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Background: In the context of the coronavirus disease 2019 (COVID-19) pandemic, a rapid and reliable point-of-care test is an essential tool for controlling the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In particular, an immunochromatography test (ICT) that uses saliva specimens for rapid antigen detection not only reduces the risk of secondary infections but also reduces the burden on medical personnel., Methods: The newly developed salivary antigen test kit "Inspecter Kowa® SARS-CoV-2" is an ICT to which saliva specimens can be directly applied. We evaluated its usefulness in comparison with reverse transcription quantitative PCR (RT-qPCR) and the Espline® SARS-CoV-2 Kit for the detection of SARS-CoV-2 using nasopharyngeal swab specimens. In this study, 140 patients with suspected symptomatic COVID-19 who visited our hospital were enrolled, and nasopharyngeal swab and saliva specimens were collected after they consented to participate in the study., Results: Inspector Kowa SARS-CoV-2 was positive in 45 of 61 (73.8%) saliva that were positive by RT-qPCR and the Espline® SARS-CoV-2 Kit was also positive in 56 of 60 (93.3%) Np swabs that were positive by RT-qPCR. Good antigen detection was achieved by ICT with saliva and nasopharyngeal swab specimens when viral load was ≥10 5 copies/mL, whereas detection sensitivity was low when viral load was <10 5 copies/mL, especially in saliva specimens., Conclusion: This ICT for the detection of SARS-CoV-2 salivary antigen is an attractive tool that does not require specialized equipment and allows patients to perform the entire process from sample collection to self-diagnose and to reduce the burden on medical care during a pandemic., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Okadaic acid (OA) group are diarrheal shellfish poison that accumulates in the midgut glands of shellfish. It is difficult to remove these poisons by normal cooking because they are thermally stable and hydrophobicity. Therefore, in order to prevent foodborne disease due to shellfish poison, analysis by liquid chromatography (LC)-tandem mass spectrometry (MS/MS) before shipment is necessary. Herein the selective analytical method for OA group in shellfish sample using fluorous derivatization coupled with LC-MS/MS was developed. OA group were derivatized with the fluorous alkylamine reagent by condensing agent, and the obtained derivatives were separated with fluorous LC column (Fluofix-II 120E, 250 × 2.0 mm i.d., 5 μm, Fujifilm Wako Pure Chemical). The derivatized OA group were selective retained by fluorous LC column and accurate analysis was enabled. The present method was applied to the analysis of OA and dinophysistoxin-1 (DTX-1) in scallop midgut gland which is the certified reference material provided by national metrology institute of Japan. As a result of analysis using the present method with DTX-2 as the internal standard, the quantitative value were in agreement with the certified value., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We report the transient response of gliding microtubules on a virtual cathode. In vivo activities, microtubule-kinesin systems are known to act as motor proteins with respect to cell motility cytokinesis and cellular transport by hydrolyzing ATP molecules. With development of in vitro assays, motor proteins have been attracting much attention as a key component for highly efficient nano-transportation systems. The molecular functions based on structural states are affected by changing the ionic condition of the molecular functions and by changing the electrical field in solution because of electrical charges of the molecules. The virtual cathode, which was generated on the SiN display surface by a low energy electron beam, locally induced electrochemical reactions and electric field around the targeted molecules on the display surface, and then the gliding motions of the targeted microtubules were regulated. In this study, we demonstrated that the virtual cathode display temporally stops a selected gliding microtubule by only applying the virtual cathode to the microtubule. The pause mode of the microtubule was easily canceled by simply turning the virtual cathode off, and then the gliding motion was restarted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We report the case of acute myocardial infarction in a 25-year-old woman with sitosterolemia. She was treated using statins, but her low-density lipoprotein cholesterol (LDL-C) levels did not decrease appreciably. Genetic analysis revealed mutations in the ABCG8 gene. Ezetimibe treatment was initiated, and her LDL-C levels decreased substantially. Sitosterolemia must be considered in the differential diagnosis of familial hypercholesterolemia in case of early onset cardiovascular disease patient with high LDL-C., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Mutations