirmed the presence of bilateral mediastinal lymphadenopathy and hilar lymphadenopathy, which caused pulmonary artery and superior vena cava stenosis. A superior vena cavagram demonstrated narrowing of the vessel. Mediastinoscopy was performed for definite diagnosis. Pathologic examination of the specimen revealed noncaseating epithelioid cell granuloma consistent with sarcoidosis. He was asymptomatic. Pulmonary function and arterial blood gas studies yielded almost normal results. A roentgenographic stage of intrathoracic change was Stage I. On the basis of these findings, he was observed carefully without systemic corticosteroid therapy. One month later, the swelling of his face and upper arms was improved, and the pulmonary functions and arterial blood gases remained almost normal. Only seven cases of sarcoidosis causing superior vena cava syndrome have been reported. This is the first case reported in Japan.

[A case of primary lung cancer with initial symptoms due to orbital metastases].

We encountered a case of lung cancer in which symptoms due to orbital metastasis were recognized. A 55-year-old man presented with a chief complaint of double vision. Orbital MR image demonstrated a right intraorbital mass with bone destruction, which resulted in oculomotor nerve palsy and optic nerve disturbance. Chest CT scan showed a 4 cm mass in the right S6, which was diagnosed on biopsy as a poorly differentiated adenocarcinoma. A whole-body scintigram revealed multiple bone metastases: the right orbital wall, the lower cervical spine, the left knee joint, and so on. Based on the clinical findings, we believed that the orbital tumor was a metastasis from the lung. Systemic chemotherapy and irradiation of the right orbital tumor and the left knee joint were performed. Though a favorable response was achieved in ocular movement, the patient died 3 months after initial treatment because of progression of the primary lesion. Including this case, seventeen reported cases in which lung cancer metastasized to the orbit in Japan were also reviewed.

An investigation of monoamine receptors involved in antinociceptive effects of antidepressants.

UNLABELLED: We attempted to determine which monoamine receptor subtypes are predominantly involved in antidepressant-induced antinociception. Antinociceptive effects were evaluated by using formalin tests with rats. Antidepressants acting as potent inhibitors of norepinephrine reuptake (nisoxetine, nortriptyline, and maprotiline) or inhibiting reuptake of both norepinephrine and serotonin (5-HT) (imipramine and milnacipran) induced dose-dependent antinociception. Simultaneous intraperitoneal administration of antidepressants and either prazosin (alpha(1) antagonist) or ketanserin (5-HT(2) antagonist) significantly antagonized antinociceptive effects. Fluvoxamine (selective serotonin reuptake inhibitor) induced antinociception less potently than other antidepressants and was significantly antagonized by ketanserin, but not prazosin. Ondansetron (5-HT(3) antagonist) significantly antagonized antinociception by 10 mg/kg of imipramine. In contrast, SDZ-205,557 (5-HT(4) antagonist) markedly enhanced antinociception by small-dose (2.5 mg/kg) imipramine. Imipramine-induced antinociception was significantly antagonized by intracerebroventricular administration of prazosin or ketanserin, but not by yohimbine (alpha(2) antagonist) or ondansetron, and was significantly enhanced by intracerebroventricularly administered SDZ-205,557. These findings suggest that alpha(1) adrenoceptors and 5-HT(2) receptors in the brain are involved in antidepressant-induced antinociception. In addition, the results suggested functional interactions between noradrenergic and serotonergic neurons as mechanisms for antidepressant-induced antinociception. IMPLICATIONS: Formalin tests of rats treated with antidepressants and antagonists of monoamine receptors indicate that alpha(1) adrenoceptors, serotonin (5-HT)(2) receptors, and 5-HT(3) receptors are involved in antidepressant-induced antinociception, suggesting functional interactions between noradrenergic and serotonergic neurons as mechanisms of antidepressant-induced antinociception.