Cytosolic DNA initiates a vicious circle of aging-related endothelial inflammation and mitochondrial dysfunction via STING: the inhibitory effect of Cilostazol.

Endothelial senescence, aging-related inflammation, and mitochondrial dysfunction are prominent features of vascular aging and contribute to the development of aging-associated vascular disease. Accumulating evidence indicates that DNA damage occurs in aging vascular cells, especially in endothelial cells (ECs). However, the mechanism of EC senescence has not been completely elucidated, and so far, there is no specific drug in the clinic to treat EC senescence and vascular aging. Here we show that various aging stimuli induce nuclear DNA and mitochondrial damage in ECs, thus facilitating the release of cytoplasmic free DNA (cfDNA), which activates the DNA-sensing adapter protein STING. STING activation led to a senescence-associated secretory phenotype (SASP), thereby releasing pro-aging cytokines and cfDNA to further exacerbate mitochondrial damage and EC senescence, thus forming a vicious circle, all of which can be suppressed by STING knockdown or inhibition. Using next-generation RNA sequencing, we demonstrate that STING activation stimulates, whereas STING inhibition disrupts pathways associated with cell senescence and SASP. In vivo studies unravel that endothelial-specific Sting deficiency alleviates aging-related endothelial inflammation and mitochondrial dysfunction and prevents the development of atherosclerosis in mice. By screening FDA-approved vasoprotective drugs, we identified Cilostazol as a new STING inhibitor that attenuates aging-related endothelial inflammation both in vitro and in vivo. We demonstrated that Cilostazol significantly inhibited STING translocation from the ER to the Golgi apparatus during STING activation by targeting S162 and S243 residues of STING. These results disclose the deleterious effects of a cfDNA-STING-SASP-cfDNA vicious circle on EC senescence and atherogenesis and suggest that the STING pathway is a promising therapeutic target for vascular aging-related diseases. A proposed model illustrates the central role of STING in mediating a vicious circle of cfDNA-STING-SASP-cfDNA to aggravate age-related endothelial inflammation and mitochondrial damage.

Neuromuscular electrical stimulation of humeral adductors in subjects with rotator cuff tear.

INTRODUCTION: In symptomatic patients with rotator cuff tear, MRI and radiographic studies have ascribed the pain symptom to insufficient humeral head depression during arm elevations. The arm adductors such as the teres major and pectoralis major may contribute to depression of the humerus head during arm elevations. Researchers have demonstrated that neuromuscular electrical stimulation (NMES) of the serratus anterior and lower trapezius can control scapular motions and improve acromiohumeral distance. It is unknown, however, if adductor neuromuscular training could help patients with rotator cuff tear. MATERIALS AND METHODS: A cross-sectional study of NMES of the teres major and pectoralis major was conducted on 30 symptomatic subjects with rotator cuff tear. We measured the acromiohumeral distance by ultrasonography and scapular kinematics during arm elevation with a three-dimensional motion tracking system. RESULTS: The acromiohumeral distance significantly increased during NMES of the teres major (0.73 mm, p < 0.001). However, the distance significantly decreased with NMES of the pectoralis major (0.78 mm, p < 0.001). Additionally, scapular upward rotation was greater during NMES of the teres major than during NMES of the pectoralis major (3.4°, p < 0.001). Scapular external rotation decreased significantly more during NMES of the pectoralis major than during NMES of the teres major (1.6°, p = 0.003). CONCLUSIONS: NMES of the teres major can increase acromiohumeral distance and scapular upward rotation during arm elevation. However, the decreased upward and external rotation of the scapula during arm elevation with NMES of the pectoralis major may be associated with subacromial impingement.

Development of an online calculator for the prediction of seizure freedom following pediatric hemispherectomy using the Hemispherectomy Outcome Prediction Scale (HOPS).

OBJECTIVES: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. METHODS: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). RESULTS: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.

