Targeted inhibition of branched-chain amino acid metabolism drives apoptosis of glioblastoma by facilitating ubiquitin degradation of Mfn2 and oxidative stress.

Glioblastoma is one of the most challenging malignancies with high aggressiveness and invasiveness and its development and progression of glioblastoma highly depends on branched-chain amino acid (BCAA) metabolism. The study aimed to investigate effects of inhibition of BCAA metabolism with cytosolic branched-chain amino acid transaminase (BCATc) Inhibitor 2 on glioblastoma, elucidate its underlying mechanisms, and explore therapeutic potential of targeting BCAA metabolism. The expression of BCATc was upregulated in glioblastoma and BCATc Inhibitor 2 precipitated apoptosis both in vivo and in vitro with the activation of Bax/Bcl2/Caspase-3/Caspase-9 axis. In addition, BCATc Inhibitor 2 promoted K63-linkage ubiquitination of mitofusin 2 (Mfn2), which subsequently caused lysosomal degradation of Mfn2, and then oxidative stress, mitochondrial fission and loss of mitochondrial membrane potential. Furthermore, BCATc Inhibitor 2 treatment resulted in metabolic reprogramming, and significant inhibition of expression of ATP5A, UQCRC2, SDHB and COX II, indicative of suppressed oxidative phosphorylation. Moreover, Mfn2 overexpression or scavenging mitochondria-originated reactive oxygen species (ROS) with mito-TEMPO ameliorated BCATc Inhibitor 2-induced oxidative stress, mitochondrial membrane potential disruption and mitochondrial fission, and abrogated the inhibitory effect of BCATc Inhibitor 2 on glioblastoma cells through PI3K/AKT/mTOR signaling. All of these findings indicate suppression of BCAA metabolism promotes glioblastoma cell apoptosis via disruption of Mfn2-mediated mitochondrial dynamics and inhibition of PI3K/AKT/mTOR pathway, and suggest that BCAA metabolism can be targeted for developing therapeutic agents to treat glioblastoma.

Effects of the low Fowler's sleep position and methazolamide treatment on sleep bruxism: A randomized controlled trial.

Intracranial pressure is one of the determinants of sympathetic activities, and sleep bruxism is associated with increased sympathetic activities. This study aimed to investigate effects of the low Fowler's sleep position and methazolamide treatment on the occurrence of rhythmic masticatory muscle activities/sleep bruxism episodes in patients with sleep bruxism in a randomized controlled trial. Polysomnographic recordings were performed on the patients with sleep bruxism sleeping in the low Fowler's (15°-30°) or supine position (n = 11), and with methazolamide or placebo treatment (100 mg, 3-4 hr before bedtime, P.O., n = 9), and changes in sleep variables and heart rate variance during sleep in the low Fowler's position or with methazolamide treatment were determined. Sleep bruxism index, number of masseter muscle electromyographic bursts per hour of sleep, ratio of rhythmic masticatory muscle activities/sleep bruxism duration to the total sleep duration, index of total limb movements, index of limb movements with rhythmic masticatory muscle activities, and number of sleep bruxism clusters per hour of sleep in the low Fowler's position and after methazolamide intake were significantly smaller (p < 0.05-0.001) than those in the supine position and after placebo intake, respectively. The low-frequency heart rate variance powers during non-rapid eye movement sleep stage 2 (N2) in the low Fowler's position and with methazolamide treatment were significantly lower (p < 0.05) than those during sleep in the supine position and with placebo treatment, respectively. In conclusion, sleep in the low Fowler's position and methazolamide treatment were associated with significant decreases in the occurrence of rhythmic masticatory muscle activities/sleep bruxism episodes, which might be due to a reduction in intracranial pressure and sympathetic activities mainly during non-rapid eye movement sleep stage 2.

Effects of CPAP treatment on electroencephalographic activity in patients with obstructive sleep apnea syndrome during deep sleep: Preliminary findings of a cross-sectional study.

