MELD-GRAIL-Na Is a Better Predictor of Mortality Than MELD in Korean Patients with Cirrhosis.

Background and Objectives: The Child-Pugh (CP) score and Model for End-Stage Liver Disease (MELD) are classical systems for predicting mortality in patients with liver cirrhosis (LC). The MELD-GFR assessment in liver disease-sodium (MELD-GRAIL-Na) was designed to better reflect renal function and, therefore, provide better mortality predictions. This study aimed to compare the prediction accuracy of MELD-GRAIL-Na compared to CP and MELD in predicting short-term (1- and 3-month) mortality in Korean patients. Materials and Methods: Medical records of patients with LC admitted to the Konkuk University Hospital from 2015 to 2020 were retrospectively reviewed. Predictive values of the CP, MELD, and MELD-GRAIL-Na for 1-month and 3-month mortality were calculated using the area under the receiver operating curve (AUROC) and were compared using DeLong's test. Results: In total, 1249 patients were enrolled; 102 died within 1 month, and 146 within 3 months. AUROCs of CP, MELD, and MELD-GRAIL-Na were 0.831, 0.847, and 0.857 for 1-month mortality and 0.837, 0.827, and 0.835 for 3-month mortality, respectively, indicating no statistical significance. For patients with CP classes B and C, AUROCs of CP, MELD, and MELD-GRAIL-Na were 0.782, 0.809, and 0.825 for 1-month mortality and 0.775, 0.769, and 0.786 for 3-month mortality, respectively. There was a significant difference between CP and MELD-GRAIL-Na in predicting 1-month mortality (p = 0.0428) and between MELD and MELD-GRAIL-Na in predicting 1-month (p = 0.0493) and 3-month mortality (p = 0.0225). Conclusions: Compared to CP and MELD, MELD-GRAIL-Na was found to be a better and more useful system for evaluating short-term (1- and 3-month) mortality in Korean patients with cirrhosis, especially those with advanced cirrhosis (CP class B and C).

The interplay between partisanship, risk perception, and mental distress during the early stages of the COVID-19 pandemic in the United States.

COVID-19 is a profoundly partisan issue in the U.S., with increasing polarization of the Republicans' and Democrats' responses to the COVID-19 pandemic and their precautionary actions to reduce virus transmission. Nevertheless, it remains unclear whether and how partisan gaps in many aspects of the pandemic are linked to mental health, which has increasingly been a major concern. This study examined the association between political partisanship and mental health by assessing the mediating and moderating relationships between risk perception, expected infection severity of COVID-19, and partisanship in terms of mental health during the early stages of the pandemic. The data were drawn from a cross-sectional web survey conducted between March 20 and 30, 2020, with a sample of U.S. adults (N = 4,327). Of those participants, 38.9% and 29.6% were Democrats and Republicans, respectively. The results indicate that Democrats were more likely to experience COVID-induced mental distress than Republicans, and higher risk perception and expected infection severity were associated with mental distress. Furthermore, risk perception and expected infection severity of COVID-19 mediated approximately 24%-34% of the associations between political partisanship and mental distress. Finally, the adverse mental health impact of risk perception and expected infection severity appeared to be much stronger for Republicans than Democrats. The findings suggest that political partisanship is a key factor to understanding mental health consequences of the COVID-19 outbreak in the U.S.

The Moderating Effect of Gender on the Relationship Between Self-neglect and Suicidal Ideation in Older Adults of Korea.

OBJECTIVES: Previous studies have reported that self-neglect, which may be a sign of elder abuse, can result in suicide among older adults. The signs of self-neglect and its impact on the risk of suicide may differ by gender. Thus, this study explored the association between self-neglect and suicide risk in older Korean adults and examined the potential moderating effect of gender on this relationship. METHODS: Data were collected from 356 Korean adults aged 65 or older through an online survey. Multiple regression analysis was used to test the research hypothesis. First, the associations between 4 sub-dimensions of self-neglect (i.e., daily life management issues, personal hygiene issues, financial management issues, and relational issues) and suicidal ideation were examined. Then, the moderating effect of gender on these relationships was investigated by including interaction terms. RESULTS: Self-neglect was significantly associated with suicidal ideation in older adults. Aspects of self-neglect related to daily life management and relational factors were key predictors of suicidal ideation. Gender significantly moderated the effect of the relational dimension of self-neglect on suicidal ideation. The relational dimension of self-neglect was more strongly associated with suicidal ideation in older women than in older men. CONCLUSIONS: The findings suggest the importance of screening older adults with signs of self-neglect for suicide risk. Special attention should be paid to older women who experience relational issues as a high-risk group for suicidal ideation. Public programs and support systems should be established to improve daily life management and promote social relationships among older adults.

