Clinical validity of the Japanese below-the-knee chronic total occlusion scoring system for the prediction of successful guidewire crossing.

OBJECTIVE: To validate Japanese below-the-knee (J-BTK) chronic total occlusion (CTO) score for the prediction of successful guidewire crossing in angiographic evaluation. METHODS: A prospective, multicenter, non-randomized study examined 751 consecutive BTK CTOs in 497 patients treated with endovascular therapy (EVT) in 16 Japanese medical centers from April 2021 to March 2022. The cohort was classified into 2 groups: a successful guidewire crossing (S-GC) group and a failed guidewire crossing group. RESULTS: The J-BTK CTO score which assigned one point to "Blunt type at the proximal entry point", one point to "Calcification at the proximal entry point", one point to "Reference vessel diameter < 2.0mm", one point to "CTO length ≥ 200mm", and two points to "No outflow of the target vessel" was utilized to categorize BTK CTOs into 4 grades with varying probabilities of successful guidewire crossing: grade A (J-BTK CTO score of 0 and 1), grade B (score of 2 and 3), grade C (score of 4 and 5), and grade D (score of 6). Rates of successful guidewire crossing in each grade (grade A, B, C, and D) were 97.5%, 89.1%, 62.5%, and 27.3%, respectively. The area under the receiver-operating characteristic (ROC) curve for successful guidewire crossing was 0.8304. Although the previous J-BTK CTO study enrolled only de novo lesions, both de novo and restenotic lesions were evaluated in this study. De novo lesions have a lower chance of S-GC (odds ratio: 0.24, 95% confidence interval: 0.09-0.67) in the multivariate analysis and the area under the ROC curve of the modified J-BTK CTO score, which additionally assigned two points to "De novo lesion", was 0.846. The modified J-BTK CTO score showed an appropriate calibration (Hosmer-Lemeshow p=0.957). CONCLUSION: The J-BTK CTO score and the modified J-BTK CTO score predict the probability of a S-GC of BTK CTOs and stratify the difficulty of EVT for BTK CTOs in angiographic evaluation.

Efficacy of autologous platelet-rich plasma gel in patients with hard-to-heal diabetic foot ulcers: a multicentre study in Japan.

OBJECTIVE: To evaluate the healing outcome of a platelet-rich plasma (PRP) gel prepared using TKKT01 (a wound care device to prepare the PRP gel) in patients with hard-to-heal diabetic foot ulcers (DFUs) and who showed an inadequate response to ≥4 weeks of standard of care (SoC). METHOD: This open-label, single-arm, multicentre study was conducted in 15 centres in Japan. Eligible patients received PRP gel treatment twice a week for eight weeks, followed by a final evaluation after the completion of week 8 (day 57). The primary endpoint was the percentage of patients who achieved ≥50% reduction in wound radius at the final evaluation (achievement criterion, ≥60% of patients). Secondary endpoints included: wound area and volume reduction rates; time to possible wound closure by secondary intention; time to possible wound closure using a relatively simple procedure (e.g., skin graft and suture); and safety at the final evaluation. RESULTS: A total of 54 patients were included in the full analysis set, with 47 patients included in the per protocol set; the primary endpoint was met in 38/47 (80.9%) (95% confidence interval: 66.7-90.9%) patients who achieved ≥50% wound radius reduction at the final evaluation. High rates of wound area (72.8%) and volume (92.7%) reduction were observed at the final evaluation. The median time to possible wound closure by secondary intention and by use of a relatively simple procedure was 57 and 43 days, respectively. Complete wound closure at the final evaluation was achieved in 27 (57.4%) patients. No safety concerns were raised. CONCLUSION: In this study, the efficacy and safety of PRP gel treatment with TKKT01 in patients with hard-to-heal DFUs in Japan were confirmed by our findings. DECLARATION OF INTEREST: This study was funded by Rohto Pharmaceutical Co., Ltd., Japan. NO has been paid a consulting fee by Rohto Pharmaceutical Co., Ltd. KH is the Chief Medical Officer of Rohto Pharmaceutical. Co., Ltd. The other authors have no conflict of interest to declare.

