Characteristics of Tongue Pressure Measured by Novel Multisite Flexible Sensors in Nasopharyngeal Carcinoma Patients With Dysphagia.

OBJECTIVE: To explore characteristics of tongue pressure changes in nasopharyngeal carcinoma (NPC) patients with dysphagia after radiotherapy using a novel system with multisite flexible sensors. DESIGN: Prospective observational study. SETTING: Inpatient rehabilitation centers and community dwellings. PARTICIPANTS: Nineteen patients with dysphagia after radiotherapy for NPC and 19 healthy participants were recruited for this study (N=38). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: A new 9-site (3 × 3) flexible tongue pressure sensor was used to measure tongue-to-palate pressure across different parts of the tongue. The oral tongue was divided into 3 parts: anterior tongue region (TAR), central tongue region (TCR), and posterior tongue region (TPR); 3 sensors were placed on each part. The mean tongue pressure and endurance time at the 3 sites in the TAR, TCR, and TPR were analyzed. The ratios of the mean TAR, TCR, and TPR values were calculated. RESULTS: Pressures of TAR, TCR, and TPR in NPC patients with dysphagia were significantly lower than those in healthy participants (P<.05). The pressure in TPR decreased most significantly, followed by that in TCR. The endurance times of TAR and TCR were longer than those of healthy participants (P<.05). The endurance time of TPR was not significantly different between the patients and healthy participants (P>.05). Ratios of pressure between TAR and TCR and TAR and TPR in patients were lower than that in healthy participants (P<.05). There was no significant difference in the TCR to TPR pressure ratio between patients and healthy participants (P>.05). CONCLUSIONS: Tongue pressure significantly decreased in NPC patients with dysphagia, and the drop in pressure was most pronounced in the TPR area. The results of our study indicate that we should pay attention to the pressure training of the TPR during treatments. The endurance time of the TAR and TCR increased significantly, which may be due to bolus transport compensation. Therefore, clinical rehabilitation strategies should aim to increase the endurance time training in NPC patients after radiotherapy to help increase the effectiveness of the swallowing process in patients.

Analgesic Effect of Perineural Injection of BoNT/A on Neuropathic Pain Induced by Chronic Constriction Injury of Sciatic Nerve in Rats.

This study was designed to investigate the analgesic effect of perineural injection of BoNT/A on neuropathic pain induced by sciatic nerve chronic constriction injury (CCI) and possible mechanisms. SD rats were randomly divided into Sham group, CCI group and BoNT/A group. Paw mechanical withdrawal threshold (pMWT) and paw thermal withdrawal latency (pTWL) of each group were detected at different time points after surgery. The expression of myelin markers, autophagy markers and NLRP3 inflammasome-related molecules in injured sciatic nerves were examined at 12 days after surgery. Moreover, C-fiber evoked potential in spinal dorsal horn was recorded. The expression of SNAP-25, neuroinflammation and synaptic plasticity in spinal dorsal horn of each group were examined. Then rats treated with BoNT/A were randomly divided into DMSO group and Wnt agonist group to further explore the regulatory effect of BoNT/A on Wnt pathway. We found that pMWT and pTWL of ipsilateral paw were significantly decreased in CCI group compared with Sham group, which could be improved by perineural injection of BoNT/A at days 7, 9 and 12 after surgery. The peripheral analgesic mechanisms of perineural injection of BoNT/A might be related to the protective effect on myelin sheath by inhibiting NLRP3 inflammasome and promoting autophagy flow, while the central analgesic mechanisms might be associated with inhibition of neuroinflammation and synaptic plasticity in spinal dorsal horn due to inhibiting SNAP-25 and Wnt pathway. As a new route of administration, perineural injection of BoNT/A can relieve CCI induced neuropathic pain probably via both peripheral and central analgesic mechanisms.

Community-based group rehabilitation program for stroke patients with dysphagia on quality of life, depression symptoms, and swallowing function: a randomized controlled trial.

