UV-LED irradiation reduces the infectivity of herpes simplex virus type 1 by targeting different viral components depending on the peak wavelength.

Herpes simplex virus type 1 (HSV-1) is an enveloped virus that mainly infects humans. Given its high global prevalence, disinfection is critical for reducing the risk of infection. Ultraviolet-light-emitting diodes (UV-LEDs) are eco-friendly irradiating modules with different peak wavelengths, but the molecules degraded by UV-LED irradiation have not been clarified. To identify the target viral molecules of UV-LEDs, we exposed HSV-1 suspensions to UV-LED irradiation at wavelengths of 260-, 280-, 310-, and 365-nm and measured viral DNA, protein, and lipid damage and infectivity in host cells. All UV-LEDs substantially reduced by inhibiting host cell transcription, but 260- and 280-nm UV-LEDs had significantly stronger virucidal efficiency than 310- and 365-nm UV-LEDs. Meanwhile, 260- and 280-nm UV-LEDs induced the formation of viral DNA photoproducts and the degradation of viral proteins and some phosphoglycerolipid species. Unlike 260- and 280-nm UV-LEDs, 310- and 365-nm UV-LEDs decreased the viral protein levels, but they did not drastically change the levels of viral DNA photoproducts and lipophilic metabolites. These results suggest that UV-LEDs reduce the infectivity of HSV-1 by targeting different viral molecules based on the peak wavelength. These findings could facilitate the optimization of UV-LED irradiation for viral inactivation.

Irradiation by a Combination of Different Peak-Wavelength Ultraviolet-Light Emitting Diodes Enhances the Inactivation of Influenza A Viruses.

Influenza A viruses (IAVs) pose a serious global threat to humans and their livestock. This study aimed to determine the ideal irradiation by ultraviolet-light emitting diodes (UV-LEDs) for IAV disinfection. We irradiated the IAV H1N1 subtype with 4.8 mJ/cm2 UV using eight UV-LEDs [peak wavelengths (WL) = 365, 310, 300, 290, 280, 270, and 260 nm)] or a mercury low pressure (LP)-UV lamp (Peak WL = 254 nm). Inactivation was evaluated by the infection ratio of Madin-Darby canine kidney (MDCK) cells or chicken embryonated eggs. Irradiation by the 260 nm UV-LED showed the highest inactivation among all treatments. Because the irradiation-induced inactivation effects strongly correlated with damage to viral RNA, we calculated the correlation coefficient (RAE) between the irradiant spectrum and absorption of viral RNA. The RAE scores strongly correlated with the inactivation by the UV-LEDs and LP-UV lamp. To increase the RAE score, we combined three different peak WL UV-LEDs (hybrid UV-LED). The hybrid UV-LED (RAE = 86.3) significantly inactivated both H1N1 and H6N2 subtypes to a greater extent than 260 nm (RAE = 68.6) or 270 nm (RAE = 42.2) UV-LEDs. The RAE score is an important factor for increasing the virucidal effects of UV-LED irradiation.

Inactivation of Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli by UVA-LED irradiation system.

The prevalence of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli is increasing rapidly and spreading worldwide, particularly in Asia, compared to other regions. In the last ten years, in our hospital, in particular, there has been a < 30% increase. To prevent the spread of ESBL in hospitals and the community, the ultraviolet (UV) A-light-emitting diode (LED) irradiation device was used to inactivate ESBL-E. coli in human livestock and the environment. ESBL-E. coli and E. coli bacterial samples were collected from patients at Tokushima University Hospital (Tokushima City, Japan). The UVA-LED irradiation system had 365 nm single wavelength, and the current of the circuit was set to 0.23 or 0.50 A consistently. Results demonstrated that UVA-LED was useful for the inactivation of ESBL-E. coli and E. coli. The minimum energy dosage required to inactivate ESBL-E. coli and E. coli was 40.76 J/cm2 (45 min) in the first type of UVA-LED and 38.85 J/cm2 (5 min) in the second type. There were no significant differences between ESBL-E. coli and E. coli. The inactivation of ESBL-E. coli was dependent on energy. These findings suggest that UVA-LED with 365 nm single wavelength could be useful for surface decontamination in healthcare facilities. J. Med. Invest. 67 : 163-169, February, 2020.

