Non-invasive hERG channel screening based on electrical impedance tomography and extracellular voltage activation (EIT-EVA).

hERG channel screening has been achieved based on electrical impedance tomography and extracellular voltage activation (EIT-EVA) to improve the non-invasive aspect of drug discovery. EIT-EVA screens hERG channels by considering the change in extracellular ion concentration which modifies the extracellular resistance in cell suspension. The rate of ion passing in cell suspension is calculated from the extracellular resistance Rex, which is obtained from the EIT measurement at a frequency of 500 kHz. In the experiment, non-invasive screening is applied by a novel integrated EIT-EVA printed circuit board (PCB) sensor to human embryonic kidney (HEK) 293 cells transfected with the human ether-a-go-go-related gene (hERG) ion channel, while the E-4031 antiarrhythmic drug is used for hERG channel inhibition. The extracellular resistance Rex of the HEK 293 cells suspension is measured by EIT as the hERG channels are activated by EVA over time. The Rex is reconstructed into extracellular conductivity distribution change Δσ to reflect the extracellular K+ ion concentration change Δc resulting from the activated hERG channel. Δc is increased rapidly during the hERG channel non-inhibition state while Δc is increased slower with increasing drug concentration cd. In order to evaluate the EIT-EVA system, the inhibitory ratio index (IR) was calculated based on the rate of Δc over time. Half-maximal inhibitory concentration (IC50) of 2.7 nM is obtained from the cd and IR dose-response relationship. The IR from EIT-EVA is compared with the results from the patch-clamp method, which gives R2 of 0.85. In conclusion, EIT-EVA is successfully applied to non-invasive hERG channel screening.

A noise-controlling method by hybrid current-stimulation and voltage-measurement for electrical impedance tomography (HCSVM-EIT).

Image reconstruction in electrical impedance tomography (EIT) is a typical ill-posed inverse problem, from which the stability of conductivity reconstruction affects the reliability of physiological parameters evaluation. In order to improve the stability, the effect of boundary voltage noise on conductivity reconstruction should be controlled. A noise-controlling method based on hybrid current-stimulation and voltage-measurement for EIT (HCSVM-EIT) is proposed for stable conductivity reconstruction. In HCSVM-EIT, the boundary voltage is measured by one current-stimulation and voltage-measurement pattern (high-SNRpattern) with a higher signal-to-noise ratio (SNR); the sensitivity matrix is calculated by another current-stimulation and voltage-measurement pattern (low-condpattern) with a lower condition number; the boundary voltage is then transformed from thehigh-SNRpattern into thelow-condpattern by multiplying by an optimized transformation matrix for image reconstruction. The stability of conductivity reconstruction is improved by combining the advantages of thehigh-SNRpattern for boundary voltage measurement and thelow-condpattern for sensitivity matrix calculation. The simulation results show that the HCSVM-EIT increases the correlation coefficient (CC) of conductivity reconstruction. The experiment results show that theCCof conductivity reconstruction of the human lower limb is increased from 0.3424 to 0.5580 by 62.97% compared to the quasi-adjacent pattern, and from 0.4942 to 0.5580 by 12.91% compared to the adjacent pattern. In conclusion, the stable conductivity reconstruction with higherCCin HCSVM-EIT improves the reliability of physiological parameters evaluation for disease detection.

"I Want My Loved One Back Virtually": Exploring the Desire of Bereaved People to Create and Maintain Digital Bonds With Their Deceased Loved Ones.

With the rapid development of digital technology in recent years, virtual funerals and the reproduction of deceased persons in digital spaces have become possible. However, few empirical studies have been conducted on this topic. This study assessed the attitudes of bereaved people toward digital bonds with their deceased relatives, and explored related factors. A survey was administered to bereaved, middle-aged Japanese citizens who had lost a first-degree relative within the previous 10 years. The results showed that most respondents did not seek digital bonds, but nearly 20% wanted to be reunited with their deceased in a digital space. The desire to maintain digital bonds was significantly related to other variables, such as the deceased's age and years since their death. Regression analysis revealed that the desire for digital bonds predicted complicated grief 5 months later. The findings suggest that digital bonds may influence post-bereavement maladjustment.

Feasibility of brief online gatekeeper training for Japanese university students: A randomized controlled trial.

Gatekeeper training for university students is a promising suicide prevention approach. However, there is a lack of comparative studies with control groups and the effectiveness of online gatekeeper training programs is unclear. We investigated the effectiveness of brief online gatekeeper training for Japanese university students. Participants were divided into two groups (training or control) and answered surveys at three time points (pretest, posttest, follow-up). The gatekeeper training improved students' knowledge. Skills were also improved post-training but returned to baseline level at follow-up. A brief online program may improve knowledge, but the effect is limited.

