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Motoki Sonohata,1,2,* Atsushi Doi,3,* Kazuyoshi Uchihashi,4 Akira Hashimoto,2 Sakumo Kii,1 Takao Inoue,5 Masaaki Mawatari1 1Department of Orthopaedic Surgery, Faculty of Medicine, Saga University, Saga, Japan; 2Department of Orthopaedic Surgery, Saga Central Hospital, Saga, Japan; 3Department of Rehabilitation, Kumamoto Health Science University, Kumamoto, Japan; 4Department of Surgical Pathology, National Hospital Organization Saga Hospital, Saga, Japan; 5Organization of Research Initiatives, Yamaguchi University, Yamaguchi, Japan*These authors contributed equally to this workCorrespondence: Atsushi Doi, Department of Rehabilitation, Kumamoto Health Science University, 324, Izumi, Kumamoto-kitaku, Kumamoto, 861-5598, Japan, Tel +81-96-275-2111, Email atsushidoi01@gmail.comPurpose: This study used a sciatic nerve injury rat model to investigate the short-term effects of a polyglycolic acid (PGA)-collagen tube for nerve injury in continuity.Materials and Methods: Sixteen female Wistar rats (6– 8 weeks) were used, and the left sciatic nerve was crushed with a Sugita aneurysm clip. Sciatic nerve model rats were randomly categorized into two groups (n = 8; control group, n = 8; nerve wrapping group). Then, we measured four sensory thresholds, magnetically stimulated the lumbar region to induce motor-evoked potentials (MEPs), and evaluated the sciatic nerve histopathologically.Results: In the sensory thresholds, there were significant differences for the main effect in 250 and 2000 Hz stimulation (p = 0.048 and 0.006, respectively). Further, a significant difference was observed with 2000 Hz stimulation at 1 week (p = 0.003). In the heat stimulation, there were significant differences for the main effect in both weeks and groups (p = 0.0002 and 0.0185, respectively). The post-hoc test showed a significant difference between groups only in 2W (p = 0.0283). Three weeks after the surgery, both 2nd and 3rd MEPs waves-related latencies in the nerve wrapping group were significantly shorter than those in the control group (p = 0.0207 and 0.0271, respectively). Histological evaluation of the sciatic nerve revealed considerable differences in the number of axons between the two groups (p = 0.0352).Conclusion: The short-term PGA-collagen tube nerve wrapping facilitated motor and sensory recovery from nerve degeneration in the sciatic nerve injury rat model.Keywords: polyglycolic acid-collagen tube, nerve wrapping, sciatic nerve injury, sensory threshold, motor and sensory recovery

Atrial fibrillation (AF) is mainly initiated by arrhythmogenic triggers originating from the pulmonary veins, and ganglion plexus often plays a crucial role in the induction and maintenance of AF. In this report, we describe a case of successful cryoballoon ablation of focal atrial tachycardia originating from the left inferior pulmonary, in which vagal response was observed, and discuss its tachycardia mechanism.

A 72-year-old female with frequent palpitation was referred for radiofrequency ablation. The baseline 12-lead electrocardiogram and echocardiography results were normal. At baseline, the atrio-His (AH) and His-ventricular (HV) intervals were 90 and 41 ms, respectively. Dual atrioventricular (AV) nodal physiology or ventriculoatrial (VA) conduction was not observed during programmed atrial and ventricular stimulation. After isoproterenol infusion, VA conduction became decremental and concentric, with the earliest atrial activation seen at the His bundle (HB) region during ventricular pacing. A supraventricular tachycardia with a long RP interval (SVT) was induced by atrial extra-stimulation, without any jump-up in the AH interval. During the SVT, the AH and HV intervals were 180 and 180 ms, respectively, and the earliest atrial activation was recorded in the HB region (Figure 1A). During the SVT, transient 2:1AV conduction was observed (Figure 1B). Ventricular overdrive pacing at a pacing cycle length (CL) of 360 ms was performed during the SVT with a CL of 390ms (Figures 2A and B). Based on these observations, what is the mechanism of this tachycardia?