BACKGROUND: Community-based exercise programs have demonstrated potential for implementation in older adults; however, it remains imperative to ascertain whether this strategy will yield comparable benefit in stroke patients with dysphagia. METHODS: This was a single blinded, randomized, matched pairs clinical trial. Sixty-four stroke patients with dysphagia were recruited from patients who had been discharged the Rehabilitation Department of the Third Affiliated Hospital of Sun Yat-sen University. A single blinded, randomized and controlled trial was conducted. Participants were randomly assigned to either the intervention group (n = 32) or the control group (n = 32). Patients in the intervention group received health education followed by swallowing function training in community public spaces for 5 days every week over an eight-week period (60 minutes per day). Patients in the control group received swallowing rehabilitation training, and booster educational information about dysphagia, as well as instructions on how to improve quality of life. Swallowing function (Functional Oral Intake Scale (FOIS) and Standardized Swallowing Assessment (SSA)), depressive symptoms (Geriatric Depression Scale-15), and quality of life (Swallowing-Quality of Life, SWAL-QOL) were assessed before and after all the treatment. RESULTS: Before treatment, the two groups did not differ statistically. After the intervention, the swallowing function (SSA and FOIS) showed a significant improvement in both groups (All p < 0.001). But there was no significant difference in Functional Oral Intake Scale change between groups (P = 0.479). Compared with the control group, the intervention group had a significant improvement in depressive symptoms (P = 0.002), with a greater reduction in the number of depressed patients (13 to 6).The control group showed no significant improvements in depressive symptoms or a reduction in the number of depressed patients before and after treatment (P = 0.265, 14 to 12). The Swallowing-Quality of Life scores showed significant improvement in both the intervention and control group (P < 0.001). Specifically within Swallowing-Quality of Life sub-domains, greater changes were observed in symptoms and frequency (P < 0.001), communication (P = 0.012), and sleep (P = 0.006) for participants in the intervention group. And the cost-effectiveness of group rehabilitation surpasses that of rehabilitation training. CONCLUSION: Community-based group rehabilitation program is more effective than traditional treatment in improving patients' depressive symptoms and quality of life, as well as being more cost-effective.

Association of Circulating Trimethylamine-N Oxide With Malnutrition and the Risk of Coronary Artery Disease in Patients With Maintenance Hemodialysis.

OBJECTIVES: Malnutrition is a serious complication frequently observed in dialysis patients. Therefore, nutrition status evaluation and the early identification of malnutrition are clinically important. Trimethylamine N-oxide (TMAO) is reportedly associated with deteriorating metabolic profiles and cardiovascular diseases. The aim of our study was to investigate correlations between circulating TMAO levels and malnutrition and the risk of major adverse cardiovascular events in patients on maintenance hemodialysis. METHODS: This retrospective observational study involved 228 subjects. Fasting plasma TMAO levels were detected using liquid chromatography-tandem mass spectrometry. RESULTS: TMAO levels were significantly elevated in patients with malnutrition (8728.78 ± 704.12 ng/mL) when compared with those without (6532.1 ± 570.41 ng/mL, P < .01). TMAO levels were positively correlated with Subjective Global Assessment scores (ρ = 0.56, P = .02) and were independent risk factors for malnutrition after adjustment for multiple traditional risk factors (odds ratio = 2.07, 95% confidence interval: 1.41-3.62, P < .01). Furthermore, TMAO levels were good predictors of major adverse cardiovascular events in a 2-year follow-up period (area under the curve = 0.68, P < .01) and accuracy was increased to 74% when TMAO levels were combined with Subjective Global Assessment scores (area under the curve = 0.74, P = .02). CONCLUSIONS: Elevated TMAO levels were independently associated with a risk of malnutrition and cardiovascular disease, and could be a useful predictive biomarker for risk stratification and cardiovascular disease management for patients on dialysis.

Videofluoroscopic Swallowing Study Features and Resting-State Functional MRI Brain Activity for Assessing Swallowing Differences in Patients with Mild Cognitive Impairment and Risk of Dysphagia.

