Ameliorating effect of Trigonella foenum-graecum L. (fenugreek) extract tablet on exhaustive exercise-induced fatigue in rats by suppressing mitophagy in skeletal muscle.

OBJECTIVE: Trigonella foenum-graecum L. (fenugreek) is widely used as a leafy vegetable and spice in China and North Africa. Recent studies have reported that fenugreek can reduce fatigue; however, its antifatigue mechanism remains unclear. Therefore, this study aimed to investigate the potential antifatigue effects of fenugreek extract (FE) on mitophagy and the underlying mechanisms. MATERIALS AND METHODS: We evaluated the potential effects of FE tablet on an exhaustive exercise-induced fatigue (EEF) rat model. Oxidative stress indicators and fatigue biomarkers in the serum and skeletal muscle were detected. Mitophagy and mitochondrial morphology were observed using transmission electron microscopy. The expression levels of mitochondrial autophagy-related proteins were detected using western blot and immunofluorescence. RESULTS: Compared with the model group, FE enhanced the activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase as well as total antioxidant capacity; however, it decreased the level of malondialdehyde in the serum and skeletal muscle after a 7-day treatment. Moreover, certain indicators of mitochondrial function, such as reactive oxygen species levels, ATP levels, cellular and mitochondrial Ca2+ levels, and ATPase activity, were significantly improved in the FE group compared with the model group. Finally, we found that mitophagy was induced by exhaustive exercise and inhibited by FE. Regarding mitochondrial autophagy-related proteins, the expression levels of LC3B, FUNDC1, PGAM5, PARKIN, and PINK1 in the skeletal muscle tissue were increased in the EEF group compared with the control group. After administration of FE and a positive control drug, a significant reversal in the expression of the above-mentioned proteins was noted. CONCLUSIONS: Our findings demonstrate that FE exerted antifatigue effects in the EEF rat model by regulating the mitophagy-related FUNDC1/LC3B signaling pathway rather than the PINK1/PARKIN signaling pathway.

The role of hepatic antioxidant capacity and hepatobiliary transporter in liver injury induced by isopsoralen in zebrafish larvae.

Isopsoralen is the main component of the Chinese medicine psoralen, which has antitumour activity and can be used for the treatment of osteoporosis. However, the mechanism behind its hepatotoxicity has not yet been elucidated. In this study, the hepatotoxicity of isopsoralen was investigated using zebrafish. Isopsoralen treatment groups of 25, 50 and 100 µM were established. The mortality, liver morphology changes, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver histopathology and mRNA levels of liver injury-related genes in zebrafish larvae were measured. The results showed that isopsoralen resulted in the development of malformed zebrafish, dose-dependent increases in ALT and AST, decreased liver fluorescence and weakened fluorescence intensity. Histopathological examination showed that high-dose isopsoralen caused a large number of vacuolated structures in the larvae liver. The polymerase chain reaction results showed a significant decrease in the mRNA levels of genes related to antioxidant capacity ( lfabp, gstp2 and sod1) and drug transport ( mdr1, mrp1 and mrp2), indicating that isopsoralen significantly inhibited liver antioxidant capacity and drug efflux capacity in zebrafish larvae. Isopsoralen is hepatotoxic to zebrafish larvae via inhibition of drug transporter expression resulting in the accumulation of isopsoralen in the body and decreased antioxidant capacity, leading to liver injury.

[The effect of breast massage at different time in the early period after cesarean section].

Objective: To evaluate the effect of breast massage at different time in the early period on maternal lactation after cesarean section. Methods: 80 women delivered by cesarean section were randomly selected from maternity ward of a hospital in Shandong province during Jan. 2013 to Jan. 2015; which were divided into four groups, with 20 patients in each. Three groups received 3 times of breast massage every 24 hoursbeginning from 2, 12 and 24 h after cesarean section, respectively. The control group didn't receive any breast massage. The starting time and status of lactation were observed and recorded after cesarean section. 5 ml venous blood sample was drawn from each patient respectively at 2 h before cesarean, 6, 12, 24, 48 and 72 h after cesarean to test the level of serum prolactin. The lactation status of each group was compared. Results: The P(50) (P(25)-P(75)) of starting time of lactation of the three massage groups and control group were 3 (2-6) h, 4 (2-8) h, 4 (3-12) h and 4 (2-12) h, respectively, whose differences showed no statistical significance (H=3.32, P=0.345).The number of delivered women with adequate lactation 24 hours after cesarean was 10 in the group who received massage beginning from 2 h after cesarean; while the number was only 2 in the control group. The number of delivered women with adequate lactation 48 hours after cesarean was 18 in the group who received massage beginning from 2 h after cesarean; while the number was 8 in the control group. The differences showed statistical significances (P values were 0.021 and 0.008, respectively). The serum prolactin level in the group of delivered women who received massage from 2 h after cesarean was separately (195.9±78.5), (176.0±96.5), (216.4±110.0), (190.0±56.8) and (184.8±69.6) µg/L at 2, 12, 24, 48 and 72 h after cesarean, which were significantly higher than those in the control group (which were (128.8±40.6), (127.3±66.8), (162.2±58.8), (145.1±64.7) and (141.7±49.3) µg/L, respectively) (P=0.007). Conclusion: Breast massage beginning from 2 hours after cesarean section can effectively improve the lactation status of delivered women.