Comparison of the Pre-Established and Finally Selected Treatment Strategies for Endovascular Treatment in Femoropopliteal Artery Lesions.

This study aimed to compare lower limb events associated with preplanned and finally selected treatment strategies-the validity and usefulness of the physician-chosen strategy were verified.We examined the data of 1003 patients in the registry of multicenter endovascular treatment for superficial femoral and popliteal artery disease study and prospectively enrolled patients who underwent endovascular treatment (EVT) of the femoropopliteal (FP) artery between February 2017 and June 2018 from 67 Japanese institutes. The outcome measures were major adverse limb events (MALE) and target vessel revascularization.The EVT strategies were classified into balloon angioplasty-alone (37.3%), primary stenting (26.7%), and provisional stenting (36.0%) groups. In the initial strategy analysis for the balloon angioplasty-alone, primary stenting, and provisional stenting groups, two-year rates of freedom from MALE (95% confidence interval) were 0.680 (0.620-0.732), 0.754 (0.688-0.808), and 0.798 (0.746-0.840), respectively. Additionally, the rate of MALE was significantly higher among patients in the balloon angioplasty-alone group than among those in the primary or provisional stenting groups in the initial strategy analysis (P = 0.007). Changes in treatment strategy were more frequent in the primary stenting group than in the other groups. Furthermore, the rate of MALE did not significantly differ among the three groups in the final strategy analysis (P = 0.56).Limb outcomes for the final applied strategy did not differ among the three strategies. Additionally, the physician's selection bias was mostly appropriate in the EVT of the FP artery.

Twelve-month safety and effectiveness of TCD-17187 drug-coated balloon for the treatment of atherosclerotic lesions in the superficial femoral and proximal popliteal artery.

PURPOSE: The aim of this preapproval trial was to evaluate the 12-month safety and effectiveness of the TCD-17187 drug-coated balloon (DCB) for the treatment of atherosclerotic lesions in the superficial femoral artery (SFA) and/or proximal popliteal artery (PA). METHODS: This was a prospective, multicenter, core laboratory adjudicated, single-arm trial. From October 2019 to November 2020, a total of 121 symptomatic peripheral artery disease patients with SFA and/or proximal PA lesions were enrolled. The primary effectiveness endpoint was 12-month primary patency defined as freedom from restenosis as determined by duplex ultrasonography in the absence of clinically driven target lesion revascularization (CD-TLR). The safety endpoint was the major adverse event (MAE) rate defined as freedom from a composite of device- and procedure-related death within 30 days, and index limb major amputation and/or CD-TLR through follow-up. RESULTS: Average age was 74.5 ± 7.3 years and the frequency of diabetes mellitus was 67.5%. Average lesion length and vessel diameter were 106.0 ± 52.6 and 5.2 ± 0.8 mm, respectively. The frequency of chronic total occlusion and bilateral calcification was 17.5% and 50.8% of patients, respectively. The 12-month primary patency rate calculated by Kaplan-Meier analysis was 81.1%, while 12-month freedom from CD-TLR was 95.8%. The MAE rate at 30 days was 1.7% and all events comprised CD-TLR. There were no instances of device- or procedure-related deaths, major amputations, or thrombosis throughout the 12-month evaluation period. CONCLUSION: This preapproval trial confirmed the safety and effectiveness of TCD-17187 DCB in the treatment of atherosclerotic lesions in the SFA and/or proximal PA.

Clinical Safety and Efficacy of Rotational Atherectomy in Japanese Patients with Peripheral Arterial Disease Presenting Femoropopliteal Lesions: The J-SUPREME and J-SUPREME II Trials.