We have developed a scanning probe microscope to evaluate the device with high spatial resolution in a power semiconductor device with a voltage applied. Specifically, we observed the cross sectional structure exposed SiC planar MOS-FET using a multifunctional probe microscope, which combines atomic force microscopy, Kelvin probe force microscopy, and scanning capacitance force microscopy. By observing the channel formation and carrier concentration change in response to the applied voltage, we were able to visualize the internal state of the SiC power MOSFET.

A 77-year-old woman with palpitations was referred for a second radiofrequency ablation for persistent atrial tachycardia (AT). She previously underwent pulmonary vein (PV) isolation for paroxysmal atrial fibrillation, linear ablation between the 3’o clock position of the mitral annulus (MA) and left PV from the endocardium, and ablation inside the coronary sinus (CS) for perimitral atrial tachycardia (PMAT) in the first procedure. A baseline 12-lead electrocardiogram in the second procedure showed stable AT with a cycle length (CL) of 250 ms. No PV reconnection was observed. The CS catheter was placed from 3:30 to 5:00 on the MA, and a proximal-to-distal pattern of CS activation during AT was observed. Activation mapping in the left atrial (LA) endocardium using a three-dimensional mapping system (CARTO3, Biosense Webster, Diamond Bar, CA, USA) revealed a sequence of counterclockwise rotations of the MA. Figures 1A and 1B show the intracardiac electrograms during high-output (20 V) and low-output (5 V) atrial entrainment pacing at a pacing CL of 240ms from CS 3,4, which corresponds to the 4’o clock position of the MA. Dose residual conduction occur across the mitral isthmus (MI) endocardium, epicardium, or both? What is the electrophysiological mechanism during high- and low-output entrainment pacing?

Background Functional capacity (FC) correlates with mortality in various cardiovascular diseases. The aim of this study was to examine whether cardiac pacemaker implantations improve the FC and affect the prognosis. Methods and Results We prospectively enrolled 621 de novo pacemaker recipients (age 76 ± 9 years, 50.7% male). The FC was assessed by metabolic equivalents (METs) during the implantation and periodically thereafter. The patients were a priori classified into poor FC (, We examined the temporal trends in the functional capacity (FC) and the relationship between the FC and prognosis in patients receiving an initial pacemaker implantation. The major findings of this study were that (i) 43% of the patients with a poor or moderate FC improved to a good FC 3 months after the pacemaker implantation, (ii) a poor FC was an independent predictor of both hospitalization and the total mortality, and (iii) the lack of an improvement in the FC at 1 year after the pacemaker implantation was associated with an increased risk of mortality.

Background Subcutaneous implantable cardioverter–defibrillator (S-ICD) represents an efficient alternative to transvenous ICD in patients who do not require pacing. The intraoperative defibrillation test (DFT) is recommended during S-ICD implantation to confirm appropriate sensing and successful 65-J termination of induced ventricular fibrillation (VF). However, few cases of oversensing of noise inhibiting therapies have been reported. Case summary We report the case of a 50-year-old man who underwent S-ICD implantation for secondary prevention of sudden cardiac death. Immediately after S-ICD implantation, VF was induced using a 50-Hz burst; however, shock was not delivered owing to sustained noise on the electrogram in the primary vector. Therefore, an external rescue shock was needed at 150 J. We changed the sensing vector from primary to secondary and performed a second DFT. The S-ICD could deliver an appropriate shock and was able to successfully terminate VF without noise markers in the secondary vector. During the second DFT, one back-up pacing was delivered after the shock; the sensing vector then automatically switched from the secondary to the alternate vector. However, noise was observed in the alternate vector despite sinus rhythm restoration. Discussion The present case demonstrated that noise was recorded in two different vectors during DFT, possibly supporting the hypothesis that the muscle spasm of the diaphragm induced by the 50-Hz burst causes oversensing of noise by the S-ICD.

