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Chih-Ying Wu,1– 3 Li-Wei Chou,4– 6 Shih-Wei Huang,7 Wen-Ling Liao,1,8 Shiaw-Meng Chang,9 Han-Chung Lee,10 Cheng-Di Chiu,3,11– 14 Chih-Hsin Tang,13,15– 18 Ching-Liang Hsieh16,19,20 1Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; 2Department of Neurosurgery, China Medical University Hsinchu Hospital, China Medical University, Hsinchu, Taiwan; 3Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan; 4Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; 5Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; 6Department of Physical Medicine and Rehabilitation, Asia University Hospital, Asia University, Taichung, Taiwan; 7Department of Traditional Chinese Medicine, China Medical University Hsinchu Hospital, China Medical University, Hsinchu, Taiwan; 8Center for Personalized Medicine, China Medical University Hospital, Taichung, Taiwan; 9Department of Industrial Engineering and Engineering Management, National Tsing Hua University, Hsinchu, Taiwan; 10Neuroscience center, Everan Hospital, Taichung, Taiwan; 11Spine Center, China Medical University Hospital, Taichung, Taiwan; 12School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; 13Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan; 14Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; 15Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan; 16Chinese Medicine Research Center, China Medical University, Taichung, Taiwan; 17Department of Medical Laboratory Science and Biotechnology, College of Health Science, Asia University, Taichung, Taiwan; 18Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan; 19Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; 20Graduate Institute of Acupuncture Science, China Medical University, Taichung, TaiwanCorrespondence: Chih-Hsin Tang, Graduate Institute of Biomedical Science, College of Medicine, China Medical University, Taichung, 40402, Taiwan, Email chtang@mail.cmu.edu.tw Ching-Liang Hsieh, Graduate Institute of Acupuncture Science, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan, Tel +886-4-22053366, Fax +886-4-22037690, Email clhsieh0826@gmail.comBackground: Fu’s subcutaneous needling (FSN) is a novel acupuncture technique for pain treatment. This study investigated the effects of postsurgical FSN on postoperative pain in patients receiving surgery for degenerative spinal disorders.Methods: This single-center, single-blind, randomized-controlled study involved patients undergoing surgery for degenerative spinal disorders. Participants were randomized into either an FSN group or a control group that received sham FSN. The primary outcomes were scores on the Brief Pain Inventory Taiwan version (BPI-T) and Oswestry Disability Index before and at 1, 24, and 48 hours after surgery. Secondary outcomes were muscle hardness, pethidine use, and inflammatory biomarker presence.Results: Initially, 51 patients met the inclusion criteria and were allocated (26 in the FSN group and 25 in the control group). Two patients were lost to follow-up, and finally, 49 patients (25 in the FSN group and 24 in the control group) who completed the study were analyzed. The FSN group had significantly lower pain intensity measured on the BPI-T compared with the control group at 1, 24, 48, and 72 hours after surgical treatment (all p < 0.001). Additionally, pain interference as measured on the BPI-T was lower in the FSN group than in the control group 1 hour (p = 0.001), 24 hours (p = 0.018), 48 hours (p = 0.001), and 72 hours (p = 0.017) after surgical treatment. Finally, the FSN group exhibited less muscle hardness in the latissimus dorsi and gluteus maximus 24, 48, and 72 hours (all p < 0.05) after surgery compared with the control group; patients in the FSN group also exhibited less muscle hardness in the L3 paraspinal muscle 48 hours (p = 0.001) and 72 hours (p < 0.001) after surgery compared with the control group. There were no significant differences in serum CRP, IL-1β, IL-2, IL-6, and TNF-α levels between the FSN and control groups at 24 hours, 72 hours, and 1-month post-surgery (all p > 0.05).Conclusion: FSN treatment can reduce postoperative pain in patients receiving surgery for degenerative spinal disorders. However, larger sample sizes and multicenter clinical trials are required to verify these findings.Keywords: Fu’s subcutaneous needling, degenerative spinal disorders, postoperative pain, surgical treatment, clinical trial

Cheng-Hao Huang,1,2 Mei-Chen Lin,3,4 I-Ching Chou,5,6 Ching-Liang Hsieh2,7,8 1Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung City, 40402, Taiwan; 2Department of Chinese Medicine, China Medical University Hospital, Taichung City, 40447, Taiwan; 3Management Office for Health Data, China Medical University Hospital, Taichung, 40447, Taiwan; 4College of Medicine, China Medical University, Taichung, 40402, Taiwan; 5School of Chinese Medicine, China Medical University, Taichung City, 40402, Taiwan; 6Division of Pediatric Neurology, China Medical University Children’s Hospital, Taichung City, 40447, Taiwan; 7Chinese Medicine Research Center, China Medical University, Taichung City, 40402, Taiwan; 8Graduate Institute of Acupuncture Science, China Medical University, Taichung City, 40402, TaiwanCorrespondence: Ching-Liang Hsieh, Graduate Institute of Acupuncture Science, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan, Tel +886-4-22053366 ext. 3128, Fax +886-4-22037690, Email clhsieh@mail.cmuh.org.twBackground: Migraine is a recurrent headache disease that has been identified as a risk factor for subsequent dementia. The present study collected data from Taiwan’s National Health Insurance Research Database (NHIRD) to investigate the incidence of dementia in patients with migraine who did or did not concurrently receive acupuncture treatment.Methods: A 1:1 propensity score method was used to match an equal number of patients (N = 4813) in the acupuncture and nonacupuncture cohorts based on sex, age, migraine diagnosis year, index year, insurance amount, urbanization level, baseline comorbidities, and medication usage. We employed Cox proportional hazards models to evaluate the risk of dementia.Results: Patients with migraine who received acupuncture treatment were found to have a lower risk of dementia (adjusted hazard ratio [aHR] = 0.51, 95% CI = 0.40– 0.65) than those who did not undergo acupuncture treatment. The cumulative incidence of dementia was significantly lower in the acupuncture cohort than in the nonacupuncture cohort (Log rank test, p < 0.001). This propensity score–matched cohort study demonstrated an association between acupuncture treatment and dementia development in patients with migraine in Taiwan.Conclusion: The results suggest that acupuncture treatment significantly reduced the development of dementia in patients with migraine.Keywords: acupuncture, migraine, dementia, National Health Insurance Research Database, NHIRD, propensity score, cohort

