An analog-AI chip for energy-efficient speech recognition and transcription.

Models of artificial intelligence (AI) that have billions of parameters can achieve high accuracy across a range of tasks1,2, but they exacerbate the poor energy efficiency of conventional general-purpose processors, such as graphics processing units or central processing units. Analog in-memory computing (analog-AI)3-7 can provide better energy efficiency by performing matrix-vector multiplications in parallel on 'memory tiles'. However, analog-AI has yet to demonstrate software-equivalent (SWeq) accuracy on models that require many such tiles and efficient communication of neural-network activations between the tiles. Here we present an analog-AI chip that combines 35 million phase-change memory devices across 34 tiles, massively parallel inter-tile communication and analog, low-power peripheral circuitry that can achieve up to 12.4 tera-operations per second per watt (TOPS/W) chip-sustained performance. We demonstrate fully end-to-end SWeq accuracy for a small keyword-spotting network and near-SWeq accuracy on the much larger MLPerf8 recurrent neural-network transducer (RNNT), with more than 45 million weights mapped onto more than 140 million phase-change memory devices across five chips.

Histiocytic sarcoma of the palate: a case report.

Histiocytic sarcoma is a malignant proliferation of cells that exhibit morphological and immunophenotypic features of mature histiocytes. Owing to its rarity, its clinical features and standard treatment have not yet been established. This report describes a case of histiocytic sarcoma of the palate that developed in a 76-year-old man, the first report of an intraoral histiocytic sarcoma. An extended resection was performed; however, establishing the excision line was extremely difficult because assessing the tumour boundary on imaging was challenging and the tumour underwent dynamic gross morphological changes following biopsy. Complete resection is required to obtain a favourable prognosis for high-grade tumours with indistinct borders. In this case, an intraoperative rapid examination with frozen section analysis was performed along the planned excision line to completely resect the tumours exhibiting such behaviour. At 28 months postoperatively, the patient demonstrated no recurrence or metastasis; however, he is under careful monitoring.

Community structure of denitrifying and total bacteria during nitrogen accumulation in an ammonia-loaded biofilter.

AIMS: To obtain insight into the complex behaviour of denitrifying and total bacterial groups during the nitrogen accumulation process in an ammonia-loaded biofiltration system. METHODS AND RESULTS: Denitrifying and total bacterial communities in a laboratory-scale rockwool biofilter with intermittent water recirculation were analysed by using denaturing gradient gel electrophoresis targeting nosZ and metabarcoding sequencing of the 16S rRNA gene. Gene abundance was evaluated by quantitative PCR. The nosZ number increased from 6·59 × 106 to 3·33 × 108 copies per gram dry sample over the 436 days of operation, during which nitrogen mass balance errors increased to 39%. The nosZ sequences associated with the genera Castellaniella, Hyphomicrobium and Pseudomonas were detected. Metabarcoding sequencing analysis indicated that the proportions of the genera for which at least one denitrifying strain or species possessing nosZ had been characterized corresponded well to the nitrogen loss. In addition, the genus Nitrosococcus (γ-proteobacteria) increased its relative abundance at days 317 and 436. CONCLUSIONS: The increased proportion of denitrifying bacteria in this ammonia-loaded biofiltration system could be related to the nitrogen loss. SIGNIFICANCE AND IMPACT OF THE STUDY: These results will help to clarify the complex behaviour of nitrifiers and denitrifiers within ammonia-loaded biofiltration systems.

Blood identification and discrimination between human and nonhuman blood using portable Raman spectroscopy.

Raman spectroscopy is commonly used in chemistry to identify molecular structure. This technique is a nondestructive analysis and needs no sample preparation. Recently, Raman spectroscopy has been shown to be effective as a multipurpose analytical method for forensic applications. In the present study, blood identification and discrimination between human and nonhuman blood were performed by a portable Raman spectrometer, which can be used at a crime scene. To identify the blood and to discriminate between human and nonhuman blood, Raman spectra of bloodstains from 11 species (human, rat, mouse, cow, horse, sheep, pig, rabbit, cat, dog, and chicken) were taken using a portable Raman spectrometer. Raman peaks for blood (742, 1001, 1123, 1247, 1341, 1368, 1446, 1576, and 1619 cm-1) could be observed by the portable Raman spectrometer in all 11 species, and the human bloodstain could be distinguished from the nonhuman ones by using a principal component analysis. This analysis can be performed on a bloodstain sample of at least 3 months old. The portable Raman spectrometer can be used at a crime scene, and this analysis is useful for forensic examination.