in WDR45 are responsible for beta-propeller protein-associated neurodegeneration (BPAN), which is an X-linked form of neurodegeneration with brain iron accumulation. BPAN mainly affects females and is characterized by seizures and developmental delay or intellectual disability until adolescence or early adulthood, followed by severe dystonia, parkinsonism, and progressive dementia. However, rare male patients have recently been reported with hemizygous germline mutations in WDR45 and severe clinical manifestations, such as epileptic encephalopathies. We report here a 4-year-old boy presenting with profound developmental delay, non-syndromic epileptic encephalopathy, and early brain atrophy. The level of serum neuron specific enolase (NSE) was elevated, but the level of serum phosphorylated neurofilament heavy chain was not detectable. Targeted next-generation sequencing identified a de novo hemizygous splice donor site mutation, c.830+1G > A in WDR45, which resulted in a splicing defect evidenced by reverse transcriptase-PCR. Mutations in WDR45 should be considered as a cause for epileptic encephalopathies in males with profound developmental delay and brain atrophy. Furthermore, elevation of serum NSE may contribute to early diagnosis of BPAN., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: Lower heart rate variability (HRV) is associated with the inflammation that is linked with the progression of atherosclerosis. We examined this association, taking insulin sensitivity into consideration, as it is related to both HRV and inflammation., Methods: Subjects were 1728 individuals ages 30-79 years who did not smoke between 2009 and 2012. C-reactive protein (CRP) concentrations and white blood cell (WBC) counts were assessed as markers of inflammation. The homeostasis model assessment index for insulin resistance (HOMA-IR) and Gutt's insulin sensitivity index (ISI) were calculated based on fasting and 2h-post-load glucose and insulin concentrations in a 75-g oral glucose tolerance test. Pulse was recorded for 5 min, and time-domain HRV indices of standard deviation of NN intervals (SDNN) and root mean square of successive differences (RMSSD) were calculated. Power spectral analysis provided frequency domain measures of HRV: high frequency (HF) power, low frequency (LF) power and LF/HF., Results: Sex and age-adjusted logistic models presented quartiles of SDNN, RMSSD, LF, and HF significantly associated with the highest quartile of CRP or WBC. After adjustment for body mass index and ISI, the associations were attenuated for WBC; however, even after further adjustment for several variables, SDNN, RMSSD, LF, and HF remained significantly associated with elevated CRP concentrations. When results were stratified by weight, the associations appeared more evident among non-overweight individuals., Conclusion: Lowered HRV, primarily due to parasympathetic dysfunction, was associated with elevated inflammation, independent of weight, insulin sensitivity, and other related factors., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aims: There is a growing body of evidence suggesting that epigallocatechin gallate (EGCG), a major catechin isolated from green tea, has several beneficial effects, such as anti-oxidant and anti-inflammatory activities. However, whether treatment with EGCG can suppress the endothelin-1 (ET-1)-induced contraction in carotid arteries from type 2 diabetic rats is unknown, especially at the chronic stage of the disease. We hypothesized that long-term treatment with EGCG would attenuate ET-1-induced contractions in type 2 diabetic arteries., Main Methods: Otsuka Long-Evans Tokushima fatty (OLETF) rats (43 weeks old) were treated with EGCG (200 mg/kg/day for 2 months, p.o.), and the responsiveness to ET-1, phenylephrine (PE), acetylcholine (ACh) and sodium nitroprusside (SNP) was measured in common carotid artery (CA) from EGCG-treated and -untreated OLETF rats and control Long-Evans Tokushima Otsuka (LETO) rats., Key Findings: In OLETF rats, EGCG attenuated responsiveness to ET-1 in CA compared to untreated groups. However, EGCG did not alter PE-induced contractions in CA from OLETF rats. In endothelium-denuded arteries, EGCG did not affect ET-1-induced contractions in either the OLETF or LETO group. Acetylcholine-induced relaxation was increased by EGCG treatment in CA from the OLETF group. The expressions of ET receptors, endothelial nitric oxide synthase, superoxide dismutases, and gp91(phox) [an NAD(P)H oxidase component] in CA were not altered by EGCG treatment in either group., Significance: Our data suggest that, within the timescale investigated here, EGCG attenuates ET-1-induced contractions in CA from type 2 diabetic rats, and one of the mechanisms may involve normalizing endothelial function., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To determine an appropriate M-mode method in assessing left ventricular (LV) dyssynchrony