Chi-Lun Rau,1 Jing-Lan Yang,2 Jiu-Jenq Lin,2,3 Pei-Chi Wu,4 Chieh-Yi Hou,5 Chen-Yi Song,6 Ching-Lin Hsieh2,7,8 1Department of Physical Medicine and Rehabilitation, Shuang Ho Hospital, Taipei Medical University, Taiwan; 2Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taiwan; 3School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan University, Taiwan; 4Department of Physical Medicine and Rehabilitation, E-Da Hospital, Taiwan; 5Department of Physical Medicine and Rehabilitation, E-Da Cancer Hospital, Taiwan; 6Department of Long-Term Care, National Taipei University of Nursing and Health Sciences, Taiwan; 7School of Occupational Therapy, College of Medicine, National Taiwan University, Taiwan; 8Department of Occupational Therapy, College of Medical and Health Science, Asia University, Taiwan Background: Pain quality assessment is applicable to pain evaluation and treatment. However, shoulder pain quality descriptors mostly remain unknown. Furthermore, sex-related differences considerably affect clinical pain experience. The aim of this study was to investigate pain quality descriptors and to compare sex-related differences in using pain descriptors among patients with shoulder pain. Materials and methods: A sample of 120 patients (41 males and 79 females) with shoulder pain was recruited from Department of Physical Medicine and Rehabilitation. Shoulder pain quality descriptors were investigated using a 36-item pain quality list. Sex-related differences in the number and frequency of pain quality descriptors were compared using independent t-test and X2 test, respectively. Results: Fifteen commonly used shoulder pain quality descriptors were identified. Among them, “sore” was the most frequently used, followed by “pulled”. Deep pain sensations (eg, sore, pulled, torsion, and taut) were relatively more predominant than superficial pain sensations (eg, pricking and lacerating). In terms of sex-related differences, female patients used more pain quality descriptors than the male patients (5.5 vs 3.7, P

Lung-Shuo Wang,1–4 Chih-Yu Wang,2 Chih-Hui Yang,5 Chen-Ling Hsieh,3,5 Szu-Yu Chen,3,5 Chi-Yen Shen,1 Jia-Jung Wang,2 Keng-Shiang Huang3 1Department of Electrical Engineering, I-Shou University, Kaohsiung, Taiwan; 2Department of Biomedical Engineering, I-Shou University, Kaohsiung, Taiwan; 3The School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan; 4Department of Chinese Medicine, E-Da Hospital, Kaohsiung, Taiwan; 5Department of Biological Science and Technology, I-Shou University, Kaohsiung, Taiwan Abstract: Silver nanoparticles have been used in various fields, and several synthesis processes have been developed. The stability and dispersion of the synthesized nanoparticles is vital. The present article describes a novel approach for one-step synthesis of silver nanoparticles–embedded chitosan particles. The proposed approach was applied to simultaneously obtain and stabilize silver nanoparticles in a chitosan polymer matrix in-situ. The diameter of the synthesized chitosan composite particles ranged from 1.7 mm to 2.5 mm, and the embedded silver nanoparticles were measured to be 15±3.3 nm. Further, the analyses of ultraviolet-visible spectroscopy, energy dispersive spectroscopy, and X-ray diffraction were employed to characterize the prepared composites. The results show that the silver nanoparticles were distributed over the surface and interior of the chitosan spheres. The fabricated spheres had macroporous property, and could be used for many applications such as fungicidal agents in the future. Keywords: silver, nanoparticles, chitosan, anti-fungal

Sheng-Shing Lin,1,2 Chiu-Lin Tsai,3 Ching-Yeh Tu,3 Ching-Liang Hsieh2,4,5 1Graduate Institute of Chinese Medicine, College of Chinese Medicine, China Medical University, 2Department of Chinese Medicine, China Medical University Hospital, 3Division of Chinese Medicine, Department of Pharmacy, China Medical University Hospital, 4Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, 5Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung, Taiwan Background: Traditional Chinese medicine (TCM) and Western medicine are both popular in Taiwan. Approximately 14.1% of Taiwanese residents use Western drugs and Chinese herbs concurrently; therefore, drug–herb interaction is critical to patient safety. This paper presents a new procedure for reducing the risk of drug interactions.Methods: Hospital computer systems are modified to ensure that drug–herb interactions are automatically detected when a TCM practitioner is writing a prescription. A pop-up reminder appears, warning of interactions, and the practitioner may adjust doses, delete herbs, or leave the prescription unchanged. A pharmacist will receive interaction information through the system and provide health education to the patient.Results: During the 2011–2013 study period, 256 patients received 891 herbal prescriptions with potential drug–herb interactions. Three of the 50 patients who concurrently used ginseng and antidiabetic drugs manifested hypoglycemia (fasting blood sugar level ≤70 mg/dL).Conclusion: Drug–herb interactions can cause adverse reactions. A computerized reminder system can enable TCM practitioners to reduce the risk of drug–herb interactions. In addition, health education for patients is crucial in avoiding adverse reaction by the interactions. Keywords: Traditional Chinese medicine, Western medicine, adverse reaction