Multicenter randomized phase II study of cisplatin and fluorouracil plus docetaxel (DCF) compared with cisplatin and fluorouracil plus Adriamycin (ACF) as preoperative chemotherapy for resectable esophageal squamous cell carcinoma (OGSG1003).

BACKGROUND: This phase II trial evaluated the efficacy of cisplatin and fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an alternative regimen in a new phase III trial investigating the optimal neoadjuvant treatment of patients with ESCC. PATIENTS AND METHODS: Patients with resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 7 days) every 4 weeks or DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The primary end point was RFS, analyzed by the intention-to-treat. RESULTS: Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, all of whom were eligible and randomly assigned to the two groups (81 to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and DCF groups were equivalent (95.9% versus 96.2%, P = 0.93). The 2-year RFS and overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio 0.53, 95% confidence interval 0.33-0.83, P = 0.0057) and 78.6% versus 65.4% (P = 0.08), respectively. CONCLUSION: Compared with ACF, DCF chemotherapy was associated with prolonged RFS for patients with resectable advanced ESCC. Thus, DCF chemotherapy has potential as a standard neoadjuvant therapy for resectable ESCC. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN000004555/000004616).

Long-term prognosis of IgA nephropathy presenting with minimal or no proteinuria: A single center experience.

The long-term prognosis of patients with IgA nephropathy (IgAN) who present with preserved renal function and minimal proteinuria is not well described. We investigated the long-term outcomes of IgAN patients with an apparently benign presentation and evaluated prognostic factors for renal survival and clinical remission. We studied Japanese patients with biopsy-proven IgAN who had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and proteinuria <0.5 g/day at the time of renal biopsy. The renal biopsies were reviewed using the Oxford classification. Twenty patients met the inclusion criteria. At diagnosis, the median eGFR (interquartile range) was 76.8 (65.2-91.1) mL/min/1.73 m(2), and the median proteinuria level was 0.31 (0.16-0.39) g/day. Only one patient had an increase in serum creatinine of over 50% and no patient progressed to end-stage renal disease. The 15-year renal survival rate was 93.8%. Clinical remission was observed in 9 (45%) patients. Baseline proteinuria was the only factor significantly associated with the absence of clinical remission. The long-term prognosis of Japanese patients with IgAN who presents with minor urinary abnormalities and preserved renal function is excellent.

Effects of new over-the-counter periodontal ointment-containing applicator with single-tuft brush on cytokine levels in gingival crevicular fluid during supportive periodontal therapy phase: a randomized double-blind clinical trial.

BACKGROUND AND OBJECTIVE: The biochemical effects of an over-the-counter (OTC) medication were studied, which consists of a single-tuft brush containing cetylpyridinium chloride as a bactericidal agent, dipotassium glycyrrhizate as an anti-inflammatory drug and allantoin as a promoter of cell proliferation and wound healing, for delivery to hardly brushed sites. MATERIAL AND METHODS: This randomized controlled double-blind study was performed in 61 subjects with chronic periodontitis in supportive periodontal therapy phase (test group: n = 27; placebo group: n = 28; dropout: n = 6). The OTC medication was self-applied twice a day for 12 wk to two molars with probing pocket depths of 4-6 mm. Biochemical indicators were evaluated at baseline and 12 wk using the suspension array system for eight cytokines and chemokines (interleukin [IL]-1ß, IL-1ra, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 and tumor necrosis factor [TNF]-α) in gingival crevicular fluid. RESULTS: The levels of IL-1ß, IL-6, IL-8 and TNF-α remained significantly lower in the test group compared to the placebo group. In the placebo group, when the probing pocket depth at baseline was 4 mm, IL-1ß increased, particularly in the second molar tooth, and the greatest increase was seen when PPD at baseline was 5-6 mm. In the test group, IL-1ß decreased markedly in cases with furcation involvement and low bleeding on probing at baseline. In both groups, IL-1ß, IL-6 and TNF-α were closely correlated with each other. CONCLUSION: This OTC medication is biochemically effective for steady chronic periodontitis in the supportive periodontal therapy phase.