Chronic refractory myofascial pain and denervation supersensitivity as global public health disease.

Chronic pain with a 30.3% global prevalence significantly impacts universal health. Low back pain has a 9.4% prevalence worldwide causing the most widespread disability. Neck pain ranks 4th highest regarding years lived with disability with a 4.9% prevalence worldwide. The principal cause of pain in 85% of patients visiting a tertiary pain clinic has a myofascial origin. The root cause is multifocal neuromuscular ischaemia at myofascial trigger points from muscle tightening and shortening following spondylotic radiculopathy induced partial denervation. Chronic refractory myofascial pain (CRMP) is a neuromusculoskeletal disease needing management innovations. Using electrical twitch-obtaining intramuscular stimulation (eToims), we provide objective evidence of denervation supersensitivity in multiple myotomes as cause, aggravation and maintenance of CRMP. This study underscores our previous findings that eToims is safe and efficacious for long-term use in CRMP. eToims aids potential prevention (pre-rehabilitation), simultaneous diagnosis, treatment (rehabilitation) and prognosis in real time for acute and CRMP management.

Observation of universal strong orbital-dependent correlation effects in iron chalcogenides.

Establishing the appropriate theoretical framework for unconventional superconductivity in the iron-based materials requires correct understanding of both the electron correlation strength and the role of Fermi surfaces. This fundamental issue becomes especially relevant with the discovery of the iron chalcogenide superconductors. Here, we use angle-resolved photoemission spectroscopy to measure three representative iron chalcogenides, FeTe0.56Se0.44, monolayer FeSe grown on SrTiO3 and K0.76Fe1.72Se2. We show that these superconductors are all strongly correlated, with an orbital-selective strong renormalization in the dxy bands despite having drastically different Fermi surface topologies. Furthermore, raising temperature brings all three compounds from a metallic state to a phase where the dxy orbital loses all spectral weight while other orbitals remain itinerant. These observations establish that iron chalcogenides display universal orbital-selective strong correlations that are insensitive to the Fermi surface topology, and are close to an orbital-selective Mott phase, hence placing strong constraints for theoretical understanding of iron-based superconductors.

Dynamic competition between spin-density wave order and superconductivity in underdoped Ba(1-x)K(x)Fe2As2.

An intriguing aspect of unconventional superconductivity is that it always appears in the vicinity of other competing phases, whose suppression brings the full emergence of superconductivity. In the iron pnictides, these competing phases are marked by a tetragonal-to-orthorhombic structural transition and a collinear spin-density wave (SDW) transition. There has been macroscopic evidence for competition between these phases and superconductivity as the magnitude of both the orthorhombicity and magnetic moment are suppressed in the superconducting state. Here, using angle-resolved photoemission spectroscopy on detwinned underdoped Ba(1-x)K(x)Fe2As2, we observe a coexistence of both the SDW gap and superconducting gap in the same electronic structure. Furthermore, our data reveal that following the onset of superconductivity, the SDW gap decreases in magnitude and shifts in a direction consistent with a reduction of the orbital anisotropy. This observation provides direct spectroscopic evidence for the dynamic competition between superconductivity and both SDW and electronic nematic orders in these materials.

Detection delay of pulmonary tuberculosis patients among migrants in China: a cross-sectional study.

OBJECTIVES: 1) To explore the characteristics of patient and diagnostic delays among migrant tuberculosis (TB) patients in Shandong, China; and 2) to identify factors associated with patient and diagnostic delays, for the development and improvement of TB control strategy among migrants in China. DESIGN: A cross-sectional study was conducted in 12 counties of Shandong Province using a semi-structured questionnaire. A total of 314 smear-positive pulmonary migrant TB patients registered with the county TB dispensary of the sampling sites from 1 August 2007 to 31 July 2008 were selected. RESULTS: Among 314 migrant TB patients, the median patient delay was 10 days, and the median diagnostic delay was 8 days. A quarter of the participants had a patient delay of >22 days and a diagnostic delay of >16 days. Factors affecting detection delay included financial conditions, health insurance status, working time, patient age, severity of initial symptoms, geographic access to TB-related care and the health facilities first visited. CONCLUSIONS: Interventions such as expansion of the free service package and education about TB diagnosis among community health personnel are urgently required for early case detection among migrants.

