Case Report: Event-Related Desynchronization Observed During Volitional Swallow by Electroencephalography Recordings in ALS Patients With Dysphagia

Dysphagia is a severe disability affecting daily life in patients with amyotrophic lateral sclerosis (ALS). It is caused by degeneration of both the bulbar motor neurons and cortical motoneurons projecting to the oropharyngeal areas. A previous report showed decreased event-related desynchronization (ERD) in the medial sensorimotor areas in ALS dysphagic patients. In the process of degeneration, brain reorganization may also be induced in other areas than the sensorimotor cortices. Furthermore, ALS patients with dysphagia often show a longer duration of swallowing. However, there have been no reports on brain activity in other cortical areas and the time course of brain activity during prolonged swallowing in these patients. In this case report, we investigated the distribution and the time course of ERD and corticomuscular coherence (CMC) in the beta (15-25 Hz) frequency band during volitional swallow using electroencephalography (EEG) in two patients with ALS. Case 1 (a 71-year-old man) was diagnosed 2 years before the evaluation. His first symptom was muscle weakness in the right hand; 5 months later, dysphagia developed and exacerbated. Since his dietary intake decreased, he was given an implantable venous access port. Case 2 (a 64-year-old woman) was diagnosed 1 year before the evaluation. Her first symptom was open-nasal voice and dysarthria; 3 months later, dysphagia developed and exacerbated. She was given a percutaneous endoscopic gastrostomy. EEG recordings were performed during volitional swallowing, and the ERD was calculated. The average swallow durations were 7.6 ± 3.0 s in Case 1 and 8.3 ± 2.9 s in Case 2. The significant ERD was localized in the prefrontal and premotor areas and lasted from a few seconds after the initiation of swallowing to the end in Case 1. The ERD was localized in the lateral sensorimotor areas only at the initiation of swallowing in Case 2. CMC was not observed in either case. These results suggest that compensatory processes for cortical motor outputs might depend on individual patients and that a new therapeutic approach using ERD should be developed according to the individuality of ALS patients with dysphagia

HLA-A*0201-restricted CTL epitope of a novel osteosarcoma antigen, papillomavirus binding factor

<p>Abstract</p> <p>Background</p> <p>To develop peptide-based immunotherapy for osteosarcoma, we previously identified papillomavirus binding factor (PBF) as a CTL-defined osteosarcoma antigen in the context of HLA-B55. However, clinical application of PBF-based immunotherapy requires identification of naturally presented CTL epitopes in osteosarcoma cells in the context of more common HLA molecules such as HLA-A2.</p> <p>Methods</p> <p>Ten peptides with the HLA-A*0201 binding motif were synthesized from the amino acid sequence of PBF according to the BIMAS score and screened with an HLA class I stabilization assay. The frequency of CTLs recognizing the selected PBF-derived peptide was determined in peripheral blood of five HLA-A*0201⁺patients with osteosarcoma using limiting dilution (LD)/mixed lymphocyte peptide culture (MLPC) followed by tetramer-based frequency analysis. Attempts were made to establish PBF-specific CTL clones from the tetramer-positive CTL pool by a combination of limiting dilution and single-cell sorting. The cytotoxicity of CTLs was assessed by ⁵¹Cr release assay.</p> <p>Results</p> <p>Peptide PBF A2.2 showed the highest affinity to HLA-A*0201. CD8+ T cells reacting with the PBF A2.2 peptide were detected in three of five patients at frequencies from 2 × 10^-7to 5 × 10^-6. A tetramer-positive PBF A2.2-specific CTL line, 5A9, specifically lysed allogeneic osteosarcoma cell lines that expressed both PBF and either HLA-A*0201 or HLA-A*0206, autologous tumor cells, and T2 pulsed with PBF A2.2. Five of 12 tetramer-positive CTL clones also lysed allogeneic osteosarcoma cell lines expressing both PBF and either HLA-A*0201 or HLA-A*0206 and T2 pulsed with PBF A2.2.</p> <p>Conclusion</p> <p>These findings indicate that PBF A2.2 serves as a CTL epitope on osteosarcoma cells in the context of HLA-A*0201, and potentially, HLA-A*0206. This extends the availability of PBF-derived therapeutic peptide vaccines for patients with osteosarcoma.</p

Case report: A novel approach of closed-loop brain stimulation combined with robot gait training in post-stroke gait disturbance