This study aimed to determine the effect of pool gait exercise using fibromyalgia-induced model mice. The sensory threshold, locomotive behavior, electrocardiogram, and onset time after the gait test in shallow water using male C57BL/6J mice (weight, 30-35 g; n=21) were investigated. To induce fibromyalgia in model mice, reserpine was injected intraperitoneally into wild-type mice once a day for 3 days. Subsequently, the fibromyalgia-induced model mice were randomly classified into two groups as follows: the control group (n=11) and the pool gait group (n=10). The mice in the pool gait group walked in the same cage containing shallow warm water 5 times per week. Both groups underwent sensory thresholds and video recordings to determine locomotive behaviors weekly. Further, both heart rate and video recordings for observation of a recovery after the gait test in shallow water were undertaken (control group; n=5, pool gait group; n=5). The pool gait did not affect sensory thresholds and locomotive behavior; however, in the pool gait group, both the recovery after the test, such as onset time and gait distance, were considerably better than those of the control group. Furthermore, changes in heart rate and heart rate irregularity after the test were more apparent in the control group than in the pool gait group. The free gait in a shallow pool accelerated recovery after exercise, unlike the sensory threshold.

It is still difficult to treat acute limb ischemia (ALI) in the non-stenting zone such as the popliteal artery. We describe a temporary endoluminal bypass technique for ALI in the non-stenting zone using a guide extension catheter. An 83-year-old female was admitted and diagnosed with ALI in her left leg. The angiogram showed a thrombotic obstruction of the left popliteal artery. Aspiration and dilation by angioplasty could not revascularize. Although Fogarty thrombectomy can be applicable, we avoided it because of its risk of complications and performed a temporary endoluminal bypass technique. After evaluating the occluded lesion by intravascular ultrasound, we delivered a guide extension catheter to fully cover it. Because it played the role of an endoluminal bypass, the blood flow to the distal tibial arteries could be confirmed in the angiogram. A thrombolytic drug was administered intra-arterially for the whole day, and the angiogram showed a reduction of the thrombus on postoperative day (POD) 1. On POD 2, the blood flow was maintained without flow limitation even after removing the catheter. Finally, she was discharged without any complications. This technique might be an alternative in cases of failed conventional treatments for ALI although further investigation needs to be undertaken.

The liver microphysiological system (MPS) model is an in-vitro culture method that mimics physiological blood flow, which enhances basal cellular functions. However, the liver MPS model has not been tested in the preclinical stage because of its obscure utility. It can overcome the major problem of conventional systems-rapid loss of mitochondrial activity in cultured hepatocytes due to limited oxygen supply-by supplying oxygen to cultured hepatocytes using a perfusion device. In this study, we developed a new perfusion culture system that can detect mitochondrial toxicity. Primary mouse hepatocytes were cultured under perfusion condition for 48 hr. The hepatocytes showed increased oxygen consumption and reduced lactate release. These results indicated that the ATP-production pathway was switched from glycolysis to mitochondrial oxidative phosphorylation in the perfusion culture system. Furthermore, ATP levels were considerably reduced in the perfusion culture system after exposure to phenformin, a mitochondrial complex I inhibitor. To summarize, the perfusion culture system could improve the mitochondrial activity in primary mouse hepatocytes, and thus, has potential implications in the detection of mitochondrial toxicity.

How T follicular (Tfh) cells contribute to many different B-cell class-switching events during T-cell-dependent immune responses has been unclear. Diseases with polarized isotype switching offer a unique opportunity for the exploration of Tfh subsets. Secondary and tertiary lymphoid organs in patients with elevated tissue expression levels of IgE (Kimura disease, KD) and those of IgGWe sought to identify disease-specific Tfh cell subsets in secondary and tertiary lymphoid organs expressing IL-10 or IL-13 and thus identify different cellular drivers of class switching in 2 distinct types of fibrotic disorders: allergic fibrosis (driven by type 2 immune cells) and inflammatory fibrosis (driven by cytotoxic T lymphocytes).Single-cell RNA sequencing, in situ sequencing, and multicolor immunofluorescence analysis were used to investigate B cells, Tfh cells, and infiltrating type 2 cells in lesion tissues from patients with KD or IgGInfiltrating Tfh cells in tertiary lymphoid organs from IgGOur analysis revealed a novel subset of IL-10