in left bundle branch block (LBBB), and to assess feasibility of the method to predict cardiac resynchronization therapy (CRT) responses., Methods and Results: Fifty-one patients with LBBB were enrolled. Among them 31 patients underwent CRT. In addition to original septal to posterior wall motion delay (SPWMD), first peak-SPWMD was proposed as time of difference between the first septal displacement and the maximum displacement of the posterior. If an early septal point was not present, anatomical M-mode was used to visualize an early septal displacement spreading scan-area until inferoseptal wall. CRT responders were defined as LV end-systolic volume reduction (>15%) at 6 months after CRT. Twenty patients (65%) were identified as CRT responders. First peak-SPWMD in responders was significantly higher than those in nonresponders, although SPWMD did not differ between groups. Strong predicting ability of first peak-SPWMD was revealed (first peak-SPWMD: 80/90/83%; SPWMD: 35/100/58%), and area under the curve in receiver operating characteristic analysis of first peak-SPWMD (0.88) was significantly higher than that of SPWMD (0.61) (p<0.05)., Conclusion: In patients with LBBB, time differences between early septal and delayed displacement of posterolateral wall on M-mode images were the appropriate dyssynchrony parameter, and could improve the predictive ability for CRT responses., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

The properties of substrates and extracellular matrices (ECM) are important factors governing the functions and fates of mammalian adherent cells. For example, substrate stiffness often affects cell differentiation. At focal adhesions, clustered-integrin bindings link cells mechanically to the ECM. In order to quantitate the affinity between cell and substrate, the cell adhesion force must be measured for single cells. In this study, forcible detachment of a single cell in the vertical direction using AFM was carried out, allowing breakage of the integrin-substrate bindings. An AFM tip was fabricated into an arrowhead shape to detach the cell from the substrate. Peak force observed in the recorded force curve during probe retraction was defined as the adhesion force, and was analyzed for various types of cells. Some of the cell types adhered so strongly that they could not be picked up because of plasma membrane breakage by the arrowhead probe. To address this problem, a technique to reinforce the cellular membrane with layer-by-layer nanofilms composed of fibronectin and gelatin helped to improve insertion efficiency and to prevent cell membrane rupture during the detachment process, allowing successful detachment of the cells. This method for detaching cells, involving cellular membrane reinforcement, may be beneficial for evaluating true cell adhesion forces in various cell types., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims: Vector flow mapping (VFM) can be used to assess intraventricular hemodynamics quantitatively. This study assessed the magnitude of the suction flow kinetic energy with VFM and investigated the relation between left ventricular (LV) function and geometry in patients with an estimated elevated LV filling pressure., Materials and Methods: We studied 24 subjects with an elevated LV filling pressure (EFP group) and 36 normal subjects (normal group). Suction was defined as flow directed toward the apex during the period from soon after systolic ejection to before mitral inflow. The flow kinetic energy index was quantified as the sum of the product of the blood mass and velocity vector and its magnitude to the peak value was measured., Key Findings: Suction flow was observed in 12 (50%) EFP-group patients and 36 (100%) normal-group subjects. The magnitude of the suction kinetic energy index was significantly smaller in EFP versus normal group (2.7 ± 3.8 vs. 5.7 ± 4.4 g/s/cm(2), P<0.01). The EFP-group patients with suction had a smaller LV end-systolic volume (ESV) (P<0.01), greater ellipsoidal geometry (P<0.05) and untwisting rate (P<0.01) than the EFP-group patients without suction. A regression analysis indicated a significant linear relation between the suction kinetic energy index and LVEF (r=0.43, P=0.04), ESV (r=-0.40, P=0.05), eccentricity index (r=0.44, P=0.04), and untwisting rate (r=0.51, P=0.04)., Significance: The magnitude of the suction flow kinetic energy index derived from VFM may allow the quantitative assessment of the suction flow, which correlates with LV systolic function, geometry, and untwisting mechanics., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Novel 3-dimensional echocardiography with speckle tracking imaging (3D-STE) may have advantages in assessing left ventricular (LV) volume through a cardiac cycle. The feasibility of 3D-STE may be affected by image quality and LV morphology., Methods and Results: We studied 64 patients (38 men, age 55±12 years) who underwent