Adenosine derivatives from Cordyceps exert antitumor effects against ovarian cancer cells through ENT1-mediated transport, induction of AMPK signaling, and consequent autophagic cell death.

Cordyceps militaris is rich in adenosine derivatives, including 3'-deoxyadenosine, also known as cordycepin. It has been reported for antitumor effects, but its underlying molecular mechanism has yet to be elucidated. We investigated how adenosine derivatives exerted antitumor effects against ovarian cancer using human ovarian cancer cells and a xenograft mouse model. Treatment with adenosine derivatives effectively resulted in cell death of ovarian cancer cells through AMPK activation and subsequently mTOR-mediated autophagic induction. Intriguingly, the effect required membrane transport of adenosine derivatives via ENT1, rather than ADORA-mediated cellular signaling. Our data suggest that adenosine derivatives may be an effective therapeutic intervention in ovarian cancer through induction of ENT1-AMPK-mTOR-mediated autophagic cell death.

Nanoscale fluorescence imaging of biological ultrastructure via molecular anchoring and physical expansion.

Nanoscale imaging of biological samples can provide rich morphological and mechanistic information about biological functions and dysfunctions at the subcellular and molecular level. Expansion microscopy (ExM) is a recently developed nanoscale fluorescence imaging method that takes advantage of physical enlargement of biological samples. In ExM, preserved cells and tissues are embedded in a swellable hydrogel, to which the molecules and fluorescent tags in the samples are anchored. When the hydrogel swells several-fold, the effective resolution of the sample images can be improved accordingly via physical separation of the retained molecules and fluorescent tags. In this review, we focus on the early conception and development of ExM from a biochemical and materials perspective. We first examine the general workflow as well as the numerous variations of ExM developed to retain and visualize a broad range of biomolecules, such as proteins, nucleic acids, and membranous structures. We then describe a number of inherent challenges facing ExM, including those associated with expansion isotropy and labeling density, as well as the ongoing effort to address these limitations. Finally, we discuss the prospect and possibility of pushing the resolution and accuracy of ExM to the single-molecule scale and beyond.

Multilaboratory Collaborative Study of a Nontarget Data Acquisition for Target Analysis (nDATA) Workflow Using Liquid Chromatography-High-Resolution Accurate Mass Spectrometry for Pesticide Screening in Fruits and Vegetables.