Protective effect of electroacupuncture at ST36 against damage of intestinal mucosa, oxidative stress and apoptosis induced by 5-FU chemotherapy in mice with colon cancer. / 电针"足三里"å‡è½»å¤§è‚ ç™Œå°é¼ åŒ–ç–—åŽè‚ é»è†œæŸä¼¤åŠå ¶å¯¹æ°§åŒ–åº”æ¿€å’Œç»†èƒžå‡‹äº¡çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) on intestinal mucosal damage, intestinal mucosal oxidative stress injury and apoptosis induced by 5-fluorouraeil (5-FU) chemotherapy in colorectal cancer-bearing mice. METHODS: Thirty male BALB/c mice were randomly divided into normal control, colorectal cancer (CT26), 5-FU, non-acupoint and ST36 groups, with 6 mice in each group. Except for those of the normal control group, mice of the remaining 4 groups received subcutaneous implantation of colorectal CT26 cell suspension (0.1 mL) in the right armpit for establishing colorectal cancer model. Rats of the 5-FU group, non-acupoint group and ST36 group were given with 5 mg/mL 5-FU solution once every 3 days for a total of 21 days. For mice of the non-acupoint group and ST36 group, EA (2 Hz, 1-2 mA) was applied to bilateral ST36 or non-acupoints (the bilateral sunken spots about 3 mm to the midpoint between the tail root and the anus) for 5 min after each intraperitoneal infusion of 5-FU, once every 3 days, for a total of 21 days. After the intervention, the diarrhea index was assessed. The length of colon (from the endpoint of cecum to the anal orifice) was measured. Histopathological changes of colonic mucosa were observed by H.E. staining, and the length of colonic villi was measured. The content of malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of colonic tissue were detected by thibabituric acid, xanthine oxidase and colorimetric method, respectively. The rate of cell apoptosis in the colonic tissue was measured by TUNEL assay. The positive expressions of Bax and Bcl-2 in colonic tissue were determined by immunohistochemistry. RESULTS: The CT26 model group didn't show any significant changes in the diarrhea index, colon length, colon villus length, MDA content, SOD and GSH-Px activities, colonic cell apoptosis rate, and Bax and Bcl-2 expression levels when compared with the normal group. Compared with the CT26 group, the 5-FU group had a remarkable increase in the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level (P<0.01, P<0.05), and a marked decrease in the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level (P<0.01), suggesting the side effects of administration of 5-FU. Compared with the 5-FU group, the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level were markedly decreased (P<0.05, P<0.01) and those of the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level were obviously increased (P<0.01) in the ST36 group. Compared with the 5-FU group, the non-acupoint group also had an increase in the colon villus length, SOD and GSH-Px activities (P<0.01, P<0.05) and a decrease in the cell apoptosis rate (P<0.01). CONCLUSIONS: EA at ST36 has a positive effect in reducing intestinal mucosal damage induced by 5-FU chemotherapy in cancer-bearing mice, which may be related to its function in relieving oxidative stress injury and inhibiting apoptosis of colonic tissue.

Phosphorylation of the AMPARs regulated by protein kinase C (PKC) and protein interacting with C-kinase 1 (PICK1) contribute to orofacial neuropathic pain.

The α-amino-3-hydroxy-5-methylisoxazole-4-isoxazolepropionic acid receptor (AMPAR) has been recognized to play a vital role in the development of neuropathic pain. Recent studies have indicated that protein kinase C (PKC) and protein interacting with C-kinase 1 (PICK1) are involved in the phosphorylation of AMPARs. However, whether PKC and PICK1 were involved in the AMPAR phosphorylation in the trigeminal ganglion (TG) to participate in orofacial neuropathic pain remains enigmatic. A behavioral test was utilized to evaluate the head withdrawal threshold (HWT) after chronic constriction injury of the infraorbital nerve (CCI-ION). The distribution and expression of GluA1, GluA2, PKC, and PICK1 were examined in the trigeminal ganglion (TG) by immunofluorescence, real-time reverse transcription-quantitative polymerase chain reaction, immunoblotting, and co-immunoprecipitation. Intra-ganglionic injections of drugs were performed to investigate the regulation mechanism. The present study demonstrated that CCI-ION-induced mechanical allodynia was maintained over at least 21 days. GluA1 and GluA2 were mainly expressed in the neurons. Trigeminal nerve injury potentiated the phosphorylation of GluA1, GluA2, and PKC in the TG, which was prevented by inhibiting PKC with chelerythrine chloride. Additionally, PICK1 colocalized and interacted with GluA2 in the TG. Following blocking PICK1 with FSC-231, the phosphorylation of GluA2 decreased. Finally, inhibition of PKC and PICK1 both alleviated mechanical allodynia in the whisker pad of CCI-ION mice. In conclusion, activation of PKC and PICK1 contribute to orofacial allodynia by regulating AMPAR phosphorylation in the TG of male mice, which provides potential therapeutic targets for alleviating orofacial neuropathic pain.