Li-Chen Tung,1,# Chin-Kai Lin,2,# Ching-Lin Hsieh,3,4 Ching-Chi Chen,1 Chin-Tsan Huang,1 Chun-Hou Wang5,6 1Department of Physical Medicine and Rehabilitation, Chi Mei Medical Center, Tainan, 2Program of Early Intervention, Department of Early Childhood Education, National Taichung University of Education, Taichung, 3School of Occupational Therapy, College of Medicine, National Taiwan University, Taipei, 4Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, 5School of Physical Therapy, College of Medical Science and Technology, Chung Shan Medical University, Taichung, 6Physical Therapy Room, Chung Shan Medical University Hospital, Taichung, Taiwan#These authors contributed equally Background: Articulation disorders in young children are due to defects occurring at a certain stage in sensory and motor development. Some children with functional articulation disorders may also have sensory integration dysfunction (SID). We hypothesized that speech therapy would be less efficacious in children with SID than in those without SID. Hence, the purpose of this study was to compare the efficacy of speech therapy in two groups of children with functional articulation disorders: those without and those with SID.Method: A total of 30 young children with functional articulation disorders were divided into two groups, the no-SID group (15 children) and the SID group (15 children). The number of pronunciation mistakes was evaluated before and after speech therapy.Results: There were no statistically significant differences in age, sex, sibling order, education of parents, and pretest number of mistakes in pronunciation between the two groups (P > 0.05). The mean and standard deviation in the pre- and posttest number of mistakes in pronunciation were 10.5 ± 3.2 and 3.3 ± 3.3 in the no-SID group, and 10.1 ± 2.9 and 6.9 ± 3.5 in the SID group, respectively. Results showed great changes after speech therapy treatment (F = 70.393; P > 0.001) and interaction between the pre/post speech therapy treatment and groups (F = 11.119; P = 0.002).Conclusions: Speech therapy can improve the articulation performance of children who have functional articulation disorders whether or not they have SID, but it results in significantly greater improvement in children without SID. SID may affect the treatment efficiency of speech therapy in young children with articulation disorders.Keywords: children, functional articulation disorders, sensory integration dysfunction, speech therapy, efficacy

Significant progress in obtaining high performance discharges lasting many energy confinement times in the DIII-D tokamak has been realized in recent experimental campaigns. Normalized performance ∼10 has been sustained for more than 5>E with qmin > 1.5. (The normalized performance is measured by the product βNH89, indicating the proximity to the conventional β limits and energy confinement quality, respectively.) These H mode discharges have an ELMing edge and β < 5%. The limit to increasing β is a resistive wall mode, rather than the tearing modes as previously observed. Confinement remains good despite qmin > 1. The global parameters were chosen to optimize the potential for fully non-inductive current sustainment at high performance, which is a key program goal for the DIII-D facility. Measurement of the current density and loop voltage profiles indicate that ≈75% of the current in the present discharges is sustained non-inductively. The remaining ohmic current is localized near the half-radius. The electron cyclotron heating system is being upgraded to replace this remaining current with ECCD. Density and β control, which are essential for operating advanced tokamak discharges, were demonstrated in ELMing H mode discharges with βNH89 ≈ 7 for up to 6.3 s or ≈34τE. These discharges appear to have stationary current profiles with qmin ≈ 1.05 in agreement with the current profile relaxation time ≈1.8 s.

The goals of DIII-D advanced tokamak (AT) experiments are investigation and optimization of the upper limits of energy confinement and MHD stability in a tokamak plasma, and simultaneous maximization of the fraction of non-inductive current drive. Significant overall progress has been made in the past two years, as the performance figure of merit βNH89P of 9 has been achieved in ELMing H mode for over 16τE without sawteeth. The tokamak was also operated at βNH ≈ 7 for over 35τE or 3τR, with the duration limited by the hardware. Real time feedback control of β (at 95% of the stability boundary), optimizing the plasma shape (e.g., δ, divertor strike and X points, double/single null balance) and particle control (ne/nGW ≈ 0.3, Zeff < 2.0) were necessary for the long pulse results. A new quiescent double barrier (QDB) regime with simultaneous inner and edge transport barriers and no ELMs has been discovered with a βNH89P of 7. The QDB regime has been obtained to date only with counter NBI. Further modification and control of internal transport barriers (ITBs) has also been demonstrated with impurity injection (broader barrier), pellets and ECH (strong electron barrier). The new Divertor-2000, a key ingredient in all these discharges, provides effective density, impurity and heat flux control in the high triangularity plasma shapes. Discharges at ne/nGW ≈ 1.4 have been obtained with gas puffing by maintaining the edge pedestal pressure; this operation is easier with Divertor-2000. We are developing several other tools required for AT operation, including real time feedback control of resistive wall modes with external coils and control of neoclassical tearing modes with ECCD.

Advanced tokamaks seek to achieve a high bootstrap current fraction without sacrificing fusion power density or fusion gain. Good progress has been made towards the DIII-D research goal of demonstrating a high-β advanced tokamak plasma in steady state with a relaxed, fully non-inductive current profile and a bootstrap current fraction greater than 50%. The limiting factors for transport, stability, and current profile control in advanced operating modes are discussed in this paper.

Strong shaping, favourable for stability and improved energy confinement, together with a significant expansion of the central region of improved confinement in negative central magnetic shear target plasmas, increased the maximum fusion power produced in DIII-D by a factor of 3. Using deuterium plasmas, the highest fusion power gain, the ratio of fusion power to input power, Q, was 0.0015, corresponding to an equivalent Q of 0.32 in a deuterium-tritium plasma, which is similar to values achieved in tokamaks of larger size and magnetic field. A simple transformation relating Q to the stability parameters is presented.