To examine the swallowing characteristics in patients with mild cognitive impairment (MCI) and dysphagia risk and explore brain activity changes using regional homogeneity (ReHo) with resting-state functional magnetic resonance imaging (rs-fMRI). We included 28 patients with MCI and dysphagia risk and 17 age-matched older adults. All participants underwent neurological, cognitive examinations, and a videofluoroscopic swallowing study (VFSS). We quantitatively analyzed the VFSS temporal and kinetic parameters of the 5- and 10-mL swallows. The participants underwent rs-fMRI, and the ReHo values were calculated. Differences in the swallowing physiology and rs-fMRI findings between participants with MCI and controls were analyzed. Correlation analyses were also conducted. Compared to the control group, patients with MCI and dysphagia risk had lower global cognition scores, longer 10-mL oral transit times (OTTs), and lower executive function scores. ReHo in the bilateral inferior occipital lobes (IOLs) and left prefrontal lobe decreased in patients with MCI and dysphagia risk compared to participants in the control group. In patients with MCI, the 10-mL OTT was negatively correlated with the Montreal Cognitive Assessment (MoCA) score, and the ReHo values were positive correlated with quantitative temporal swallowing measurements using canonical correlation analysis. Mediation analysis revealed that the ReHo values of the left and right IOL acted as significant mediators between the MoCA score and the 10-mL OTT. We found that individuals with MCI and dysphagia risk, verified by reduced MoCA scores, demonstrated prolonged OTTs when swallowing larger boluses compared with age-matched controls. There was a negative correlation between the MoCA score and 10-mL OTT, which was partially mediated by the left and right IOL ReHo values, suggesting that functional changes in the IOLs and left prefrontal lobe associated with oral swallowing status and cognitive level in individuals with MCI and dysphagia risk.

The Effect of Combined Guidance of Botulinum Toxin Injection with Ultrasound, Catheter Balloon, and Electromyography on Neurogenic Cricopharyngeal Dysfunction: A Prospective Study.

BACKGROUND: Cricopharyngeal botulinum toxin (BTX) injection is one of the treatments for neurogenic cricopharyngeal dysfunction (CPD). We conducted this prospective study to investigate the effect and safety of BTX injection for neurogenic CPD with a novel guidance. METHODS: Twenty-one patients with neurogenic CPD whose symptoms did not reduce after conventional swallowing therapy were included in this study. The impact of BTX injection on the swallowing function of the patients was evaluated. KEY RESULTS: After the injection, the Functional Oral Intake Scale (FOIS) score increased in 17 of 21 patients (80.9%), which ranged from 1 to 3 (P < 0.001). Moreover, there was a significant reduction in the UES opening impairment (P < 0.01), UES residual pressure (P < 0.05), duration of UES relaxation, penetration-aspiration scale score (P < 0.05), secretion (P < 0.05), vallecular residue (P < 0.01), and left (P < 0.05) and right (P < 0.05) pyriform sinus residue. With at least 6 months of follow-up, we found that FOIS continued to increase in patients who showed improvement after the injection (i.e., FOIS 5-7 points), while it remained unchanged in patients without improvement after the injection. There were no side effects reported in this study. CONCLUSION & INFERENCES: BTX injection into the cricopharyngeal muscle guided by ultrasound, catheter balloon, and electromyography possibly has a long-lasting effect that can effectively and safely improve the swallowing function of patients with neurogenic CPD.

Pareuzebyella sediminis gen. nov., sp. nov., a novel marine bacterium in the family Flavobacteriaceae, isolated from a tidal flat sediment.

Two marine bacterial strains, designated S2-4-21T and MT2-5-19, were isolated from two tidal flat sediments of cordgrass Spartina alterniflora and adjacent oyster culture field in Quanzhou bay, China, respectively. Both strains were Gram-staining-negative, rod-shaped, non-flagellated, non-motile, aerobic, had NaCl requirements, and contained carotenoid and flexirubin pigments. The 16S rRNA gene sequence similarity (99.8%), average nucleotide identity value (99.4%) and average amino acid identity (99.3%) between strain S2-4-21T and strain MT2-5-19 strongly supported that they belonged to a single species. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S2-4-21T and strain MT2-5-19 formed a monophyletic branch affiliated to the family Flavobacteriaceae, sharing similarities of 94.6% with Euzebyella marina CY01T and E. saccharophila 7SM30T, and of 94.1 and 92.8% with E. algicola MEBiC 12267T and Pseudozobellia thermophile DSM 19858T, respectively. Phylogenomic analysis based on the whole genome sequences supported that the two strains formed a distinct monophyletic clade within Flavobacteriaceae members, which was phylogenetically different from the clades of Euzebyella and Pseudozobellia. The major respiratory quinone was menaquinone MK-6. The major fatty acids (>10%) consisted of C15 : 0 iso, C16 : 0, summed feature 9 (C17 : 1 iso ω9c/C16 : 0 10-methyl) and C17 : 0 iso 3-OH. The polar lipid profiles of strain S2-4-21T and strain MT2-5-19 are identical, including phosphatidylethanolamine, four unidentified aminolipids, and four unidentified lipids. The genomic size was 4.9-5.0 Mb with genomic DNA G+C content of 41.5 mol%. Based on the above characteristics, strains S2-4-21T and MT2-5-19 represented a novel species of a novel genus in the family Flavobacteriaceae. Thus, Pareuzebyella sediminis gen. nov. sp. nov. is proposed with type strain S2-4-21T (=MCCC 1K03818T=KCTC 72152T), and another strain MT2-5-19 (=KCTC 72539=MCCC 1K03874).