Scapula-focused exercises with or without biofeedback increase corticospinal excitability in recreational overhead athletes with shoulder impingement.

CONTEXT: Individuals with shoulder impingement syndrome (SIS) exhibit changed corticospinal excitability, scapular kinematics, and scapular muscle activation patterns. To restore the scapular kinematics and muscle activation patterns in individuals with SIS, treatment protocols usually include scapula-focused exercises, such as scapular orientation training and strength training. OBJECTIVE: To investigate whether these two types of scapular exercise can reverse the changed corticospinal excitability of recreational overhead athletes with SIS. DESIGN: Randomized Controlled Clinical Trial. SETTING: University laboratory. PATIENTS OR OTHER PARTICIPANTS: Forty-one recreational overhead athletes with SIS (n=20 in the scapular orientation group with age= 26.45±4.13 years; height= 171.85±7.88 cm; mass= 66.70±10.68 kg; n=21 in the strengthening group with age= 26.43±5.55 years; height= 171.62±5.87 cm; mass= 68.67±10.18 kg). INTERVENTIONS: Both groups performed a 30-minute training protocol consisting of three exercises to strengthen the lower trapezius and serratus anterior muscles without overactivating the upper trapezius. Participants in the scapular orientation group were instructed to consciously activate their scapular muscles with electromyographic biofeedback and cues, whereas the strengthening group did not have biofeedback or cues for scapular motion. MAIN OUTCOME MEASURES: Corticospinal excitability was assessed using transcranial magnetic stimulation. Scapular kinematics and muscle activation during arm elevation were also measured. RESULTS: After the training, both groups demonstrated a significant increase in motor evoked potentials in lower trapezius (P=0.004) and significant increases in scapular upward rotation (P=0.032), lower trapezius activation (P<0.001), and serratus anterior activation (P<0.001) during arm elevation. Moreover, the scapular orientation group showed higher lower trapezius activation levels during arm elevation following the training, compared with the strengthening group (P=0.028). CONCLUSIONS: With or without biofeedback and cues, scapula-focused exercises improved scapular control and increased corticospinal excitability. Adding biofeedback and cues for scapular control during exercise helped facilitate greater lower trapezius activation, and thus, feedback and cues are recommended during scapula-focused training.

Evolutionary and Pan-genome Analysis of Three Important Black-pigmented Periodontal Pathogens.

OBJECTIVE: To analyse the pan-genome of three black-pigmented periodontal pathogens: Porphyromonas gingivalis, Prevotella intermedia and Prevotella nigrescens. METHODS: Pan-genome analyses of 66, 33 and 5 publicly available whole-genome sequences of P. gingivalis, P. intermedia and P. nigrescens, respectively, were performed using Pan-genome Analysis Pipeline software (version 1.2.1; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, PR China). Phylogenetic trees were constructed based on the entire pan-genome and single nucleotide polymorphisms within the core genome. The distribution and abundance of virulence genes in the core and dispensable genomes were also compared in the three species. RESULTS: All three species possess an open pan-genome. The core genome of P. gingivalis, P. intermedia and P. nigrescens included 1001, 1514 and 1745 orthologous groups, respectively, which were mainly related to basic cellular functions such as metabolism. The dispensable genome of P. gingivalis, P. intermedia and P. nigrescens was composed of 2814, 2689 and 906 orthologous groups, respectively, and it was enriched in genes involved in pathogenicity or with unknown functions. Phylogenetic trees presented a clear separation of P. gingivalis, P. intermedia and P. nigrescens, verifying the reclassification of the black-pigmented species. Furthermore, the three species shared almost the same virulence factors involved in adhesion, proteolysis and evasion of host defences. Some of these virulence genes were conserved across species whereas others belonged to the dispensable genome, which might be acquired through horizontal gene transfer. CONCLUSION: This study highlighted the usefulness of pan-genome analysis to infer evolutionary cues for black-pigmented species, indicating their homology and phylogenomic diversity.