Study objectives: To investigate whether electroencephalographic (EEG) activities during non-rapid eye movement sleep stage 3 (N3) in obstructive sleep apnea syndrome (OSAS) patients were changed with continuous positive airway pressure (CPAP) treatment.Methods: A cross-sectional study of EEG activity during N3 sleep was conducted in 15 patients with moderate to severe OSAS without and with CPAP treatment compared to 15 normal controls. The amplitude, and absolute and relative power of delta, theta, alpha and beta waves as well as the absolute power ratio of slow to fast EEG waves (i.e., absolute power of delta and theta waves/absolute power of alpha and beta waves) and the spectral power density of 0-30 Hz EEG activities were analyzed.Results: CPAP significantly increased N3 sleep, the absolute and relative powers, amplitudes of delta and theta waves, and absolute power ratio of slow to fast EEG waves, but decreased relative alpha and beta powers during N3 sleep. However, there were no significant differences in those parameters between the OSAS patients with CPAP treatment and normal controls.Conclusions: CPAP prolongs N3 sleep and increases the power and amplitude of slow EEG waves during N3 sleep, which indicates an improvement in sleep quality and further provides evidence for recommendation of CPAP treatment for OSAS patients.

Myoclonic epilepsy with ragged red fibers syndrome associated with mitochondrial 3302A>G mutation in the MT­TL1 gene: A case report.

A 37-year-old woman presented with proximal limb weakness, an unstable gait, tiredness and paroxysmal jitters. Neurological examination showed decreased deep tendon reflexes and positive signs indicating damage to the cerebellum. The patient's children reported no symptoms but were found to have the mitochondrial 3302A>G mutation in the mitochondrially encoded tRNA-Leu (UUA/G) 1 gene. The patient presented with increased blood lactic acid and lactic acid dehydrogenase levels, myopathy-related limb muscle electromyographic activities, ragged red fibers (RRFs), cytochrome oxidase-negative muscle fibers and mitochondrial 3302A>G mutation. Inverted lactic acid peaks in the basal ganglia, an atrophied cerebellum and multiple electroencephalographic spike waves were also observed. Therefore, myoclonic epilepsy with RRFs syndrome with the 3302A>G mutation was considered.

Endovascular treatment over 24 hours after ischemic stroke onset: a single-center retrospective study.

PURPOSE: The aim of this study is to evaluate the safety and effectiveness of endovascular treatment (EVT) for acute ischemic stroke caused by large-vessel obstruction or stenosis (AIS-LVO/S) over 24 h after first AIS symptom recognition (FAISSR). METHODS: A total of 33 AIS-LVO/S cases with EVT over 24 h after FAISSR during the period from January 2019 to February 2022 in our hospital were divided into the 90d mRS ≤ 2 group [favorable outcome (FO) group] and 90d mRS > 2 group [unfavorable outcome (UFO) group] and retrospectively analyzed. RESULTS: The reperfusion was successfully established with EVT in 97% (32/33) of cases, and most (63.6%, 21/33) had 90d mRS ≤ 2 and only 36.4% (12/33) had 90d mRS > 2. Preoperative DWI-ASPECT and ASITN/SIR scores were significantly higher and NIHSS scores were significantly lower in the FO group than those in the UFO group (P < 0.05). In addition, the FAISSR to exacerbation time, FAISSR to groin puncture time, and FAISSR to reperfusion time were significantly longer, and the groin puncture to reperfusion time was significantly shorter in the FO group than those in the UFO group (P < 0.05), but there was no significant difference in the stroke exacerbation to groin puncture time (P > 0.05). The patients with cerebral infarction due to artery dissection had more favorable EVT outcomes, but the patients with posterior cerebral circulation infarction had very poor EVT outcomes. CONCLUSIONS: The FAISSR to groin puncture time over 24 h may not be a taboo for EVT and it may be safe and effective for AIS-LVO/S in anterior cerebral circulation, especially with lower preoperative NIHSS scores.