Accurate equilibrium reconstruction and detailed stability analysis of a strongly shaped, double-null, βT=11% discharge shows that the plasma core is in the second stable regime to ideal ballooning modes. The equilibrium reconstruction using all the available data (coil currents, poloidal magnetic loops, motional Stark effect data, the kinetic pressure profile, the magnetic axis location, and the location of the two q=1 surfaces) shows a region of negative magnetic shear near the magnetic axis, an outer positive shear region, and a low shear region connecting the two. The inner negative shear region allows a large positive shear region near the boundary, even at low q (q95=2.6), permitting a large outer region pressure gradient to be first regime stable. The inner region is in the second stable regime, consistent with the observed axial beta [βT(0)=44%]. In the low shear region p′ vanishes, consistent with Mercier stability. This is one way to extend the ballooning limit in shaped plasmas while maintaining stability against external kinks. The n=1 analysis shows that the plasma is unstable to an ideal internal mode, consistent with the experimental observations of a saturated internal m/n=l/l mode. The core plasma pressure, not being limited by ballooning stability, appears to be reaching a local equilibrium limit at the magnetic axis. © 1992 American Institute of Physics.

Recent results from the DIII-D tokamak have provided significant contributions to the understanding of many of the elements of tokamak physics and the application of this understanding to the design of next generation devices including ITER and CIT. The limitations of magnetohydrodynamic stability on the values of plasma beta (the ratio of kinetic pressure to the containing pressure of the magnetic field) that can be attained has been experimentally demonstrated and found to be described by existing theory. Values of beta (10.7%) well in excess of those required for proposed devices (ITER and CIT) have been demonstrated. Regimes of confinement (H-mode) have been established that scale favorably to proposed next generation devices, and experiments demonstrating the dependence of the energy confinement on plasma size have been completed. Understanding of confinement is rapidly developing especially in the areas of bulk transport and the role of turbulence in the plasma edge. Key experimental results in areas of plasma transport and edge plasma phenomena are in agreement with theories based on short wavelength turbulence. Control of the divertor heat loads and impurity influx has been demonstrated, and new progress has been made in the understanding of plasma edge phenomena. Experiments with ion Bernstein wave heating have not found regimes in which these waves can produce effective central ion heating. Electron cyclotron current drive experiments have demonstrated 70 kA of driven current in 400 kA discharges.

The authors' data indicate that the L-mode to H-mode transition in the DIII-D tokamak is associated with the sudden reduction in anomalous, fluctuation-connected transport across the outer midplane of the plasma. In addition to the reduction in edge density and magnetic fluctuations observed at the transition, the edge radial electric field becomes more negative after the transition. They have determined the scaling of the H-mode power threshold with various plasma parameters; the roughly linear increase with plasma density and toroidal field are particularly significant. Control of the ELM frequency and duration by adjusting neutral beam input power has allowed us to produce H-mode plasmas with constant impurity levels and durations up to 5 s. Energy confinement time in ohmic H-mode plasmas and in deuterium H-mode plasmas with deuterium beam injection can exceed saturated ohmic confinement times by at least a factor of two. Energy confinement times above 0.3 s have been achieved in these beam-heated plasmas with plasma currents in the range of 2.0 to 2.5 MA. Local transport studies have shown that electron and ion thermal diffusivities and angular momentum diffusivity are comparable in magnitude and all decrease with increasing plasma current.

We prospectively followed up patients with carpal tunnel syndrome (CTS) in our previous study for 1 year. A total of 77 consecutive patients with electrophysiologically confirmed mild-to-moderate idiopathic CTS were randomized and assigned into 2 treatment arms: 1) 2 weeks of prednisolone 20 mg daily followed by 2 weeks of prednisolone 10 mg daily (n = 39); and 2) acupuncture administered in 8 sessions over 4 weeks (n = 38). In the current study, the patients were further followed up at 7 and 13 months using Global symptom score (GSS) assessments and nerve conduction studies repeated again at 13 months. When comparing with baseline levels, the percentages of patients with treatment failure, moderate improvement, and good improvement were significantly different between the 2 groups at month 7 [10.5, 2.6, and 86.8% for the acupuncture group and 33.3, 7.7, and 59% for the steroid group, respectively (P = .014)] and month 13 [15.8, 2.6, and 81.6% versus 51.3, 0, and 48.7%, respectively (P = .002)]. The acupuncture group had a significantly better improvement in GSS, distal motor latencies and distal sensory latencies when compared to the steroid group throughout the 1-year follow-up period (P < .01). Furthermore, significant correlation was observed between changes of GSS (month 13-baseline) and all parameters of the electrophysiological assessments except for compound muscle action potential amplitude. PERSPECTIVE: This article demonstrates that short-term acupuncture treatment may result in long-term improvement in mild-to-moderate idiopathic CTS. Acupuncture treatment can be considered as an alternative therapy to other conservative treatments for those who do not opt for early surgical decompression. [ABSTRACT FROM AUTHOR]

Purpose: The survival rate of cervical cancer is increasing due to early diagnosis and timely treatment. As a result, the availability of a valid and reliable general HRQoL is important. The purpose of this study was to evaluate the psychometric properties of the EuroQol questionnaire (EQ-5D) in patients with cervical cancer in Taiwan.Method: Outpatients with cervical cancer were recruited from three medical centers across Taiwan. Test-retest reliability and ceiling effect were evaluated. Construct validity including convergent and discriminate validities were examined using the EORTC QLQ C-30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) and the clinical indicators of the functional performance assessment using the Karnofsky Performance Scale (KPS) and disease status.Results: A total of 530 patients completed the questionnaire. The intraclass correlation coefficient for the EQ-5D index was 0.83, and the Cohen's kappa values for the EQ-5D dimensions ranged from 0.54 to 0.73. The EQ-5D index and VAS scores were higher for patients with a higher KPS score and disease-free status. The EQ-5D index was strongly correlated with all EORTC QLQ-C30 functioning scales.Conclusion: The EQ-5D questionnaire is reliable and valid for the assessment of health-related quality of life in patients with cervical cancer in Taiwan. [ABSTRACT FROM AUTHOR]