Purpose: We investigated the effects of noradrenaline (NA) on physiologically evoked synaptic responses of substantia gelatinosa (SG) neurons using anesthetized animals. Methods: Male Sprague-Dawley rats (6-8 weeks, 200-300 g, n=21) were anesthetized. The lumbar spinal cord was exposed from L3 to L5; subsequently, the rats were fixed to a stereotaxic apparatus. The electrode was advanced at an angle of 30-45 degrees into the SG using a micromanipulator. We recorded excitatory post-synaptic currents (EPSC). Under these conditions, innocuous or noxious mechanical stimuli were applied to the receptive field of the ipsilateral hindlimb with or without NA, respectively. Results: NA (50 μM) pre-application induced three types of responses for pinch-evoked EPSCs. The number of neurons showing inhibition, facilitation, and no-effect was 15 (71.4%), 2 (9.5%), and 4 (19%), respectively (n=21). Pre-treatment with NA also induced three different types of responses for puff-evoked EPSC (n=21). The number of neurons showing inhibition, facilitation, and no-effect was 9 (42.9%), 9 (42.9%), and 3 (14.2%), respectively. Further, there was a significant difference in the rate distribution (inhibition, facilitation, and no change) between puff- and pinch-evoked responses. Conclusion: Our present data indicate that NA acts on noxious and innocuous mechanical transmission in the SG. Considering the distinct sensory inputs to the SG, the different actions of NA on the transmission of sensory information imply that NA exerts its analgesic effects in a manner more complicated than previously believed.

We discover a new cavitation phenomenon in amorphous polymers sandwiched between two thick slide glasses from the static melt induced by thermal treatment. By quenching atactic polystyrene (aPS) samples from the static melt under the glass transition temperature (Tg) and annealing them above Tg for thick slide glasses, cavities are created to relax the negative pressure. Cavity growth undergoes an Ostwald ripening-like process in cases of large molecular weight, while it undergoes a viscous fingering process in cases of small molecular weight. The induction time for cavity formation is found to decrease with the increase of the annealing temperature and with the decrease of molecular weight. In contrast, no cavities are observed in an aPS sample between two thin cover glasses because the negative pressure can be relaxed by bending the whole thin cover glasses. We discover a new cavitation phenomenon in amorphous polymers sandwiched between two thick slide glasses from the static melt induced by thermal treatment. By quenching atactic polystyrene samples from the static melt under the glass transition temperature (Tg) and annealing them above Tg, cavities are created to relax the negative pressure. Cavity growth undergoes an Ostwald ripening-like process in cases of large molecular weight while it undergoes a viscous fingering process in cases of small molecular weight.

The treatment of digital ulcer (DU) in systemic sclerosis (SSc) has not been established. A 77-year-old female with a refractory DU in SSc on the right foot was transferred to our hospital. Wound healing had not been achieved despite several endovascular treatments (EVT) and minor amputations. We started Waon therapy 5 days per week as an adjunct therapy. She was placed in a far-infrared-ray dry sauna maintained at 45 °C for 15 min, and was subsequently kept to rest with soothing warmth using a blanket for additional 30 min outside the room. Gradually, the wound had become smaller and the skin perfusion pressure (SPP) had increased. The increase of the blood flow to the wound could be observed in the angiogram on day 109. An additional EVT on day 109 also accelerated wound healing. Finally, wound healing was completely achieved without additional amputations on day 173. In this presented case, Waon therapy contributed to increase of the blood flow to the wound, evidenced by SPP value. Waon therapy may serve as an effective adjunct therapy of DU in SSc.