Non-invasive imaging of ion concentration distribution around cell spheroids by electrical impedance tomographic sensor printed on circuit board under temporal compensation by ion transport impedance model.

A non-invasive imaging called as PCB-EIT imaging has been proposed in order to image spatio-temporal ion concentration distribution around cell spheroids in 0.1 s of temporal resolution by a newly developed electrical impedance tomographic sensor printed on circuit board (PCB-EIT sensor). To realize the high temporal resolution in PCB-EIT imaging, the temporal compensation by the ion transport impedance model interpolating the extracted resistance of extracellular solution Rex obtained from the Cole-Cole equation is employed. To confirm the performance of PCB-EIT imaging, the ion concentration distribution around three cell spheroid types (GFP type (GFPT), Histone type (HT) and wild type (WT)) which are electrically different due to green fluorescent protein expressed in cytoplasm and nucleus of MRC-5. As a result, spatio-temporal ion concentration distributions due to ion transport from cell spheroid are successfully reconstructed by PCB-EIT imaging. The images by PCB-EIT imaging are validated with those by fluorescence ratio imaging within the distribution error εdis of 0.046 ± 0.0038 in maximum. For an evaluation of the ion diffusivity Dm of each cell spheroid type by the mass transfer simulation based on Fick's law, Dm of GFPT shows the highest value among the three cell types in the earlier time range from 4 s, while Dm of HT shows the highest one in the time range from 15 s, which indicates that PCB-EIT imaging is able to evaluate the ion transport characteristics of each cell type.

Simultaneous electrical online estimation of changes in blood hematocrit and temperature in cardiopulmonary bypass.

Two equations have been developed from multi-frequency measurements of blood impedance Zb for a simultaneous electrical online estimation of changes in blood hematocrit ΔH [%] and temperatures ΔT [K] in cardiopulmonary bypass (CPB). Zb of fixed blood volumes at varying H and T were measured by an impedance analyzer and changes in blood conductivity σb and relative permittivity εb computed. Correlation analysis were based on changes in σb with H or T at f = 1 MHz while H and T equations were developed by correlating changes in εb with H and T at dual frequencies of f = 1 MHz and f = 10 MHz which best capture blood plasma Zp and red blood cell cytoplasm Zcyt impedances respectively. Results show high correlations between σb and H (R2 = 0.987) or σb and T (R2 = 0.9959) indicating dependence of the electrical parameters of blood on its H and T. Based on computed εb, changes in blood hematocrit ΔH and temperature ΔT at a given time t are estimated as ΔH(t) = 1.7298Δεb (f = 1 MHz) - 1.0669Δεb (f = 10 MHz) and ΔT(t) = -2.186Δεb (f = 1 MHz) + 2.13Δεb (f = 10 MHz). When applied to a CPB during a canine mitral valve plasty, ΔH and ΔT had correlations of R2 = 0.9992 and R2 = 0.966 against H and T respectively as measured by conventional devices.

Study of transmembrane ion transport under tonicity imbalance using a combination of low frequency-electrical impedance spectroscopy (LF-EIS) and improved ion transport model.

Transmembrane ion transport under tonicity imbalance has been investigated using a combination of low frequency-electrical impedance spectroscopy (LF-EIS) and improved ion transport model, by considering the cell diameterd[m] and the initial intracellular ion concentrationcin[mM] as a function of tonicity expressed by sucrose concentrationcs[mM]. The transmembrane ion transport is influenced by extracellular tonicity conditions, leading to a facilitation/inhibition of ion passage through the cell membrane. The transmembrane transport coefficientP[m s-1], which represents the ability of transmembrane ion transport, is calculated by the extracellular ion concentrations obtained by improved ion transport model and LF-EIS measurement.Pis calculated as 4.11 × 10-6and 3.44 × 10-6m s-1atcsof 10 and 30 mM representing hypotonic condition, 2.44 × 10-6m s-1atcsof 50 mM representing isotonic condition, and 3.68 × 10-6, 5.16 × 10-6, 9.51 × 10-6, and 14.89 × 10-6m s-1atcsof 75, 100, 125 and 150 mM representing hypertonic condition. The LF-EIS results indicate that the transmembrane ion transport is promoted under hypertonic and hypotonic conditions compared to isotonic condition. To verify the LF-EIS results, fluorescence intensityF[-] of extracellular potassium ions is observed to obtain the temporal distribution of average potassium ion concentration within the region of 3.6µm from cell membrane interfacecROI[mM]. The slopes of ∆cROI/cROI1to timetare 0.0003, 0.0002, and 0.0006 under hypotonic, isotonic, and hypertonic conditions, wherecROI1denotes initialcROI, which shows the same tendency with LF-EIS result that is verified by the potassium ion fluorescence observation.