Nontarget data acquisition for target analysis (nDATA) workflows using liquid chromatography-high-resolution accurate mass (LC-HRAM) spectrometry, spectral screening software, and a compound database have generated interest because of their potential for screening of pesticides in foods. However, these procedures and particularly the instrument processing software need to be thoroughly evaluated before implementation in routine analysis. In this work, 25 laboratories participated in a collaborative study to evaluate an nDATA workflow on high moisture produce (apple, banana, broccoli, carrot, grape, lettuce, orange, potato, strawberry, and tomato). Samples were extracted in each laboratory by quick, easy, cheap, effective, rugged, and safe (QuEChERS), and data were acquired by ultrahigh-performance liquid chromatography (UHPLC) coupled to a high-resolution quadrupole Orbitrap (QOrbitrap) or quadrupole time-of-flight (QTOF) mass spectrometer operating in full-scan mass spectrometry (MS) data-independent tandem mass spectrometry (LC-FS MS/DIA MS/MS) acquisition mode. The nDATA workflow was evaluated using a restricted compound database with 51 pesticides and vendor processing software. Pesticide identifications were determined by retention time (tR, ±0.5 min relative to the reference retention times used in the compound database) and mass errors (δM) of the precursor (RTP, δM ≤ ±5 ppm) and product ions (RTPI, δM ≤ ±10 ppm). The elution profiles of all 51 pesticides were within ±0.5 min among 24 of the participating laboratories. Successful screening was determined by false positive and false negative rates of <5% in unfortified (pesticide-free) and fortified (10 and 100 µg/kg) produce matrices. Pesticide responses were dependent on the pesticide, matrix, and instrument. The false negative rates were 0.7 and 0.1% at 10 and 100 µg/kg, respectively, and the false positive rate was 1.1% from results of the participating LC-HRAM platforms. Further evaluation was achieved by providing produce samples spiked with pesticides at concentrations blinded to the laboratories. Twenty-two of the 25 laboratories were successful in identifying all fortified pesticides (0-7 pesticides ranging from 5 to 50 µg/kg) for each produce sample (99.7% detection rate). These studies provide convincing evidence that the nDATA comprehensive approach broadens the screening capabilities of pesticide analyses and provide a platform with the potential to be easily extended to a larger number of other chemical residues and contaminants in foods.

Perceived neighborhood disorder and psychological distress among Latino adults in the United States: Considering spousal/partner relationship.

It has been well-established that neighborhood disorder and disadvantage are detrimental to mental health and psychological well-being. There has been growing research interest in minority stress issues, however, less is known about how perceived neighborhood disorder matters for psychological well-being among Latino adults in the United States. Analyzing data from National Latino Asian American Study, 2002-2003, the present study investigates the relationships among perceived neighborhood disorder, spousal/partner relationships (i.e., spousal/partner strain and support), and psychological distress. The findings indicated that perceived neighborhood disorder and spousal/partner strain were positively associated with increased psychological distress, whereas spousal/partner support had no protective effect against psychological distress. Moreover, mediation analysis showed that the association between perceived neighborhood disorder and psychological distress was partially mediated by spousal/partner strain (i.e., 15.13%), not spousal support. Finally, moderation analysis revealed that the presence of spousal/partner strain exacerbated the relationship between perceived neighborhood disorder and psychological distress. Conversely, the absence of spousal/partner strain appeared to buffer the adverse impact of neighborhood disorder on psychological distress. These findings highlighted the ill effect of problematic neighborhood environments on the quality of the spousal/partner relationship and subsequently Latino's psychological well-being.

Evaluation of equine coronavirus fecal shedding among hospitalized horses.

BACKGROUND: Currently, diagnosis of equine coronavirus (ECoV) relies on the exclusion of other infectious causes of enteric disease along with molecular detection of ECoV in feces or tissue. Although this approach is complete, it is costly and may not always be achievable. OBJECTIVE: We hypothesized that the overall fecal shedding of ECoV in hospitalized horses is low. Our objective was to determine whether systemically healthy horses and horses with gastrointestinal disorders shed ECoV in their feces at the time of admission to a referral hospital and after 48 hours of stress associated with hospitalization. ANIMALS: One-hundred thirty adult horses admitted to the Washington State University Veterinary Teaching Hospital for gastrointestinal disease (n = 65) or for imaging under anesthesia (n = 65) that were hospitalized for 48 hours. Owner consent was obtained before sampling. METHODS: Fecal samples were collected at admission and 48 hours later. Polymerase chain reaction (PCR) for ECoV and electron microscopy (EM) were performed on all samples. RESULTS: Only 1 of 258 fecal samples was PCR-positive for ECoV. Electron microscopy identified ECoV-like particles in 9 of 258 samples, parvovirus-like particles in 4 of 258 samples, and rotavirus-like particles in 1 of 258 samples. CONCLUSIONS AND CLINICAL IMPORTANCE: The presence of ECoV in feces of hospitalized adult horses was low. Thus, fecal samples that are PCR-positive for ECoV in adult horses that have clinical signs consistent with this viral infection are likely to be of diagnostic relevance. The clinical relevance of the viruses observed using EM remains to be investigated.

