A Review of Robotic Interventional Neuroradiology.

Robotic interventional neuroradiology is an emerging field with the potential to enhance patient safety, reduce occupational hazards, and expand systems of care. Endovascular robots allow the operator to precisely control guidewires and catheters from a lead-shielded cockpit located several feet (or potentially hundreds of miles) from the patient. This has opened up the possibility of expanding telestroke networks to patients without access to life-saving procedures such as stroke thrombectomy and cerebral aneurysm occlusion by highly-experienced physicians. The prototype machines, first developed in the early 2000s, have evolved into machines capable of a broad range of techniques, while incorporating newly automated maneuvers and safety algorithms. In recent years, preliminary clinical research has been published demonstrating the safety and feasibility of the technology in cerebral angiography and intracranial intervention. The next step is to conduct larger, multisite, prospective studies to assess generalizability and, ultimately, improve patient outcomes in neurovascular disease.

Elevated expression of protease-activated receptor 1 via ΔNp63 down-regulation contributes to nodal metastasis in oral squamous cell carcinoma.

Protease-activated receptor 1 (PAR1) is known as a thrombin receptor. Recent studies have reported PAR1 expression in various malignancies; however, its role in oral squamous cell carcinoma (OSCC) requires clarification. A previous study showed that down-regulation of ΔNp63, a homolog of p53, augments PAR1 expression in OSCC. In the present study, the association of PAR1 expression with clinicopathological findings in OSCC was examined retrospectively. Expression of PAR1, thrombin, and ΔNp63 was examined immunohistochemically in OSCC specimens. Patients were divided into three groups based on the expression pattern of PAR1 at the invasive front: group A, PAR1-negative in both cancer and stromal cells; group B, positive in stromal cells but negative in cancer cells; group C, positive in both cancer and stromal cells. Histologically high-grade tumours were significantly more common in group C. Patients in group C had the highest incidence rate of nodal metastasis (P<0.001) and a lower survival rate (P=0.085) than those in the other groups. At the invasive front, in group C, thrombin was expressed but ΔNp63 expression was weak. These results indicate that increased PAR1 expression in both cancer and stromal cells could be a useful predictive marker of nodal metastasis and that ΔNp63 is involved in regulating PAR1 expression.

Influence of Olfactory Function on Appetite and Nutritional Status in the Elderly Requiring Nursing Care.

OBJECTIVE: To investigate olfactory function in elderly subjects requiring nursing care to clarify its association with appetite and nutritional status. SETTING: Facility for the elderly requiring nursing care. PARTICIPANTS: The subjects were 158 elderly people requiring nursing care and 37 elderly people not requiring nursing care. MEASUREMENTS: Experiment I: Olfactory function and factors (cognitive function, appetite, and nutritional status) that may be associated with it were compared between the elderly subjects requiring nursing care and those not requiring nursing care using covariance analysis in consideration of age. For evaluation, the OSIT-J was used for olfactory function, the HDS-R for cognitive function, the CNAQ for appetite, and BMI for nutritional status. Experiment II: The subjects were the same elderly subjects requiring nursing care in Experiment I, and food intake was surveyed in addition to the OSIT-J, HDS-R, CNAQ, and BMI. A univariate linear regression analysis was performed with OSIT-J as the response variable, and age, HDS-R, CNAQ, BMI, and food intake as the explanatory variables. RESULTS: Experiment I: On covariance analysis, the OSIT-J score was significantly lower for the elderly subjects requiring nursing care than for those not requiring nursing care (p<0.01). The mean score was 8 or lower in both groups, demonstrating lower olfactory function in both groups. Regarding factors that may be associated with olfactory function, a significant difference was noted in the HDS-R (p<0.01), confirming significantly lower cognitive function in the elderly subjects requiring nursing care. No significant difference was noted in the CNAQ or BMI. Experiment II: On a univariate linear regression analysis, an association with the OSIT-J was noted for age and HDS-R. Age was inversely correlated and the HDS-R was positively correlated. Factors associated with lower olfactory function in the elderly subjects requiring nursing were age and cognitive function, whereas appetite, nutritional status, and food intake were not associated. CONCLUSION: Olfactory function in elderly subjects requiring nursing care was poorer than that in those not requiring nursing care, suggesting that aging and cognitive decline are associated with lower olfactory function. In addition, no association of lower olfactory function with appetite, nutritional status, or food intake was noted in the elderly subjects requiring nursing care.

Precise absolute Seebeck coefficient measurement and uncertainty analysis using high-Tc superconductors as a reference.