Most post-stroke patients have long-lasting gait disturbances that reduce their daily activities. They often show impaired hip and knee joint flexion and ankle dorsiflexion of the lower limbs during the swing phase of gait, which is controlled by the corticospinal tract from the primary motor cortex (M1). Recently, we reported that gait-synchronized closed-loop brain stimulation targeting swing phase-related activity in the affected M1 can improve gait function in post-stroke patients. Subsequently, a gait-training robot (Orthobot®) was developed that could assist lower-limb joint movements during the swing phase of gait. Therefore, we investigated whether gait-synchronized closed-loop brain stimulation combined with robot-assisted training targeting the swing phase could enhance the recovery of post-stroke gait disturbance. A 57-year-old female patient with chronic post-stroke hemiparesis underwent closed-loop brain stimulation combined with robot-assisted training for 10 min 2 years after left pons infarction. For closed-loop brain stimulation, we used transcranial oscillatory electrical current stimulation over the lesioned M1 foot area with 1.5 mA of DC offset and 0–3 mA of sine-wave formed currents triggered by the paretic heel contact to set the maximum current just before the swing phase (intervention A; two times repeated, A1 and A2). According to the N-of-1 study design, we also performed sham stimulation (intervention B) and control stimulation not targeting the swing phase (intervention C) combined with robot-assisted training in the order of A1-B-A2-C interventions. As a result, we found larger improvements in gait speed, the Timed Up and Go test result, and muscle strength after the A1 and A2 interventions than after the B and C interventions. After confirming the short-term effects, we performed an additional long-term intervention twice a week for 5 weeks, for a total of 10 sessions. Gait parameters also largely improved after long-term intervention. Gait-synchronized closed-loop brain stimulation combined with robot-assisted training targeting the swing phase of gait may promote the recovery of gait function in post-stroke patients. Further studies with a larger number of patients are necessary

Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84

食事性肥満から肝炎発症に関わる制御因子の同定 --中鎖脂肪酸油による予防・GPR84標的NASH治療薬の可能性--. 京都大学プレスリリース. 2023-01-18.Medium-chain triglycerides (MCTs), which consist of medium-chain fatty acids (MCFAs), are unique forms of dietary fat with various health benefits. G protein–coupled 84 (GPR84) acts as a receptor for MCFAs (especially C10:0 and C12:0); however, GPR84 is still considered an orphan receptor, and the nutritional signaling of endogenous and dietary MCFAs via GPR84 remains unclear. Here, we showed that endogenous MCFA-mediated GPR84 signaling protected hepatic functions from diet-induced lipotoxicity. Under high-fat diet (HFD) conditions, GPR84-deficient mice exhibited nonalcoholic steatohepatitis (NASH) and the progression of hepatic fibrosis but not steatosis. With markedly increased hepatic MCFA levels under HFD, GPR84 suppressed lipotoxicity-induced macrophage overactivation. Thus, GPR84 is an immunomodulating receptor that suppresses excessive dietary fat intake–induced toxicity by sensing increases in MCFAs. Additionally, administering MCTs, MCFAs (C10:0 or C12:0, but not C8:0), or GPR84 agonists effectively improved NASH in mouse models. Therefore, exogenous GPR84 stimulation is a potential strategy for treating NASH

UVA-LED disinfect hydroponic solution

The number of plant factories in which crops are cultivated in an artificial environment has been increasing every year. In cultivation techniques involving hydroponics, plants are supplied with a circulating nutrient solution, which can become contaminated by pathogens that can propagate and spread throughout plant factories. Therefore, strategies to disinfect hydroponic nutrient solutions are needed. In this study, we developed a new disinfection device equipped with an ultraviolet A (UVA) light emitting diode (LED) that can be used to disinfect hydroponic nutrient solutions in plant factories. We first evaluated the basic disinfection capability of the device and then estimated its bactericidal effect in a small scale model system. The log survival ratio was related to UVA irradiation fluence and the volume of nutrient solution. From the assay results, we devised a kinetics equation to describe the relationship between nutrient solution volume, log survival ratio, and UVA fluence. Together our results show that UVA irradiation could be used to disinfect hydroponic nutrient solutions, and the derived kinetics equations can be used to determine optimal conditions, such as nutrient solution volume, UVA irradiation, and killing activity, to develop devices that disinfect hydroponic nutrient solutions

Combined treatment of UVA and antibiotics

The presence of antibiotics in the environment and their subsequent impact on the development of multi-antibiotic resistant bacteria has raised concerns globally. Consequently, much research is focused on a method to produce a better disinfectant. We have established a disinfectant system using UVA-LED that inactivates pathogenic bacteria. We assessed the bactericidal efficiency of a combination of UVA-LED and antibiotics against Vibrio parahaemolyticus. Combined use of antibiotic drugs and UVA irradiation was more bactericidal than UVA irradiation or antibacterial drugs alone. The bactericidal synergy was observed at low concentrations of each drug that are normally unable to kill the bacteria. This combination has the potential to become a sterilization technology