Discrimination, Mental Disorders, and Suicidal Ideation in Latino Adults: Decomposing the Effects of Discrimination.

Experiences of discrimination and mental disorder have been recognized as risks for suicidality. Yet, few studies have examined the direct and indirect effects of discrimination on suicidal ideation through mental disorder among Latino adults in the U.S. This study aimed to examine whether everyday discrimination and racial/ethnic discrimination is associated with suicidal ideation and if mental disorder (i.e., DSM-IV depressive, anxiety, and substance use) mediates the association. Discrimination was operationalized with self-reported discriminatory experience. This study applied a mediation analysis to the data from National Latino and Asian American Survey, 2002-2003. The key findings are: (a) everyday discrimination had an independent association with suicidal ideation as well as exerted an indirect effect through anxiety disorder. (b) Racial/ethnic discrimination was not directly associated with suicidal ideation, but its adverse effect on suicidal ideation was mediated by the depressive disorder.

Religious Heterogamy and Partnership Quality in Later Life.

OBJECTIVES: Prior research points to the importance of couple-level religious similarity for multiple dimensions of partnership quality and stability but few studies have investigated whether this association holds for older couples. METHOD: The current article uses dyadic data from the National Social Life, Health, and Aging Project (NSHAP), a representative sample of 953 individuals age 62-91 plus their marital or cohabiting partners. We use modified actor-partner interdependence models. RESULTS: Religious service heterogamy predicted lower relationship happiness and satisfaction. Both associations were partially explained by the fact that religiously dissimilar partners report relatively little free time in joint activity. Further, religiously heterogamous couples had less frequent sex and engaged in less nonsexual touch than their more similar counterparts. CONCLUSIONS: Taken together, results attest to the ongoing importance of religious similarity-service attendance, in particular-for partnership quality in late life. Future research is needed to more fully examine which mechanisms account for these patterns.

Buckling-Based Non-Linear Mechanical Sensor.

Mechanical sensors provide core keys for high-end research in quantitative understanding of fundamental phenomena and practical applications such as the force or pressure sensor, accelerometer and gyroscope. In particular, in situ sensitive and reliable detection is essential for measurements of the mechanical vibration and displacement forces in inertial sensors or seismometers. However, enhancing sensitivity, reducing response time and equipping sensors with a measurement capability of bidirectional mechanical perturbations remains challenging. Here, we demonstrate the buckling cantilever-based non-linear dynamic mechanical sensor which addresses intrinsic limitations associated with high sensitivity, reliability and durability. The cantilever is attached on to a high-Q tuning fork and initially buckled by being pressed against a solid surface while a flexural stress is applied. Then, buckling instability occurs near the bifurcation region due to lateral movement, which allows high-sensitive detection of the lateral and perpendicular surface acoustic waves with bandwidth-limited temporal response of less than 1 ms.

Adhesive force measurement of steady-state water nano-meniscus: Effective surface tension at nanoscale.

When the surface of water is curved at nanoscale as a bubble, droplet and meniscus, its surface tension is expected to be smaller than that of planar interface, which still awaits experimental studies. Here, we report static and dynamic force spectroscopy that measures the capillary force of a single nanoscale water meniscus at constant curvature condition. Based on the Young-Laplace equation, the results are used to obtain the effective surface tension (ST) of the meniscus, which decreases to less than 20% of the bulk value at the radius-of-curvature (ROC) below 25 nm, while indicating the bulk behaviour above ~130 nm ROC. Interestingly, such a possibility provides a qualitative resolution of the unsettled discrepancies between experiments and theories in the thermodynamic activation processes for the mentioned three types of nano-curvatured water. Our results may not only lead to development of microscopic theories of ST as well as further experimental investigations, but also help better understanding of the ST-induced nanoscale dynamics such as cluster growth or protein folding, and the ST-controlled design of nano-biomaterials using the nano-meniscus.

Bifurcation-enhanced ultrahigh sensitivity of a buckled cantilever.