Non-invasive brain–computer interfaces (BCIs) based on common electroencephalography (EEG) are limited to specific instrumentation sites and frequency bands. These BCI induce certain targeted electroencephalographic features of cognitive tasks, identify them, and determine BCI's performance, and use machine-learning to extract these electroencephalographic features, which makes them enormously time-consuming. In addition, there is a problem in which the neurorehabilitation using BCI cannot receive ambulatory and immediate rehabilitation training. Therefore, we proposed an exploratory BCI that did not limit the targeted electroencephalographic features. This system did not determine the electroencephalographic features in advance, determined the frequency bands and measurement sites appropriate for detecting electroencephalographic features based on their target movements, measured the electroencephalogram, created each rule (template) with only large “High” or small “Low” electroencephalograms for arbitrarily determined thresholds (classification of cognitive tasks in the imaginary state of moving the feet by the size of the area constituted by the power spectrum of the EEG in each frequency band), and successfully detected the movement intention by detecting the electroencephalogram consistent with the rules during motor tasks using a fuzzy inference-based template matching method (FTM). However, the electroencephalographic features acquired by this BCI are not known, and their usefulness for patients with actual cerebral infarction is not known. Therefore, this study clarifies the electroencephalographic features captured by the heuristic BCI, as well as clarifies the effectiveness and challenges of this system by its application to patients with cerebral infarction.

SUMMARYFused in sarcoma/translated in liposarcoma (FUS) is a causative gene of amyotrophic lateral sclerosis (ALS). Mutated FUS causes accumulation of DNA damage and cytosolic stress granule (SG) formation, thereby motor neuron (MN) death. However, key molecular aetiology remains unclear. Here, we applied a novel platform technology, iBRN, “Non-biased” Bayesian gene regulatory network analysis based on induced pluripotent stem cell (iPSC)-derived cell model, to elucidate the molecular aetiology using transcriptome of iPSC-derived MNs harboring FUSH517D. iBRN revealed “hub molecules”, which strongly influenced transcriptome network, such as miR-125b-5p-TIMELESS axis and PRKDC for the molecular aetiology. Next, we confirmed miR-125b-5p-TIMELESS axis in FUSH517D MNs such that miR-125b-5p regulated several DNA repair-related genes including TIMELESS. In addition, we validated both introduction of miR-125b-5p and knocking down of TIMELESS caused DNA damage in the cell culture model. Furthermore, PRKDC was strongly associated with FUS mis-localization into SGs by DNA damage under impaired DNA-PK activity. Collectively, our iBRN strategy provides the first compelling evidence to elucidate molecular aetiology in neurodegenerative diseases.HighlightsA new platform technology, “iBRN”, Bayesian gene regulatory network analysis based on iPSC cellsiBRN identifies hub molecules to strongly influence the gene network in FUS-ALSPRKDC specifically acts as a guardian against FUS mis-localization during DNA damage stressmiR-125b-5p-TIMELESS axis regulates DNA repair-related genes in FUS-ALS.

Power semiconductor devices are progressing towards high-withstand voltage using wide bandgap semiconductor materials as well as having the ability to flow a significant amount of current by multi-parallel integration using the microfabrication technique. A power semiconductor device under a bias voltage applied condition by a scanning probe microscope (SPM) was successfully observed, combined with atomic force microscopy (AFM), Kelvin probe force microscopy (KFM), and scanning capacitance force microscopy (SCFM). Using the SPM analysis, both, a high spatial-resolution and high sensitivity was achieved.

BackgroundFibromyalgia patients experience cardiovascular complications in addition to musculoskeletal pain. This study aimed to investigate the cardiac effects of a prolonged shallow water gait in a fibromyalgia-induced young mouse model.MethodsTo produce a fibromyalgia mouse model, wild-type mice were administered an intraperitoneal injection of reserpine once a day for three days, and two primary experiments were performed. First, three types of gait tests were performed before and after the reserpine injections as follows: (i) 5 minutes of free gait outside the water, (ii) 1 minute of free gait in shallow warm water, and (iii) 5 minutes of free gait in shallow warm water. Second, electrocardiogram recordings were taken before and after the three gait tests. The average heart rate and heart rate irregularity scores were analyzed.ResultsExercise-induced cardiac arrhythmia was observed at 1-minute gait in shallow water during the acute stage of induced FM in young mice. Further, both cardiac arrhythmia and a decrease in HR have occurred at 5-minute gait in shallow water at the same mice. However, this phenomenon was not observed in the wild-type mice under any test conditions.ConclusionAlthough a short-term free gait in shallow warm water may be advantageous for increasing the motor activity of FM-model mice, we should be aware of the risk of prolonged and excessive exercise-induced cardiac arrhythmia. For gait exercises in shallow water as a treatment in FM patients. We suggest a gradual increase in exercise duration may be warranted.