PURPOSE: The purpose of the J-SUPREME (J-S) and J-SUPREME II (J-SII) trials was to evaluate the performance of the Jetstream Atherectomy System for the treatment of Japanese patients with symptomatic occlusive atherosclerotic lesions in the superficial femoral and popliteal arteries. MATERIALS AND METHODS: The J-S and J-SII trials were both prospective, multicenter, single-arm clinical trials. Patients in J-S underwent Jetstream atherectomy followed by percutaneous transluminal angioplasty (PTA), whereas those in J-SII had adjunctive drug-coated balloon (DCB) treatment following atherectomy. Patients were adults with Rutherford category 2, 3, or 4 and had stenotic, restenotic, or occlusive lesion(s) with a degree of stenosis ≥70 in the superficial femoral artery and/or proximal popliteal artery. In J-S, lesions were required to be calcified, and in J-SII lesions were required to be severely calcified. RESULTS: A total of 50 patients were enrolled in J-S (mean age 72.3±8.7 years, lesion length 82.0±41.5 mm, 36% calcification PACSS Grade 3, 22% Grade 4) and 31 patients in J-SII (mean age 72.5±7.7 years, lesion length 122.6±55.6 mm, 19.4% calcification PACSS Grade 3, 77.4% Grade 4). No bailout stenting or bypass conversions were required. No major adverse events (MAEs) were reported for either trial through 1 month. The 6-month primary patency for J-S, with PTA alone following atherectomy, was 40.4% (19/47). The 6-month primary patency for J-SII, with DCB treatment following atherectomy, was 96.7% (29/30). At 6-month post-procedure, 79.2% (38/48) of patients in J-S, and 100% (30/30) of patients in J-SII had improved by at least 1 Rutherford category. CONCLUSION: J-SUPREME trial results demonstrate procedural safety and efficacy of the Jetstream Atherectomy System and J-SII showed sustained patency through 6 months following combination treatment with Jetstream atherectomy and DCB.

One-year results for Japanese patients in RANGER II SFA.

The RANGER II SFA objective was to evaluate the safety and effectiveness of the Ranger Drug-Coated Balloon (DCB) for treating superficial femoral artery and/or proximal popliteal artery lesions; the purpose of this cohort analysis is to assess the results among Japanese study participants. Patients eligible for RANGER II SFA had symptomatic lower limb ischemia (Rutherford classification 2-4) and were randomly assigned (3:1) to treatment with the Ranger DCB or standard percutaneous transluminal angioplasty (PTA). At 12 months, assessments included freedom from major adverse events (i.e., target lesion revascularization, major amputations, or death within 1 month of the index procedure) and core laboratory-assessed primary patency. Japanese patients (n = 102) comprised 27.1% of the overall study sample. Mean lesion lengths were 79.5 ± 44.0 mm and 84.0 ± 56.8 mm among Japanese patients treated with Ranger DCB (n = 77) or PTA (n = 25), respectively. All major adverse events were clinically driven TLRs (6.6% [5/76] for Ranger DCB and 16.0% [4/25] for PTA; p = 0.2194). Kaplan-Meier estimates of primary patency were 89.3% and 72.0%, respectively, at 12 months (log-rank p = 0.2134). Japanese patients treated with Ranger DCB maintained a high patency rate through 12 months and a low re-intervention rate.Trial registration clinicaltrials.gov identifier: NCT03064126.

Facial radiance influences facial attractiveness and affective impressions of faces.

OBJECTIVE: Facial attractiveness has been reported to be influenced by visual features such as facial shape and the colour and texture of the skin. However, no empirical studies have examined the effects of facial skin radiance on facial attractiveness. The present study investigated whether types of skin reflection (i.e. radiant, oily and shiny, and matte) and the position of the reflection on the face influence facial attractiveness and other affective impressions. METHODS: A total of 160 female participants (1) estimated the ages and (2) evaluated attractiveness and other impressions of unfamiliar female faces in a total of seven skin reflection conditions. These conditions incorporated three types of reflection (i.e. radiant, oily and shiny, and matte) and three positions of the reflection on the face (i.e. entire facial skin, only cheeks, and only T-zone). RESULTS: The facial images of radiance on entire faces were rated as appearing younger than the facial images of oily shine on entire faces and the matte faces. Attractiveness ratings and other positive impressions increased in the order of the matte (ranked lowest), the oily shine on entire face, and the radiance on entire face (ranked highest) conditions. The reflection position also influenced facial attractiveness: attractiveness ratings and other positive impressions were higher in the radiance on entire face condition than in the radiant cheeks and the radiant T-zone conditions. Interestingly, the radiant cheek faces were rated more radiant and healthier but less feminine and less bright than the radiant T-zone faces. CONCLUSION: These results suggest that facial radiance enhances facial attractiveness and conveys a wide variety of positive impressions on the observer. The magnitude of the effects of cheek radiance and T-zone radiance differs across various affective impressions. Nevertheless, the results demonstrate that cheek and the T-zone radiance both contribute to higher attractiveness and other positive impressions of the radiance on entire faces. We believe that our findings can contribute as a guide to the enhancement of positive facial impressions by means of skin radiance, thereby leading to a better understanding of the value of skincare and base makeup.