Suicide Attitudes Among Suicide Loss Survivors and Their Adaptation to Loss: A Cross-Cultural Study in Japan and the United States.

Survivors' adaptation to a suicide loss is likely influenced by their attitudes toward suicide and their respective sociocultural contexts. Our study aimed to compare suicide attitudes and their association with depressive symptoms and sense of community safety in Japanese and American suicide loss survivors. A total of 193 Japanese survivors and 232 American survivors completed online surveys. The results show that Japanese survivors tended not to consider suicide as an illness or to recognize that others understood their experience but were more likely than American survivors to consider suicide as justifiable. Regression analyses indicated that taking suicide as a right was associated with depressive symptoms. Further, their sense of being understood by others was positively correlated with perceived community safety in both samples, but justifying suicide and considering it to be an illness was positively related to perceived community safety only among Japanese survivors.

Grief literacy: A call to action for compassionate communities.

The compassionate communities movement challenges the notion that death and dying should be housed within clinical and institutional contexts, and works to normalize conversations about death and dying by promoting death literacy and dialogue in public spaces. Community-based practices and conversations about grief remain marginal in this agenda. We aimed to theorize how grief could be better conceptualized and operationalized within the compassionate communities movement. We develop the concept of Grief Literacy and present vignettes to illustrate a grief literate society. Grief literacy augments the concept of death literacy, thereby further enhancing the potential of the compassionate communities approach.

A High Accuracy Voltage Approximation Model Based on Object-oriented Sensitivity Matrix Estimation (OO-SME Model) in Electrical Impedance Tomography.

The image reconstruction in electrical impedance tomography (EIT) has low accuracy due to the approximation error between the measured voltage change and the approximated voltage change, from which the object cannot be accurately reconstructed and quantitatively evaluated. A voltage approximation model based on object-oriented sensitivity matrix estimation (OO-SME model) is proposed to reconstruct the image with high accuracy. In the OO-SME model, a sensitivity matrix of the object-field is estimated, and the sensitivity matrix change from the background-field to the object-field is estimated to optimize the approximated voltage change, from which the approximation error is eliminated to improve the reconstruction accuracy. Against the existing linear and nonlinear models, the approximation error in the OO-SME model is eliminated, thus an image with higher accuracy is reconstructed. The simulation shows that the OO-SME model reconstructs a more accurate image than the existing models for quantitative evaluation. The relative accuracy (RA) of reconstructed conductivity is increased up to 83.98% on average. The experiment of lean meat mass evaluation shows that the RA of lean meat mass is increased from 7.70% with the linear model to 54.60% with the OO-SME model. It is concluded that the OO-SME model reconstructs a more accurate image to evaluate the object quantitatively than the existing models.

In-vivoviscoelastic properties estimation in subcutaneous adipose tissue by integration of poroviscoelastic-mass transport model (pve-MTM) into wearable electrical impedance tomography (w-EIT).

In-vivoviscoelastic properties have been estimated in human subcutaneous adipose tissue (SAT) by integration of poroviscoelastic-mass transport model (pve-MTM) into wearable electrical impedance tomography (w-EIT) under the influence of external compressive pressure-P.Thepve-MTM predicts the ion concentration distributioncmod(t)by coupling the poroviscoelastic and mass transport model to describe the hydrodynamics, rheology, and transport phenomena inside SAT. Thew-EIT measures the time-difference conductivity distribution∆γ(t)in SAT resulted from the ion transport. Based on the integration, the two viscoelastic properties which are viscoelastic shear modulus of SATGvand relaxation time of SATτvare estimated by applying an iterative curve-fitting between the normalized average ion concentration distributioncˆmod(t)predicted frompve-MTM and the experimental normalized average ion concentration distributioncˆexp(t)derived fromw-EIT. Thein-vivoexperiments were conducted by applying external compressive pressure-Pon human calf boundary to induce interstitial fluid flow and ion movement in SAT. As a result, the value ofGvwas range from 4.9-6.3 kPa and the value ofτvwas range from 27.50-38.5 s with the value of average goodness-of-fit curve fittingR2 > 0.76. These values ofGvandτvwere compared to the human and animal tissue from the literature in order to verify this method. The results frompve-MTM provide evidence thatGvandτvplay a role in the predicted value ofcˆmod.