The intrinsic properties of superconductors enable the direct determination of the absolute Seebeck coefficient at low temperature due to the disappearance of the Seebeck effect to obey the Meissner effect. We report a precision absolute Seebeck coefficient measurement for the fine Pt sample determined using the high-Tc YBa2Cu3O7-x (YBCO) superconductor as a reference and an analysis of the measurement uncertainty. To make a precision measurement and aid in the verification of the uncertainty components, we developed a cryostat system that enables temperature control in a stable manner. The expected performance of the reference superconductor yielded a zero value well below Tc, which was validated by a superconductor-superconductor thermocouple experiment. Uncertainty analysis shows that the main limiting factor for this measurement is the accuracy of the temperature difference measurement using the resistance temperature sensors, along with its analog noise. We obtained values of S = 5.6 ± 0.2 µV/K with a relative expanded uncertainty of 3% at 80 K and precisely compared the Pt value with that determined by the high-Tc Bi2Sr2Ca2Cu3O8+δ (Bi-2223) superconductor, which has a higher Tc. We found that there was no difference between the Seebeck coefficient values obtained from the YBCO and Bi-2223 references up to its Tc within the expanded measurement uncertainties of 0.3 µV/K (2σ). These results provide accurate validation that the high-Tc superconductor is a useful reference up to the liquid nitrogen temperature.

New neurons use Slit-Robo signaling to migrate through the glial meshwork and approach a lesion for functional regeneration.

After brain injury, neural stem cell-derived neuronal precursors (neuroblasts) in the ventricular-subventricular zone migrate toward the lesion. However, the ability of the mammalian brain to regenerate neuronal circuits for functional recovery is quite limited. Here, using a mouse model for ischemic stroke, we show that neuroblast migration is restricted by reactive astrocytes in and around the lesion. To migrate, the neuroblasts use Slit1-Robo2 signaling to disrupt the actin cytoskeleton in reactive astrocytes at the site of contact. Slit1-overexpressing neuroblasts transplanted into the poststroke brain migrated closer to the lesion than did control neuroblasts. These neuroblasts matured into striatal neurons and efficiently regenerated neuronal circuits, resulting in functional recovery in the poststroke mice. These results suggest that the positioning of new neurons will be critical for functional neuronal regeneration in stem/progenitor cell-based therapies for brain injury.

Significant association of increased PD-L1 and PD-1 expression with nodal metastasis and a poor prognosis in oral squamous cell carcinoma.

Programmed cell death ligand 1 (PD-L1) and its receptor PD-1 are immune checkpoint molecules that attenuate the immune response. Blockade of PD-L1 enhances the immune response in a variety of tumours and thus serves as an effective anti-cancer treatment. However, the biological and prognostic roles of PD-L1/PD-1 signalling in oral squamous cell carcinoma (OSCC) remain to be elucidated. The purpose of this study was to examine the correlation of PD-L1/PD-1 signalling with the prognosis of OSCC patients to assess its potential therapeutic relevance. The expression of PD-L1 and of PD-1 was determined immunohistochemically in 97 patients with OSCC and the association of this expression with clinicopathological characteristics was examined. Increased expression of PD-L1 was found in 64.9% of OSCC cases and increased expression of PD-1 was found in 61.9%. Univariate and multivariate analysis revealed that increased expression of PD-L1 and PD-1 positively correlated with cervical lymph node metastasis. The expression of CD25, an activated T-cell marker, was negatively correlated with the labelling index of PD-L1 and PD-1. Moreover, the patient group with PD-L1-positive and PD-1-positive expression showed a more unfavourable prognosis than the group with PD-L1-negative and PD-1-negative expression. These data suggest that increased PD-L1 and PD-1 expression is predictive of nodal metastasis and a poor prognosis and is possibly involved in cancer progression via attenuating the immune response.

Identification of patterns of factors preceding severe or life-threatening asthma exacerbations in a nationwide study.