A novel balance training approach: Biomechanical study of virtual reality-based skateboarding.

Introduction: The use of virtual reality (VR) technology in training and rehabilitation gained increasing attention in recent years due to its potential to provide immersive and interactive experiences. We developed a novel VR-based balance training, VR-skateboarding, for improving balance. It is important to investigate the biomechanical aspects of this training, as it would have benefited both health professionals and software engineers. Aims: This study aimed to compare the biomechanical characteristics of VR-skateboarding with those of walking. Materials and Methods: Twenty young participants (10 males and 10 females) were recruited. Participants underwent VR-skateboarding and walking at the comfortable walking speed, with the treadmill set at the same speed for both tasks. The motion capture system and electromyography were used to determine joint kinematics and muscle activity of the trunk and legs, respectively. The force platform was also used to collect the ground reaction force. Results: Participants demonstrated increased trunk flexion angles and muscle activity of trunk extensor during VR-skateboarding than during walking (p < 0.01). For the supporting leg, participants' joint angles of hip flexion and ankle dorsiflexion, as well as muscle activity of knee extensor, were higher during VR-skateboarding than during walking (p < 0.01). For the moving leg, only hip flexion increased in VR-skateboarding when compared to walking (p < 0.01). Furthermore, participants increased weight distribution in the supporting leg during VR-skateboarding (p < 0.01). Conclusion: VR-skateboarding is a novel VR-based balance training that has been found to improve balance through increased trunk and hip flexion, facilitated knee extensor muscles, and increased weight distribution on the supporting leg compared to walking. These differences in biomechanical characteristics have potential clinical implications for both health professionals and software engineers. Health professionals may consider incorporating VR-skateboarding into training protocols to improve balance, while software engineers may use this information to design new features in VR systems. Our study suggests that the impact of VR-skateboarding particularly manifest when focusing on the supporting leg.

Pitching Biomechanics and Shoulder Function in Baseball Pitchers with Scapular Dyskinesis.

The primary purpose was to investigate the influence of scapular dyskinesis (SD) on pitching biomechanics and shoulder function in high school baseball pitchers. The secondary purpose was to identify possible factors associated with shoulder function in pitchers with SD. Thirty-eight pitchers were classified into the SD group (n=26) or the non-SD group (n=12). They were evaluated with the Kerlan-Jobe Orthopaedic Clinic shoulder and elbow (KJOC) scale and clinical measurements of shoulder characteristics, and with measurements of scapular kinematics, muscle activation, and ball speed during fastball pitching. Compared to the controls, the pitchers with SD had less scapular external rotation (difference=11.3 degrees, ES=0.92, p=0.012) during overall pitching and less upper trapezius (UT) activation during the late cocking (difference=7.1%, ES=0.79, p=0.019) and acceleration phases (difference=12.5%, ES=0.75, p=0.035). Higher UT activation during the late cocking phase was significantly associated with higher KJOC scores (standardized ß=0.415, p=0.039). In conclusion, deficits in scapular external rotation and decreased UT activation during pitching were found in pitchers with SD. Higher UT activation may be important for shoulder function in pitchers with SD.

Metabotropic glutamate receptor 5-mediated inhibition of inward-rectifying K+ channel 4.1 contributes to orofacial ectopic mechanical allodynia following inferior alveolar nerve transection in male mice.