miR-3607-3p suppresses non-small cell lung cancer (NSCLC) by targeting TGFBR1 and CCNE2.

Accumulating evidence indicates that miRNAs can be promising diagnostic and/or prognostic markers for various cancers. In this study, we identified a novel miRNA, miR-3607-3p, and its targets in non-small cell lung cancer (NSCLC). The expression of miR-3607-3p was measured and its correlation with patient prognosis was determined. Ectopic expression in NSCLC cells, xenografts, and metastasis models was used to evaluate the effects of miR-3607-3p on proliferation and migration of NSCLC. Luciferase assay and western blotting were performed to validate the potential targets of miR-3607-3p after preliminary screening by microarray analysis and computer-aided algorithms. We demonstrated that miR-3607-3p was downregulated in NSCLC tissues and that miR-3607-3p might act as an independent predictor for overall survival in NSCLC. Moreover, serum miR-3607-3p may be a novel and stable marker for NSCLC. We found that overexpression of miR-3607-3p inhibited cell proliferation, colony formation, migration and invasion, and hampered the cell cycle of NSCLC cell lines in vitro. Our results suggested that miR-3607-3p directly targets TGFBR1 and CCNE2. In accordance with in vitro studies, we confirmed that miR-3607-3p functions as a potent suppressor miRNA of NSCLC. We showed that miR-3607-3p agomir could reduce tumor growth and inhibit TGFBR1 and CCNE2 protein expression. Taken together, our findings indicate that miR-3607-3p can inhibit NSCLC cell growth and metastasis by targeting TGFBR1 and CCNE2 protein expression, and provide new evidence of miR-3607-3p as a potential non-invasive biomarker and therapeutic target for NSCLC.

Effect of ticagrelor on brain natriuretic peptide, heart rate and myocardial enzymes in patients with coronary atherosclerotic heart disease after stenting.

The main aim of the current work was to investigate the application of ticagrelor in patients with coronary atherosclerotic heart disease (CAHD) and its effects on brain natriuretic peptide (BNP), heart rate (HR) and myocardial enzymes. Seventy-four postoperative patients who underwent stenting for CAHD were selected as subjects, randomly divided into control group (n=37) and observation group (n=37). The control group was treated with clopidogrel after operation, while the observation group was given ticagrelor treatment. The plasma BNP, HR, myocardial zymogram and adverse cardiac events were compared between the two groups. SPSS18.0 software was used for statistical analysis and the count data was analyzed by χ2 test and the measurement data was detected by t-test The levels of BNP, HR, creatine kinase isoenzyme (CK-MB) and troponin (cTnI) in the observation group were all lower than those in the control group at 3 months after treatment (P<0.05). There was no significant difference in the incidence of myocardial infarction, angina pectoris and arrhythmia between the two groups at 3 months after treatment (P>0.05). The utilization of ticagrelor in patients with postoperative stenting for CAHD improved the BNP, HR and myocardial enzyme level in patients, and also reduced the incidence of adverse cardiac events.

Change in Excitability of Cortical Projection After Modified Catheter Balloon Dilatation Therapy in Brainstem Stroke Patients with Dysphagia: A Prospective Controlled Study.