Buckling, first introduced by Euler in 1744 [Euler L (1744) Opera Omnia I 24:231], a sudden mechanical sideways deflection of a structural member under compressive stress, represents a bifurcation in the solution to the equations of static equilibrium. Although it has been investigated in diverse research areas, such a common nonlinear phenomenon may be useful to devise a unique mechanical sensor that addresses the still-challenging features, such as the enhanced sensitivity and polarization-dependent detection capability. We demonstrate the bifurcation-enhanced sensitive measurement of mechanical vibrations using the nonlinear buckled cantilever tip in ambient conditions. The cantilever, initially buckled with its tip pinned, flips its buckling near the bifurcation point (BP), where the buckled tip becomes softened. The enhanced mechanical sensitivity results from the increasing fluctuations, unlike the typical linear sensors, which facilitate the noise-induced buckling-to-flipping transition of the softened cantilever. This allows the in situ continuous or repeated single-shot detection of the surface acoustic waves of different polarizations without any noticeable wear of the tip. We obtained the sensitivity above 106 V(m/s)-1, a 1,000-fold enhancement over the conventional seismometers. Our results lead to development of mechanical sensors of high sensitivity, reproducibility, and durability, which may be applied to detect, e.g., the directional surface waves on the laboratory as well as the geological scale.

Neuronal Glutamate Transporters Control Dopaminergic Signaling and Compulsive Behaviors.

There is an ongoing debate on the contribution of the neuronal glutamate transporter EAAC1 to the onset of compulsive behaviors. Here, we used behavioral, electrophysiological, molecular, and viral approaches in male and female mice to identify the molecular and cellular mechanisms by which EAAC1 controls the execution of repeated motor behaviors. Our findings show that, in the striatum, a brain region implicated with movement execution, EAAC1 limits group I metabotropic glutamate receptor (mGluRI) activation, facilitates D1 dopamine receptor (D1R) expression, and ensures long-term synaptic plasticity. Blocking mGluRI in slices from mice lacking EAAC1 restores D1R expression and synaptic plasticity. Conversely, activation of intracellular signaling pathways coupled to mGluRI in D1R-containing striatal neurons of mice expressing EAAC1 leads to reduced D1R protein level and increased stereotyped movement execution. These findings identify new molecular mechanisms by which EAAC1 can shape glutamatergic and dopaminergic signals and control repeated movement execution.SIGNIFICANCE STATEMENT Genetic studies implicate Slc1a1, a gene encoding the neuronal glutamate transporter EAAC1, with obsessive-compulsive disorder (OCD). EAAC1 is abundantly expressed in the striatum, a brain region that is hyperactive in OCD. What remains unknown is how EAAC1 shapes synaptic function in the striatum. Our findings show that EAAC1 limits activation of metabotropic glutamate receptors (mGluRIs) in the striatum and, by doing so, promotes D1 dopamine receptor (D1R) expression. Targeted activation of signaling cascades coupled to mGluRIs in mice expressing EAAC1 reduces D1R expression and triggers repeated motor behaviors. These findings provide new information on the molecular basis of OCD and suggest new avenues for its treatment.

Obesity and Sexuality Among Older Couples: Evidence From the National Social Life, Health, and Aging Project.

OBJECTIVE: We investigate whether obesity is associated with sexual activity, sexual frequency, and the range of sexual behaviors in heterosexual older couples. We assess to what extent associations between obesity and sexuality are explained by physical, psychological, and sexual health, and by relationship quality. METHOD: We use data from 1,698 older adults in 849 partnered dyads in the 2010-2011 wave of the National Social Life, Health, and Aging Project and conduct couple-level analysis featuring women's and men's characteristics. RESULTS: Women's obesity-particularly at severe levels-is negatively associated with coupled sexual activity, but the association is not mediated by hypothesized mediators. Men's obesity did not have any association with sexual activity. There was no significant difference between overweight and normal weight adults across all three sexuality measures. DISCUSSION: The growing number of older adults with high levels of body mass index, particularly women, may face certain difficulties in maintaining active sexual lives.

Body Mass Index, Perceived Weight, and Self-Rated Health among South Korean Adults: Conjoint Effect on Health?