Inward-rectifying K+ channel 4.1 (Kir4.1), which regulates the electrophysiological properties of neurons and glia by affecting K+ homeostasis, plays a critical role in neuropathic pain. Metabotropic glutamate receptor 5 (mGluR5) regulates the expression of Kir4.1 in retinal Müller cells. However, the role of Kir4.1 and its expressional regulatory mechanisms underlying orofacial ectopic allodynia remain unclear. This study aimed to investigate the biological roles of Kir4.1 and mGluR5 in the trigeminal ganglion (TG) in orofacial ectopic mechanical allodynia and the role of mGluR5 in Kir4.1 regulation. An animal model of nerve injury was established via inferior alveolar nerve transection (IANX) in male C57BL/6J mice. Behavioral tests indicated that mechanical allodynia in the ipsilateral whisker pad lasted at least 14 days after IANX surgery and was alleviated by the overexpression of Kir4.1 in the TG, as well as intraganglionic injection of an mGluR5 antagonist (MPEP hydrochloride) or a protein kinase C (PKC) inhibitor (chelerythrine chloride); Conditional knockdown of the Kir4.1 gene downregulated mechanical thresholds in the whisker pad. Double immunostaining revealed that Kir4.1 and mGluR5 were co-expressed in satellite glial cells in the TG. IANX downregulated Kir4.1 and upregulated mGluR5 and phosphorylated PKC (p-PKC) in the TG; Inhibition of mGluR5 reversed the changes in Kir4.1 and p-PKC that were induced by IANX; Inhibition of PKC activation reversed the downregulation of Kir4.1 expression caused by IANX (p < .05). In conclusion, activation of mGluR5 in the TG after IANX contributed to orofacial ectopic mechanical allodynia by suppressing Kir4.1 via the PKC signaling pathway.

Alteration in coracohumeral ligament and distance in people with symptoms of subcoracoid impingement.

BACKGROUND: Differentiation between subacromial impingement versus subcoracoid impingement are important for the treatment target. We evaluated the correlations between coracohumeral ligament (CHL) thickness and distance (CHD) and characterized the CHL and subscapularis (SSC) in subcoracoid impingement subjects. METHODS: An observational, cross-sectional study was carried out. Twenty subcoracoid impingement subjects and age/gender matched controls were assessed in 4 different shoulder positions by ultrasonography. RESULTS: Moderate correlations between CHL thickness with CHD (r = 0.455 in neutral rotation, p = 0.044; r = 0.483 in interior rotation, p = 0.031) were found in subacromial subjects. Subcoracoid impingement subjects had greater CHL thickness (difference = 0.3 mm, effect size = 0.85, p = 0.006), SSC tendon thickness (difference = 0.7 mm, effect size = 0.92, p = 0.01) and SSC/CHD occupation ratio (difference = 8%, effect size = 0.95, p = 0.005) compared with the control. CONCLUSIONS: Coracohumeral distance is related to ligament thickness, especially in subacromial impingement subjects. Increased coracohumeral ligament and subscapularis thickness as well as decreased subscapularis/coracohumeral distance occupation ratio are characterized in subcoracoid impingement subjects. These quantitative measurements can be useful in identifying patients at risk of subcoracoid impingement from subacromial impingement.

Intramolecular Cyclization: A Convenient Strategy to Realize Efficient BT.2020 Blue Multi-Resonance Emitter for Organic Light-Emitting Diodes.

Rationally tuning the emission position and narrowing the full width at half-maximum (FWHM) of an emitter is of great importance for many applications. By synergistically improving rigidity, strengthening the resonant strength, inhibiting molecular bending and rocking, and destabilizing the HOMO energy level, a deep-blue emitter (CZ2CO) with a peak wavelength of 440 nm and an ultranarrow spectral FWHM of 16 nm (0.10 eV) was developed via intramolecular cyclization in a carbonyl/N resonant core (QAO). The dominant υ0-0 transition character of CZ2CO gives a Commission Internationale de I'Éclairage coordinates (CIE) of (0.144, 0.042), nicely complying with the BT.2020 standard. Moreover, a hyper-fluorescent device based on CZ2CO shows a high maximum external quantum efficiency (EQEmax ) of 25.6 % and maintains an EQE of 22.4 % at a practical brightness of 1000 cd m-2 .