Automatic droplet transportation on a plastic microfluidic device having wettability gradient surface.

This paper presents a microfluidic device that can automatically transport a droplet on a plastic plate. This device consists of a Cyclo Olefin Polymer (COP) plate and a SiO2 membrane and has wettability gradient surface. Lithographic patterns of hydrophilic SiO2 permitted wettability modification of a hydrophobic COP surface. A series of alternate hydrophobic and hydrophilic wedge-shaped patterns generated a required gradient in wettability. When we dropped a droplet on the wettability gradient surface, it moved along the wettability gradient due to an imbalance between surface tension forces acting on the opposite sides of the droplet edge. The droplet transportation test was carried out using water of 5 µl. As a result, we succeeded in automatically transporting the droplet on the SiO2/COP wettability gradient pattern. We also carried out droplet transportation in an enclosed microchannel for preventing droplet evaporation using DI (Deionized) water of 5 µl. In this case, the droplet was automatically transported by forming the wettability gradient pattern at the top and bottom in an enclosed microchannel without evaporation.

Pro-inflammatory responses and oxidative stress induced by ZnO nanoparticles in vivo following intravenous injection.

OBJECTIVE: To determine the toxicological effect of ZnO nanoparticles (NPs), inflammatory responses, serum biological parameters and oxidative stress markers of Superoxide dismutase (SOD) were evaluated followed by intravenous treatment of ZnO NPs in mice. MATERIALS AND METHODS: Inflammatory responses induced by a dose of 0.2 mg/kg ZnO NPs, followed by a single intravenous treatment were examined in mice. In addition, the serum biological parameters and oxidative stress markers were evaluated. Blood and spleen were collected following treatment. The mRNA transcript levels of inflammatory-related genes (TNF-α and IL1-ß) were elevated in the spleen cells of mice treated with ZnO NPs at 12h. RESULTS: The elevated levels of TNF-α and IL1-ß in supernatants of spleen cell cultures of mice treated with ZnO NPs were also observed at 24h. The serum aspartate aminotransferase, glutamate pyruvate alanine aminotransferase, and lactate dehydrogenase levels significantly increased at 6h and 12h in ZnO NPs treated group, indicating liver cell injury and tissue damage. On the other hand, no elevation was observed in BUN and Cre, biochemical markers of kidney damage. SOD activities were significantly elevated at 24 h and 48 h. CONCLUSIONS: This study shows the ZnO induced pro-inflammatory response in vivo, that this response may be related to oxidative stress, and to show hepatic damage at an early stage.

Feasibility of a novel diagnostic chart of intramedullary spinal cord tumors in magnetic resonance imaging.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: Each type of intramedullary spinal cord tumor (IMSCT) has specific anatomical and pathological features visible on magnetic resonance (MR) imaging. The purpose of this study was to investigate the accuracy of preoperative IMSCT diagnosis using our diagnostic chart of tumor-specific MR imaging findings. SETTING: Hamamatsu, Japan. METHODS: From 2009 to 2013, 28 consecutive patients with IMSCT who underwent surgery in our university hospital were included in this study. There were 17 men and 11 women with an average age of 49 years (12-81). The pathological diagnoses were hemangioblastoma (12), ependymoma (11), astrocytoma (4) and squamous cell carcinoma (1). Tumor-specific MR imaging findings were as follows: ependymoma ((a) spinal cord swelling, (b) contrast effect with necrosis, (c) tumor in the center of the spinal cord), hemangioblastoma ((a) spinal cord swelling, (b) homogeneous contrast effect) and astrocytoma ((a) spinal cord swelling, (b) contrast effect is either, (c) eccentric tumor). Based on these features, we generated a diagnostic chart to investigate the MR imaging diagnosis accuracy for IMSCTs. RESULTS: The accuracy of preoperative diagnosis was 89% (25/28 cases). Correct diagnoses were made in 100% of hemangioblastomas (12/12 cases), 90% of ependymomas (9/11 cases) and 100% of astrocytomas (4/4 cases). CONCLUSIONS: Different types of IMSCTs exhibit unique MR imaging characteristics. These features can be used to preoperatively diagnose IMSCTs with high accuracy.