Rheumatoid meningitis without a history of rheumatoid arthritis: a case report and literature review.

Rheumatoid meningitis (RM) is a rare extra-articular manifestation of rheumatoid arthritis, usually with non-specific symptoms. In most cases, head magnetic resonance imaging (MRI) shows lamellar enhancements in leptomeninges and pachymeninges, but definitive diagnosis relies on meningeal biopsies. Here, we reported a 43-year-old RM patient without a previous history of rheumatoid arthritis. He came to seek medical assistance because of fever and headache. The head MRI showed bilateral enhancements in leptomeninges and pachymeninges, and blood tests showed that serum IgM rheumatoid factor (RF) (1010.0 IU/ml) and anti-cyclic citrullinated peptide (CCP) antibody (654.24 RU/ml) became positive with a further increase with the progression of the disease. After treatment with steroids, clinical symptoms were relieved. We also reviewed previous history, symptoms, and serum, cerebrospinal fluid and imaging findings in 15 RM cases without a history of rheumatoid arthritis published since 2010. Consistent with previous reported cases, the current case suggests importance of meningeal biopsies and increases in serum RF and anti-CCP antibody in diagnosis of RM. In addition, previous joint symptoms and chronic headaches, and leptomeningeal and pachymeningeal lesions on head MRI are also of great significance for the diagnosis.

Effects of CPAP Treatment on Electroencephalographic Activity in Patients with Obstructive Sleep Apnea Syndrome During Deep Sleep with Consideration of Cyclic Alternating Pattern.

Objective: To investigate whether continuous positive airway pressure (CPAP) treatment would change EEG activities associated with cyclic alternating pattern (CAP subtype A1, A2, and A3) and non-CAP (NCAP) during non-rapid eye movement sleep stage 3 (N3) in patients with obstructive sleep apnea (OSA). Methods: The effects of CPAP treatment on the percentages of sleep stage N3 occupied by the CAP and NCAP, power of EEG waves in the CAP and NCAP were examined in 18 patients with moderate-to-severe OSA undergoing polysomnographic recordings. Results: Apnea and hypopnea index during sleep stage N3 was positively correlated with ratios of phases A2 and A3 duration to total phase A duration [Phase (A2+A3) /Phase A] and negatively correlated with phase A1/phase A. With CPAP treatment, percentages of sleep stage N3 occupied by total CAPs and subtypes A2 and A3, as well as CAP A2 and CAP A3 indexes were significantly decreased while percentages of sleep stage N3 occupied by NCAP (NCAP/N3) and CAP A1 index were significantly increased. In addition, CPAP treatment significantly decreased percentage of respiratory events associated CAPs and increased percentage of non-respiratory related CAPs. Moreover, absolute and relative delta power was significantly increased during phase A1, unchanged during phase A2 and phase B2, and significantly decreased during phases B1, A3 and B3. The absolute power of faster frequency EEG waves in CAPs showed a general trend of decrease. The absolute and relative power of delta waves with amplitudes ≥75 µV, but not <75 µV, was significantly increased. Conclusion: CPAP treatment improves the sleep quality in OSA patients mainly by increasing delta power and decreasing power of higher frequency waves during phase A1, and decreasing CAP A2 and A3 indexes as well as increasing NCAP/N3 and power of delta waves with amplitudes ≥75 µV during NCAP.

Diagnostic Accuracy of Interferon-Gamma Release Assays for Tuberculous Meningitis: A Systematic Review and Meta-Analysis.