Machine-learning-based detection of degenerative temporomandibular joint diseases using lateral cephalograms.

INTRODUCTION: Degenerative temporomandibular joint diseases (DJDs) are common diseases in dental practice, characterized by a series of degenerative processes in the temporomandibular joint. Early clinical detection of DJD by dental practitioners can be beneficial to prevent or alleviate the further progression of the disease. This study aimed to develop a cephalogram-based multidimensional nomogram to screen DJD. METHODS: A total of 502 patients (170 normal and 332 with DJD) were randomly assigned to a training set (n = 351) or a validation set (n = 151). Thirty-six cephalometric parameters were extracted from the cephalograms to be used as input for a predictive machine-learning algorithm. Multivariable logistic regression was used to construct a combined model for visualization in the form of a nomogram. Receiver operating characteristic curve, calibration testing, and decision curve analyses were conducted to evaluate the performance of the combined model. RESULTS: A Ceph score consisting of 22 cephalometric parameters were significantly associated with DJD (P <0.01). A combined model that consisted of Ceph scores and clinical features (including age, gender, limited mouth opening, crepitus, etc.) performed well in the receiver operating characteristic curve (area under the curve, 0.893), calibration test, and decision curve analyses, indicating its potential clinical value. CONCLUSIONS: This study constructed and verified a multidimensional nomogram consisting of Ceph scores and clinical features, which may contribute to the clinical screening of DJD in dental practice. Future studies are needed to test the reliability of the model with similar parameters.

The Effects of Interactive Virtual Reality in Patients with Chronic Musculoskeletal Disorders: A Systematic Review and Meta-Analysis.

Objective: Interactive virtual reality (iVR) has been widely used for treatment purposes in patients with chronic musculoskeletal disorders. However, no consensus has been reached on the effects of iVR on pain, psychological distress, and functional disability. Therefore, this study aims to investigate the effects of iVR on pain, psychological distress, and functional disability in patients with chronic musculoskeletal disorders compared with no rehabilitation and conventional rehabilitation. Methods: Five electronic databases (PubMed, Cochrane CENTRAL, Scopus, EMBASE, and Web of Science) were searched from January 2016 to December 2021. All randomized controlled trials using iVR for treating pain, psychological distress, and functional disability in patients with chronic musculoskeletal disorders were included. A subgroup analysis was conducted to compare the effects of nonimmersive and immersive types of iVR on the outcomes of interest. Results: Our study provides good quality evidence that iVR reduced overall pain by 9.28 points as compared with no rehabilitation and by 8.09 points as compared with conventional rehabilitation. In the subgroup analysis, nonimmersive iVR showed a reduction in psychological distress (standardized mean differences = -0.35) as compared with no rehabilitation. However, no statistically significant difference in the outcomes existed between nonimmersive and immersive iVR. Furthermore, there were no statistically significant differences in the outcomes of functional disability. Conclusions: iVR is recommended for reducing pain intensity more than no rehabilitation or conventional rehabilitation. Meanwhile, nonimmersive iVR has been proposed for psychological distress improvement, with effects similar to those of conventional rehabilitation. However, iVR may not be an effective intervention in the case of functional disability.

Return to work in head and neck cancer survivors: its relationship with functional, psychological, and disease-treatment factors.