Development of a novel automatic ascites filtration and concentration equipment with multi-ring-type roller pump units for cell-free and concentrated ascites reinfusion therapy.

Cell-free and concentrated ascites reinfusion therapy (CART) is an effective therapy for refractory ascites. However, CART is difficult to perform as ascites filtration and concentration is a complicated procedure. Moreover, the procedure requires the constant assistance of a clinical engineer or/and the use of an expensive equipment for the multi-purpose blood processing. Therefore, we developed a CART specialized equipment (mobility CART [M-CART]) that could be used safely with various safety measures and automatic functions such as automatic washing of clogged filtration filter and self-regulation of the concentration ratio. Downsizing, lightning of the weight, and automatic processing in M-CART required the use of newly developed multi-ring-type roller pump units. This equipment was approved under Japanese regulations in 2018. In performing 41 sessions of CART (for malignant ascites, 22 sessions; and hepatic ascites, 19 sessions) using this equipment in 17 patients, no serious adverse event occurred. An average of 4494 g of ascites was collected and the total amount of ascites was processed in all the sessions without any trouble. The mean weight of the processed ascites was 560 g and the mean concentration ratio was 8.0. The ascites were processed at a flow rate of 50 mL/min. The mean ascites processing time was 112.5 minutes and a 106.5-minutes (95.2%) ascites processing was performed automatically. The operator responded to alarms or support information 3.2 times on average (3.1 minutes, 2.1% of ascites processing time). Human errors related to ascites processing were detected by M-CART at 0.4 times per session on average and were appropriately addressed by the operator. The frequencies of automatic washing of clogged filtration filter and self-regulation of the concentration ratio were 31.7% and 53.7%, respectively. The mean recovery rates (recovery dose) of protein, albumin, and immunoglobulin G were 72.9%, 72.9%, and 71.2% (65.9 g, 34.9 g, and 13.2 g), respectively. Steroids were administered in 92.7% of the sessions to prevent fever and the mean increase in body temperature was 0.53°C. M-CART is a compact and lightweight automatic CART specialized equipment that can safely and easily process a large quantity of ascites without the constant assistance of an operator.

Bacterial Contamination of Hemodialysis Devices in Hospital Dialysis Wards.

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 acommon cause of hemodialysis catheterrelated 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. J. Med. Invest. 66 : 148-152, February, 2019.

Irradiation by ultraviolet light-emitting diodes inactivates influenza a viruses by inhibiting replication and transcription of viral RNA in host cells.

Influenza A viruses (IAVs) pose a serious global threat to humans and their livestock, especially poultry and pigs. This study aimed to investigate how to inactivate IAVs by using different ultraviolet-light-emitting diodes (UV-LEDs). We developed sterilization equipment with light-emitting diodes (LEDs) those peak wavelengths were 365 nm (UVA-LED), 310 nm (UVB-LED), and 280 nm (UVC-LED). These UV-LED irradiations decreased dose fluence-dependent plaque-forming units of IAV H1N1 subtype (A/Puerto Rico/8/1934) infected Madin-Darby canine kidney (MDCK) cells, but the inactivation efficiency of UVA-LED was significantly lower than UVB- and UVC-LED. UV-LED irradiations did not alter hemagglutination titer, but decreased accumulation of intracellular total viral RNA in infected MDCK cells was observed. Additionally, UV-LED irradiations suppressed the accumulation of intracellular mRNA (messenger RNA), vRNA (viral RNA), and cRNA (complementary RNA), as measured by strand-specific RT-PCR. These results suggest that UV-LEDs inhibit host cell replication and transcription of viral RNA. Both UVB- and UVC-LED irradiation decreased focus-forming unit (FFU) of H5N1 subtype (A/Crow/Kyoto/53/2004), a highly pathogenic avian IAV (HPAI), in infected MDCK cells, and the amount of FFU were lower than the H1N1 subtype. From these results, it appears that IAVs may have different sensitivity among the subtypes, and UVB- and UVC-LED may be suitable for HPAI virus inactivation.

Combined treatment of UVA irradiation and antibiotics induces greater bactericidal effects on Vibrio parahaemolyticus.

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.

High-resolution body-surface electrocardiograph system and survey of possible applications.