Background: In this study, we evaluated and compared the accuracy of blood and cerebrospinal fluid (CSF) interferon release tests [interferon-gamma release assays (IGRAs)] in the diagnosis of tuberculous meningitis (TBM) by a meta-analysis of the relevant literature. Methods: We searched for studies published before 2021 in Medline, Embase, the Cochrane database, and Chinese databases. All studies used the QuantiFERON-TB Gold In-Tube and/or T-SPOT.TB method. Blood and/or CSF tests that met the guidelines for the quality assessment of studies with diagnostic accuracy were included. We used the revised diagnostic accuracy study quality assessment to assess the quality of the included studies. Begg's funnel plots were used to assess publication bias in the meta-analysis of the diagnostic studies, and statistical analyses were performed by using Stata (Version 12) software. Results: A total of 12 blood and/or CSF IGRA studies were included in this meta-analysis, with 376 patients and 493 controls. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve (SROC) of the blood IGRAs in the pooled data from 12 studies were 74% (95% CI: 0.65-0.82), 78% (95% CI: 0.68-0.86), 3.38 (95% CI 2.26-5.06), 0.33 (95% CI: 0.23-0.46), 10.25 (95% CI: 5.46-19.25), and 0.83 (95% CI: 0.79-0.86), respectively. For CSF IGRAs, these values for the pooled data from the 10 studies included were 79% (95% CI: 0.71-0.85), 95% (95% CI: 0.88-0.98), 16.30 (95% CI 6.5-40.83), 0.22 (95% CI: 0.16-0.31), 57.93 (95% CI: 22.56-148.78), and 0.91 (95% CI: 0.88-0.93), respectively. Conclusion: CSF IGRAs exhibited a better diagnostic accuracy than blood IGRAs in diagnosing TBM.

Distribution of mature and newly regenerated nerve fibres after tooth extraction and dental implant placement: An immunohistological study.

BACKGROUND: The time-dependent peri-implant innervation needs to be elucidated in detail. OBJECTIVES: To examine the distribution of mature and newly regenerated nerves around the implant with immunofluorescence during 28-day follow-up after implantation. METHODS: 35 male Sprague-Dawley rats were grouped into non-operated (n = 5), extraction (n = 5) and implant (n = 25) groups. For rats in the extraction and implant groups, three right maxillary molars were extracted. One month later, a titanium implant was placed into the healed alveolar ridge in the implant group. The implant group was further divided into 5 subgroups according to day 1, 3, 7, 14 or 28 after implantation, on which day serial histological sections were prepared for immunohistochemistry. On day 28, the serial sections were also prepared in the non-operated and extraction groups. Soluble protein-100 and growth-associated protein-43 were used to immunolabel mature and newly regenerated nerve fibres, respectively. RESULTS: In the peri-implant soft tissues, the number of both mature and newly regenerated nerves showed an increasing trend in 28 days. In the bone tissues, the number of mature or newly regenerated nerves in both areas at less than 100 µm and 100-200 µm from the implant surface on day 28 grew significantly compared with that on day 1 or 3. In addition, the closest distance from mature nerves to the implant surface decreased evidently. CONCLUSION: The number of peri-implant nerves increased in 28 days since implantation. The innervation in the soft tissue took place faster than in the bone tissue. The mature nerves in the bone tissue approached the implant gradually.

Influence of sleep bruxism on QTc interval and QT variability in patients with OSA: A pilot study.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increases in QT interval corrected for heart rate (QTc interval) and QT variability index (QTVI) and sleep bruxism (SB) is prevalent in OSA patients. OBJECTIVES: To examine whether QTc interval and QT variability were changed during episodes of rhythmic masticatory muscle activities (RMMAs)/SB in SB patients with and without OSA. METHODS: The RR and QTc intervals, and QTVI during RMMAs with or without accompanied limb movements (RMMAs/LMs) in 10 normal controls and 10 SB patients without OSA and during apneic and recovery periods of OSA in 10 SB patients with OSA were analysed. RESULTS: In the SB patients without OSA and controls, QTc intervals and QTVI were significantly increased during RMMAs/LMs compared with those during the 10 s periods (from 10th to 20th s) before the onset and after the offset of RMMAs/LMs, and significantly increased during RMMAs/LMs with awakenings compared with those with microarousals and no arousals. In addition, QTc interval and QTVI were positively correlated with the duration of RMMAs/LMs. Moreover, in the SB patients with OSA, QTc interval and QTVI during the recovery period of OSA events were significantly longer and higher than those during the apneic period regardless of accompanied RMMAs/LMs, and QTc interval and QTVI during the apneic and recovery periods accompanied with RMMAs/LMs were significantly longer and higher than those without accompanied RMMAs/LMs. CONCLUSION: OSA and RMMAs/LMs events were associated with longer QTc intervals and higher QTVI, and RMMAs/LMs might contribute to these changes associated with OSA events accompanied with RMMAs/LMs.