Susceptibility anisotropy in an iron arsenide superconductor revealed by x-ray diffraction in pulsed magnetic fields.

In addition to unconventional high-T(c) superconductivity, the iron arsenides exhibit strong magnetoelastic coupling and a notable electronic anisotropy within the a-b plane. We relate these properties by studying underdoped Ba(Fe(1-x)Co(x))2As2 by x-ray diffraction in pulsed magnetic fields up to 27.5 T. We exploit magnetic detwinning effects to demonstrate anisotropy in the in-plane susceptibility, which develops at the structural phase transition despite the absence of magnetic order. The degree of detwinning increases smoothly with decreasing temperature, and a single-domain condition is realized over a range of field and temperature. At low temperatures we observe an activated behavior, with a large hysteretic remnant effect. Detwinning was not observed within the superconducting phase for accessible magnetic fields.

Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness.

PURPOSE: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated. RESULTS: A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported. CONCLUSIONS: A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome.

Hyperbaric oxygen for neurologic indications--action plan for multicenter trials in: stroke, traumatic brain injury, radiation encephalopathy & status migrainosus.

The 2008 Toronto Hyperbaric Medicine Symposium was convened to discuss research into neurologic indications for hyperbaric oxygen therapy (HBO2T). Four topics were particularly addressed: acute ischemic stroke; acute traumatic brain injury; brain radiation necrosis; and status migrainosus. Four multicenter trials were designed and proposed to evaluate the efficacy of HBO2T for these indications and are presented here in addition to brief reviews of the rationale behind each.

eToims twitch relief method in chronic refractory myofascial pain (CRMP).

INTRODUCTION: CRMP management involves electrical stimulation of motor points. OBJECTIVE: To demonstrate that Electrical Twitch-Obtaining Intramuscular Stimulation (eToims) using ET127 system for noninvasive motor point stimulation is safe and efficacious in CRMP management. METHOD: Longitudinal observation of consecutive self-pay outpatients treated from 10/06 through 4/08, divided into Preferred Group ("PG", N = 49, 3 Hz, 4 stimuli/site) and Basic Group ("BG", N = 43, 1 Hz stimulation, 1 stimulus/site). PG and BG had comparable ages, symptom durations, treatment session durations and treatment intervals. Each session involved treatment to large muscles of C4-C7 and L3-S1 myotomes. Outcome measures include prior week's verbal pain levels, pre and immediate post-session pain levels, blood pressure (BP), pulse rate (PR), symptomatic (S) and asymptomatic (A) side range-of-motion (ROM) for neck rotation (NR), shoulder external rotation (ER), shoulder internal rotation (IR), straight leg raising (SLR) and FABERE testing. RESULTS: PG and BG showed significant improvements (p < 0.01) in immediate post-session pain levels and measured ROM. Significantly higher ERS (pre and post session percentage changes) noted for BG over PG (p < 0.05). Post-session PR decreased in both groups, more so in PG Systolic BP was mildly elevated in PG but was mildly reduced in BG Both groups showed no diastolic BP changes. Significant negative correlation noted between increasing number of treatments and pain level only in PG (r = -0.3, p = 0.00). Increasing number of treatments in PG correlated significantly with improvement in NRS, NRA, IRS, SLRS, LRA, FABERES and FABEREA whereas BG significantly correlated only for improvement in LRS. PG had lower average pain levels than BG (3.4 +/- 1.9 vs. 4.3 +/- 2.5, p < 0.02). CONCLUSION: eToims using ET127 electrical stimulator appears safe and efficacious in CRMP management.

Effect of compounds of Galla chinensis on remineralisation of initial enamel carious lesions in vitro.