Although the modified balloon dilatation therapy has been demonstrated to improve pharyngeal swallowing function post stroke, the underlying neural mechanisms of improvement are unknown. Our aims are (1) to investigate the effect of modified balloon dilatation on the excitability of corticobulbar projections to the submental muscle in dysphagic patients with brainstem stroke and (2) the relation between changes in excitability and pharyngeal kinematic modifications. Thirty patients with upper esophageal sphincter (UES) dysfunction due to unilateral brainstem stroke were recruited into two groups. The patients in dilatation group received modified balloon dilatation and conventional therapies, and those in control were only treated by conventional therapies (twice per day). The amplitudes of bilateral submental motor evoked potentials (MEPs) induced by transcranial magnetic stimulations over bilateral motor cortex, diameters of UES opening (UOD) and maximal displacement of hyoid (HD) were all assessed at baseline and the endpoint of treatments. Repeated ANOVA analysis revealed significant main effect of group, time and MEP laterality on MEP amplitudes (p = 0.02). There were no differences in the pretreatment measures between groups (all p > 0.05). After treatment, the amplitudes of affected submental MEP evoked by ipsilateral cortical pulse as well as UOD and HD were significantly different in dilatation group compared to control (amplitude: p = 0.02, UOD: p < 0.001, HD: p = 0.03). The differences of pre- and post-treatment amplitudes of the affected MEP evoked by ipsilateral stimulation showed a positive correlation with the improvement of HD (dilatation: R 2 = 0.51, p = 0.03; control: R 2 = 0.39, p = 0.01), rather than UOD in both groups (all p > 0.05). In conclusion, modified balloon dilatation therapy can increase the excitability of affected projection in patients with unilateral brainstem stroke.

[Study based on sonoelastography technology for spastic gastrocnemius in rat with spinal cord injure].

OBJECTIVE: To investigate the pathological characteristic of gastrocnemius (GM) and quantitatively assess GM tissue stiffness in spinal cord injury (SCI) rat models; to explore the novel method in evaluation of GM stiffness. METHODS: A total of 54 SD male rats (weight 260-280 g) were allocated into normal control group (0 w) and model groups (2, 4, 8 and 12 w) in this study. Complete SCI (T10 level) was applied in model groups. At the above different time points, Modified Ashworth Scale (MAS) was used to assess the GM spasticity; Basso, Beattie, and Bresnahan Locomotor Rating Scale (BBB) was used to assess the movement ability of lower limb. GM stiffness was assessed with shear wave sonoelastography technology in these groups. All GM at right side of rats was further checked by pathological examinations (muscle weight, ATP staining, myosin heavy chain (MyHC) electrophoretic analysis) after sonoelastography imaging examinations. RESULTS: After removing the overweight and underweight rat models which were alive, six rats were included in each group. There were some pathologic changes in GM in SCI rat models. Compared with normal control group, data from model groups showed ankle dorsiflexors MAS (1.5±0.8-0.8±0.7 score) was increased (P≤0.05), BBB scores of lower limb (3.2±1.0-7.2±1.3score) were decreased (P≤0.05). The GM elastic modulus was increased at dorsiflexion location in model group (25.1±2.4-37.4±5.5 kPa, P≤0.05); GM weights were decreased, ratio of type Ⅰ fibers was decreased and ratio of type Ⅱ fibers was increased in GM. Compared with normal control group, MyHC-Ⅰ was decreased, while MyHC-Ⅱ was increased according electrophoretic analysis. CONCLUSIONS: Both pathological characteristic and muscle stiffness of GM change after SCI. Shear-wave sonoelastography technology can be used to assess the GM stiffness in SCI rat models.

[Relationship between electrocardiographic and genetic mutation (MYH7-H1717Q, MYLK2-K324E and KCNQ1-R190W) phenotype in patients with hypertrophic cardiomyopathy].

OBJECTIVE: To explore the relationship between electrocardiographic (ECG) and genetic mutations of patients with hypertrophic cardiomyopathy (HCM), and early ECG changes in HCM patients. METHODS: Clinical, 12-lead ECG and echocardiographic examination as well as genetic examinations were made in a three-generation Chinses HCM pedigree with 8 family members (4 males). The clinical characterization and ECG parameters were analyzed and their relationship with genotypes in the family was explored. RESULTS: Four missense mutations (MYH7-H1717Q, MYLK2-K324E, KCNQ1-R190W, TMEM70-I147T) were detected in this pedigree. The proband carried all 4 mutations and 5 members carried 2 mutations. Corrected QTc interval of KCNQ1-H1717Q carriers was significantly prolonged and was consistent with the ECG characterization of long QT syndrome. MYLK2-K324E and KCNQ1-R190W carriers presented with Q wave and(or) depressed ST segment, as well as flatted or reversed T waves in leads from anterolateral and inferior ventricular walls. ECG results showed ST segment depression, flat and inverted T wave in the gene mutation carriers with normal echocardiographic examination results. ECG and echocardiographic results were normal in TMEM70-I147T mutation carrier. CONCLUSIONS: The combined mutations of the genes associated with cardiac ion channels and HCM are linked with the ECG phenotype changes in this HCM pedigree. The variations in ECG parameters due to the genetic mutation appear earlier than the echocardiography and clinical manifestations. Variation in ECG may become one of the indexes for early diagnostic screening and disease progression of the HCM gene mutation carriers.