Responses of neurons in rostral ventromedial medulla to nociceptive stimulation of craniofacial region and tail in rats.

The rostral ventromedial medulla (RVM) plays a key role in the endogenous modulation of nociceptive transmission in the central nervous system (CNS). The primary aim of this study was to examine whether the activities of RVM neurons were related to craniofacial nociceptive behaviour (jaw-motor response, JMR) as well as the tail-flick response (TF). The activities of RVM neurons and TF and JMR evoked by noxious heating of the tail or perioral skin were recorded simultaneously in lightly anaesthetized rats. Tail or perioral heating evoked the TF and JMR, and the latency of the JMR was significantly shorter (P < 0.001) than that of the TF. Of 89 neurons recorded in RVM, 40 were classified as ON-cells, 27 as OFF-cells, and 22 as NEUTRAL-cells based on their responsiveness to heating of the tail. Heating at either site caused an increase in ON-cell and decrease in OFF-cell activity before the occurrence of the TF and JMR, but did not alter the activity of NEUTRAL cells. Likewise, noxious stimulation of the temporomandibular joint had similar effects on RVM neurons. These findings reveal that the JMR is a measure of the excitability of trigeminal and spinal nociceptive circuits in the CNS, and that the JMR as well as TF can be used for studying processes related to descending modulation of pain. The findings also support the view that RVM ON- and OFF-cells play an important role in the elaboration of diverse nociceptive behaviours evoked by noxious stimulation of widely separated regions of the body.

Heart rate changes associated with rhythmic masticatory muscle activities and limb movements in sleep bruxers: Preliminary findings.

Objective: To investigate the relationship of rhythmic masticatory muscle activities (RMMAs) and limb movements (LMs) with heart rate (HR) acceleration. Methods: The amplitude and duration of HR increases, the time to reach peak HR associated with RMMAs/LMs during sleep, duration of movement events, and their relationships with cortical arousal levels were determined in 9 sleep bruxers and 10 normal controls. Results: A total of 48.15% and 49.44% HR increased before the onset of RMMAs/LMs in the sleep bruxers and controls, respectively. All of the parameters of HR increases were significantly different between the sleep bruxers and the controls (p < 0.05-0.001) and between different cortical arousal levels (p < 0.01), and the duration of RMMAs/LMs was positively correlated with the parameters (Sleep bruxers: r2 = 0.18-0.88, p < 0.0001; Controls: r2 = 0.16-0.78, p < 0.0001). Discussion: These data suggest the HR increases are associated with the movement events and changes in cortical arousal levels in the sleep bruxers and controls. Abbreviations: LMs: Limb movements; HR: Heart rate; RMMAs: Rhythmic masticatory muscle activities; SB: Sleep bruxism; PSG: Polysomnographic; EEG: Electroencephalographic; PLMS: Periodic leg movements; SSRIs: Selective serotonin reuptake inhibitors; ECG: Electrocardiographic; EOG: Electrooculographic; EMG: Electromyographic; SD: Standard deviation; Fig: Figure; SEM: Standard error of mean; N1: Non-rapid eye movement sleep stage 1; N2: Non-rapid eye movement sleep stage 2; N3: Non-rapid eye movement sleep stage 3; REM: Rapid eye movement ; NA: No arousal; mAR: Microarousal; AW: Awakening.