A body-surface electrocardiograph system employs unique spring-loaded metal-rod electrodes encased in metal housings to minimize set-up time and noise. 124 electrodes spaced at 35 mm intervals acquire body-surface potential with a 10 kHz sampling rate to capture and image (time sequentially) electrical activity of the heart not observable with standard 12-lead electrocardiography. Possible applications surveyed include assessing cardiopulmonary facility, examining age-related effects, and quantifying warning signs for myocardial infarction.

Signal shape feature for automatic snore and breathing sounds classification.

Snore analysis techniques have recently been developed for sleep studies. Most snore analysis techniques require reliable methods for the automatic classification of snore and breathing sounds in the sound recording. In this study we focus on this problem and propose an automated method to classify snore and breathing sounds based on the novel feature, 'positive/negative amplitude ratio (PNAR)', to measure the shape of the sound signal. The performance of the proposed method was evaluated using snore and breathing recordings (snore: 22,643 episodes and breathing: 4664 episodes) from 40 subjects. Receiver operating characteristic (ROC) analysis showed that the proposed method achieved 0.923 sensitivity with 0.918 specificity for snore and breathing sound classification on test data. PNAR has substantial potential as a feature in the front end of a non-contact snore/breathing-based technology for sleep studies.

Vegetable surface sterilization system using UVA light-emitting diodes.

Surface sterilization of fresh produce has been needed in the food manufacturing/processing industry. Here we report a UVA-LED (Ultra Violet A-Light Emitting Diode) system for surface sterilization that is safe, efficacious, low cost, and apparently harmless to fresh produce. To test the system, Escherichia coli strain DH5α was spot-inoculated onto vegetable tissues, and treated under UVA-LED. Tissues were homogenized and bacteria quantified by colony-forming assay. Possible effects of UVA-LED on vegetable quality were evaluated by HPLC. Tissue weight changes were checked after treatment at 4℃, 15℃, and 30℃. Bacterial inactivation by UVA-LED radiation was observed after a 10 min treatment and increased with increasing time of irradiation. The log survival ratio reached -3.23 after a 90 min treatment. Bacterial cells surviving treatment grew slowly compared to non-irradiated control cells. Cabbage tissue lost weight over time after treatment, and weight loss increased with increasing incubation temperature, but there was no difference between losses by UVA-LED treated and control tissues at any temperature tested. In addition, no differences of Vitamin C content in cabbage tissue were detected by HPLC after UVA-LED treatment. These results suggest that UVA-LED treatment has great potential for vegetable surface sterilization in the food manufacturing/processing industry.

Anxiety affects the amplitudes of red and green color-elicited flash visual evoked potentials in humans.

It has been reported that negative emotional changes and conditions affect the visual faculties of humans at the neural level. On the other hand, the effects of emotion on color perception in particular, which are based on evoked potentials, are unknown. In the present study, we investigated whether different anxiety levels affect the color information processing for each of 3 wavelengths by using flash visual evoked potentials (FVEPs) and State-Trait Anxiety Inventory. In results, significant positive correlations were observed between FVEP amplitudes and state or trait anxiety scores in the long (sensed as red) and middle (sensed as green) wavelengths. On the other hand, short-wavelength-evoked FVEPs were not correlated with anxiety level. Our results suggest that negative emotional conditions may affect color sense processing in humans.

A neuronal network model with simplified tonotopicity for tinnitus generation and its relief by sound therapy.

Tinnitus is the perception of sound in the ears or in the head where no external source is present. Sound therapy is one of the most effective techniques for tinnitus treatment that have been proposed. In order to investigate mechanisms of tinnitus generation and the clinical effects of sound therapy, we have proposed conceptual and computational models with plasticity using a neural oscillator or a neuronal network model. In the present paper, we propose a neuronal network model with simplified tonotopicity of the auditory system as more detailed structure. In this model an integrate-and-fire neuron model is employed and homeostatic plasticity is incorporated. The computer simulation results show that the present model can show the generation of oscillation and its cessation by external input. It suggests that the present framework is promising as a modeling for the tinnitus generation and the effects of sound therapy.

ARMA-based spectral bandwidth for evaluation of bowel motility by the analysis of bowel sounds.