OBJECTIF: Selon certaines études, l'attractivité du visage viendrait de caractéristiques visuelles telles que la forme du visage ainsi que la couleur et la texture de la peau. Cependant, aucune étude empirique n'a examiné les effets de l'éclat de la peau sur l'attractivité du visage. La présente étude s'est intéressée aux divers types de reflets de la peau (par exemple une peau lumineuse, une peau grasse et luisante ou une peau mate) et à leur position sur le visage, et a cherché à savoir s'ils influençaient l'attractivité du visage et d'autres impressions d'ordre affectif. MÉTHODES: Au total, 160 participantes 1) ont estimé l'âge et 2) ont évalué l'attractivité et d'autres impressions de visages féminins inconnus sur sept types de reflets de la peau au total. Ces états comprenaient trois types de reflets (lumineux, gras et mat) et trois positions des reflets sur le visage (toute la peau du visage, joues uniquement et partie yeux-nez [« zone T ¼] uniquement). RÉSULTATS: Les photos de visages caractérisées par un éclat sur tout le visage ont été considérées comme étant plus jeunes que celles dont la peau était grasse-luisante sur l'ensemble du visage et que les visages à peau mate. Les notes attribuées pour l'attractivité et les autres impressions positives augmentent dans l'ordre suivant : peau mate (note la plus basse), peau grasse-luisante sur tout le visage et luminosité sur tout le visage (note la plus haute). La position du reflet a elle aussi joué un rôle sur les notes attribuées à l'attractivité des visages, et les autres impressions positives ont obtenu des scores plus élevés pour une luminosité de tout le visage que pour des joues lumineuses et une zone T lumineuse. Il est intéressant de noter que les visages aux joues lumineuses ont été jugés plus lumineux et plus sains, mais moins féminins et moins éclatants que les visages présentant une zone T lumineuse. CONCLUSION: Ces résultats suggèrent que l'éclat du visage améliore l'attractivité du visage et communique toutes sortes d'impressions positives à l'observateur. L'ampleur des effets de l'éclat sur les joues et sur la zone T diffère selon les différentes impressions d'ordre affectif. Néanmoins, les résultats démontrent que la luminosité des joues et de la zone T contribue à rendre le visage plus séduisant ainsi qu'à d'autres impressions positives suscitées par la luminosité de l'ensemble du visage. Nous sommes convaincus que nos résultats peuvent servir à guider la façon de renforcer l'impression positive produite par un visage en faisant ressortir la luminosité de la peau, et amener ainsi à mieux comprendre la valeur des soins de la peau et des bases de maquillage.

Targeting Chemosensory Ion Channels in Peripheral Swallowing-Related Regions for the Management of Oropharyngeal Dysphagia.

