Effects of Neuromuscular Electrical Stimulation (NMES) on salivary flow in healthy adults

Neuromuscular electrical stimulation (NMES) is a method used for enhancing suprahyoid muscle activity and is widely applied as a treatment for dysphagia. Patients often complain of saliva pooling in the pharynx during NMES. Therefore, the purpose of this study was to investigate the changes in salivary flow during NMES. Twenty healthy adults participated in this study. Electrical stimulation was applied at constant strength for 60 minutes to the suprahyoid muscles using VitalStim®. Participants were examined under three conditions of NMES: sensory threshold plus 75% of the difference between sensory and pain thresholds (75% Stim), SensoryStim, and Sham. Saliva collections, using a 10-min spitting method, were performed seven times: before stimulation (S1), during stimulation (S2-S6), and 5 min after stimulation ended (S7). Significant differences were observed in saliva flow between S1 and S7, as well as S2 and S7 in 75% Stim. This study indicates that an increase in saliva flow was promoted after NMES. Therefore, NMES may have effects on patients with xerostomia

Low-Dose Intravenous Alteplase in Wake-Up Stroke

Background and Purpose—We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods—This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0–1). Results—Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68–1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06–12.58]; P>0.999), respectively. Conclusions—No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Effects of interferential current electrical stimulation (IFCS) on mastication and swallowing function in healthy young adults: A preliminary study

Abstract Objectives This study aimed to investigate the effects of interferential current electrical stimulation (IFCS) on masticatory and swallowing function. Materials and Methods Twenty healthy young adults were enrolled. The measurement items were spontaneous swallowing frequency (SSF), voluntary swallowing frequency (VSF), saliva secretion volume (SSV), glucose elution volume (GEV), and velocity of chew (VOC). All participants underwent both IFCS and sham stimulation (without stimulation, sham). Two sets of independent IFCS electrodes were placed on the bilateral neck. The precise location of the upper electrodes was just below the angle of the mandible, while the lower electrodes were placed at the anterior border of the sternocleidomastoid muscle. The intensity of IFCS was determined to be one level below the perceptual threshold that all participants felt discomfort. Statistical analysis was performed using a two‐way repeated measures analysis of variance. Results For IFCS, the results of each measurement before and during stimulation were SSF: 1.16 and 1.46, VSF: 8.05 and 8.45, SSV: 5.33 and 5.56 g, GEV: 171.75 and 208.60 mg/dL, and VOC: 87.20 and 95.20, respectively. SSF, GEV, and VOC during stimulation were significantly increased by IFCS (SSF, p = .009; GEV, p = .048; and VOC, p = .007). Following sham stimulation, the results were SSF: 1.24 and 1.34, VSF: 7.75 and 7.90, SSV: 5.65 and 6.04 g, GEV: 176.45 and 187.35 mg/dL, and VOC: 91.35 and 88.25, respectively. Conclusion While no significant differences were observed in the sham group, our findings suggest that IFCS of the superior laryngeal nerve may impact not only the swallowing function but also the masticatory function

Do Open Source Software Projects Conduct Tests Enough?

PROFES 2014 : Product-Focused Software Process Improvement, December 10-12, 2014, Helsinki, FinlandDo open source software projects provide and maintain tests? What metrics are correlated with the test success? This paper answers these questions by executing tests of 452 open source software projects in GitHub and measuring 13 metrics from 77 projects. Only 117 projects passed all test cases. Additionally, the results are correlated with the comment density, public documented API density, and test coverage

Wax Thickness and Distribution Monitoring Inside Petroleum Pipes Based on External Temperature Measurements

A method to estimate wax thickness inside petroleum pipes from the external pipe temperature measurements is proposed. When wax is deposited inside the pipe, the external pipe surface temperature decreases because the heat resistance of the wax reduces the heat flow from the fluid inside the pipe to the fluid outside the pipe. The decrease in the external pipe temperature can be calculated by solving a heat equation about the heat transfer from the pipe inner fluid to external ambient fluid, and thus the wax thickness can be estimated by measuring the pipe surface temperature. An experiment to validate the method was performed. Crude oil was passed through a pipe with an inner diameter of about 8 mm. Ten thermocouples were installed on the pipe. The pipe was covered by a heat-shrink tube as a substitute for an insulation material. The pipe was cooled by a coolant jacket, and wax about 0.8 mm thick was deposited in the pipe. The wax thickness estimated from the temperature measurements agreed well with the thickness estimated from the pressure rise because of the wax layer and from the final gross weight of the wax. The difference between wax thickness estimated from the temperature measurements and from the final gross weight was less than 0.2 mm

Dysphagia And Oral Morbidities In Chemoradiation-Treated Head And Neck Cancer Patients

This study prospectively evaluated relationships between oral morbidities and swallowing ability in head/neck cancer patients following chemoradiation therapy (CRT) and at 3 months following CRT. Thirty patients with confirmed head/neck cancer undergoing chemoradiation were assessed with a battery of swallowing measures and measures of oral morbidities related to chemoradiation (xerostomia, mucositis, pain, taste/smell, oral moisture). All measures were completed at baseline (within the first week of CRT), at 6 weeks (end of treatment), and at 3 months following chemoradiation. Descriptive and univariate statistics were used to depict change over time in swallowing and each oral morbidity. Correlation analyses evaluated relationships between swallowing function and oral morbidities at each time point. Most measures demonstrated significant negative change at 6 weeks with incomplete recovery at 3 months. At 6 weeks, mucositis ratings, xerostomia, and retronasal smell intensity demonstrated significant inverse relationships with swallowing function. In addition, oral moisture levels demonstrated significant positive relationships with swallowing function. At 3 months, mucositis ratings maintained a significant, inverse relationship with swallow function. Taste and both orthonasal and retronasal smell intensity ratings demonstrated inverse relationships with measures of swallow function. Swallow functions and oral morbidities deteriorate significantly following CRT with incomplete recovery at 3 months post treatment. Furthermore, different patterns of relationships between swallow function measures and oral morbidities were obtained at the 6-week versus the 3-month assessment point suggesting that different mechanisms may contribute to the development versus the maintenance of dysphagia over the trajectory of treatment in these patients