BACKGROUND: Reducing near-fatal asthma exacerbations is a critical problem in asthma management. OBJECTIVES: To determine patterns of factors preceding asthma exacerbations in a real-world setting. METHODS: In a nationwide prospective study of 190 patients who had experienced near-fatal asthma exacerbation, cluster analysis was performed using asthma symptoms over the 2-week period before admission. RESULTS: Three distinct clusters of symptoms were defined employing the self-reporting of a visual analogue scale. Cluster A (42.1%): rapid worsening within 7.4 hours from moderate attack to admission, young to middle-aged patients with low Body mass index and tendency to depression who had stopped anti-asthma medications, smoked, and hypersensitive to environmental triggers and furred pets. Cluster B (40.0%): fairly rapid worsening within 48 hours, mostly middle-aged and older, relatively good inhaled corticosteroid (ICS) or ICS/long-acting beta-agonist (LABA) compliance, and low perception of dyspnea. Cluster C (17.9%): slow worsening over 10 days before admission, high perception of dyspnea, smokers, and chronic daily mild-moderate symptoms. There were no differences in overuse of short-acting beta-agonists, baseline asthma severity, or outcomes after admission for patients in these 3 clusters. CONCLUSION: To reduce severe or life-threatening asthma exacerbation, personalized asthma management plans should be considered for each cluster. Improvement of ICS and ICS/LABA compliance and cessation of smoking are important in cluster A. To compensate for low perception of dyspnea, asthma monitoring of peak expiratory flow rate and/or exhaled nitric oxide would be useful for patients in cluster B. Avoidance of environmental triggers, increase usual therapy, or new anti-type 2 response-targeted therapies should be considered for cluster C.

Population differences in S-warfarin pharmacokinetics among African Americans, Asians and whites: their influence on pharmacogenetic dosing algorithms.

Using population pharmacokinetic analysis (PPK), we attempted to identify predictors of S-warfarin clearance (CL(S)) and to clarify population differences in S-warfarin pharmacokinetics among a cohort of 378 African American, Asian and white patients. Significant predictors of CL(S) included clinical (age, body weight and sex) and genotypic (CYP2C9*2,*3 and *8) factors, as well as African American ethnicity, the median CL(S) being 30% lower in the latter than in Asians and whites (170 versus 243 and 250 ml h-1, P<0.01). The plasma S-warfarin (Cp(S)) time courses following the genotype-based dosing algorithms simulated using the PPK estimates showed African Americans with CYP2C9*1/*1 and any of the VKORC1 genotypes would have an average Cp(S) at steady state 1.5-1.8 times higher than in Asians and whites. These results indicate warfarin dosing algorithms should be evaluated in each respective ethnic population. Further study of a large African American cohort will be necessary to confirm the present findings.

Severe or life-threatening asthma exacerbation: patient heterogeneity identified by cluster analysis.

BACKGROUND: Severe or life-threatening asthma exacerbation is one of the worst outcomes of asthma because of the risk of death. To date, few studies have explored the potential heterogeneity of this condition. OBJECTIVES: To examine the clinical characteristics and heterogeneity of patients with severe or life-threatening asthma exacerbation. METHODS: This was a multicentre, prospective study of patients with severe or life-threatening asthma exacerbation and pulse oxygen saturation < 90% who were admitted to 17 institutions across Japan. Cluster analysis was performed using variables from patient- and physician-orientated structured questionnaires. RESULTS: Analysis of data from 175 patients with severe or life-threatening asthma exacerbation revealed five distinct clusters. Cluster 1 (n = 27) was younger-onset asthma with severe symptoms at baseline, including limitation of activities, a higher frequency of treatment with oral corticosteroids and short-acting beta-agonists, and a higher frequency of asthma hospitalizations in the past year. Cluster 2 (n = 35) was predominantly composed of elderly females, with the highest frequency of comorbid, chronic hyperplastic rhinosinusitis/nasal polyposis, and a long disease duration. Cluster 3 (n = 40) was allergic asthma without inhaled corticosteroid use at baseline. Patients in this cluster had a higher frequency of atopy, including allergic rhinitis and furred pet hypersensitivity, and a better prognosis during hospitalization compared with the other clusters. Cluster 4 (n = 34) was characterized by elderly males with concomitant chronic obstructive pulmonary disease (COPD). Although cluster 5 (n = 39) had very mild symptoms at baseline according to the patient questionnaires, 41% had previously been hospitalized for asthma. CONCLUSIONS & CLINICAL RELEVANCE: This study demonstrated that significant heterogeneity exists among patients with severe or life-threatening asthma exacerbation. Differences were observed in the severity of asthma symptoms and use of inhaled corticosteroids at baseline, and the presence of comorbid COPD. These findings may contribute to a deeper understanding and better management of this patient population.

Log-normal diameter distribution of Pd-based metallic glass droplet and wire.

We have studied the formation of Pd42.5Cu30Ni7.5P20 metallic glass droplets and wires in the gas atomization process. We demonstrate that the sizes of droplets and wires can be distinguished by the Ohnesorge number (Oh), which is the proportion of the spinnability to the capillary instability, and the diameter distributions follow a log-normal distribution function, implying cascade fragmentation. For droplets, the number significantly increases at Oh < 1 but the diameter gradually decreases. For wires, the number greatly increases at Oh > 1 while the diameter steadies below 400 nm. Further, the wire diameter is quadrupled at Oh = 16 due to the high viscosity which suppresses both capillary breakup and ligament elongation.