Oropharyngeal dysphagia, or difficulty in swallowing, is a major health problem that can lead to serious complications, such as pulmonary aspiration, malnutrition, dehydration, and pneumonia. The current clinical management of oropharyngeal dysphagia mainly focuses on compensatory strategies and swallowing exercises/maneuvers; however, studies have suggested their limited effectiveness for recovering swallowing physiology and for promoting neuroplasticity in swallowing-related neuronal networks. Several new and innovative strategies based on neurostimulation in peripheral and cortical swallowing-related regions have been investigated, and appear promising for the management of oropharyngeal dysphagia. The peripheral chemical neurostimulation strategy is one of the innovative strategies, and targets chemosensory ion channels expressed in peripheral swallowing-related regions. A considerable number of animal and human studies, including randomized clinical trials in patients with oropharyngeal dysphagia, have reported improvements in the efficacy, safety, and physiology of swallowing using this strategy. There is also evidence that neuroplasticity is promoted in swallowing-related neuronal networks with this strategy. The targeting of chemosensory ion channels in peripheral swallowing-related regions may therefore be a promising pharmacological treatment strategy for the management of oropharyngeal dysphagia. In this review, we focus on this strategy, including its possible neurophysiological and molecular mechanisms.

Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain.

Neuropathic pain conditions including neuropathic orofacial pain (NOP) are difficult to treat. Contemporary therapeutic agents for neuropathic pain are often ineffective in relieving pain and are associated with various adverse effects. Finding new options for treating neuropathic pain is a major priority in pain-related research. Cannabinoid-based therapeutic strategies have emerged as promising new options. Cannabinoids mainly act on cannabinoid 1 (CB1) and 2 (CB2) receptors, and the former is widely distributed in the brain. The therapeutic significance of cannabinoids is masked by their adverse effects including sedation, motor impairment, addiction and cognitive impairment, which are thought to be mediated by CB1 receptors in the brain. Alternative approaches have been developed to overcome this problem by selectively targeting CB2 receptors, peripherally restricted CB1 receptors and endocannabinoids that may be locally synthesized on demand at sites where their actions are pertinent. Many preclinical studies have reported that these strategies are effective for treating neuropathic pain and produce no or minimal side effects. Recently, we observed that inhibition of degradation of a major endocannabinoid, 2-arachydonoylglycerol, can attenuate NOP following trigeminal nerve injury in mice. This review will discuss the above-mentioned alternative approaches that show potential for treating neuropathic pain including NOP.

A histopathological analysis of spontaneous neoplastic and non-neoplastic lesions in aged male RccHan:WIST rats.

Histopathological information about spontaneous lesions in aged Hannover Wistar rats is limited. In this study, we describe spontaneous lesions found in 39 male RccHan:WIST rats used as a control in a carcinogenicity study. Neoplastic lesions were frequently seen in the endocrine system, such as pituitary adenomas in the pars distalis. This strain exhibited a high incidence of thymoma (10.3%), compared to other strains. We encountered an oligodendroglioma, a pituitary adenoma of the pars intermedia, and a prostate adenocarcinoma, which are comparatively rare in rats. While the variety and incidence of non-neoplastic lesions were similar to those in other strains, several interesting lesions occurred with relatively high incidence, including "harderianization" of the extraorbital lacrimal gland, common bile duct ectasia, and hyperplasia of pulmonary endocrine cells in the lung. Furthermore, comparative analyses demonstrated that the severity of chronic progressive nephropathy and murine progressive cardiomyopathy in RccHan:WIST rats was less than that in F344 rats.

Effective connectivity within the ventromedial prefrontal cortex-hippocampus-amygdala network during the elaboration of emotional autobiographical memories.

Autobiographical memories (AMs) are often colored by emotions experienced during an event or those arising following further appraisals. However, how affective components of memories affect the brain-wide network recruited during the recollection of AMs remains largely unknown. Here, we examined effective connectivity during the elaboration of AMs - when retrieved episodic details are integrated to form a vivid construct - in the network composed by ventromedial prefrontal cortex (vmPFC), hippocampus and amygdala, three key regions associated with memory and affective processes. Functional MRI data was collected while volunteers recollected personal events of different types of valence and emotional intensity. Using dynamic causal modeling, we characterized the connections within the triadic network, and examined how they were modulated by the emotional intensity experienced during an event, and the valence of the affect evoked when recollecting the associated memory. Results primarily indicated the existence of a vmPFC to hippocampus effective connectivity during memory elaboration. Furthermore, the strength of the connectivity increased when participants relived memories of highly emotionally arousing events or that elicited stronger positive affect. These results indicate that the vmPFC drives hippocampal activity during memory elaboration, and plays a critical role in shaping affective responses that emanate from AMs.