Concentration profiles of ions and particles under hydrodynamic focusing in Y-shaped square microchannel.

Three-dimensional ion and particle concentrations under hydrodynamic focusing in a Y-shaped square microchannel are numerically simulated to clarify the decrease of the ion concentration along the flow direction within the focused particle stream. The simulation model is theoretically governed by the laminar flow and advection-diffusion equations. The governing equations are solved by the finite volume method. The ion and particle concentration distributions at five cross sections after the confluence of the branch channels are analyzed in 30 cases in which the sheath to sample flow rate ratio Qsh/Qsam and the Reynolds number Re are varied as parameters. The results show that the decrease of the cross-sectional average ion concentration along the flow direction within the particle stream [Formula: see text] is described by the diffusion length during the residence time with a characteristic velocity scale. In addition, the deformation of the particle stream due to inertial effects is described by a scaled Reynolds number that is a function of the flow rate ratio. The simulated particle stream thicknesses are validated by theory and a simple experiment. This paper reveals the relationship between the ion and particle concentrations and the dimensionless parameters for hydrodynamic focusing in the Y-shaped square microchannel under typical conditions.

End-of-Life Activities Among Community-Dwelling Older Adults in Japan.

This study explored end-of-life (EOL) activities among community-dwelling Japanese older adults and the relationships between EOL activities and related variables. One hundred twenty-three older adults (38 men, 87 women; mean age = 72.54 years) who attended EOL seminars were surveyed regarding EOL activities, attitudes toward death, and mental health status. Cluster analysis of EOL activities revealed three clusters: Planning (e.g., had planned own funeral arrangements), Preference (e.g., had talked about EOL care with their family), and Preparation (e.g., already written their will). The number of EOL-related events attended was positively correlated with Preparation, while fear of death was negatively associated with Preference. Older adults with bereavement experience had higher Planning and Preparation scores than those without such experience.

Low-Frequency Impedance-Based Cell Discrimination Considering Ion Transport Model in Cell Suspension.

Low-frequency impedance-based (LFI) cell discrimination as a novel non-destructive and non-invasive cell discrimination is proposed. LFI cell discrimination discriminates the cell type by considering an ion transport model in cell suspension. Ion transport model in cell suspension is constructed on the basis of Fick's laws of diffusion in the extracellular region under ion permeability P which represents the characteristics of cell type. P is achieved using the ion transport model equation through an iterative curve fitting to an ion concentration in extracellular region obtained from low-frequency impedance which is assumed to be linearly related to the ion concentration in extracellular region. In experiment, the electrical impedance spectra from the frequency of 200 kHz to 2.0 MHz are measured over time during producing ions from intracellular region to extracellular one in cell suspension using an impedance analyzer and an interdigitated array electrode system. As a target cell type, two different cell types based on Medical Research Council 5 (MRC-5), which are different in intracellular component are used. The curve fitting is performed for the low-frequency impedance at 200 kHz at which impedance reflects the ion concentration in extracellular region in order to obtain P of each cell type. As a result, each cell type has its own P. The proposed LFI cell discrimination successfully discriminates the cell type.

Is Suicide Beautiful?

Background: The sociocultural context shapes attitudes toward suicide. Japanese literary works such as the Hagakure and the Bunraku Sonezaki-Shinju depict suicide as beautiful and honorable. Although suicide acceptance is likely to affect suicide rates and prevention efforts in Japan, studies in this area are limited. Aims: This study aimed to explore suicide acceptance and related factors among Japanese participants. Method: Using an Internet research company, questionnaires were distributed that measured acceptance of suicide, suicide stigma, mental health, an opinion on suicide prevention efforts, and demographic variables. Data from 2,051 participants were analyzed using t tests, analysis of variance (ANOVA), and hierarchical regression analysis. Results: We found a two-factor model (comprising beautification and justification factors) for the suicide acceptance scale and confirmed the scale's validity and reliability. The results showed significant differences in suicide acceptance by gender, age, educational level, employment status, and bereavement experience. A hierarchical regression analysis model revealed that suicide beautification was negatively related to positive opinion on suicide prevention efforts. Limitations: This study only focused on Japanese participants; therefore, further studies and cross-cultural comparisons are needed. Conclusion: The results revealed that suicide beautification was negatively associated with positive opinion on suicide prevention efforts after controlling for other variables.

Numerical Study of Enhancement of Positive Dielectrophoresis Particle Trapping in Electrode-Multilayered Microfluidic Device.