Neutralization of hepatitis B virus with vaccine-escape mutations by hepatitis B vaccine with large-HBs antigen

優れたB型肝炎予防ワクチン開発に成功 --既存ワクチンの弱点克服へ--. 京都大学プレスリリース. 2022-09-07.Although the current hepatitis B (HB) vaccine comprising small-HBs antigen (Ag) is potent and safe, attenuated prophylaxis against hepatitis B virus (HBV) with vaccine-escape mutations (VEMs) has been reported. We investigate an HB vaccine consisting of large-HBsAg that overcomes the shortcomings of the current HB vaccine. Yeast-derived large-HBsAg is immunized into rhesus macaques, and the neutralizing activities of the induced antibodies are compared with those of the current HB vaccine. Although the antibodies induced by the current HB vaccine cannot prevent HBV infection with VEMs, the large-HBsAg vaccine-induced antibodies neutralize those infections. The HBV genotypes that exhibited attenuated neutralization via these vaccines are different. Here, we show that the HB vaccine consisting of large-HBsAg is useful to compensate for the shortcomings of the current HB vaccine. The combined use of these HB vaccines may induce antibodies that can neutralize HBV strains with VEMs or multiple HBV genotypes

Cold start cycling durability of fuel cell stacks for commercial automotive applications

System durability is crucial for the successful commercialization of polymer electrolyte fuel cells (PEFCs) in fuel cell electric vehicles (FCEVs). Besides conventional electrochemical cycling durability during long-term operation, the effect of operation in cold climates must also be considered. Ice formation during start up in sub-zero conditions may result in damage to the electrocatalyst layer and the polymer electrolyte membrane (PEM). Here, we conduct accelerated cold start cycling tests on prototype fuel cell stacks intended for incorporation into commercial FCEVs. The effect of this on the stack performance is evaluated, the resulting mechanical damage is investigated, and degradation mechanisms are proposed. Overall, only a small voltage drop is observed after the durability tests, only minor damage occurs in the electrocatalyst layer, and no increase in gas crossover is observed. This indicates that these prototype fuel cell stacks successfully meet the cold start durability targets for automotive applications in FCEVs

Accelerated durability testing of fuel cell stacks for commercial automotive applications : a case study

System durability is crucially important for the successful commercialization of fuel cell electric vehicles (FCEVs). Conventional accelerated durability testing protocols employ relatively high voltage to hasten carbon corrosion and/or platinum catalyst degradation. However, high voltages are strictly avoided in commercialized FCEVs such as the Toyota MIRAI to minimize these degradation modes. As such, conventional durability tests are not representative of real-world FCEV driving conditions. Here, modified start-stop and load cycle durability tests are conducted on prototype fuel cell stacks intended for incorporation into commercial FCEVs. Polarization curves are evaluated at beginning of test (BOT) and end of test (EOT), and the degradation mechanisms are elucidated by separating the overvoltages at both 0.2 and 2.2 A cm-2. Using our modified durability protocols with a maximum cell voltage of 0.9 V, the prototype fuel cell stacks easily meet durability targets for automotive applications, corresponding to 15-year operation and 200,000 km driving range. These findings have been applied successfully in the development of new fuel cell systems for FCEVs, in particular the second-generation Toyota MIRAI

Infection risk in hemodialysis patient

Chronic care patients undergoing hemodialysis for treatment of end-stage renal failure experience higher rates of bloodstream-associated infection due to the patients' compromised immune system and management of the bloodstream through catheters. Staphylococcus species are a common cause of hemodialysis catheter-related bloodstream infections. We investigated environmental bacterial contamination of dialysis wards and contamination of hemodialysis devices to determine the source of bacteria for these infections. All bacterial samples were collected by the swab method and the agarose stamp method. And which bacterium were identified by BBL CRYSTAL Kit or 16s rRNA sequences. In our data, bacterial cell number of hemodialysis device was lower than environment of patient surrounds. But Staphylococcus spp. were found predominantly on the hemodialysis device (46.8%), especially on areas frequently touched by healthcare-workers (such as Touch screen). Among Staphylococcus spp., Staphylococcus epidermidis was most frequently observed (42.1% of Staphylococcus spp.), and more surprising, 48.2% of the Staphylococcus spp. indicated high resistance for methicillin. Our finding suggests that hemodialysis device highly contaminated with bloodstream infection associated bacteria. This study can be used as a source to assess the risk of contamination-related infection and to develop the cleaning system for the better prevention for bloodstream infections in patients with hemodialysis