Ear acupuncture stimulation has been used for body weight reduction as early as the 1970s. Several hypotheses have been proposed in literature regarding its mechanism of action, among which are the effects of the stimulation of the hypothalamic satiety center on decreased neuropeptide Y production. Here, we present another possible mechanism to account for the temporary and short-term effects of ear acupuncture stimulation in the treatment of obesity, the sympathetic effects of the autonomic nervous system. 14 female volunteers underwent a randomized clinical trial of the ear acupuncture stimulation. A prospective, sham-point control, crossover study was performed with two sequential four-week stimulation periods separated by a two-week washout interval. The clinical features of and effects on the autonomic nervous system were recorded and analyzed. Decreased body weight was observed in both the experimental and the control groups in the first 4 weeks of stimulation. Sympathomimetic effects were also noted in both groups. Whereas the sympathomimetic effects and body weight reduction were sustained in the experimental group in the second 4 weeks of stimulation, such effects were not observed in the control group. Some sympathomimetic effects were noted in both the experimental and the control groups initially. This effect remained apparent in the experimental group in sequential stimulation but was lost in the control group. Consequently, we believe that sympathomimetic effects may account for the reduction in body weight by temporarily increasing basal metabolic rate and decreasing appetite, but the body may regain weight after the termination of such effects. Accordingly, the combination of an optimal exercise and diet program with repeated acupoint therapy may be necessary to maintain a healthy body weight. [ABSTRACT FROM AUTHOR]

Panax Notoginseng Burk (PN) has been reported to improve blood circulation, as well as learning and memory functions. The purpose of the present study was to investigate the effect of PN on learning and memory functions in chronic cerebral infarct rats. A cerebral infarct animal model was established by blocking the blood flow of both common carotid arteries and right middle cerebral artery for 90 min followed by reperfusion for 4 weeks. PN (0.5 g/kg) was administered orally 3 days per week for 4 weeks, whereas the control group provided bait and water only. The learning and memory functions were estimated by measuring how successful rats were able to negotiate an 8-arm radial maze test; the test was performed after operation once a week for 4 weeks. Finally, the rats were sacrificed and their brains were removed. The brains were sectioned and analyzed for ED1, glial fibrillary acid protein (GFAP), nuclear factor-kappaB, and brain derivative neurotrophin factor (BDNF) and beta-secretase by immunostaining. Cerebral infarct rats given PN were able to successfully navigate the 8-arm radial maze test four weeks after cerebral infarction. PN also increased ED1, BDNF and beta-secretase immunoreactive cells, but did not increase GFAP and NF-kappaB immunoreactive cells. PN attenuated the reduction in learning and memory functions induced by cerebral infarction in cerebral ischemia-reperfusion injured rats; it also increased the amount of activated microglia and BDNF. These data suggest that the effect of PN, at least in part, is closely related to the increase in BDNF that was generated by activated microglia. The effect that PN has on astrocytes, NF-kappaB and beta-secreatase immunoreactive cells requires further study. [ABSTRACT FROM AUTHOR]

OBJECTIVE: . This study examined test-retest agreement and measurement errors for the Rivermead Mobility Index (RMI) and the Mobility subscale of the Stroke Rehabilitation Assessment of Movement (M-STREAM) in patients with chronic stroke and mild to moderate disability. The authors aimed to determine the level of agreement between test and retest as well as the extent to which a mobility score varies on test-retest measurements. METHODS: . Both mobility measures were tested on 50 chronic stroke patients twice, 7 days apart. Intraclass correlation coefficient (ICC(2,1)), a relative reliability index, was used to examine the level of agreement between test and retest. Absolute reliability indices, including the standard error of measurement and the smallest real differences, were used to determine the extent to which the mobility scores varied due to chance variation in measurement. RESULTS: Test-retest agreements were excellent for both mobility measures. The standard errors of measurement of the RMI and the M-STREAM, representing the smallest change threshold that indicates a real improvement (beyond measurement error) for a group of individuals, were 0.8 and 1.5, respectively. The smallest real differences of the RMI and the M-STREAM, exhibiting the smallest change threshold that indicates a real improvement for a single individual, were 2.2 and 4.2, respectively. CONCLUSION: . The RMI and the M-STREAM have high agreement between the test-retest measurements with acceptable measurement errors due to variation in measurement. The 2 measures can be used by clinicians and researchers to assess the mobility performance and monitor changes over time in stroke patients. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: A prospective interview study. OBJECTIVE: To determine whether items of the Frenchay Activities Index (FAI) measure Instrumental Activities of Daily Living (IADL), as a unidimensional construct, in patients with spinal cord injury (SCI). To examine whether the response categories of the FAI are useful in discerning the various ability levels of IADL. SUMMARY OF BACKGROUND DATA: No known IADL scale has been designed for SCI patients. The FAI, to our knowledge, has never been validated in patients with SCI. METHODS: A total of 233 persons with SCI participated in this study. The FAI was administered to the patients by interview at locations convenient for the participants. A Rasch analysis was used to examine the unidimensionality and appropriateness of the response categories of the FAI. RESULTS: All but 2 items ('going outside' and 'reading books') of the FAI fitted the model's expectations. The results of Rasch analysis indicated that the response categories for the remaining 13 items of the FAI should be collapsed to create more suitable response categories (4 items, into dichotomies, and the remaining 9 items, into trichotomies). Thus, a revised 13-item FAI was formed by deleting the 2 misfitting items and collapsing the response categories of the items. CONCLUSIONS: This study demonstrated that the revised 13-item FAI assesses a single, unidimensional IADL for SCI patients living in the community. The revised FAI shows potential for assessment of IADL in SCI patients. [ABSTRACT FROM AUTHOR]