Meningeal norepinephrine produces headache behaviors in rats via actions both on dural afferents and fibroblasts.

BACKGROUND: Stress is commonly reported to contribute to migraine although mechanisms by which this may occur are not fully known. The purpose of these studies was to examine whether norepinephrine (NE), the primary sympathetic efferent transmitter, acts on processes in the meninges that may contribute to the pain of migraine. METHODS: NE was applied to rat dura using a behavioral model of headache. Primary cultures of rat trigeminal ganglia retrogradely labeled from the dura mater and of rat dural fibroblasts were prepared. Patch-clamp electrophysiology, Western blot, and ELISA were performed to examine the effects of NE. Conditioned media from NE-treated fibroblast cultures was applied to the dura using the behavioral headache model. RESULTS: Dural injection both of NE and media from NE-stimulated fibroblasts caused cutaneous facial and hindpaw allodynia in awake rats. NE application to cultured dural afferents increased action potential firing in response to current injections. Application of NE to dural fibroblasts increased phosphorylation of ERK and caused the release of interleukin-6 (IL-6). CONCLUSIONS: These data demonstrate that NE can contribute to pro-nociceptive signaling from the meninges via actions on dural afferents and dural fibroblasts. Together, these actions of NE may contribute to the headache phase of migraine.

Diazaquinomycins E-G, novel diaza-anthracene analogs from a marine-derived Streptomyces sp.

As part of our program to identify novel secondary metabolites that target drug-resistant ovarian cancers, a screening of our aquatic-derived actinomycete fraction library against a cisplatin-resistant ovarian cancer cell line (OVCAR5) led to the isolation of novel diaza-anthracene antibiotic diazaquinomycin E (DAQE; 1), the isomeric mixture of diazaquinomycin F (DAQF; 2) and diazaquinomycin G (DAQG; 3), and known analog diazaquinomycin A (DAQA; 4). The structures of DAQF and DAQG were solved through deconvolution of X-Ray diffraction data of their corresponding co-crystal. DAQE and DAQA exhibited moderate LC50 values against OVCAR5 of 9.0 and 8.8 µM, respectively. At lethal concentrations of DAQA, evidence of DNA damage was observed via induction of apoptosis through cleaved-PARP. Herein, we will discuss the isolation, structure elucidation, and biological activity of these secondary metabolites.

Genomic insights into differentiation and adaptation of Amorphophallus yunnanensis in the mountainous region of Southwest China.

The role of geographical isolation and environmental adaptation in driving the differentiation and radiation of species has been a hotspot in evolutionary biology. The extremely complicated and fragmented geography of the mountainous region of Southwest China provides an excellent system for investigating the process of species divergence in heterogeneous habitats. Amorphophallus yunnanensis is a species of extreme habitat preference that resides mainly in the mountainous region of Southwest China. Here, we used restriction site-associated DNA sequencing (RAD-seq) to characterize the geographic pattern of genetic variation among 19 populations of A. yunnanensis as well as the genomic basis of environmental adaptation. A pattern of low population genetic diversity and high level of genetic differentiation was observed. The genomic data revealed a clear east-west genetic differentiation, with two distinct genetic lineages corresponding to the Guizhou plateau and Yunnan plateau, respectively. However, we discovered demographic expansion of the Guizhou Plateau lineage and recent hybridization in populations at the contact region. Significant levels of isolation by distance along with isolation by environment were detected. Outlier tests and genome-environment association analyses identified 89 putatively adaptive loci that might play a role in environmental adaptation. Our results suggest that the genetic divergence of A. yunnanensis is attributed to geographical isolation together with divergent selection in the mountainous region of Southwest China.

pH-evoked dural afferent signaling is mediated by ASIC3 and is sensitized by mast cell mediators.