Enhancement of positive dielectrophoresis (pDEP) particle trapping by a co-occurring fluid flow under an ac electric field in an electrode-multilayered microfluidic device is investigated by three-dimensional particle-fluid flow simulations. The particle motion near one cross section of the microfluidic device is simulated under a zero flow condition by the Eulerian-Lagrangian method incorporating the ac electrothermal effect, thermal buoyancy, and dielectrophoresis. The mean trapping rate under the steady state Rm is evaluated from the simulated number of trapped particles Ntrap for 54 cases with four parameters: electrode excitation pattern, medium conductivity σ, applied voltage ϕe, and the real part of the Clausius-Mossotti factor Re[K(ω)]. The simulated pDEP velocity in the upper part of the flow channel is validated by an experiment using cell suspension and is fitted so that the non-dimensional velocity error is within 15% of a typical velocity of pDEP. The mean trapping rate Rm is greatly increased by the fluid flow only in the high conductivity and high voltage cases. Regardless of the electrode excitation pattern, Rm increased almost proportionally to the inflow rate into the capture region, where the pDEP force is effective. From a fitted equation of the results, the increase of Rm when Re[K(ω)] = 0.1 to 0.5 is found to be about 20% to 30% of the number of particles transported into the capture regions. The results quantify the enhancement of pDEP trapping by the fluid flow occurring under practical conditions in the device.

Parental Grief After Offspring Suicide and Adaptation to the Loss in Japan.

Several reports have indicated that grief and mental health outcomes of people bereaved by suicide vary by their relationship to the deceased. Parents who have lost offspring experience higher levels of distress than those with other relationships to the deceased. However, there are limited studies investigating the experience of parental bereavement by suicide, and further research is needed. The present study aimed to clarify the differences in grief reactions between bereaved parents and those with other relationships to the deceased in Japan and explore a statistical model of adaptation to the loss. In total, 105 bereaved participants completed a questionnaire covering grief reaction, meaning reconstruction, mental health, social context, and demographic variables. Parents scored higher on several grief reaction items and lower in sense-making than those with other relationships. In addition, path analysis showed that sense-making acted as a moderator in the experience of loss of offspring and grief reaction.

Meaning Reconstruction Process After Suicide: Life-Story of a Japanese Woman Who Lost Her Son to Suicide.

Although Japan has a high suicide rate, there is insufficient research on the experiences of suicide-bereaved individuals. We investigated the qualitative aspects of the meaning reconstruction process after a loss to suicide. We conducted a life-story interview using open-ended questions with one middle-aged Japanese woman who lost her son to suicide. We used a narrative approach to transcribe and code the participant's narratives for analysis. The analysis revealed three meaning groups that structured the participant's reactions to the suicide: making sense of her son's death and life, relationships with other people, and reconstruction of a bond with the deceased. The belief that death is not an eternal split and that there is a connection between the living and the deceased reduced the pain felt by our participant. Furthermore, the narratives worked as scaffolds in the meaning reconstruction process. We discuss our results in the light of cross-cultural differences in the grieving process.

Comparing Facilitator Priorities of Suicide Survivor Support Groups: A Cross-Cultural Comparison Between Japanese and American Groups.

A total of 56 Japanese and 59 American survivor of suicide support group facilitators were asked to rank the mutual aid objectives of their groups following Shulman's scheme in terms of their frequency and importance. Both American and Japanese facilitators showed an emphasis on personal adaptation goals (such as helping bereaved feel less isolated in their grief or encouraging bereaved to share their coping with loss experiences) over collective goals (such as raising monies for more research on mental illness or trying to combat societal suicide stigma in their local communities). Differences were also noted with American facilitators evaluating helping with problem solving, sharing different ways of coping, viewing personal issues as societal problems, and advocating for promoting social change as significantly higher than the Japanese did. We believe some of these contrasts reflect differences in American and Japanese cultural values.

A Herpesvirus Specific Motif of Epstein-Barr Virus DNA Polymerase Is Required for the Efficient Lytic Genome Synthesis.

Epstein-Barr virus (EBV) is associated with several malignancies, including Burkitt lymphoma and nasopharyngeal carcinoma. To overcome such disorders, understanding the molecular mechanisms of the EBV replication is important. The EBV DNA polymerase (Pol) is one of the essential factors for viral lytic DNA replication. Although it is well known that its C-terminal half, possessing DNA polymerase and 3'-5' exonuclease activity, is highly conserved among Family B Pols, the NH2-terminal half has yet to be characterized in detail. In this study, we show that a stretch of hydrophobic amino acids within the pre-NH2-terminal domain of EBV Pol plays important role. In addition, we could identify the most essential residue for replication in the motif. These findings will shed light on molecular mechanisms of viral DNA synthesis and will help to develop new herpesviruses treatments.