Characterization of swine leukocyte antigen alleles and haplotypes on a novel miniature pig line, Microminipig.

Microminipigs are extremely small-sized, novel miniature pigs that were recently developed for medical research. The inbred Microminipigs with defined swine leukocyte antigen (SLA) haplotypes are expected to be useful for allo- and xenotransplantation studies and also for association analyses between SLA haplotypes and immunological traits. To establish SLA-defined Microminipig lines, we characterized the polymorphic SLA alleles for three class I (SLA-1, SLA-2 and SLA-3) and two class II (SLA-DRB1 and SLA-DQB1) genes of 14 parental Microminipigs using a high-resolution nucleotide sequence-based typing method. Eleven class I and II haplotypes, including three recombinant haplotypes, were found in the offspring of the parental Microminipigs. Two class I and class II haplotypes, Hp-31.0 (SLA-1*1502-SLA-3*070102-SLA-2*1601) and Hp-0.37 (SLA-DRB1*0701-SLA-DQB1*0502), are novel and have not so far been reported in other pig breeds. Crossover regions were defined by the analysis of 22 microsatellite markers within the SLA class III region of three recombinant haplotypes. The SLA allele and haplotype information of Microminipigs in this study will be useful to establish SLA homozygous lines including three recombinants for transplantation and immunological studies.

Serum antibody to Porphyromonas gingivalis in chronic kidney disease.

Potentially significant associations between periodontal disease and chronic kidney disease (CKD) have been reported in recent studies. The aim of this cross-sectional study was to investigate the association between serum antibody to the periodontal pathogen Porphyromonas gingivalis (P. gingivalis) and CKD in 215 Japanese individuals, aged 79 yrs. Serum antibody levels to P. gingivalis were measured by enzyme-linked immunosorbent assay. An elevated serum antibody response was defined as the upper quartile and was compared with the bottom three quartiles. Participants were classified as having CKD when their glomerular filtration rate was between 15 and 59 mL/min/1.73 m(2). A multivariable logistic regression model was used to evaluate the association between elevated antibody status and the presence of CKD. Study participants with an elevated serum antibody to P. gingivalis were 2.6 times more likely to have CKD. The adjusted odds ratio of CKD for participants in the highest quartile of serum antibody to P. gingivalis was 2.59 (95% confidence interval, 1.05-6.34) when compared with others in lower quartiles after simultaneous adjustment for other covariates. In conclusion, the present study suggests that elevated serum antibody to P. gingivalis was significantly associated with decreased kidney function in a community-based cohort of elderly Japanese.

Tablets containing a cysteine protease, actinidine, reduce oral malodor: a crossover study.

Tongue coating (TC) mainly consists of protein mostly from exfoliated epithelial cells. Until now, to reduce TC accumulation, only mechanical measures have been available, and the procedure involves unpleasant side effects, such as gagging reflex or carcinogenesis related to mechanical stimulation. We expected that protease might be effective in reducing the accumulation of TC causing oral malodor. The purpose of this study was to determine the effect of long-term use of candy tablets containing protease, actinidine, on both TC accumulation and concentration of volatile sulfur compounds (VSCs) in mouth air. We employed 14 subjects aged 24 to 54 years old for this study, and conducted a double-blind randomized crossover trial. The subjects sucked the tablets containing actinidine three times a day until the sixth day after starting the study. The tablets without actinidine were utilized as a placebo. Measurements of VSC concentration and TC accumulation were carried out before and after chewing tablets on the first day, and also on the seventh day. The levels of VSC and TC significantly (p < 0.05) decreased after tablets were taken on the first day in both the test and placebo groups. There was a statistically significant decrease (p < 0.05) in VSC after seven days of use only in the test group. The results of the study suggest that the tablets containing actinidine had an accumulative effect in reducing VSC in mouth air with long-term use.

The effect of K201 on isolated working rabbit heart mechanical function during pharmacologically induced Ca2+ overload.