Aim: Most transplant centres use SV40 large T antigen (TAg) staining for the diagnosis and assessment of BK polyomavirus-associated nephropathy (BKPyVAN). This study was performed to evaluate the significance of capsid protein VP1 expression in BKPyVAN. Methods: We performed immunohistochemical staining using anti-SV40 TAg and anti-BKPyV VP1 antibodies in 16 index biopsies and 12 re-biopsies of BKPyVAN and compared the patterns of positivity and the percentage of positive tubules by counting whole specimens. We investigated the correlation between serum creatinine increase from baseline and the percentage of positive tubules for both markers in 16 index biopsies. Results: In VP1 staining, positive findings were observed not only in the nuclei of tubular epithelial cells but also in the cytoplasm, cells shedding into the lumen, intra-tubular casts, and in the interstitium. Two of 28 biopsies (7.1%) showed TAg-positive and VP1-negative results, in which TAg-positive cells were detected only in a single tubule. The median (interquartile range) percentage of positive tubules was 2.8% (0.7–9.8%) for TAg and 1.4% (0.5–3.9%) for VP1 staining (p = 0.2). In 16 index biopsies, serum creatinine increases significantly correlated with the percentage of VP1-positive tubules (r = 0.49, p = 0.02), while this correlation revealed borderline significance with TAg-positive tubules. Conclusions: VP1 expression showed various patterns, but was detected in half as many tubules as TAg staining, which might lead to false negatives in the samples with minimal viral replication. However, increased VP1-positive tubules indicate advanced tubular damage and possible association with graft dysfunction.

Background: Tolvaptan is a vasopressin type 2 receptor antagonist used in heart failure (HF) with refractory diuretic resistance. However, since tolvaptan is also ineffective in some HF patients with reduced ejection fraction (HFrEF), the identification of responders is important. Methods: The study population consisted of 51 HFrEF patients who were administered tolvaptan (EF, 28 ± 7%). We defined responders as patients with a ≥50% increase in urine volume during the 24-hours after administration of tolvaptan. All patients underwent comprehensive transthoracic echocardiography before administration of tolvaptan. Patients were followed for 120 days to ascertain secondary events (cardiac death and rehospitalization for HF). Results: Multiple regression analysis indicated that right ventricular (RV) enlargement (defined as basal RV diameter > 41 mm and midlevel RV diameter > 35 mm, according to guidelines) remained a predictor of response after adjustment for age, sex, starting dosage of tolvaptan, and estimated glomerular filtration rate (odds ratio, 4.88; 95%-confidence interval, 1.26–18.9; P

Thrombotic microangiopathy (TMA) develops from various etiologies, and it is often difficult to distinguish the etiology of TMA in kidney transplantation. Antiphospholipid syndrome (APS) is one of the differential diagnoses for TMA that may cause acute loss of graft function or fatal thrombotic complications. This report details a 66-year-old male patient with polycythemia after ABO-incompatible kidney transplantation. Antibody screening tests were negative before transplant. Despite administration of an adequate desensitization therapy including plasmapheresis and rituximab, he developed acute graft dysfunction on postoperative day 112 and graft biopsy revealed prominent microvascular inflammation in the glomerular capillaries without immunoglobulin deposits. Flow cytometric panel-reactive antibody screening failed to detect donor-specific antibodies at both pre-transplant and episode biopsies. Anticardiolipin antibody was repeatedly positive, but neither thrombosis nor previous thrombotic episodes were detected. After excluding several differential diagnoses, the graft dysfunction with unexplained TMA was treated with steroid pulse, plasmapheresis and rituximab re-induction. Anticardiolipin antibody disappeared after this intensive treatment and graft function recovered gradually and stabilized for 52 months. This report suggests that asymptomatic anticardiolipin antibody may be associated with acute graft dysfunction. Even if thrombotic episodes are not observed, an exist of anticardiolipin antibody may be one of the risk factors of renal TMA after kidney transplantation.