NMDA and purinergic processes modulate neck muscle activity evoked by noxious stimulation of dura.

BACKGROUND: Adenosine triphosphate (ATP) and glutamate are associated with some headache conditions, and purinergic (P2X) and glutamatergic N-methyl-D-aspartate (NMDA) receptor-related processes in the medulla can modulate the effects of trigeminal nociceptive afferent inputs into the brainstem on craniofacial sensorimotor circuits. This study aimed to test whether neck muscle activity can be induced in rats by noxious stimulation of the frontal dura or superior sagittal sinus that involves P2X or NMDA receptor-dependent mechanisms. METHODS: While electromyographic activities of neck and craniofacial muscles were being recorded in anesthetized rats (n = 46), the inflammatory irritant mustard oil (0.2 µL, 20% MO) or vehicle (mineral oil) was topically applied to the dura or sinus, preceded by 10 µL of the ATP antagonist 2',3'-O-(2,4,6- trinitrophenyl) adenosine 5'-triphosphate (TNP-ATP, 0.1 mmol/L; n = 8) or 2-amino-5-phosphonopentanoic acid (APV, 0.05 mmol/L; n = 7) or phosphate-buffered saline (PBS as vehicle control; n = 10). RESULTS: Application of MO but not vehicle to the frontal dura significantly increased (P < .05) neck electromyographic activity whereas MO application to the superior sagittal sinus did not significantly increase neck electromyographic activity unless MO had previously been applied to the dura. Pre-treatment (i.t.) with TNP-ATP or APV but not vehicle control significantly reduced neck electromyographic activity evoked by MO application to the dura. CONCLUSIONS: These data suggest that noxious stimulation of the frontal dura (but not superior sagittal sinus) may enhance neck muscle activity that is P2X and NMDA receptor-dependent. These effects may contribute to neck muscle stiffness that occurs in some headache conditions.

Report of a case of necrotizing autoimmune myopathy with thymoma-associated myasthenia gravis.

Purpose: Myasthenia gravis (MG) is an autoimmune disease and closely related to thymoma. Inflammatory myopathy may accompany with other autoimmune diseases. However, concurrence of inflammatory myopathy and MG is very rare. Necrotizing autoimmune myopathy (NAM), a rare form of inflammatory myopathy, is characterized by necrosis and regeneration of myocytes in proximal muscles without significant inflammation. The aim of the study was to report a rare case of NAM and concomitant thymoma-associated MG after thymectomy.Materials and methods/results: A 27-year-old female patient presented with muscle soreness and weakness in four limbs. Eyelid fatigue and neostigmine tests were negative, and no ptosis was found but the electromyographic examination (EMG) showed myogenic damage and a gradual decrease in the amplitude (20%) of EMG activities evoked by repetitive electrical stimulation. Antibodies against AChR and increased titer of creatine kinase were detected and plaque-like signals in both legs were found in magnetic resonance imaging. Myositis-related antibodies were negative but necrotic myocytes without inflammatory cell infiltration, and MHC-1 positive muscle fibers were found in muscle biopsy. Pathological examination confirmed anterior mediastinal B2 type thymoma. Five weeks after thymectomy, she started to show typical MG symptoms. No recurrence of thymoma was found but immunoassay showed a higher titer of AChR-Ab. Myositis-related antibodies negative necrotizing autoimmune myopathy (NAM) was reported to be associated with thymoma-associated MG.Conclusions: The patient showed symptoms related NAM but developed MG-related symptoms only after thymectomy. The mechanisms for the phenomena may be related to immune dysfunction associated with thymoma.

Changes in heart rate related to rhythmic masticatory muscle activities and limb movements in patients with sleep bruxism.