Background: Atypical teratoid rhabdoid tumor (ATRT) is an aggressive brain tumor that mainly affects young children. Our recent study reported a promising therapeutic strategy to trigger DNA damage, impede homologous recombination repair, and induce apoptosis in ATRT cells by targeting ribonucleotide reductase regulatory subunit M2 (RRM2). COH29, an inhibitor of RRM2, effectively reduced tumor growth and prolonged survival in vivo. Herein, we explored the underlying mechanisms controlling these functions to improve the clinical applicability of COH29 in ATRT., Methods: Molecular profiling of ATRT patients and COH29-treated cells was analyzed to identify the specific signaling pathways, followed by validation using a knockdown system, flow cytometry, q-PCR, and western blot., Results: Elevated E2F1 and its signaling pathway were correlated with poor prognosis. RRM2 inhibition induced DNA damage and activated ATM, which reduced Rb phosphorylation to promote Rb-E2F1 interaction and hindered E2F1 functions. E2F1 activity suppression led to decreased E2F1-dependent target expressions, causing cell cycle arrest in the G1 phase, decreased S phase cells, and blocked DNA damage repair., Conclusion: Our study highlights the role of ATM/Rb/E2F1 pathway in controlling cell cycle arrest and apoptosis in response to RRM2 inhibition-induced DNA damage. This provides insight into the therapeutic benefits of COH29 and suggests targeting this pathway as a potential treatment for ATRT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Allergic asthma is a chronic bronchial inflammatory disease closely associated with abnormal immune responses of dendritic cells (DCs) and allergen-specific type 2 T helper (Th2) cells. Indirubin (IR), a natural aryl hydrocarbon receptor (AhR) ligand, exerts anti-inflammatory and immunomodulatory properties., Purpose: In this study, we aimed to clarify whether IR exhibits immunomodulatory action on DCs via AhR activation and investigated the antiallergic effects of IR in a mouse model of allergic asthma., Methods: Lipopolysaccharide (LPS)-activated bone marrow-derived DCs were treated with IR. Their mRNA expressions, cytokine production, and phenotype patterns were determined by a quantitative real-time PCR, ELISA, flow cytometry, and RNA sequencing. The mixed lymphocyte reaction was utilized to evaluate the regulatory function of IR-treated DCs on T-cell differentiation. Moreover, mice with ovalbumin (OVA)-induced allergic asthma were treated with IR. Thereafter, the airway hyperresponsiveness (AHR), allergen-specific IgE production, cytokine levels, airway inflammation, and T-cell responses were evaluated., Results: Treatment of LPS-stimulated DCs with 20 μM IR significantly reduced IL-12 and TNF-α production while increasing IL-10 secretion. Meanwhile, these DCs expressed decreased levels of CD80 but increased levels of Jagged 1 surface molecules. However, the effects of IR on DCs were reversed by pretreatment with the AhR antagonist, CH223191. Additionally, the coculture of these tolerogenic-like DCs with allogeneic CD4 + T cells promoted the generation of Foxp3 + regulatory T (Treg) cells. A transcriptomic analysis identified several downregulated genes that are involved in regulating cell migration, cytokine secretion, and inflammatory responses in DCs after IR treatment. In an asthmatic murine model, oral administration of 25 mg kg -1 body weight of IR efficiently alleviated the development of AHR, OVA-specific IgE production, and levels of Th2-type cytokines (IL-4, IL-5, and IL-13) and the CCL11 chemokine. IR treatment also attenuated inflammatory cell recruitment and mucus production in the lungs. Notably, an enhanced frequency of Foxp3 + Treg cells and reduced effector T-cell proliferation associated with increased levels of IL-10 and TGF-β were observed in IR-treated mice., Conclusion: IR can induce tolerogenic-like BMDCs which promote the differentiation of Treg cells. Importantly, the expansion of Foxp3 + Treg cells contributed to the therapeutic efficacy of IR against allergic asthma., Competing Interests: Declaration of competing interest The authors declare that they have no financial conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: A specific type of prostate cancer (PC) that exhibits neuroendocrine (NE) differentiation is known as NEPC. NEPC has little to no response to androgen deprivation therapy and is associated with the development of metastatic castration-resistant PC (CRPC), which has an extremely poor prognosis. Our understanding of genetic drivers and activated pathways in NEPC is limited, which hinders precision medicine approaches. L1 cell adhesion molecule (L1CAM) is known to play an oncogenic role in metastatic cancers, including CRPC. However, the impact of L1CAM on NEPC progression remains elusive., Methods: L1CAM expression level was investigated using public gene expression databases of PC cohorts and patient-derived xenograft models. L1CAM knockdown was performed in different PC cells to study in vitro cell functions. A subline of CRPC cell line CWR22Rv1 was established after long-term exposure to abiraterone to induce NE differentiation. The androgen receptor-negative cell line PC3 was cultured under the tumor sphere-forming condition to enrich cancer stemness features. Several oxidative stress inducers were tested on PC cells to observe L1CAM-mediated gene expression and cell death., Results: L1CAM expression was remarkably high in NEPC compared to CRPC or adenocarcinoma tumors. L1CAM was also correlated with NE marker expressions and associated with the adenocarcinoma-to-NEPC progression in gene expression databases and CRPC cells with NE differentiation. L1CAM also promoted cancer stemness and NE phenotypes in PC3 cells under cancer stemness enrichment. L1CAM was also identified as a reactive oxygen species-induced gene, by which L1CAM counteracted CRPC cell death triggered by ionizing radiation., Conclusions: Our results unveiled a new role of L1CAM in the acquisition of the NE phenotype in PC, contributing to the NE differentiation-related therapeutic resistance of CRPC., (© 2024 Wiley Periodicals LLC.)