cardiac magnetic resonance imaging (CMRI) and 3D-STE on the same day. LV end-diastolic volume (EDV) and end-systolic volume (ESV) were measured by both modalities. Imaging qualities were quantified in each of 6 LV segments by an imaging quality score (IQS) of 1-3, and scores were averaged (mean IQS) at end-diastole and end-systole. Compared to CMRI, 3D-STE showed a tendency to underestimate LV volume measurements, but not significantly (EDV: bias=-18±37ml; ESV: bias=-10±34ml), and measurements correlated well with those by CMRI (EDV: R=0.80, ESV: R=0.86, ejection fraction: R=0.75, p<0.001). The absolute differences of LVEDV and ESV between 3D-STE and CMRI correlated significantly with mean IQS (LVEDV, R=-0.35, p=0.005; LVESV, R=-0.30, p=0.02). Based on the medium value of LVEDV by CMRI (127ml), subjects were classified into the small (<127ml) and large LVEDV (≧127ml) groups. In the large LVEDV group, mean IQS significantly correlated with the absolute differences of LVEDV (mean IQS, r=-0.45, p=0.01), despite no significant correlation in the small LVEDV group., Conclusion: 3D-STE could measure LV volume as well as CMRI, however, its accuracy depends on the quality of the acquired image and particularly on enlargement of the left ventricle., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: The incremental prognostic impact on cardiovascular outcomes of assessment of carotid plaque ultrasound characteristics in addition to inflammatory biomarkers remains controversial in coronary artery disease (CAD) patients receiving optimal medical treatment. The present study prospectively compared carotid ultrasonic imaging with several biomarkers to stratify cardiovascular risk., Methods: One hundred and sixty patients with angiographically confirmed stable CAD underwent carotid ultrasonography and were prospectively followed with optimal medical therapy including statins. Carotid atherosclerotic burden was assessed by mean intima-media thickness (IMT) at the far-wall from the common carotid to proximal internal carotid artery. Carotid plaque echolucency was quantified by measuring gray-scale median value (GSM). Major cardiovascular event was defined as cardiovascular death, newly developed myocardial ischemia, or cerebrovascular infarction., Results: Of 154 subjects completing follow-up, 27 experienced a major cardiovascular event during a median 41-month follow-up period. Events comprised cardiovascular death (n = 6), newly developed myocardial ischemia (n = 16), and ischemic stroke (n = 5). Univariate Cox regression analysis showed C-reactive protein (CRP) and several ultrasonic parameters to be significant determinants for cardiovascular events. Multivariate Cox analysis determined CRP and plaque echolucency to be independent variables predicting cardiovascular events after adjustment for classic CAD risk factors. In Kaplan-Meier plots, patients with both high CRP (≥ 1.0mg/L) and echolucent plaque (GSM ≤ 65) showed higher event rates than did patients with high CRP but without echolucent plaque., Conclusion: Ultrasonic findings of echolucent carotid plaque may have incremental prognostic impact on risk assessment by CRP in CAD patients receiving contemporary optimal medical therapy., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To report the incidence, intraoperative findings, and surgical outcome of secondary ptosis that developed after a sub-Tenon injection of triamcinolone acetonide (TA)., Study Design: Retrospective, cross-sectional study., Participants: One hundred forty-seven cases with a total of 286 sub-Tenon TA injections., Methods: The medical records of 163 eyes of 147 cases treated with a sub-Tenon injection of 10 mg or 20 mg TA were reviewed. The incidence of secondary ptosis (palpebral fissure >2 mm narrower than that of the fellow eye) after a sub-Tenon TA injection was determined. The preoperative levator function and margin reflex distance (MRD) of the affected eyes, and the intraoperative findings in eyes that underwent reconstructive surgery, were evaluated., Results: Eight eyes (5%) developed secondary ptosis after the injection and 6 eyes were treated by reconstructive surgery. The preoperative levator function of the affected eyes did not differ from that of the fellow eyes. Intraoperatively, no septal disruption or fat herniation was noted, but an aponeurotic disinsertion was identified and repaired with an advancement of the leading edge to the anterior tarsal plate. The surgery led to satisfactory results, with improvement of the MRD from -1.3 (SD 1.5) mm preoperatively to 2.3 (SD 0.5) mm postoperatively (p = 0.027). Additional sub-Tenon TA injections were required in 2 eyes after eyelid surgery but the ptosis did not worsen., Conclusions: A sub-Tenon TA injection can occasionally cause ptosis by inducing a disinsertion of the levator aponeurosis. However, surgical reconstruction can lead to successful resolution of the ptosis.

