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Dysphagia is one of the main serious issues for amyotrophic lateral sclerosis (ALS) patients because of causing malnutrition and aspiration pneumonia. Early detection and management of dysphagia are essential for the long-term survival. In this study, videofluoroscopic swallowing study (VFSS) results of bulbar and spinal onset ALS patients were compared. VFSS results and revised ALS Functional Rating Scale (ALSFRS-R) score were also analyzed to assess the correlation between dysphagia and functional status of patients. ALS patients with swallowing difficulties who underwent VFSS were recruited retrospectively. Two oral, seven pharyngeal, and two esophageal components of VFSS were evaluated. An ALSRFRS-R bulbar subtype score 9 was used to divide the groups with severe bulbar symptoms. Total 109 Korean ALS patients (39 bulbar vs 70 spinal) were included. Bulbar ALS patients exhibited a significantly longer oral transit time (OTT) then spinal ALS patients, especially in severe bulbar patients with low ALSRFRS-R bulbar subscale. In bulbar ALS patients, penetration (thick liquid), aspiration, OTT, and Penetration-Aspiration Scale (PAS) were significantly correlated with ALSFRS-R bulbar subscale score. However, in spinal ALS patients, only OTT (thin liquid) and aspiration (thick liquid) were significantly correlated with ALSFRS-R bulbar subscale score. Bulbar ALS patients demonstrated significantly longer OTT than spinal ALS patients, and ALSFRS-R bulbar subscale score also correlated well with bulbar ALS patients. Therefore, high vigilance and aggressive treatment for dysphagia especially in bulbar ALS patients rather than spinal ALS patients are mandatory.

BACKGROUND Mannitol is a hyperosmolar agent and the combination of mannitol and furosemide is a widely used treatment for intracranial pressure control. Considering the hypertonic properties of mannitol to move water out of intracellular spaces, we hypothesized that mannitol combined with furosemide could relieve focal tissue swelling in refractory lymphedema. CASE SUMMARY A 90-year-old female had been diagnosed with intracranial hemorrhage and received a combination of mannitol and furosemide for intracranial pressure control. Independent of the intracranial hemorrhage, she had refractory lymphedema of the left lower extremity since 1998. Remarkably, after receiving the mannitol and furosemide, the patient’s lower extremity lymphedema improved dramatically. After the mannitol and furosemide were discontinued, the lymphedema worsened in spite of complete decongestive therapy (CDT) and intermittent pneumatic compression treatment (IPC). To identify the presumed effect of mannitol and furosemide on the lymphedema, these agents were resumed, and the lymphedema improved again. CONCLUSION The present case raises the possibility that a combination of mannitol and furosemide might be considered another effective therapeutic option for refractory lymphedema when CDT and IPC are ineffective.

The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons. The dorsal raphe nucleus (DRN) secretes 5-hydroxytryptamine (5-HT, serotonin), promoting wakefulness. Melatonin secreted from the pineal gland also promotes wakefulness in rats. Our laboratory recently demonstrated that daily changes in nitric oxide (NO) production regulates a signaling pathway involving with-no-lysine kinase (WNK), Ste20-related proline alanine rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1), and cation-chloride co-transporters (CCC) in rat DRN serotonergic neurons. This study was designed to investigate the effect of melatonin on NO-regulated WNK-SPAK/OSR1-CCC signaling in wake-inducing DRN neurons to elucidate the mechanism underlying melatonin’s wake-promoting actions in rats. Ex vivo treatment of DRN slices with melatonin suppressed neuronal nitric oxide synthase (nNOS) expression and increased WNK4 expression without altering WNK1, 2, or 3. Melatonin increased phosphorylation of OSR1 and the expression of sodium-potassium-chloride co-transporter 1 (NKCC1), while potassium-chloride co-transporter 2 (KCC2) remained unchanged. Melatonin increased the expression of tryptophan hydroxylase 2 (TPH2, serotonin-synthesizing enzyme). The present study suggests that melatonin may promote its wakefulness by modulating NO-regulated WNK-SPAK/OSR1-KNCC1 signaling in rat DRN serotonergic neurons.