Objective: To examine the test-retest reliability, responsiveness, and clinical utility of the machine learning-based short-form of the Berg Balance Scale (BBS-ML) in persons with stroke., Design: Repeated measures design., Setting: A department of rehabilitation in a medical center., Participants: This study recruited two groups: 50 persons who were more than 6 months post-stroke to examine the test-retest reliability, and 52 persons who were within 3 months post-stroke to examine the responsiveness. Test-retest reliability was investigated by administering assessments twice at a 2-week interval. Responsiveness was investigated by gathering data at admission and discharge from hospital., Interventions: Not applicable., Main Outcome Measure: BBS-ML., Results: The BBS-ML exhibited excellent test-retest reliability (intraclass correlation coefficient = 0.99), acceptable minimal random measurement error (minimal detectable change % = 13.6%), and good responsiveness (Kazis' effect size and standardized response mean values ≥ 1.34). On average, the participants completed the BBS-ML in around 6 minutes per administration., Conclusions: Our findings indicate that the BBS-ML appears an efficient measure with excellent test-retest reliability and responsiveness. Moreover, the BBS-ML may be utilized as a substitute for the original BBS to monitor the progress of balance function in persons with stroke., Competing Interests: Declaration of interest statement The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier Inc.)

The 6th Asia Partnership Conference of Regenerative Medicine (APACRM) was held in person with online on April 20, 2023, to promote the regulatory harmonization of regenerative medicine products throughout Asia. Recognizing domestic regulatory guidelines within each country and region and the underlying rationales are important initial steps toward harmonizing regulations. The 6th APACRM featured an open dialog regarding non-clinical evaluation for advanced CAR-T products, regulation of clinical trials for AAV-based gene therapies, and cell and gene therapies provided to patients as medical care/medical practices without market authorization through presentations from the industry and panel discussions with regulatory agencies. The latest updates on regenerative medicine in each country and region are introduced. This paper summarizes the proceedings of the 6th APACRM for public dissemination to foster future discussions., (© 2024 The Author(s).)

The quality of protective immunity plays a critical role in modulating vaccine efficacy, with native antigens often not able to trigger sufficiently strong immune responses for pathogen killing. This warrants creation of structure-based vaccine design, leveraging high-resolution antigen structures for mutagenesis to improve protein stability and efficient immunization strategies. Here, we investigated the mechanisms underlying structure-based vaccine design using CspZ-YA, a vaccine antigen from Borrelia burgdorferi , the bacteria causing Lyme disease (LD), the most common vector-borne disease in the Northern Hemisphere. Compared to wild-type CspZ-YA, we found CspZ-YA I183Y and CspZ-YA C187S required lower immunization frequency to protect mice from LD-associated manifestations and bacterial colonization. We observed indistinguishable human and mouse antigenicity between wild-type and mutant CspZ-YA proteins after native infection or active immunization. This supports our newly generated, high-resolution structures of CspZ-YA I183Y and CspZ-YA C187S , showing no altered surface epitopes after mutagenesis. However, CspZ-YA I183Y and CspZ-YA C187S favored the interactions between helices H and I, consistent with their elevated thermostability. Such findings are further strengthened by increasing ability of protective CspZ-YA monoclonal antibodies in binding to CspZ-YA at a physiological temperature (37°C). Overall, this study demonstrated enhanced intramolecular interactions improved long-term stability of antigens while maintaining protective epitopes, providing a mechanism for structure-based vaccine design. These findings can ultimately be extended to other vaccine antigens against newly emerging pathogens for the improvement of protective immunity.

Human cytomegalovirus (HCMV) glycoprotein B (gB) is a class III membrane fusion protein required for viral entry. HCMV vaccine candidates containing gB have demonstrated moderate clinical efficacy, but no HCMV vaccine has been approved. Here, we used structure-based design to identify and characterize amino acid substitutions that stabilize gB in its metastable prefusion conformation. One variant containing two engineered interprotomer disulfide bonds and two cavity-filling substitutions (gB-C7), displayed increased expression and thermostability. A 2.8 Å resolution cryoelectron microscopy structure shows that gB-C7 adopts a prefusion-like conformation, revealing additional structural elements at the membrane-distal apex. Unlike previous observations for several class I viral fusion proteins, mice immunized with postfusion or prefusion-stabilized forms of soluble gB protein displayed similar neutralizing antibody titers, here specifically against an HCMV laboratory strain on fibroblasts. Collectively, these results identify initial strategies to stabilize class III viral fusion proteins and provide tools to probe gB-directed antibody responses., Competing Interests: Competing interests statement:M.R.S., P.O.B., A.R.R., J.A.G., R.S.M., L.Z., N.V.J., C.-L.H., and J.S.M. are inventors on a patent application entitled “Prefusion-Stabilized CMV gB Proteins” (PCT/US2023/073369). J.D.C., D.Y., and M.J.B. are employees of Dynavax and hold Dynavax stock. The other authors declare that they have no competing interests.