BACKGROUND AND PURPOSE: Reduced cardiac contractility has been associated with disrupted myocardial Ca(2+) signalling. The 1,4 benzothiazepine K201 (JTV-519) acts on several Ca(2+) handling proteins and improves cardiac contractility in vivo in a variety of animal models of myocardial dysfunction. However, it is unclear whether this improvement depends on the systemic effects of K201 or if K201 reverses the effects of Ca(2+) dysregulation, regardless of the cause. EXPERIMENTAL APPROACH: The effect of K201 on cardiac mechanical function was assessed in isolated working hearts from adult rabbits, using a ventricular pressure-volume catheter. In separate experiments, the effect of K201 was investigated in hearts following pharmacologically induced Ca(2+) overload using elevated extracellular [Ca(2+) ] ([Ca(2+) ](o) ) and ß-adrenoceptor stimulation. KEY RESULTS: K201 induced a concentration-dependent decline in systolic function (peak pressure, dP/dt(max) and preload recruitable stroke work), lusitropy (reduced dP/dt(min) and increased end diastolic pressure) and stroke volume, independent of decreased heart rate. In separate experiments, mechanical function in hearts exposed to 4.5 mmol·L(-1) [Ca(2+) ](o) and 150 nmol·L(-1) isoprenaline declined until cessation of aortic flow (in 6 out of 11 hearts). However, all hearts perfused with the addition of 1 µmol·L(-1) K201 maintained aortic flow and demonstrated significantly improved peak systolic pressures, dP/dt(max) and dP/dt(min) . CONCLUSIONS AND IMPLICATIONS: K201 significantly improved mechanical function of the heart during Ca(2+) overload. This suggests that K201 can limit the detrimental effects of elevated intracellular Ca(2+) and exert beneficial effects on cardiac contractile function, independent of systemic effects previously observed in vivo.

Examination of gas desorption by B4C resin for use in neutron scattering experiment.

Gas desorption rates for several types of B(4)C resins were investigated using a throughput method. The investigation was particularly focused on determining the out gas composition, effects of dry air, grain size (density) effects on the gas desorption rates. It is found that water is the main component of out gas and that dry air can effectively reduce gas desorption.

K201 (JTV-519) alters the spatiotemporal properties of diastolic Ca(2+) release and the associated diastolic contraction during ß-adrenergic stimulation in rat ventricular cardiomyocytes.

K201 has previously been shown to reduce diastolic contractions in vivo during ß-adrenergic stimulation and elevated extracellular calcium concentration ([Ca(2+)](o)). The present study characterised the effect of K201 on electrically stimulated and spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca(2+) release and contractile events in isolated rat cardiomyocytes during ß-adrenergic stimulation and elevated [Ca(2+)](o). Parallel experiments using confocal microscopy examined spontaneous diastolic Ca(2+) release events at an enhanced spatiotemporal resolution. 1.0 µmol/L K201 in the presence of 150 nmol/L isoproterenol (ISO) and 4.75 mmol/L [Ca(2+)](o) significantly decreased the amplitude of diastolic contractions to ~16% of control levels. The stimulated free Ca(2+) transient amplitude was significantly reduced, but stimulated cell shortening was not significantly altered. When intracellular buffering was taken into account, K201 led to an increase in action potential-induced SR Ca(2+) release. Myofilament sensitivity to Ca(2+) was not changed by K201. Confocal microscopy revealed diastolic events composed of multiple Ca(2+) waves (2-3) originating at various points along the cardiomyocyte length during each diastolic period. 1.0 µmol/L K201 significantly reduced the (a) frequency of diastolic events and (b) initiation points/diastolic interval in the remaining diastolic events to 61% and 71% of control levels respectively. 1.0 µmol/L K201 can reduce the probability of spontaneous diastolic Ca(2+) release and their associated contractions which may limit the propensity for the contractile dysfunction observed in vivo.

Behaviors of physiologically active bacteria in water environment and chlorine disinfection.

Direct microscopic methods using several fluorescent staining were applied to estimate the proportion of physiologically active bacteria in the water environment and evaluate the efficacy of disinfection with chlorine. 4',6-diamidino-2-phenylindole (DAPI) was used to determine total bacterial numbers, and 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) was chosen for direct detection of respiring bacteria. BacLight kit was used to assess bacterial membrane integrity. Bacteria with growth potential were enumerated using the DVC method and microcolony technique. The total bacterial number in river was 8 x 10(6)-3 x 10(10) cells/mL, and colony forming units on R2A medium were 1 x 10(4)-4 x 10(5) cfu/mL. In the case of wastewater treatment plant, 1-10% of total bacterial cells could form colonies. Physiologically active bacteria in river and wastewater treatment plant determined by fluorescent staining were much higher than those obtained by plate counting. The effect of chlorine on the physiological viability of Escherichia coli was also investigated. Microscopic viable bacteria were even more chlorine resistant than culturable bacteria. The inactivation rate coefficients of direct viable bacteria were one-second to third those of culturable bacteria.