Introduction Nocturnal stridor, a life-threatening condition linked to respiratory failure and sudden death during sleep, is a serious issue in patients with multiple system atrophy (MSA). However, little is known about polysomnographic findings and clinical features of MSA patients with nocturnal stridor. Hence, we investigated video-polysomnography (VPSG) findings and clinical features associated with nocturnal stridor in patients with MSA. Methods We retrospectively analyzed the clinical data of patients with MSA (n = 49) who underwent overnight VPSG for the evaluation of sleep-disordered breathing. The presence of nocturnal stridor was confirmed based on overnight VPSG findings. Clinical data, including VPSG findings and clinical features, were compared between MSA patients with and without nocturnal stridor. Results Nocturnal stridor was present in 31 (63.3%) patients with MSA. Patients with stridor showed significantly higher apnea-hypopnea, respiratory disturbance, and oxygen desaturation indices than those without stridor (P = 0.024, P = 0.049, and P = 0.006, respectively). Patients with stridor had more severe axial motor features, more impaired activities of daily living, and longer disease duration than those without stridor (P = 0.012, P = 0.036, and P = 0.003, respectively). However, there were no significant between-group differences in sex, age at disease onset, MSA subtype, parkinsonian features, cerebellar ataxia, residual urine volume, or systolic and diastolic blood pressure change. Conclusions MSA with nocturnal stridor is related to higher apnea indices in conjunction with higher O2 desaturation index, more severe axial motor features, more impaired activities of daily living, and longer disease duration.

BACKGROUND Electromagnetic interference (EMI), means disturbance to the operation of implanted electrical devices caused by external sources. If cardiac pacemaker is implanted into the body, the risk of EMI should be considered when performing neuromuscular electrical stimulation (NMES). So far, no case has been reported that clinical magnets are used to safely manage the EMI risk of patients with cardiac pacemaker in NMES. CASE SUMMARY A 72-year-old male with swallowing disorder due to pure motor lacunar syndrome was transferred to rehabilitation department six days after the symptom onset. EMI risk needed be considered when implementing NMES on pharyngeal muscles, since cardiac pacemaker was implanted on his left chest due to the sick sinus syndrome. In the first NMES, the function of the pacemaker was directly monitored using telemetric instruments. From the second day, by a simple method of placing a magnet on the pacemaker, we chose to move the pacemaker into a mode that the device was not influenced by external stimulus. This magnet method has been used repeatedly for a year for the safe NMES treatment. We could remove Levin tube four months after the initial symptom and dysphagia related symptoms had not been noted during two-year follow-up period. CONCLUSION This report is the first case of dysphagia rehabilitation that EMI risk was handled using mode change of pacemaker with magnet. This method is unfamiliar to doctors, but safe and easy approach. This paper could be guidance for clinicians who need to treat patients with EMI risk.

The in situ diagnosis of cardiac activities with simultaneous therapeutic electrical stimulation of the heart is key to preventing cardiac arrhythmia. Here, we present an unconventional single-device platform that enables in situ monitoring even in a wet condition and control of beating heart motions without interferences to the recording signal. This platform consists of the active-matrix array of pressure-sensitive transistors for detecting cardiac beatings, biocompatible, low-impedance electrodes for cardiac stimulations, and an alginate-based hydrogel adhesive for attaching this platform conformally to the epicardium. In contrast to conventional electrophysiological sensing using electrodes, the pressure-sensitive transistors measured mechanophysiological characteristics by monitoring the spatiotemporal distributions of cardiac pressures during heart beating motions. In vivo tests show mechanophysiological readings having good correlation with electrocardiography and negligible interference with the electrical artifacts caused during cardiac stimulations. This platform can therapeutically synchronize the rhythm of abnormal heartbeats through efficient pacing of cardiac arrhythmia.

In this study, a realistic smart information guide solution to support multi-devices was developed. The upload of diverse realistic contents, as well as the support of smart devices with specific characteristics and the management of integrated contents, was made possible. Additionally, it was important to guarantee the quality of the contents (AR, VR) alongside the realistic smart information guide solution. Recently, there have been many positive responses from the expansion on and utilization of services of the fourth Industrial Revolution such as AR technologies, which include image recognition-based information services, and VR technologies, which include hands-on information services using motion recognition sensors. In the future, the development and planning of AR and VR content for visitors and tourists for locations such as museums and exhibition halls will be actively required.