OBJECTIVE: To evaluate the effect of compounds of Galla chinensis on the remineralisation of initial enamel carious lesions in vitro. METHODS: Sixty bovine enamel blocks with early lesions were prepared and randomly divided into six treatment groups. The lesions were subjected to a pH-cycling regime for 12 days. Each daily cycle included 4x1min applications with one of six treatments; 1000ppm F aq. (as NaF, positive control); deionized water (negative control); or 4000ppm aqueous solutions of four G. chinensis extracts (GCEs); GCE, GCE-B, GCE-B1, or GCE-B2. Surface enamel microhardness was measured on the enamel blocks before and after demineralisation, and after pH-cycling, and percentage surface microhardness recovery (%SMHR) was calculated. The enamel specimens were then sectioned (thickness ca. 80microm) and examined by polarized light microscopy. RESULTS: All samples rehardened significantly compared to baseline. Fluoride had a significantly greater effect than all other treatments. In the GCEs groups, %SMHR was significantly greater than DDW for the GCE, GCE-B and GCE-B1 groups. There was no significant difference between the GCE-B2 group and DDW. Polarized light microscopy showed that the thickness of the surface layer increased obviously in all specimens including NaF group, GCE group, GCE-B group and GCE-B1 group. Negative birefringent band appeared in the lesions body and the depth of the lesions was obviously reduced. CONCLUSION: The present study has demonstrated the potential of three GCEs (GCE, GCE-B and GCE-B1) to effect net rehardening of artificial carious lesions under dynamic pH-cyclic conditions.

Endogenous release of secretin from the hypothalamus.

Previous studies demonstrated that secretin could be released from the cerebellum, where it exerts a facilitatory action on the GABAergic inputs into the Purkinje neurons. In the present article, we provide evidence of the endogenous release of secretin in the hypothalamus and the mechanisms underlying this release. Incubation of the hypothalamic explants with KCl induces the release of secretin to 4.35 +/- 0.45-fold of the basal level. This K+-induced release was tetrodotoxin and cadmium sensitive, suggesting the involvement of voltage-gated sodium and calcium channels. The use of specific blockers further revealed the involvement of L-, N-, and P-type high voltage-activated (HVA) calcium channels. Results present in the current article provide further and more solid evidence of the role of secretin as a neuropeptide in the mammalian central nervous system.

Electrical twitch obtaining intramuscular stimulation (ETOIMS) for myofascial pain syndrome in a football player.

BACKGROUND: Flare up of acute lower back pain associated with myofascial pain syndrome (MPS) may require various forms of treatment including activity restriction and bracing. Electrical twitch obtaining intramuscular stimulation (ETOIMS) is a promising new treatment. It involves the use of a strong monopolar electromyographic needle electrode for electrical stimulation of deep motor end plate zones in multiple muscles in order to elicit twitches. CASE REPORT: An elite American football player with MPS symptoms failed to respond to standard treatments. He then received ETOIMS which completely alleviated the pain. After establishing pain control, the athlete continued with a further series of treatments to control symptoms of muscle tightness. CONCLUSIONS: ETOIMS has a promising role in pain alleviation, increasing and maintaining range of motion, and in providing satisfactory athletic performance during long term follow up.

The efficacy of automated/electrical twitch obtaining intramuscular stimulation (atoims/etoims) for chronic pain control: evaluation with statistical process control methods.

INTRODUCTION: Automated and/or electrical twitch-obtaining intramuscular stimulation (ATOIMS & ETOIMS) evoke twitches at/or near motor end plate zones to relieve muscle pain. OBJECTIVES: To demonstrate that pain levels recorded daily by patients enable statistical process control (SPC) analysis of ATOIMS & ETOIMS effects over time. METHODS: Four chronic fibromyalgic patients received ATOIMS & ETOIMS treatments to bilateral C3-C8 and L3-S1 myotomes and recorded daily pain on a visual analogue scale. Mechanical stimulation with ATOIMS involved a custom device to insert, oscillate and retract a monopolar needle (MN) at 2 Hz x2s. ETOIMS involved manual insertion of the MN and stimulating with 5 Volts, 0.5 ms pulse duration at 2 Hz for 2s to multiple sites. Positive outcome measures include two pain scales reduction. RESULTS: Patient 1-4 had 89, 38, 40, 36 treatments during a follow-up time of 625, 1018, 378, 466 days with 5.4 +/- 3.7, 8.0 +/- 4.9, 4.2 +/- 2.4 and 4.6 +/- 2.7 days between treatments (DBT) during the first 6 months and 4.7 +/- 3.0, 21.8 +/- 15.6, 6.2 +/- 4.4 and 4.3 +/- 2.5 DBT respectively in the latter phase of the therapy. The average pain level (APL) in 1st week of treatment for patient 1-4 were 6.4 +/- 1.1, 3.7 +/- 1.1, 6.6 +/- 2.8 and 7.5 +/- 0.4 and in the last week of treatment were 4.5 +/- 0.4, 1.2 +/- 0.1, 4.2 +/- 1.0 and 4.7 +/- 0.7 respectively. APL correlated negatively with time during the first 6 months for patients 2-4 and also after 6 months for patients 4 & 1 who had unchanged and reduced DBT respectively. APL correlated positively with time for patient 2 with no correlation for patient 3 (both had increased DBT) after 6 months. CONCLUSIONS: Patients will chronically record their pain scales daily enabling analysis by SPC. ATOIMS & ETOIMS applied periodically can be helpful in relieving fibromyalgic pain.