Self-Expanding Nitinol Stent vs Percutaneous Transluminal Angioplasty in the Treatment of Femoropopliteal Lesions: 3-Year Data From the SM-01 Trial.

PURPOSE: To report the midterm outcomes of a trial comparing self-expanding nitinol stents to percutaneous transluminal angioplasty (PTA) with provisional stenting in the treatment of obstructive disease in the superficial femoral and popliteal arteries. MATERIALS AND METHODS: The SM-01 study ( ClinicalTrials.gov identifier NCT01183117), a single-blinded, multicenter, randomized controlled trial in Japan, enrolled 105 consecutive patients with de novo or postangioplasty restenotic femoropopliteal lesions; after removing protocol violations (1 from each group), 51 patients (mean age 74±8 years; 36 men) in the stent group and 52 patients (mean age 73±8 years; 35 men) in the PTA group were included in the intention-to-treat analysis. The groups were well-matched at baseline. Patients were followed to 36 months with duplex imaging. Three-year primary patency was assessed based on a duplex-derived peak systolic velocity ratio <2.5. Freedom from clinically-driven target vessel revascularization (TVR) and target lesions revascularization (TLR) were estimated using the Kaplan-Meier method. RESULTS: The technical success rate was higher (100% vs 48%, p<0.001) and the frequency of vascular dissection was lower (4% vs 31%, p<0.001) in the stent group. The S.M.A.R.T stent group had a higher 3-year primary patency rate (73% vs 51%, p=0.033). Freedom from clinically-driven TVR and TLR were not significantly different between the groups. CONCLUSION: The S.M.A.R.T. stent maintained a higher primary patency rate than PTA at 3 years in this randomized trial; the need for clinically-driven revascularization was similar for both therapies.

Variations in the eicosapentaenoic acid-arachidonic acid ratio associated with age in acute myocardial infarction patients undergoing primary percutaneous coronary intervention.

Acute myocardial infarction (AMI) is a life-threatening disease, and its incidence has been increasing even in the young population. Although a low eicosapentaenoic acid (EPA)-arachidonic acid (AA) ratio is associated with an increased risk of coronary artery disease, the effect of age on EPA/AA ratios in AMI patients remains unclear. This study aimed to clarify the independent polyunsaturated fatty acid (PUFA)-related determinants of age in younger and older AMI patients. A total of 153 consecutive patients who underwent primary percutaneous coronary interventions (PCIs) for de novo AMIs were enrolled in this study. Patients' background data, including PUFA and lipid profiles during PCI, were evaluated retrospectively. The EPA/AA ratio correlated positively with age (r = 0.21; P = 0.011) and increased markedly from age 60 years. Patients aged < 60 years (n = 35) had a lower mean EPA/AA ratio (0.25 ± 0.16) than patients aged ≥ 60 years (n = 118) (0.38 ± 0.25) (P < 0.001). The AA level was more dependent on age than on EPA level (r = - 0.34, P < 0.001 vs. r = 0.12, P = 0.16). The multivariate analysis revealed that a 0.1 EPA/AA ratio increase (odds ratio 1.50; 95% confidence interval 1.09-2.06), body mass index, triglyceride level, and aspirin administration were independently associated with the age stratification of AMI patients. The EPA/AA ratio was higher in younger AMI patients who have undergone primary PCIs than in older patients. Younger population at risk for AMI should be managed with multiple interventions including PUFA profiling.

The Role of Transient Receptor Potential (TRP) Channels in the Transduction of Dental Pain.