Blockade of IL-6 signaling by MR16-1 inhibits reduction of docosahexaenoic acid-containing phosphatidylcholine levels in a mouse model of spinal cord injury.

The interleukin (IL)-6 pathway plays an important role in recovery after spinal cord injury (SCI). The anti-IL-6 receptor antibody MR16-1 has been shown to suppress inflammation after SCI and promote recovery of motor function. The purpose of this study was to analyze the effects of MR16-1 on the expression patterns of phospholipids in the spinal cord in a mouse model of SCI. Eight-week-old C57BL/6JJmsSlc mice were used in this study. Laminectomy was performed at the ninth and tenth thoracic levels (T9-T10), and contusion injury of the spinal cord was induced at level T10. Immediately after SCI, mice were intraperitoneally injected with a single dose of MR16-1 (MR16-1 group) or a single dose of phosphate-buffered saline of the same volume (control group). Imaging mass spectrometry was performed to visualize phosphatidylcholine (PC) expression in the spinal cord 7 days after SCI. We found that MR16-1 treatment suppressed the infiltration of immune cells after SCI, and was able to increase the locomotor function post-injury. Phospholipid imaging revealed that the MR16-1 was able to prevent the reduction of docosahexaenoic acid (DHA)-containing PC in comparison with the control group. We also observed high levels of glial fibrillary acidic protein (GFAP) at the site of DHA-containing PC expression in the MR16-1 group. These results suggest that MR16-1 treatment influences the DHA-containing PC composition of GFAP-positive cells at the injury site as early as 7 days post-SCI.

Effects of low-intensity, elastic band resistance exercise combined with blood flow restriction on muscle activation.

We examined the effects of blood flow-restricted, low-intensity resistance exercise (termed kaatsu) using an elastic band for resistance on muscle activation. Nine men performed triceps extension and biceps flexion exercises (four sets respectively) using an elastic band for resistance with blood flow restriction (BFR) or CON (unrestricted blood flow). During a BFR session, subjects wore pressure cuffs inflated to 170-260 mmHg on the proximal region of both arms. Surface electromyography (EMG) was recorded from the triceps brachii and biceps brachii muscles, and mean integrated EMG (iEMG) was analyzed. Blood lactate concentration was obtained before (Pre) and immediately after two exercises (Post). During triceps extension and biceps flexion exercises, muscle activation increased progressively (P < 0.05) under BFR (46% and 69%, respectively) but not under CON (12% and 23%, respectively). Blood lactate concentration at Post was higher (P < 0.05) under BFR than under CON (3.6 and 2.1 mmol/L, respectively). Blood lactate concentration at Post was significantly correlated with increased iEMG in both triceps extension (r = 0.65, P < 0.01) and biceps flexion exercises (r = 0.52, P < 0.05). We conclude that kaatsu training using elastic bands for resistance enhances muscle activation and may be an effective method to promote muscle hypertrophy in older adults or patients with a low level of activity.

Muscle size and arterial stiffness after blood flow-restricted low-intensity resistance training in older adults.

Previous studies have shown that blood flow-restricted low-intensity resistance training (BFR-RT) causes muscle hypertrophy while maintaining arterial function in young adults. We examined the effects of BFR-RT on muscle size and arterial stiffness in older adults. Healthy subjects (ages 61-84 years) were divided into BFR-RT (n = 9) or non-training control (CON; n = 10) groups. The BFR-RT group performed 20% and 30%, respectively, of one-repetition maximal (1-RM) knee extension and leg press exercises, 2 days/wk for 12 weeks. The BFR-RT group wore elastic cuffs (120-270 mmHg) on both legs during training. Magnetic resonance imaging-measured muscle cross-sectional area (CSA), 1-RM strength, chair stand (CS) test, and cardio-ankle vascular index testing (CAVI), an index of arterial stiffness, were measured before and 3-5 days after the final training session. Muscle CSA of the quadriceps (8.0%), adductors (6.5%), and gluteus maximus (4.4%), leg extension and leg press 1-RM strength (26.1% and 33.4%), and CS performance (18.3%) improved (P < 0.05) in the BFR-RT group, but not in the CON group. In CAVI testing, there were no changes in both two groups. In conclusion, BFR-RT improves muscle CSA as well as maximal muscle strength, but does not negatively affect arterial stiffness or humeral coagulation factors in older adults.