The prevalence of overweight and obesity is rising rapidly in many countries, including South Korea. The present study examined the association between weight perception and self-rated health, independent of body weight status, as well as how weight status and perceived weight status intersect and relate to the self-rated health among adults in South Korea. Data were from 722 men and 800 women in 2010 Korean General Social Survey. Results showed that over half of Korean adults perceived their weight incorrectly with a fair agreement (men ƙ = 0.36; women ƙ = 0.31). Multivariate analyses indicated that poor/fair self-rated health had no significant association with body weight status, measured by self-reported weight and height, but it had a significant association with perceived weight status in men. The intersectionality analysis in which weight status and weight perceptions were cross-classified indicated that both measured and perceived weight status should be taken into account for the indicator of self-rated health as well as for better understanding of weight-related health consequences.

Attention reorganizes connectivity across networks in a frequency specific manner.

Attention allows our brain to focus its limited resources on a given task. It does so by selective modulation of neural activity and of functional connectivity (FC) across brain-wide networks. While there is extensive literature on activity changes, surprisingly few studies examined brain-wide FC modulations that can be cleanly attributed to attention compared to matched visual processing. In contrast to prior approaches, we used an ultra-long trial design that avoided transients from trial onsets, included slow fluctuations (<0.1Hz) that carry important information on FC, and allowed for frequency-segregated analyses. We found that FC derived from long blocks had a nearly two-fold higher gain compared to FC derived from traditional (short) block designs. Second, attention enhanced intrinsic (negative or positive) correlations across networks, such as between the default-mode network (DMN), the dorsal attention network (DAN), and the visual system (VIS). In contrast attention de-correlated the intrinsically correlated visual regions. Third, the de-correlation within VIS was driven primarily by high frequencies, whereas the increase in DAN-VIS predominantly by low frequencies. These results pinpoint two fundamentally distinct effects of attention on connectivity. Information flow increases between distinct large-scale networks, and de-correlation within sensory cortex indicates decreased redundancy.

Effects of Dexmedetomidine Infusion on the Recovery Profiles of Patients Undergoing Transurethral Resection.

Transurethral resection has been the gold standard in the operative management of benign prostatic hyperplasia and bladder tumor; however, it is associated with several complications that may cause patient discomfort. We evaluated the usefulness of continuous infusion of dexmedetomidine on emergence agitation, hemodynamic status, and recovery profiles in patients undergoing elective surgery by a randomized clinical trial. Sixty patients aged 30 to 80 yr who were scheduled for elective transurethral resection under general anesthesia were included in this study. Participants were randomly assigned to two groups (control group, group C; dexmedetomidine group, group D). A total of 60 male patients were enrolled in this study and randomly assigned to group C (n=30) or group D (n=30). The quality of emergence in group D was marked by a significantly lower incidence of emergence agitation than in group C (P=0.015). Patients in group D therefore felt less discomfort induced by the indwelling Foley catheter than those in group C (P=0.022). No statistically significant differences were found between the two groups with respect to side effects including bradycardia (P=0.085), hypotension (P=0.640), and postoperative nausea and vomiting (P=0.389). Our study showed that intraoperative dexmedetomidine infusion effectively reduced the incidence and intensity of emergence agitation and catheter-induced bladder discomfort without delaying recovery time and discharge time, thus providing smooth emergence during the recovery period in patients undergoing transurethral resection (Clinical Trial Registry No. KT0001683).

Economic Segmentation and Health Inequalities in Urban Post-Reform China.

During economic reform, Chinese economic labor markets became segmented by state sector associated with a planned redistributive economy and private sector associated with the market economy. By considering an economic sector as a concrete institutional setting in post-reform China, this paper compares the extent to which socioeconomic status, measured by education and income, is associated with self-rated health between state sector and private sector. The sample is limited to urban Chinese employees between the ages of 18 and 55 who were active in the labor force. By analyzing pooled data from the 1991-2006 Chinese Health and Nutrition Survey, I find that there is a stronger association between income and self-rated health in the private sector than in the state sector. This study suggests that sectoral differences between market and redistributive economies are an important key to understanding health inequalities in post-reform urban China.