Dental pain is a common health problem that negatively impacts the activities of daily living. Dentine hypersensitivity and pulpitis-associated pain are among the most common types of dental pain. Patients with these conditions feel pain upon exposure of the affected tooth to various external stimuli. However, the molecular mechanisms underlying dental pain, especially the transduction of external stimuli to electrical signals in the nerve, remain unclear. Numerous ion channels and receptors localized in the dental primary afferent neurons (DPAs) and odontoblasts have been implicated in the transduction of dental pain, and functional expression of various polymodal transient receptor potential (TRP) channels has been detected in DPAs and odontoblasts. External stimuli-induced dentinal tubular fluid movement can activate TRP channels on DPAs and odontoblasts. The odontoblasts can in turn activate the DPAs by paracrine signaling through ATP and glutamate release. In pulpitis, inflammatory mediators may sensitize the DPAs. They could also induce post-translational modifications of TRP channels, increase trafficking of these channels to nerve terminals, and increase the sensitivity of these channels to stimuli. Additionally, in caries-induced pulpitis, bacterial products can directly activate TRP channels on DPAs. In this review, we provide an overview of the TRP channels expressed in the various tooth structures, and we discuss their involvement in the development of dental pain.

Activation of TRPV1 and TRPM8 Channels in the Larynx and Associated Laryngopharyngeal Regions Facilitates the Swallowing Reflex.

The larynx and associated laryngopharyngeal regions are innervated by the superior laryngeal nerve (SLN) and are highly reflexogenic. Transient receptor potential (TRP) channels have recently been detected in SLN innervated regions; however, their involvement in the swallowing reflex has not been fully elucidated. Here, we explore the contribution of two TRP channels, TRPV1 and TRPM8, located in SLN-innervated regions to the swallowing reflex. Immunohistochemistry identified TRPV1 and TRPM8 on cell bodies of SLN afferents located in the nodose-petrosal-jugular ganglionic complex. The majority of TRPV1 and TRPM8 immunoreactivity was located on unmyelinated neurons. Topical application of different concentrations of TRPV1 and TRPM8 agonists modulated SLN activity. Application of the agonists evoked a significantly greater number of swallowing reflexes compared with the number evoked by distilled water. The interval between the reflexes evoked by the agonists was shorter than that produced by distilled water. Prior topical application of respective TRPV1 or TRPM8 antagonists significantly reduced the number of agonist-evoked reflexes. The findings suggest that the activation of TRPV1 and TRPM8 channels present in the swallowing-related regions can facilitate the evoking of swallowing reflex. Targeting the TRP channels could be a potential therapeutic strategy for the management of dysphagia.

The Importance of Spatiotemporal Information in Biological Motion Perception: White Noise Presented with a Step-like Motion Activates the Biological Motion Area.

Humans can easily recognize the motion of living creatures using only a handful of point-lights that describe the motion of the main joints (biological motion perception). This special ability to perceive the motion of animate objects signifies the importance of the spatiotemporal information in perceiving biological motion. The posterior STS (pSTS) and posterior middle temporal gyrus (pMTG) region have been established by many functional neuroimaging studies as a locus for biological motion perception. Because listening to a walking human also activates the pSTS/pMTG region, the region has been proposed to be supramodal in nature. In this study, we investigated whether the spatiotemporal information from simple auditory stimuli is sufficient to activate this biological motion area. We compared spatially moving white noise, having a running-like tempo that was consistent with biological motion, with stationary white noise. The moving-minus-stationary contrast showed significant differences in activation of the pSTS/pMTG region. Our results suggest that the spatiotemporal information of the auditory stimuli is sufficient to activate the biological motion area.

Establishment of monoclonal antibodies against cell surface domains of ASCT2/SLC1A5 and their inhibition of glutamine-dependent tumor cell growth.

Human alanine-serine-cysteine transporter 2 (ASCT2; SLC1A5) is a major transporter of the amino acid glutamine that is known to be overexpressed in certain malignant tumors. In this study, we generated specific monoclonal antibodies (MAbs) against ASCT2 by establishing an ASCT2-expressing Chinese hamster ovary cell line that was used to immunize mice and rats. The MAbs KM4008, KM4012, and KM4018 against ASCT2 were isolated through a cell-based screen; these specifically bound to ASCT2-positive cells, as determined by flow cytometry and immunoprecipitation. In addition, the antibodies suppressed glutamine-dependent growth of WiDr colorectal cancer cells. These results provide evidence supporting the use of MAbs against ASCT2 as an effective therapeutic strategy for cancer treatment.