Responses of community structure of amoA-encoding archaea and ammonia-oxidizing bacteria in ammonia biofilter with rockwool mixtures to the gradual increases in ammonium and nitrate.

AIMS: To investigate community shifts of amoA-encoding archaea (AEA) and ammonia-oxidizing bacteria (AOB) in biofilter under nitrogen accumulation process. METHODS AND RESULTS: A laboratory-scale rockwool biofilter with an irrigated water circulation system was operated for 436 days with ammonia loading rates of 49-63 NH(3) g m(-3) day(-1). The AEA and AOB communities were investigated by denaturing gradient gel electrophoresis, sequencing and real-time PCR analysis based on amoA genes. The results indicated that changes in abundance and community compositions occurred in a different manner between archaeal and bacterial amoA during the operation. However, both microbial community structures mainly varied when free ammonia (FA) concentrations in circulation water were increasing, which caused a temporal decline in reactor performance. Dominant amoA sequences after this transition were related to Thaumarchaeotal Group I.1b, Nitrosomonas europaea lineages and one subcluster within Nitrosospira sp. cluster 3, for archaea and bacteria, respectively. CONCLUSIONS: The specific FA in circulation water seems to be the important factor, which relates to the AOB and AEA community shifts in the biofilter besides ammonium and pH. SIGNIFICANCE AND IMPACT OF THE STUDY: One of the key factors for regulating AEA and AOB communities was proposed that is useful for optimizing biofiltration technology.

Gamma-ray irradiation promotes premature meiosis of spontaneously differentiating testis-ova in the testis of p53-deficient medaka (Oryzias latipes).

In this study, the roles of p53 in impaired spermatogenic male germ cells of p53-deficient medaka were investigated by analyzing histological changes, and gene expressions of 42Sp50, Oct 4 and vitellogenin (VTG2) by RT-PCR or in situ hybridization in the testes. We found that a small number of oocyte-like cells (testis-ova) differentiated spontaneously in the cysts of type A and early type B spermatogonia in the p53-deficient testes, in contrast to the wild-type (wt) testes in which testis-ova were never found. Furthermore, ionizing radiation (IR) irradiation increased the number of testis-ova in p53-deficient testes, increased testis-ova size and proceeded up to the zygotene or pachytene stages of premature meiosis within 14 days after irradiation. However, 28 days after irradiation, almost all the testis-ova were eliminated presumably by p53-independent apoptosis, and spermatogenesis was restored completely. In the wt testis, IR never induced testis-ova differentiation. This is the first study to demonstrate the pivotal role of the p53 gene in the elimination of spontaneous testis-ova in testes, and that p53 is not indispensable for the restoration of spermatogenesis in the impaired testes in which cell cycle regulation is disturbed by IR irradiation.

Recent progress in gene therapy for Parkinson's disease.

Parkinson's disease (PD) is an age-related and the second most common neurodegenerative disorder beyond Alzheimer's disease. A neuropathological hallmark of PD is a prominent loss of dopaminergic neurons in the substantia nigra projecting into the caudate and putamen. Oral administration of L-dopa and/or dopamine agonists ameliorates cardinal motor symptoms of PD. However, an intermittent and long-term treatment with L-dopa frequently induces adverse side effects such as motor fluctuations and dyskinesia. As alternative therapeutic strategies, the following four approaches are currently under evaluation for clinical gene therapy trials in PD; 1) recombinant adeno-associated virus 2 system encoding aromatic L-amino acid decarboxylase (AADC), 2) glutamic acid decarboxylase (GAD) and 3) Neurturin, and 4) equine infectious anemia virus-based lentiviral system encoding AADC, tyrosine hydroxylase (TH) and GTP cyclohydrolase I (GCH) in a single transcriptional unit. GAD and Neurturin have been assessed in double blind placebocontrolled phase II studies; GAD showed a significant improvement in motor function, and Neurturin, although it failed to show significant effects at 12 months post-treatment, exhibited promising outcomes in additional examinations at 18 months. The other two approaches also represented significant effects in phase I or I/II studies. Adverse side effects due to surgery have not been observed. Here, we review preclinical and clinical trials encouraging further investigations of curative treatment for the patients suffering from PD.