Twitch-obtaining intramuscular stimulation in reflex sympathetic dystrophy.

BACKGROUND: Reflex Sympathetic Dystrophy (RSD) remains a painful disease entity of undetermined etiology and variable response to therapy. FINDINGS: Presented is a patient with left leg early RSD and chronic musculoskeletal back pain who received automated and electrical twitch-obtaining intramuscular stimulation (ATOIMS & ETOIMS) treatments. Diagnosis combined clinical symptoms of pain and allodynia, signs of motor/trophic changes and electromyographic evidence of especially of left L5 root level irritation, with chronic bilateral, multiple level partial lumbosacral nerve root involvement. Signs and symptoms of early RSD resolved with therapy. CONCLUSIONS: ATOIMS-ETOIMS have a promising role in the treatment of early RSD associated with neuropathic pain resulting from spondylotic radiculopathy.

The muscle twitch in myofascial pain relief: effects of acupuncture and other needling methods.

Proposed is that needling methods such as acupuncture, primarily effect pain relief in myofascial pain through a local mechanism, elicitation of muscle twitches. Occasionally, diagnostic needling procedures such as electromyography (EMG) can relieve such pain through insertional intramuscular movements of the needle electrode. This results in stimulation of the motor end-plate zones (MEPZs), eliciting muscle twitches. As needle elicitation of muscle twitches is a common diagnostic technique to identify myofascial trigger points (MTrPs), muscle twitches elicited at such points may be therapeutic, not just diagnostic. Occasionally evoked small local muscle twitches are observed in pain relieving methods using needle penetration or manipulation, such as classical or electrical acupuncture and intramuscular stimulation (IMS). Twitch elicitation has been observed to be essential to obtain myofascial pain relief associated with the needling methods of automated and electrical twitch-obtaining intramuscular stimulation (ATOIMS and ETOIMS). These two methods facilitate the elicitation of larger force twitches by mechanical or electrical stimulation respectively at motor end-plate zones.

Lumbosacral radiculopathic pain presenting as groin and scrotal pain: pain management with twitch-obtaining intramuscular stimulation. A case report and review of literature.

BACKGROUND: Chronic groin and scrotal pain is a common entity plaguing a significant population of young athletic individuals. Aside from urologic and visceral etiologies, there is a vast array of underlying musculoskeletal and spinal abnormalities that may be found in these individuals. FINDINGS: Presented is a patient found to have chronic, spine-related groin and scrotal pain diagnosed with lower lumbar discogenic disease by physical examination findings, imaging studies and multi-level chronic radiculopathy by electrodiagnostic studies who was treated with twitch-obtaining intramuscular stimulation (TOIMS). Symptoms of groin and scrotal pain abated with therapy. CONCLUSION: Twitch-obtaining intramuscular stimulation has a promising role in the treatment of groin and scrotal pain of radiculopathic origin.

Successful long-term treatment of refractory Cushing's disease with high-dose mifepristone (RU 486).

An extremely ill patient, with Cushing's syndrome caused by an ACTH-secreting pituitary macroadenoma, experienced complications of end-stage cardiomyopathy, profound psychosis, and multiple metabolic disturbances. Initially treated unsuccessfully by a combination of conventional surgical, medical, and radiotherapeutic approaches, he responded dramatically to high-dose long-term mifepristone therapy (up to 25 mg/kg x d). Treatment efficacy was confirmed by the normalization of all biochemical glucocorticoid-sensitive measurements, as well as by the significant reversal of the patient's heart failure, the resolution of his psychotic depression, and the eventual unusual return of his adrenal axis to normal. His 18-month-long mifepristone treatment course was notable for development of severe hypokalemia that was attributed to excessive cortisol activation of the mineralocorticoid receptor, which responded to spironolactone administration. This case illustrates the efficacy of high-dose long-term treatment with mifepristone in refractory Cushing's syndrome. The case also demonstrates the potential need for concomitant mineralocorticoid receptor blockade in mifepristone-treated Cushing's disease, because cortisol levels may rise markedly, reflecting corticotroph disinhibition, to cause manifestations of mineralocorticoid excess.