BACKGROUND: Prior studies have shown that decreased meningeal pH activates dural afferents via opening of acid-sensing ion channels (ASICs), suggesting one pathophysiological mechanism for the generation of headaches. The studies described here further examined the ASIC subtype mediating pH-induced dural-afferent activation and examined whether sensitization influences pH responses. OBJECTIVE: Given the potential importance of meningeal mast cells to headache, the goal of this study was to evaluate dural afferent responses to pH following sensitization with mast cell mediators. METHODS: Cutaneous allodynia was measured in rats following stimulation of the dura with decreased pH alone or in combination with mast cell mediators. Trigeminal ganglion neurons retrogradely labeled from the dura were stained with an ASIC3 antibody using immunohistochemistry. Current and action potentials evoked by changes in pH alone or in combination with mast cell mediators were measured in retrogradely labeled dural afferents using patch-clamp electrophysiology. RESULTS: pH-sensitive dural afferents generated currents in response to the ASIC3 activator 2-guanidine-4-methylquinazoline (GMQ), approximately 80% of these neurons express ASIC3 protein, and pH-evoked behavioral responses were inhibited by the ASIC3 blocker APETx2. Following exposure to mast cell mediators, dural afferents exhibited increased pH-evoked excitability, and cutaneous allodynia was observed at higher pH than with pH stimuli alone. CONCLUSIONS: These data indicate that the predominant ASIC subtype responding to decreased meningeal pH is ASIC3. Additionally, they demonstrate that in the presence of inflammation, dural afferents respond to even smaller decreases in pH providing further support for the ability of small pH changes within the meninges to initiate afferent input leading to headache.

Demographic and clinical factors associated with recovery of poststroke dysphagia: A meta-analysis.

BACKGROUND: Poststroke dysphagia (PSD) recovery depends on various factors. We aimed to provide evidence concerning predictive variables for the recovery of PSD. METHODS: PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP database of Chinese periodicals, Chinese biomedical literature service system (SinoMed), and Cochrane Library databases were systematically searched up to September 21, 2022. According to the inclusion criteria, the literature searched in the database was screened. The methodological quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed to identify the factors prognostic for PSD. RESULTS: Twenty-eight studies were eligible, and pooled analyses were allowed for 12 potential prognostic factors. We identified older age, higher National Institutes of Health Stroke Scale (NIHSS) score, lower activities of daily living (ADL) score, lower body mass index (BMI), severe dysphagia on admission, aspiration, brainstem stroke, severe cognitive impairment, and bilateral hemispheric stroke were negative factors for the recovery of PSD, while early intervention and Modified Rankin Scale (mRS) = 0 before onset were protective factors for the recovery of PSD. There was no significant association between stroke type and prognosis of PSD. CONCLUSION: Prognostic factors of PSD summarized in this meta-analysis could be useful for developing reasonable treatment plan to better promote recovery of swallowing function after stroke.

Effect of cerebellar transcranial magnetic stimulation with double-cone coil on dysphagia after subacute infratentorial stroke: A randomized, single-blinded, controlled trial.

BACKGROUND: A 10-Hz cerebellar repetitive transcranial magnetic stimulation (rTMS) could increase corticobulbar tract excitability in healthy individuals. However, its clinical efficacy for poststroke dysphagia (PSD) remains unclear. OBJECTIVE: To investigate the effectiveness of 10-Hz cerebellar rTMS in PSD patients with infratentorial stroke (IS). METHODS: In this single-blinded, randomized controlled trial, 42 PSD patients with subacute IS were allocated to three groups: bilateral cerebellar rTMS (biCRB-rTMS), unilateral cerebellar rTMS (uniCRB-rTMS), or sham-rTMS. The stimulation parameters were 5 trains of 50 stimuli at 10 Hz with an interval of 10 s at 90% of the thenar resting motor threshold (RMT). The Functional Oral Intake Scale (FOIS) was assessed at T0 (baseline), T1 (day 0 after intervention), and T2 (day 14 after intervention), whereas the Dysphagia Outcome and Severity Scale (DOSS), Penetration Aspiration Scale (PAS), and neurophysiological parameters were evaluated at T0 and T1. RESULTS: Significant time and intervention interaction effects were observed for the FOIS score (F = 3.045, p = 0.022). The changes in the FOIS scores at T1 and T2 were both significantly higher in the biCRB-rTMS group than in the sham-rTMS group (p < 0.05). The uniCRB-rTMS and biCRB-rTMS groups demonstrated greater changes in the DOSS and PAS at T1, compared with the sham-rTMS group (p < 0.05). Bilateral corticobulbar tract excitability partly increased in the biCRB-rTMS and uniCRB-rTMS groups at T1, compared with T0. The percent changes in corticobulbar tract excitability parameters at T1 showed no difference among three groups. CONCLUSIONS: A 10-Hz bilateral cerebellar rTMS is a promising, noninvasive treatment for subacute infratentorial PSD.