Muenke syndrome mutation, FgfR3P²44R, causes TMJ defects.

Muenke syndrome is characterized by various craniofacial deformities and is caused by an autosomal-dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3(P250R) ). Here, using mice carrying a corresponding mutation (FgfR3(P244R) ), we determined whether the mutation affects temporomandibular joint (TMJ) development and growth. In situ hybridization showed that FgfR3 was expressed in condylar chondroprogenitors and maturing chondrocytes that also expressed the Indian hedgehog (Ihh) receptor and transcriptional target Patched 1(Ptch1). In FgfR3(P244R) mutants, the condyles displayed reduced levels of Ihh expression, H4C-positive proliferating chondroprogenitors, and collagen type II- and type X-expressing chondrocytes. Primary bone spongiosa formation was also disturbed and was accompanied by increased osteoclastic activity and reduced trabecular bone formation. Treatment of wild-type condylar explants with recombinant FGF2/FGF9 decreased Ptch1 and PTHrP expression in superficial/polymorphic layers and proliferation in chondroprogenitors. We also observed early degenerative changes of condylar articular cartilage, abnormal development of the articular eminence/glenoid fossa in the TMJ, and fusion of the articular disc. Analysis of our data indicates that the activating FgfR3(P244R) mutation disturbs TMJ developmental processes, likely by reducing hedgehog signaling and endochondral ossification. We suggest that a balance between FGF and hedgehog signaling pathways is critical for the integrity of TMJ development and for the maintenance of cellular organization.

Biophysical properties of Na(v) 1.8/Na(v) 1.2 chimeras and inhibition by µO-conotoxin MrVIB.

BACKGROUND AND PURPOSE: Voltage-gated sodium channels are expressed primarily in excitable cells and play a pivotal role in the initiation and propagation of action potentials. Nine subtypes of the pore-forming α-subunit have been identified, each with a distinct tissue distribution, biophysical properties and sensitivity to tetrodotoxin (TTX). Na(v) 1.8, a TTX-resistant (TTX-R) subtype, is selectively expressed in sensory neurons and plays a pathophysiological role in neuropathic pain. In comparison with TTX-sensitive (TTX-S) Na(v) α-subtypes in neurons, Na(v) 1.8 is most strongly inhibited by the µO-conotoxin MrVIB from Conus marmoreus. To determine which domain confers Na(v) 1.8 α-subunit its biophysical properties and MrVIB binding, we constructed various chimeric channels incorporating sequence from Na(v) 1.8 and the TTX-S Na(v) 1.2 using a domain exchange strategy. EXPERIMENTAL APPROACH: Wild-type and chimeric Na(v) channels were expressed in Xenopus oocytes, and depolarization-activated Na⁺ currents were recorded using the two-electrode voltage clamp technique. KEY RESULTS: MrVIB (1 µM) reduced Na(v) 1.2 current amplitude to 69 ± 12%, whereas Na(v) 1.8 current was reduced to 31 ± 3%, confirming that MrVIB has a binding preference for Na(v) 1.8. A similar reduction in Na⁺ current amplitude was observed when MrVIB was applied to chimeras containing the region extending from S6 segment of domain I through the S5-S6 linker of domain II of Na(v) 1.8. In contrast, MrVIB had only a small effect on Na⁺ current for chimeras containing the corresponding region of Na(v) 1.2. CONCLUSIONS AND IMPLICATIONS: Taken together, these results suggest that domain II of Na(v) 1.8 is an important determinant of MrVIB affinity, highlighting a region of the α-subunit that may allow further nociceptor-specific ligand targeting.