Effect of Modified Pharyngeal Electrical Stimulation on Patients with Severe Chronic Neurogenic Dysphagia: A Single-Arm Prospective Study.

Current treatments for severe chronic neurogenic dysphagia (SCND) are limited. Modified pharyngeal electrical stimulation (mPES) was modified from pharyngeal electrical stimulation (PES). This prospective study aimed to explore the efficacy and safety of mPES on SCND. 30 patients with severe chronic neurogenic dysphagia were recruited. mPES was administered to patients once daily until the functional oral intake scale score (FOIS) reach 3. Videofluoroscopic swallow study (VFSS), flexible endoscopic evaluation of swallowing (FEES), and high-resolution manometry (HRM) were utilized for evaluating the swallowing function. After mPES, 24 of 30 patients (80%) reached the endpoint (FOIS = 3) (P < 0.001). 3 of 6 tracheotomized patients (50%) removed the tracheal tube. The median number of mPES sessions for the 24 patients who met the criteria was 28 (17, 38) and the median period was 43 (29, 63) days. Moreover, a significant increase was observed in hypopharyngeal peak pressure (P = 0.015), hypopharyngeal contraction duration (P = 0.023), velopharyngeal peak pressure (P = 0.044), and velopharyngeal contraction duration (P = 0.031). A reduction was observed in PAS (P < 0.001), secretion (P = 0.001), vallecular residue (P < 0.001), left (P = 0.001), and right (P < 0.001) pyriform sinus residue. The median FOIS of 30 patients at 3-month follow-up was 5 (3, 6). No serious side effects were reported. mPES is a promising effective and safe therapeutic approach that is simple to use in patients with SCND.

The sensitivity and specificity of the modified volume-viscosity swallow test for dysphagia screening among neurological patients.

Oropharyngeal dysphagia (OD) is a highly prevalent condition after stroke and other neurological diseases. The volume-viscosity swallow test (V-VST) is a screening tool for OD. Considering that the recommendations of volume and thickeners in the original V-VST limited the popularization and application of the test in the Chinese population, we provide the modified V-VST to detect OD among neurological patients. In addition, the accuracy of the modified V-VST to screen OD needs to be verified. We included 101 patients with neurological diseases. OD was evaluated by a modified V-VST and a videofluoroscopy swallowing study (VFSS) using 3 volumes (i.e., 3, 5, and 10 ml) and 4 viscosities (i.e., water, mildly thick, moderately thick, and extremely thick). In this study, to compare with the original V-VST results, a volume of 20 ml was also included. The discriminating ability of modified V-VST in detecting OD was assessed by the sensitivity and specificity values of clinical signs of impaired efficiency (impaired labial seal, piecemeal deglutition, and residue) and impaired safety of swallowing (cough, voice changes, and oxygen desaturation ≥3%) in comparison to the results of VFSS. The modified V-VST showed 96.6% sensitivity and 83.3% specificity for OD, 85.2% sensitivity and 70% specificity for impaired safety, and 90.9% sensitivity and 76.9% specificity for impaired efficacy. Our study suggests that the modified V-VST offers a high discriminating ability in detecting OD among neurological patients.

Normoxia is not favorable for maintaining stemness of human endothelial progenitor cells.

The in vitro expansion of endothelial progenitor cells (EPCs) is necessary for obtaining sufficient amounts of cells for clinical applications. However, EPC expansion is conventionally carried out under non-physiologic oxygen concentrations (normoxia, ~20% O2). We compared the effects of normoxic and hypoxic culture on the stemness of expanded EPCs. Human EPCs were cultured under hypoxia (1% O2) or normoxia (~20% O2), respectively. Cell proliferation, colony formation, in vitro angiogenesis, and the migration ability of the expanded EPCs were compared. To explore the underlying mechanism, whole transcriptome RNA sequencing (RNA-seq) was also performed to select differentially expressed genes (DEGs), which were then partially validated by western blotting. EPCs cultured under normoxia showed reduced proliferation, colony formation, in vitro angiogenesis, and migration abilities and a higher proportion of senescent cells compared with those cultured under hypoxia. A total of 48 DEGs were identified by transcriptome RNA-seq. Further bioinformatics analysis revealed that six pathways were enriched, among which the p53 signaling pathway. Finally, we confirmed the differential expression of the p53 pathway by Western blot analysis. Compared with hypoxia, normoxia is not favorable for maintaining the stemness of human EPCs. Several signaling pathways, including the p53 signaling pathway implicate in reducing stemness of EPCs under normoxia.

Bone marrow mesenchymal stem cell transplantation exerts neuroprotective effects following cerebral ischemia/reperfusion injury by inhibiting autophagy via the PI3K/Akt pathway.

Although cerebral ischemia itself is associated with a high rate of disability, secondary cerebral ischemia/reperfusion (I/R) injury following recanalization is associated with much more severe outcomes. The mechanisms underlying cerebral I/R injury are complex, involving neuronal death caused by apoptosis and autophagy. Autophagy is critical for cell survival and plays an important role in the pathogenesis of cerebral I/R injury. Research has indicated that transplantation of bone marrow mesenchymal stem cells (BMSCs) is effective in repairing and reconstructing brain tissue, and that this effect may be associated with the regulation of autophagy. To explore this hypothesis, we intravenously transplanted BMSCs into a rat model of cerebral I/R injury (middle cerebral artery occlusion [MCAO]). Our results indicated that BMSCs transplantation promoted behavioral recovery, reduced cerebral infarction volume, and decreased the number of apoptotic cells in rats exposed to cerebral I/R injury. Moreover, this effect was associated with reduced expression of the autophagy-associated proteins microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1. Furthermore, BMSCs remarkably increased the expression of p-Akt and p-mTOR following cerebral I/R injury. Expression of LC3 also increased when the PI3K pathway was blocked using LY294002. In summary, our results indicated that the protective effects of BMSCs in cerebral I/R injury may be associated with the inhibition of autophagy via the activation of the PI3K/Akt/mTOR signaling pathway.

Trends in meteorologically adjusted ozone concentrations in six Kentucky metro areas, 1998-2002.

Meteorologically adjusted ozone (O3) concentrations during five recent O3 seasons (1998-2002) were computed for six Kentucky metro areas using a nonlinear regression model originally developed for forecasting ground-level O3 concentrations. The meteorological adjustment procedure was based on modifying actual measured O3 concentrations according to model-predicted responses to climate departures with respect to a reference year. For all six Kentucky metro areas, meteorologically adjusted O3 concentrations declined over the five-year period. The linear best-fit rate of decline in mean adjusted O3 concentrations ranged from 0.9 to 2.6 ppb/yr for these metro areas; the average rate of decline was 1.6 ppb/yr. The rates of decline in meteorologically adjusted extreme value (e.g., 95th percentile) concentrations were approximately the same, but there is greater statistical uncertainty concerning the extreme value trends.