The Biomechanical Characteristics of Swallowing in Tracheostomized Patients with Aspiration following Acquired Brain Injury: A Cross-Sectional Study.

Objectives: Investigate the biomechanical characteristics in tracheostomized patients with aspiration following acquired brain injury (ABI) and further explore the relationship between the biomechanical characteristics and aspiration. Methods: This is a single-center cross-sectional study. The tracheostomized patients with aspiration following ABI and age-matched healthy controls were recruited. The biomechanical characteristics, including velopharynx (VP) maximal pressure, tongue base (TB) maximal pressure, upper esophageal sphincter (UES) residual pressure, UES relaxation duration, and subglottic pressure, were examined by high-resolution manometry and computational fluid dynamics simulation analysis. The penetration−aspiration scale (PAS) score was evaluated by a videofluoroscopic swallowing study. Results: Fifteen healthy subjects and fifteen tracheostomized patients with aspiration following ABI were included. The decreased VP maximal pressure, increased UES residual pressure, and shortened UES relaxation duration were found in the patient group compared with the control group (p < 0.05). Furthermore, the subglottic pressure significantly decreased in patients (p < 0.05), while no significant difference was found in TB maximal pressure between groups (p > 0.05). In addition, in the patient group, VP maximal pressure (rs = −0.439; p = 0.015), UES relaxation duration (rs = −0.532; p = 0.002), and the subglottic pressure (rs = −0.775; p < 0.001) were negatively correlated with the PAS score, while UES residual pressure (rs = 0.807; p < 0.001) was positively correlated with the PAS score (p < 0.05), the correlation between TB maximal pressure and PAS score (rs = −0.315; p = 0.090) did not reach statistical significance. Conclusions: The biomechanical characteristics in tracheostomized patients with aspiration following ABI might manifest as decreased VP maximal pressure and subglottic pressure, increased UES residual pressure, and shortened UES relaxation duration, in which VP maximal pressure, UES relaxation duration, subglottic pressure, and UES residual pressure were correlated with aspiration.

The effectiveness of ultrasound-guided injection of BTX-A in the management of sialorrhea in neurogenic dysphagia patients.

Objective: To evaluate the effectiveness of ultrasound-guided injection of botulinum toxin type A (BTX-A) in treating sialorrhea. Methods: We recruited 32 sialorrhea subjects and they received an ultrasound-guided injection of BTX-A. The extent of salivation was evaluated according to the Visual Analog Scale (VAS), Drooling Severity and Frequency Scale (DSFS), and Saliva Flow Rate (SFR). Laryngeal secretions were evaluated based on Fiberoptic Endoscopic Evaluation of Swallowing (FEES) rated according to the Murray Secretion Scale (MSS). We assessed the extent of salivation and laryngeal secretions before injection and at 1, 2, and 4 weeks after injection. Results: The scores for the VAS, DSFS-S, DSFS-F, and DSFS-T decreased significantly at 1, 2, and 4 weeks after injection compared with before injection (p < .05). Based on VAS, the efficacy was substantially higher at 2 and 4 weeks after injection than at 1 week after injection (p < .05). According to DSFS-S and DSFS-T, the efficacy was significantly higher at 4 weeks than at 1 week after injection (p < .05). The SFR and MSS scores at 1 and 2 weeks after injection were superior to those before injection (p < .05). Meanwhile, the SFR score 2 weeks after injection was superior to that 1 week after injection (p < .05). Conclusion: The ultrasound-guided injection of BTX-A can effectively reduce saliva secretion in patients with neurogenic dysphagia. Furthermore, it has the advantages of early onset time and lasting curative effects, which indicates that clinical promotion and application of this technique are justified. Level of Evidence: Level 3.