Approximately 10%-20% of adults and adolescents suffer from irritable bowel syndrome (IBS) worldwide. IBS is characterized by chronic gastrointestinal dysfunction which may reflect in altered motility. Currently, the diagnosis of IBS is made through expensive invasive radiographic and endoscopic examinations. However these are inconvenient and unsuited for community screening. Bowel sounds (BSs) can be easily recorded with non-invasive and low-cost equipment. Recently, several researchers have pointed out changes in features obtained from BS according to the pathological condition of bowel motility. However a widely accepted, simple automatic BS detection algorithm still has to be found, and the appropriate recording period needs to be investigated for further evaluation of bowel motility. In this study we propose a novel simple automatic method to detect the BSs based on the 3 dB bandwidth of the frequency peaks in the autoregressive moving average spectrum. We use the measure, sound-to-sound interval (SSI) obtained by the proposed method, to capture bowel motility. In this paper, we show that the proposed method for automatic detection could achieve a sensitivity of 87.8±5.88%, specificity of 91.7±4.33% and area under the curve of 0.923 when working on 16 healthy volunteers during mosapride administrations. Furthermore, we show that the measured SSI averaged over a period of 30 min can clearly capture bowel motility. Our findings should have the potential to contribute toward developing automated BS-based diagnosis of IBS.

Artificial neural networks for breathing and snoring episode detection in sleep sounds.

Obstructive sleep apnea (OSA) is a serious disorder characterized by intermittent events of upper airway collapse during sleep. Snoring is the most common nocturnal symptom of OSA. Almost all OSA patients snore, but not all snorers have the disease. Recently, researchers have attempted to develop automated snore analysis technology for the purpose of OSA diagnosis. These technologies commonly require, as the first step, the automated identification of snore/breathing episodes (SBE) in sleep sound recordings. Snore intensity may occupy a wide dynamic range (> 95 dB) spanning from the barely audible to loud sounds. Low-intensity SBE sounds are sometimes seen buried within the background noise floor, even in high-fidelity sound recordings made within a sleep laboratory. The complexity of SBE sounds makes it a challenging task to develop automated snore segmentation algorithms, especially in the presence of background noise. In this paper, we propose a fundamentally novel approach based on artificial neural network (ANN) technology to detect SBEs. Working on clinical data, we show that the proposed method can detect SBE at a sensitivity and specificity exceeding 0.892 and 0.874 respectively, even when the signal is completely buried in background noise (SNR < 0 dB). We compare the performance of the proposed technology with those of the existing methods (short-term energy, zero-crossing rates) and illustrate that the proposed method vastly outperforms conventional techniques.

Effects of a 1.5 T time-varying magnetic field on cell volume regulation of bovine adrenal chromaffin cells in hyposmotic media.

Effects of a time-varying magnetic field on cell volume regulation by hyposmotic stress in cultured bovine adrenal chromaffin cells were examined. Through regulatory volume decrease (RVD), cell volume of chromaffin cells that were incubated in a hypotonic medium initially increased, reached a peak and finally recovered to the initial value. Two hour exposure to a magnetic field and addition of cytochalasin D increased peak value and delayed return to initial value. Intracellular F-actin contents initially decreased but returned to normal levels after 10 sec. Two hour exposure to the magnetic field and addition of cytochalasin D continuously reduced the F-actin content. Results suggest that exposure to the magnetic field stimulated disruption of the actin cytoskeleton and that the disruption delayed the recovery to the volume prior to osmotic stress.

Feed-forward changes in carotid blood flow velocity during active standing.

Orthostatic changes induce temporary loss of circulatory regulation. Feedback systems react to cardiovascular alterations to compensate for the instability. To clarify the existence of anticipatory cardiovascular regulation during active standing, we continuously recorded blood flow velocity (BFV) in the common carotid artery and cerebral blood volume (CBV) in healthy men. The maximum BFV value decreased significantly before standing in the reaction-time condition. The decrease significantly correlated with the change in systolic blood pressure that accompanies upright standing from a supine position. The anticipatory BFV decrease disappeared during self-paced standing, and all BFV parameters significantly declined after the self-paced standing. The CBV recording showed a significant increase in oxyhemoglobin levels before standing in the reaction-time condition. Our study suggests that some feed-forward cardiovascular regulation triggered by central command could be activated before standing, and it may play a functional role in the maintenance of cerebral perfusion during standing.