PURPOSE: Return to work (RTW) is important for survivors of head and neck cancer (HNC). The purposes of the study were to investigate the RTW ratio among HNC survivors and identify factors significantly affecting RTW in this population. METHODS: A cross-sectional study with consecutive sampling was conducted in a medical center in Taiwan, with 111 patients with HNC who had completed major treatments within 5 years and were employed before their cancer diagnosis enrolled as participants. Cervical range of motion (CROM) functionality, handgrip and hip flexor strength, maximal mouth opening (MMO), selected symptoms, depression, and disease/treatment-related factors were assessed. All of the factors were analyzed using t-test, chi-square test, and multiple logistic regression. RESULTS: Less than half (44.1%, n = 49) of the participants had returned to work. The t-test/chi-square test results showed the RTW group to be younger in age and better educated; have better handgrip/hip flexor strength, MMO, and CROM; have less speech difficulty and pain; and have less-advanced cancer than the non-RTW group. Further analysis of the above significant variables by logistic regression revealed early cancer stage, dominant handgrip strength, and less speech difficulty were the robust factors related to RTW. CONCLUSIONS: The RTW ratio is low in HNC survivors. RTW in HNC survivors is a multifactorial and complicated issue and needs to be further examined. IMPLICATIONS FOR CANCER SURVIVORS: Assessing the factors related to RTW systematically and developing comprehensive interventions and rehabilitation programs to reduce related dysfunctions are necessary to enhance RTW ability in HNC survivors.

Impairment of scapular control in individuals with chronic obstructive pulmonary disease (COPD): Systematic review and meta-analysis.

BACKGROUND: Upper quadrant geometrical changes in individuals with chronic obstructive pulmonary disease (COPD) appear to have negative influences on geometrical arrangements of the thorax and scapula. OBJECTIVE: The purpose of this systematic review was to assess the impairment of scapular control in individuals with COPD as compared with healthy controls. METHODS: We systematically searched seven electronic databases from inception to June 2021 and updated the searches again in December 2021. Eligible studies included the participants with COPD and compared scapular control outcomes (scapular/shoulder kinematic or related muscle activity) with a control group. Two researchers independently searched for, screened, extracted data from, and evaluated the quality of all articles. RESULTS: Seven studies met the inclusion criteria and only five studies with 190 subjects were included in the meta-analyses. Subgroup analyses showed that the control group exhibited more scapular anterior tilt (SMD: 0.46; 95% CI: 0.01 to 0.90) and shoulder flexion (SMD: -1.02; 95% CI: -1.79 to -0.26) as compared with the COPD group. Conversely, the COPD group exhibited more scapular elevation (SMD: -1.03; 95% CI: -1.69 to -0.37), internal rotation (SMD: -1.65; 95% CI: -3.19 to -0.10), and protraction (SMD: -0.75; 95% CI: -1.18 to -0.32) compared with the control group. All other outcomes revealed non-significant findings. CONCLUSION: This review demonstrated scapular control impairments, such as scapular elevation, internal rotation, protraction, and anterior tilt in a static position in patients with COPD. To validate these findings, high-quality randomized control trials with large sample sizes and reliable outcome measures should be conducted.

Effects of Upper Trapezius Myofascial Trigger Points on Scapular Kinematics and Muscle Activation in Overhead Athletes.

Prolonged overactivity of the upper trapezius muscle with myofascial trigger points might cause muscle fatigue and subsequently change scapular kinematics and associated muscular activities. Scapular kinematics and associated muscular activities were investigated in 17 overhead athletes with upper trapezius myofascial trigger points and 17 controls before and after a fatigue task. Participants performed a fatigue task requiring sustained isometric scapular elevation. The outcomes included scapular kinematics (upward/downward rotation, external/internal rotation, posterior/anterior tilt) that were tracked by the Polhemus FASTRAK (Polhemus Inc., Colchester, VT, USA) system with Motion Monitor software and muscular activities (upper trapezius, lower trapezius and serratus anterior) that were collected at 1000 Hz per channel using a 16-bit analog-to-digital converter (Model MP 150, Biopac systems Inc., CA, USA) with pairs of silver chloride circular surface electrodes (The Ludlow Company LP, Chocopee, MA) during arm elevation. Mixed ANOVAs were conducted to characterize the outcomes with and without a fatigue task in participants with myofascial trigger points. Decreased scapular posterior tipping during 90 degrees of arm raising/lowering (effect sizes of 0.51 and 0.59) was likely to be elicited by the scapular elevation fatigue task in the presence of myofascial trigger points. Activity of the lower trapezius was higher in the myofascial trigger point group (6.2%, p = 0.036) than in the control group. Following the fatigue task, both groups showed increased activity in the upper trapezius (9.0%, p = 0.009) during arm lowering and in the lower trapezius (2.7%, p < 0.01) during arm raising and lowering. Decreased scapular posterior tipping during 90 degrees of arm raising/lowering after a fatigue task may lead to impingement. We found that the presence of upper trapezius myofascial trigger points in amateur overhead athletes was related to impaired scapular kinematics and associated muscular activities during arm elevation after a fatigue task, especially the decreased scapular tipping during 90 degrees of raising/lowering.