Most sleep bruxism (SB) episodes are accompanied by an increase in sympathetic tone and heart rate (HR). To characterise heart rate (HR) changes in relation to rhythmic masticatory muscle activities (RMMAs) in SB patients, polysomnographic recordings were performed on 10 SB patients and 11 normal controls. The duration of movement events, amplitude and duration of HR increases, and time to reach HR peak associated with RMMAs and limb movements (LMs) were determined, and the relationships of the parameters of HR increases with types of movements and RMMAs were analysed. All of the parameters of HR increases associated with three types of movements (RMMAs, RMMAs + LMs and LMs) and masseter activities (phasic, tonic and mixed) were significantly different (two-way ANOVA, P < .001 for all) in both SB patients and controls. The duration of RMMAs/LMs was positively correlated with the parameters (SB patients: R2  = .24-.85, P < .0001; controls: R2  = .23-.68, P < .0001). The amplitude of HR increases was also positively correlated with respiration changes in the SB patients (R2  = .3258, P < .0001) and controls (R2  = .09469, P < .05). The proportions of phasic RMMAs associated with awakenings, microarousals and no cortical arousals were significantly different and so were the proportions of tonic and mixed RMMAs (Friedman's tests, P < .05-.001). The HR increases associated with RMMAs may be intrinsic to the cortical arousal response and autonomic activation, and differences in HR increases associated with different types of movements and RMMAs might be related to the changes in respiration and differences in cortical arousal levels.

Eye movements in relation to rhythmic masticatory muscle activities in patients with sleep bruxism.

OBJECTIVES: To characterize eye movements during rhythmic masticatory muscle activities (RMMAs) in patients with sleep bruxism (SB). METHODS: Polysomnographic (PSG) recordings were performed on SB patients and normal controls during sleep (n = 8 for each group) and wakefulness (n = 9 for each group). The eye movements associated with episodes of RMMAs/SB during sleep and jaw movements during wakefulness were analyzed. RESULTS: During sleep, all episodes of RMMAs/SB in the SB patients and controls were associated with eye movements and most of the RMMAs/SB related slow eye movements (SB patients: 96.29%, 1583/1644; Controls: 97.49%, 543/557) were horizontal in the SB patients and controls. During wakefulness, all of the series of jaw movements were associated with eye movements. Most of cycles of jaw movements (SB patients: 88.89%, 200/225; Controls: 95.11%, 214/225) were associated with slow eye movements and most of the eye movements (SB patients: 52.50%, 105/200; Controls: 61.21%, 131/214) were vertical. There were significant correlations between the durations of episodes of eye movements and RMMAs/SB during sleep and between the duration of episodes of eye movements and duration of series of jaw movements during wakefulness in the SB patients and controls. CONCLUSIONS: Most of RMMAs/SB episodes during sleep and jaw movements during wakefulness are associated with eye movements in SB patients and normal controls.

Actively tunable terahertz chain-link metamaterial with bidirectional polarization-dependent characteristic.

A tunable terahertz (THz) chain-link metamaterial (CLM) is presented, which is composed of a tailored Au layer fabricated on Si substrate. CLM exhibits bidirectional polarization-dependent characteristic by applying a direct-current (dc) bias voltage on device. This CLM device can be heated up the surrounding temperature to tune the corresponding resonance. The tuning range is 0.027 THz from 0.318 THz to 0.291 THz on the bias of 0.60 V to 1.32 V. By reconfiguring the gap between CLM, there are single-resonance with red-shift at TE mode, and multi-resonance with blue-shift and red-shift at TM mode, respectively. These characterizations of CLM are polarization-dependence and bidirectional tunability. These results show the electromagnetic responses of proposed CLM device is suitable for the uses for resonator, filter, switch, and sensor in the THz frequency range.

Characterisation of the relationships between rhythmic masticatory muscle activities and limb movements in patients with sleep bruxism.