The removal of EMG in EEG by neural networks.

In this paper, it is presented that electromyography (EMG) is a shot noise based on the generation of EMG. A novel filter is proposed by applying a neural network (NN) ensemble where the noisy input signal and the desired one are the same in a learning process. Both incremental and batch mode are applied in the learning process of NNs that is better than generalized NN filters. This NN ensemble filter not only reduces additive and multiplicative white noise inside signals, but also preserves the signals' characteristics. In clinical EEG and EMG signals processing, the filter is capable of reducing EMG in the clinical EEG, and it is proved that there is randomness in EMG.

Effects of exposure to a time-varying 1.5 T magnetic field on the neurotransmitter-activated increase in intracellular Ca(2+) in relation to actin fiber and mitochondrial functions in bovine adrenal chromaffin cells.

BACKGROUND: It has been reported that exposure to electromagnetic fields influences intracellular signal transduction. We studied the effects of exposure to a time-varying 1.5 T magnetic field on membrane properties, membrane cation transport and intracellular Ca(2+) mobilization in relation to signals. We also studied the mechanism of the effect of exposure to the magnetic field on intracellular Ca(2+) release from Ca(2+) stores in adrenal chromaffin cells. METHODS: We measured the physiological functions of ER, actin protein, and mitochondria with respect to a neurotransmitter-induced increase in Ca(2+) in chromaffin cells exposed to the time-varying 1.5 T magnetic field for 2h. RESULTS: Exposure to the magnetic field significantly reduced the increase in [Ca(2+)]i. The exposure depolarized the mitochondria membrane and lowered oxygen uptake, but did not reduce the intracellular ATP content. Magnetic field-exposure caused a morphological change in intracellular F-actin. F-actin in exposed cells seemed to be less dense than in control cells, but the decrease was smaller than that in cytochalasin D-treated cells. The increase in G-actin (i.e., the decrease in F-actin) due to exposure was recovered by jasplakinolide, but inhibition of Ca(2+) release by the exposure was unaffected. CONCLUSIONS AND GENERAL SIGNIFICANCE: These results suggest that the magnetic field-exposure influenced both the ER and mitochondria, but the inhibition of Ca(2+) release from ER was not due to mitochondria inhibition. The effect of eddy currents induced in the culture medium may indirectly influence intracellular actin and suppress the transient increase in [Ca(2+)]i.

Basic study of a diagnostic modality employing a new electrical impedance tomography (EIT) method for noninvasive measurement in localized tissues.

The objective of this study is to develop a device for noninvasive local tissue electrical impedance tomography (EIT) using divided electrodes with guard electrodes and to validate its effectiveness using bioequivalent phantoms. For this purpose, we prepared a measurement device and bioequivalent phantoms, measured the electrical characteristics of the phantoms, and validated the method using the phantoms. Monolayer phantoms mimicking the brain and muscle and bilayer phantoms consisting of muscle and brain layers were prepared. The relative differences between the measured electrical conductivities of the monolayer brain and muscle phantoms and the true values determined by the 4-electrode method were both less than 10%. The relative differences between the measured and true values in the bilayer phantoms were less than 20% in both layers. The biological impedance measurement device that we developed was confirmed to be effective for impedance measurement in bilayer phantoms with different electrical impedances. To develop a device for the early diagnosis of breast diseases, the development of a multi-layer phantom and demonstration of the effectiveness of the device for its examination are necessary. If the device that we developed makes impedance measurement in breast tumors possible, it may be used as a new diagnostic modality for breast diseases.

A new colored beverage disinfection system using UV-A light-emitting diodes.

In this study we evaluated the ability of the UV-A-LED to eliminate bacteria in a colored beverage. Ten edible pigments were used to make a colored solution at concentrations of 1.0%, 0.1%, 0.01% and 0.001%. We used a colony-forming assay to monitor the bactericidal action against the bacteria. The bactericidal effect of UV-A-LED against Escherichia coli DH5 a decreased with the increasing concentration of almost all of the edible pigments. Although less effective in colored solutions and commercially available orange juice than in the positive control PBS, it holds potential for further development and use to ensure food and water safety.