Background: The adoption of Robotic Pancreaticoduodenectomy (RPD) is increasing globally. Meanwhile, reduced-port RPD (RPRPD) remains uncommon, requiring robot-specific techniques not possible with laparoscopy. We introduce a unique RPRPD technique optimizing surgical field exposure., Methods: Our RPRPD utilizes a single-site plus-two ports technique, facilitated by a single-port platform through a 5-cm incision. The configuration of robotic arms (arm1, arm2, arm3, and arm4) were strategically designed for optimal procedural efficiency, with the arms2 and arm3, alongside the assistant trocar, mounted on the single-port platform, while the arms1 and arm4 were positioned laterally across the abdomen. Drainage was established via channels created at the arm1 and arm4 insertion sites. A "gooseneck traction" was principally employed with the robotic instrument to prop up the specimen rather than grasp, improving the surgical field's visibility and access. Clinical outcomes of patients who underwent RPRPD performed between August 2020 and September 2023 by a single surgeon across two centers in Taiwan and Japan were reviewed., Results: Fifty patients underwent RPRPD using the single-site plus-two ports technique. The gooseneck traction technique enabled goodsurgical field deployment and allowed for unrestricted movement of robotic arms with no collisions with the assistant instruments. The median operative time was 351 min (250-488 min), including 271 min (219-422 min) of console time and three minutes (2-10 min) of docking time. The median estimated blood loss was 80 mL (1-872 mL). All RPRPD procedures were successfully performed without the need for conversion to open surgery. Postoperative major morbidity (i.e., Clavien-Dindo grade ≥ IIIa) was observed in 6 (12%) patients and median postoperative hospital stay was 13 days., Conclusions: The single-site plus-two ports RPRPD with the gooseneck traction proves to be a safe, feasible option, facilitating surgical field visibility and robotic arm maneuverability., (© 2024. The Author(s).)

Fracture healing complications increase with age, with higher rates of delayed unions and nonunions and an associated increase in morbidity and mortality in older adults. Macrophages have a dynamic role in fracture healing, and we have previously demonstrated that age-related changes in macrophages are associated with attenuated fracture repair in old mice. Here, we provide a single cell characterization of the immune cells involved in the early phase of fracture healing. We show that there were multiple transcriptionally distinct macrophage subpopulations present simultaneously within the healing tissue. Fracture healing was attenuated in old mice compared to young, and macrophages from the fracture callus of old mice demonstrated a pro-inflammatory phenotype compared to young. Interestingly, Trem2 expression was decreased in old macrophages compared to young. Young mice lacking Trem2 demonstrated attenuated fracture healing and inflammatory dysregulation similar to old mice. Trem2 dysregulation has previously been implicated in other age-related diseases, but its role in fracture healing is unknown. This work provides a robust characterization of the macrophage subpopulations involved in fracture healing, and further reveals the important role of Trem2 in fracture healing and may be a potential driver of age-related inflammatory dysregulation. Future work may further examine macrophages and Trem2 as potential therapeutic targets for management of fracture repair in older adults., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Importance: Patients' perception of overall recovery is a critical outcome for stroke rehabilitation. However, the perception of overall recovery cannot be obtained using multidimensional measures, because satisfaction in most domains of life does not guarantee satisfaction in overall recovery. A single overall recovery score seems a straightforward measure. However, the clinical implications of overall scores are restricted, because factors affecting patients' overall recovery are unclear, which can be prioritized to optimize the effectiveness of rehabilitation., Objective: To examine patient-reported variables affecting overall recovery scores in patients with differing stroke severity., Design: The 59 items of the Stroke Impact Scale 3.0 were selected using regression analysis with a forward selection to explain the overall recovery score (0% = no recovery; 100% = full recovery). Stroke severity was determined with the National Institutes of Health Stroke Scale., Setting: Hospitals., Participants: Data of 950 patients collected 90 days after stroke., Results: The models explained about 55% of the variance of the overall recovery scores with five to nine variables, but merely 16% of the variance was explained for patients with moderate stroke. As stroke severity increased, the number of identified variables decreased. Most identified variables were related to social participation and self-care activities (e.g., ability to help others, control the bowels, and dress the torso). Differences in the remaining variables depended on stroke severity., Conclusions and Relevance: Patients' priorities differ depending on stroke severity. The identified variables may be set as treatment goals to optimize patients' self-perceived overall recovery. Plain-Language Summary: How patients perceive their overall recovery after a stroke is a critical outcome for their stroke rehabilitation. This study demonstrated that patients with different stroke severity may have different priorities that influence their self-perceived levels of overall recovery. The variables identified in this study may help occupational therapy practitioners identify meaningful goals to optimize patients' self-perceived overall recovery., (Copyright © 2024 by the American Occupational Therapy Association, Inc.)

Patients with schizophrenia tend to have deficits in emotion recognition (ER) that affect their social function. However, the commonly-used ER measures appear incomprehensive, unreliable and invalid, making it difficult to comprehensively evaluate ER. The purposes of this study were to develop the Computerized Emotion Recognition Video Test (CERVT) evaluating ER ability in patients with schizophrenia. This study was divided into two phases. First, we selected candidate CERVT items/videos of 8 basic emotion domains from a published database. Second, we validated the selected CERVT items using Rasch analysis. Finally, the 269 patients and 177 healthy adults were recruited to ensure the participants had diverse abilities. After the removal of 21 misfit (infit or outfit mean square > 1.4) items and adjustment of the item difficulties of the 26 items with severe differential item functioning, the remaining 217 items were finalized as the CERVT items. All the CERVT items showed good model fits with small eigenvalues (≤ 2) based on the residual-based principal components analysis for each domain, supporting the unidimensionality of these items. The 8 domains of the CERVT had good to excellent reliabilities (average Rasch reliabilities = 0.84-0.93). The CERVT contains items of the 8 basic emotions with individualized scores. Moreover, the CERVT showed acceptable reliability and validity, and the scores were not affected by examinees' gender. Thus, the CERVT has the potential to provide a comprehensive, reliable, valid, and gender-unbiased assessment of ER for patients with schizophrenia., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)