BACKGROUND: Most rhythmic masticatory muscle activities (RMMAs) have been shown to be accompanied with limb movements (LMs) in sleep bruxism (SB) patients during sleep. OBJECTIVES: To compare the relationships between RMMAs and LMs in SB patients and normal subjects. METHODS: Polysomnographic recordings were performed on eight SB patients and nine normal subjects and the frequencies and durations of RMMAs as well as LMs were determined. Linear regression and correlation analysis were performed to study the relationship between durations of RMMAs and LMs when RMMAs occurred with LMs. RESULTS: Most LMs in SB patients, but not in normal subjects, were accompanied with RMMAs. RMMAs in SB patients were more likely to be isolated, phasic or mixed, while RMMAs in normal subjects were more likely to be tonic. The frequencies of LMs, isolated RMMAs and RMMAs accompanied with LMs in SB patients were significantly higher than those in normal subjects. Furthermore, linear regression and correlation analysis showed that duration of RMMAs was significantly associated with that of LMs when RMMAs occurred with LMs. The duration of RMMAs, when accompanied with LMs, in SB patients was significantly longer than that in normal subjects. CONCLUSIONS: Close relationships between LMs and RMMAs exist in SB patients and normal subjects, and SB episodes may be part of cortical arousal responses and the increased cortical activities associated with SB episodes may not just be localised to the central nervous system (CNS) that controls jaw movements but may also include other parts of CNS that controls LMs.

Effects of a single transient transfection of Ten-eleven translocation 1 catalytic domain on hepatocellular carcinoma.

Tumor suppressor genes (TSGs), including Ten-eleven translocation 1 (TET1), are hypermethylated in hepatocellular carcinoma (HCC). TET1 catalytic domain (TET1-CD) induces genome-wide DNA demethylation to activate TSGs, but so far, anticancer effects of TET1-CD are unclear. Here we showed that after HCC cells were transiently transfected with TET1-CD, the methylation levels of TSGs, namely APC, p16, RASSF1A, SOCS1 and TET1, were distinctly reduced, and their mRNA levels were significantly increased and HCC cells proliferation, migration and invasion were suppressed, but the methylation and mRNA levels of oncogenes, namely C-myc, Bmi1, EMS1, Kpna2 and c-fos, were not significantly change. Strikingly, HCC subcutaneous xenografts in nude mice remained to be significantly repressed even 54 days after transient transfection of TET1-CD. So, transient transfection of TET1-CD may be a great advance in HCC treatment due to its activation of multiple TSGs and persistent anticancer effects.

Face sensorimotor cortex undergoes neuroplastic changes in a rat model of trigeminal neuropathic pain.

Trigeminal nerve injury can result in neuropathic pain behavior and alterations in motor function, but it is unclear if such injury produces neuroplastic alterations in face sensorimotor cortex that could contribute to the alterations in motor function. Therefore, this study aimed to determine if trigeminal nerve injury in a rat neuropathic pain model induces neuroplastic changes in jaw and tongue motor representations in face sensorimotor cortex in association with facial nociceptive behavior. Right infraorbital nerve transection was performed in adult male Sprague-Dawley rats; sham-operated rats served as controls. Nociceptive behavior was assessed by testing facial mechanical sensitivity pre-operatively and post-operatively (1-28 days). Intracortical microstimulation was also applied post-operatively in a series of microelectrode penetrations to map jaw and tongue motor representations in the face sensorimotor cortex by analyzing anterior digastric and genioglossus electromyographic activities evoked by microstimulation at histologically verified sites in face primary somatosensory cortex (face-SI) as well as face primary motor cortex (face-MI). Compared to sham, infraorbital nerve injury induced a significant (2-way repeated-measures analysis of variance, P < 0.001) bilateral decrease in facial mechanical threshold that lasted up to 28 days post-operatively. Nerve injury also induced a significant bilateral decrease compared to sham (P < 0.05) in the number of anterior digastric and/or genioglossus sites in face-MI and in face-SI. These findings indicate that trigeminal nerve injury induces neuroplastic alterations in jaw and tongue motor representations in face sensorimotor cortex that are associated with facial nociceptive behavior and that may contribute to sensorimotor changes following trigeminal nerve injury.