Resistin, secreted from adipocytes, causes insulin resistance and diabetes in rodents. To determine the relation between serum resistin and diabetic microangiopathies in humans, we analyzed 238 Japanese T2DM subjects. Mean serum resistin was higher in subjects with either advanced retinopathy (preproliferative or proliferative) (P=0.0130), advanced nephropathy (stage III or IV) (P=0.0151), or neuropathy (P=0.0013). Simple regression analysis showed that serum resistin was positively correlated with retinopathy stage (P=0.0212), nephropathy stage (P=0.0052), and neuropathy (P=0.0013). Multiple regression analysis adjusted for age, gender, and BMI, revealed that serum resistin was correlated with retinopathy stage (P=0.0144), nephropathy stage (P=0.0111), and neuropathy (P=0.0053). Serum resistin was positively correlated with the number of advanced microangiopathies, independent of age, gender, BMI, and either the duration of T2DM (P=0.0318) or serum creatinine (P=0.0092). Therefore, serum resistin was positively correlated with the severity of microangiopathies in T2DM.

Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a neuron-specific ubiquitin recycling enzyme. A mutation at residue 93 and polymorphism at residue 18 within human UCH-L1 are linked to familial Parkinson's disease and a decreased Parkinson's disease risk, respectively. Thus, we constructed recombinant human UCH-L1 variants and examined their structure (using circular dichroism) and hydrolase activities. We confirmed that an I93M substitution results in a decrease in kcat (45.6%) coincident with an alteration in alpha-helical content. These changes may contribute to the pathogenesis of Parkinson's disease. In contrast, an S18Y substitution results in an increase in kcat (112.6%) without altering the circular dichroistic spectrum. These data suggest that UCH-L1 hydrolase activity may be inversely correlated with Parkinson's disease risk and that the hydrolase activity is protective against the disease. Furthermore, we found that oxidation of UCH-L1 by 4-hydroxynonenal, a candidate for endogenous mediator of oxidative stress-induced neuronal cell death, results in a loss of hydrolase activity. Taken together, these results suggest that further studies of altered UCH-L1 hydrolase function may provide new insights into a possible common pathogenic mechanism between familial and sporadic Parkinson's disease.

The effect of a single exposure to Cd on DH was studied through exposure to Cd at different time intervals in relation to antigen administration. Exposure to Cd significantly suppressed the DH reaction, with a dose-response relationship, when administered 2 or 3 days after immunization of BALB/c and DBA/2 mice with sheep red blood cells. A strain difference in sensitivity to Cd was also demonstrated. These results suggest that a single exposure to Cd impairs the cellular immune response in mice.

The effects of cadmium (Cd) on the immune organs were examined histopathologically. On 2 or 3 days after a single i.p. injection of 1.8 mg Cd/kg body weight into mice, slight loss of body weight, significant decrease of thymus weight and marked increase of spleen weight were observed. Lymph node weight did not show any change. Histopathologically, cortical atrophy of the thymus was very marked. The white pulp of the spleen tended to diminish in size any many polymorphonuclear leukocytes and myeloid cells appeared in the red pulp.

A low-Mr copper (Cu) and zinc (Zn)-binding protein was present in the liver of a control water lizard Triturus pyrrhogaster. Cadmium (Cd) accumulated in the liver of the animals after intramuscular injections of Cd salt and was bound to Cu- and Zn-binding protein of a single isoform that had properties characteristic of metallothionein (MT). Effects of Cd loading on several essential elements in the liver and kidney were also determined.

Inhalation of 60% nitrous oxide in oxygen by seven adult male volunteers for 60 min was found to increase significantly polymorphonuclear leuocyte (PMN) chemotaxis, but not to influence total white or PMN blood cell counts. Also, the addition or morphine 0.2 mg kg-1 i.v. during the breathing of nitrous oxide did not alter any variable. These results indicate that nitrous oxide and nitrous oxide incombination with morphine do not depress PMN chemotaxis.