Background/aim Oxaliplatin-based chemotherapy is associated with hepatic sinusoidal obstruction syndrome (SOS). Patients and methods We analyzed patients from two prospective trials, in which capecitabine/oxaliplatin (XELOX, 8 cycles; n=51) and S-1/oxaliplatin [SOX, continuous (SOX-C, n=50), or intermittent (discontinuation after cycle 6 and restart on progression, SOX-I, n=50)] were administered. We compared severity (splenomegaly, thrombocytopenia, liver enzyme levels, and hepatic parenchymal heterogeneity), clinical significance (delay or dose-reduction of chemotherapy), and reversibility of SOS (splenomegaly and thrombocytopenia after stopping chemotherapy) between SOX and XELOX in gastric cancer patients. Results SOX was more likely to be associated with splenomegaly, thrombocytopenia, hyperbilirubinemia, and hepatic parenchymal heterogeneity than XELOX. Splenomegaly was partially reversible after stopping chemotherapy in both regimens, but recovery rate was lower in SOX. Proportion of delayed or dose-reduced chemotherapy cycles due to thrombocytopenia was significantly higher in SOX-C than in XELOX. Conclusion S-1 combination is more likely to worsen oxaliplatin-induced hepatic sinusoidal injuries than capecitabine in gastric cancer patients.

Rectovaginal fistula, which can arise after an injury to the vaginal canal or rectum, is a troublesome obstacle for patients’ everyday life. In most cases, it can be covered with a local flap, but previous radiation therapy increases the recurrence rate, making it especially difficult to cure. As the application of stromal vascular fraction (SVF) obtained from enzymatically digested autologous adipose tissue has become increasingly common, several reports have advocated its effectiveness for the treatment of refractory wounds. In light of the angiogenic, regenerative characteristics of SVF, it was incorporated as a treatment option in two cases of rectovaginal fistula discussed here. As described in this report, irradiated rectovaginal fistulas in rectal cancer patients were successfully treated with SVF injection, and we suggest SVF as a feasible treatment option for cases of rectovaginal fistula that would otherwise be very difficult to cure.

President Moon has visited to UAE as a National Visit in March, 2018 and express to support co-develop, co-produce and co-export to the third countries of weapon system. Therefore, the paper analyzes the recent arms market in the Middle East, as one of the three major arms export market to Korea, and present an arms export strategy to customize the Middle East countries.Concerning a recent 10 year arms export by region, the ratio of Middle East countries arms export was highly increased by 12%p(17%→29%). And arms acquisition budget in 5 years(2018∼22) will be over 130 billion dollars. UAE has a highly interested in missiles, warship building, surveilance system, RWCS etc after Summit meeting. Iraq has focus on his post war rebuilding to include relevant weapon system and facilities. Also, Saudi Arabia is necessary to fulfill his Saudization policy to enter his arms market.For expanding of Middle East arms market, it is necessary to provide customized defense industry total solution for the whole weapon system lifecycles, dispatch defense cooperation director, find out co-development program between Korea and Middle East countries, and diversify cooperation system in the near future.

Despite recent advances in genome engineering technologies, traditional transgenic mice generated on a mixed genetic background of C57BL/6 and 129/Sv mice remain widely used in age-related hearing loss (AHL) research, since C57BL/6 mice exhibit early onset and progression of AHL due to a mutation in cadherin 23-encoding gene (Cdh23753G>A). In these transgenic mice, backcrossing for more than 10 generations results in replacement of the donor background (129/Sv) with that of the recipient (C57BL/6), so that approximately 99.9% of genes are C57BL/6-derived and are considered congenic. However, the regions flanking the target gene may still be of 129/Sv origin, creating a so-called "passenger gene problem" where the normal 129/Sv-derived Cdh23753G allele can travel with the target gene. In this study, we investigated the role of fatty acid-binding protein 7 (Fabp7), which is important for cellular uptake and intracellular trafficking of fatty acids in the cochlea, using traditional Fabp7 knockout (KO) mice on the C57BL/6 background. We found that Fabp7 KO mice showed delayed AHL progression and milder cochlear degeneration. However, the genotype of the Cdh23 region flanking Fabp7 was still that of 129/Sv origin (Cdh23753GG). Our findings reveal the potential risk of contamination for traditional transgenic mice generated on the C57BL/6 background.