NMDARs mediate peripheral and central sensitization contributing to chronic orofacial pain.

Peripheral and central sensitizations of the trigeminal nervous system are the main mechanisms to promote the development and maintenance of chronic orofacial pain characterized by allodynia, hyperalgesia, and ectopic pain after trigeminal nerve injury or inflammation. Although the pathomechanisms of chronic orofacial pain are complex and not well known, sufficient clinical and preclinical evidence supports the contribution of the N-methyl-D-aspartate receptors (NMDARs, a subclass of ionotropic glutamate receptors) to the trigeminal nociceptive signal processing pathway under various pathological conditions. NMDARs not only have been implicated as a potential mediator of pain-related neuroplasticity in the peripheral nervous system (PNS) but also mediate excitatory synaptic transmission and synaptic plasticity in the central nervous system (CNS). In this review, we focus on the pivotal roles and mechanisms of NMDARs in the trigeminal nervous system under orofacial neuropathic and inflammatory pain. In particular, we summarize the types, components, and distribution of NMDARs in the trigeminal nervous system. Besides, we discuss the regulatory roles of neuron-nonneuronal cell/neuron-neuron communication mediated by NMDARs in the peripheral mechanisms of chronic orofacial pain following neuropathic injury and inflammation. Furthermore, we review the functional roles and mechanisms of NMDARs in the ascending and descending circuits under orofacial neuropathic and inflammatory pain conditions, which contribute to the central sensitization. These findings are not only relevant to understanding the underlying mechanisms, but also shed new light on the targeted therapy of chronic orofacial pain.

Interactions Among Non-Coding RNAs and mRNAs in the Trigeminal Ganglion Associated with Neuropathic Pain.

Background: Recent studies have demonstrated the contribution of non-coding RNAs (ncRNAs) to neuropathic pain. However, the expression profile of ncRNAs in the trigeminal ganglion (TG) and their functional mechanism underlying trigeminal neuropathic pain are still unclear. Methods: In the present study, the trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve (CCI-ION) was used to study the expression profile and potential regulatory mechanism of miRNAs, lncRNAs, circRNAs, and mRNAs in the TG by RNA-sequencing (RNA-seq) and bioinformatics analysis. CCI-ION mice suffered from mechanical allodynia from 3 days to 28 days after surgery. Results: The RNA-seq results discovered 67 miRNAs, 216 lncRNAs, 14 circRNAs, 595 mRNAs, and 421 genes were differentially expressed (DE) in the TG of CCI-ION mice 7 days after surgery. And 39 DEGs were known pain genes. Besides, 5 and 35 pain-related DE mRNAs could be targeted by 6 DE miRNAs and 107 DE lncRNAs, respectively. And 23 pain-related DEGs had protein-protein interactions (PPI) with each other. GO analysis indicated membrane-related cell components and binding-related molecular functions were significantly enriched. KEGG analysis showed that nociception-related signaling pathways were significantly enriched for DE ncRNAs and DEGs. Finally, the competing endogenous RNA (ceRNA) regulatory network of DE lncRNA/DE circRNA-DE miRNA-DE mRNA existed in the TG of mice with trigeminal neuropathic pain. Conclusion: Our findings demonstrate ncRNAs are involved in the development of trigeminal neuropathic pain, possibly through the ceRNA mechanism, which brings a new bright into the study of trigeminal neuropathic pain and the development of novel treatments targeting ncRNAs.