A novel lesion crossing technique: Balloon deployment using FORcible Manner (BADFORM) technique.

OBJECTIVES: We evaluated the efficacy and safety of a novel endovascular technique for crossing arterial lesions: The BAlloon Deployment using FORcible Manner (BADFORM) technique. BACKGROUND: Endovascular treatment (EVT) for peripheral artery disease has been widely adopted, and developments in device technology and techniques have resulted in acceptable success rates. However, it may be difficult to deliver devices even after wire externalization, especially in the presence of an extremely long chronic total occlusion or severely calcified lesion. The BADFORM technique might be useful in these cases. METHODS: We retrospectively reviewed ten consecutive EVT cases using the BADFORM technique performed at our institution between April 2015 and September 2016. In all cases, wire externalization was established with the rendezvous technique. The BADFORM technique was performed when antegrade passage of any device was impossible after wire externalization. Physicians positioned a low-profile balloon or microcatheter just proximal to the calcified lesion and attached the device to the externalized wire using a torque device at the proximal catheter exit port. The externalized wire was then pulled retrogradely. RESULTS: All patients were receiving hemodialysis and had critical limb ischemia. All lesions were severely calcified, and 90% were chronic total occlusions. The technical success and procedure success rates were 90% and 70%, respectively. Delivered devices included five balloon catheters and four microcatheters. One procedure-related vessel injury occurred at the distal puncture site (digital artery), however, this was controlled by external manual compression. CONCLUSIONS: The efficacy and safety of the BADFORM technique might be acceptable. © 2017 Wiley Periodicals, Inc.

Neuron-Glia Crosstalk and Neuropathic Pain: Involvement in the Modulation of Motor Activity in the Orofacial Region.

Neuropathic orofacial pain (NOP) is a debilitating condition. Although the pathophysiology remains unclear, accumulating evidence suggests the involvement of multiple mechanisms in the development of neuropathic pain. Recently, glial cells have been shown to play a key pathogenetic role. Nerve injury leads to an immune response near the site of injury. Satellite glial cells are activated in the peripheral ganglia. Various neural and immune mediators, released at the central terminals of primary afferents, lead to the sensitization of postsynaptic neurons and the activation of glia. The activated glia, in turn, release pro-inflammatory factors, further sensitizing the neurons, and resulting in central sensitization. Recently, we observed the involvement of glia in the alteration of orofacial motor activity in NOP. Microglia and astroglia were activated in the trigeminal sensory and motor nuclei, in parallel with altered motor functions and a decreased pain threshold. A microglial blocker attenuated the reduction in pain threshold, reduced the number of activated microglia, and restored motor activity. We also found an involvement of the astroglial glutamate-glutamine shuttle in the trigeminal motor nucleus in the alteration of the jaw reflex. Neuron-glia crosstalk thus plays an important role in the development of pain and altered motor activity in NOP.

Effects of posture on chest-wall configuration and motion during tidal breathing in normal men.

[Purpose] The purpose of this study was to clarify the impact of postural changes during tidal breathing on the configuration and motion of chest-wall in order to further breathing motion evaluation. [Subjects and Methods] Chest-wall configuration and motion in the supine, right lateral, and sitting positions were measured using optoelectronic plethysmography in 15 healthy adult men. [Results] The anteroposterior diameters of the chest wall were significantly lower in the supine position for the pulmonary and abdominal rib cages, whereas the mediolateral diameters in the lateral position were lowest for the abdominal rib cage. Regarding chest-wall motion, both craniocaudal and anteroposterior motions of the anterior surface of the pulmonary and abdominal rib cages were significantly greater in the sitting position. Regarding motion of the left lateral abdominal rib cage, lateral motion was greatest in the lateral position. [Conclusion] Chest-wall configuration and motion changed according to posture in healthy men, particularly in the pulmonary and abdominal rib cages.