(1,3)-β-D-Glucan synthase (GS) catalyzes formation of the linear (1,3)-β-D-glucan in the fungal cell wall, and is a target of clinically approved antifungal antibiotics. The catalytic subunit of GS, FKS protein, does not exhibit significant sequence homologies to other glycosyltransferases, and thus a significant ambiguity remains about its catalytic mechanism. One of the major technical barriers in studying GS is the absence of activity assay methods that allow characterization of the lengths and amounts of (1,3)-β-D-glucan due to its poor solubility in water and organic solvents. Here, we report a successful development of a novel GS activity assay based on size-exclusion chromatography coupled with pulsed-amperometric detection and radiation counting (SEC-PAD-RC), which allows for the simultaneous characterization of the amount and length of the polymer product. The assay revealed that the purified yeast GS produces glucan with a length of 6,550 ± 760 mer, consistent with the reported degree of polymerization of (1,3)-β-D-glucan isolated from intact cells. Pre-steady state kinetics analysis revealed a highly efficient but rate-determining chain elongation rate of 51.5 ± 9.8 sec(−1), which represents the first observation of chain elongation by a nucleotide-sugar dependent polysaccharide synthase. Coupling the SEC-PAD-RC method with substrate analog mechanistic probes provided the first unambiguous evidence that GS catalyzes non-reducing end polymerization. Based on these observations, we propose a detailed model for the catalytic mechanism of GS. The approaches described here can be used to determine the mechanism of catalysis of other polysaccharide synthases.

Mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal recessive lysosomal storage disease caused by mutations in the gene that encodes the protein N-acetyl-glucosaminidase (NAGLU). Defective NAGLU activity results in aberrant retention of heparan sulfate within lysosomes leading to progressive central nervous system (CNS) degeneration. Intravenous treatment options are limited by the need to overcome the blood–brain barrier and gain successful entry into the CNS. Additionally, we have demonstrated that AAV8 provides a broader transduction area in the MPS IIIB mouse brain compared with AAV5, 9 or rh10. A triple-capsid mutant (tcm) modification of AAV8 further enhanced GFP reporter expression and distribution. Using the MPS IIIB mouse model, we performed a study using either intracranial six site or intracisterna magna injection of AAVtcm8-codon-optimized (co)-NAGLU using untreated MPS IIIB mice as controls to assess disease correction. Disease correction was evaluated based on enzyme activity, heparan sulfate storage levels, CNS lysosomal signal intensity, coordination, activity level, hearing and survival. Both histologic and enzymatic assessments show that each injection method results in supranormal levels of NAGLU expression in the brain. In this study, we have shown correction of lifespan and auditory deficits, increased CNS NAGLU activity and reduced lysosomal storage levels of heparan sulfate following AAVtcm8-coNAGLU administration and partial correction of NAGLU activity in several peripheral organs in the murine model of MPS IIIB.

Purple waxy corn is a good source of antioxidant compounds such as anthocyanins and polyphenols. Promotion of its use requires an appropriate assay to determine antioxidant activity. The aim of this study is to verify compatibility of the antioxidant activity assays by comparing five different assays in daily kernel samples of the fresh purple waxy corn during grain filling. The levels of antioxidants measured by 2,2-diphenyl-1-picrylhydrazyl, ferric reducing antioxidant power, and chemiluminescence showed significant positive correlations with the levels measured by the other assays (r = 0.761–0.893; p r = 0.798–0.924; p r = 0.764; p r > 0.699; p

Hearing loss is the third most prevalent chronic health condition affecting older adults and age-related hearing loss (ARHL) is the most common form of hearing impairment. Significant sex differences in hearing have been documented in humans and rodents. In general, the results of these studies show that men lose their hearing more rapidly than women. However, the cellular mechanism underlying sex differences in hearing or hearing loss remains largely unknown, and to our knowledge, there is no well-established animal model for studying sex differences in hearing. In the current study, we examined sex differences in body composition, voluntary wheel running activity, balance performance, auditory function, and cochlear histology in young, middle-age, and old CBA/CaJ mice, a model of age-related hearing loss. As expected, body weight of young females was lower than that of males. Similarly, lean mass and total water mass of young, middle-age, and old females were lower than those of males. Young females showed higher voluntary wheel running activity during the dark cycle, an indicator of mobility, physical activity, and balance status, compared to males. Young females also displayed higher auditory brainstem response (ABR) wave I amplitudes at 8 kHz, wave II, III, V amplitudes at 8 and 48 kHz, and wave IV/I and V/I amplitude ratios at 48 kHz compared to males. Collectively, our findings suggest that the CBA/CaJ mouse strain is a useful model to study the cellular mechanisms underlying sex differences in physical activity and hearing.