Atsushi Doi,1,2,* Juntaro Sakasaki,3,* Chikato Tokunaga,4,* Fumiya Sugita,5,* Syota Kasae,6 Keisuke Nishimura,7 Yushi Sato,8 Takako Kuratsu,9 Sariya Hashiguchi,10 Min-Chul Shin,1,2 Megumu Yoshimura11 1Department of Physical Therapy, Kumamoto Health Science University, Kumamoto, Japan; 2Graduate School of Health Sciences, Kumamoto Health Science University, Kumamoto, Japan; 3Department of Rehabilitation, Tokyo-Wangan Rehabilitation Hospital, Narashino, Japan; 4Department of Rehabilitation, Himeno Hospital, Yame, Japan; 5Department of Rehabilitation, Tamana Central Hospital, Tamana, Japan; 6Department of Rehabilitation, Shimizu Hospital, Kyoto, Japan; 7Department of Rehabilitation, Iizuka Hospital, Iizuka, Japan; 8Department of Rehabilitation, Showa Hospital, Shimonoseki, Japan; 9Department of Rehabilitation, Konan Hospital, Kumamoto, Japan; 10Department of Rehabilitation, Asahino-Sogo Hospital, Kumamoto, Japan; 11Nakamura Hospital, Nogata, Japan *These authors contributed equally to this work Purpose: This study was aimed to investigate the effect of localized vibration on sensory thresholds in mice and humans using a novel quantitative method. Participants and methods: The sensory thresholds of 7-week-old male C57BL/6J mice were measured with four sine-wave electrostimulation frequencies (5, 50, 250, and 2,000 Hz) before and after applying 2-minute vibration to the plantar side of the foot in mice. In human participants (16 males and 16 females; mean age, 21.0±0.8 years), the sensory threshold was measured at 50 Hz before and after applying 2-minute and 5-minute vibrations to the dorsal side of the foot. Results: Application of a 2-minute vibration at either the ipsilateral or contralateral side modulated the sensory thresholds elicited by a 5- or 50-Hz right electrostimulation in mice. In human participants, application of a 5-minute vibration at either the ipsilateral or contralateral side modulated the sensory threshold elicited by 50-Hz right electrostimulation, but had no effect on local skin temperature. These results suggest that the right side of pain-related Aδ fibers (50 Hz) or C fibers (5 Hz) was modulated by the localized ipsilateral or contralateral side of vibratory stimuli, respectively, in mice and humans. Conclusion: The ability of contralateral vibration to modify the right sensory thresholds suggests possible involvement of the central nervous system in vibratory modulation. Keywords: vibration, sensory threshold, electrostimulation, central modulation

Because there are limited clinical reports on the impact of human T-lymphotropic virus type 1 (HTLV-1) on organ transplantation, its effects on the development of adult T-cell leukemia-lymphoma (ATL), post-transplantation lymphoproliferative disorder (PTLD) and HTLV-1–associated myelopathy (HAM) or atypical HAM after organ transplantation remain unclear. We retrospectively analyzed the impact of HTLV-1 in 54 allogeneic hematopoietic stem cell transplantation (allo-HSCT) cases and 31 renal transplantation cases between January 2006 and December 2016. Among the 54 allo-HSCT cases, nine recipients with ATL tested positive for HTLV-1, and one was found to be an HTLV-1 carrier. All donors tested negative for HTLV-1. Only one HTLV-1 carrier did not present with ATL or HAM development after allo-HSCT. Among nine ATL cases after allo-HSCT, four eventually relapsed due to proliferation of recipient-derived ATL cells. However, in one ATL case, atypical HAM developed rapidly at 5 months after allo-HSCT. Among the 31 renal transplantation cases, all donors tested negative for HTLV-1, and only recipients tested positive. Only one HTLV-1 carrier recipient did not present with ATL or HAM development after renal transplantation. However, one HTLV-1-negative recipient developed PTLD in the brain 10 years after renal transplantation. In clinical practice, careful follow-up of HTLV-1 infected recipients after organ transplantation is important because atypical HAM can develop in ATL patients after allo-HSCT. Furthermore, to clarify the risk of ATL or HAM development in HTLV-1 infected recipients, we prospectively followed up our cohort.