Improvement and application of recommended food score for hypertension in Korean adults: the Korean Genome and Epidemiology Study.

Background: Addressing dietary factors to lower blood pressure can be a crucial strategy at the population level to mitigate the risk of hypertension. In a prior investigation, a tailored food score was used as a dietary index relevant to hypertension among Korean adults. This current study aims to assess the association between the overall quality of the diet, taking into account more precise food components, and evaluate the risk of developing hypertension. Methods: This prospective cohort study included 5,342 adults aged 40-70 without hypertension who participated in the Korean Genome and Epidemiology Study (KoGES) from 2001 to 2016. The improved Recommended Food Score for Hypertension (iRFSH) is a modified version of the Recommended Food Score to assess the consumption of foods recommended in the Dietary Approaches to Stop Hypertension (DASH) diet for Korean foods. A higher score reflects greater consumption of recommended foods, indicative of higher dietary quality. The maximum total score is 65. High blood pressure, which includes both hypertension and prehypertension, was analyzed using Cox proportional hazard regression models to examine its prospective relationship with iRFSH. Results: Among 2,478 males and 2,864 females with 10.8 mean years of follow-up, a higher score of iRFSH was associated with a lower risk of hypertension in the highest quintile compared to the lowest quintile [total: hazard ratio (HR): 0.79; 95% confidence interval (CI): 0.72, 0.87; female: HR: 0.71; 95% CI: 0.62, 0.83]. Conclusion: Higher iRFSH is associated with a lower incidence of hypertension. Our results suggest that the iRFSH may be a potential tool for assessing dietary quality and dietary patterns and predicting the risk of hypertension in Korean adults.

Automated System for Attomolar-Level Detection of MiRNA as a Biomarker for Influenza A Virus.

We have developed an automated sensing system for the repeated detection of a specific microRNA (miRNA) of the influenza A (H1N1) virus. In this work, magnetic particles functionalized with DNAs, target miRNAs, and alkaline phosphate (ALP) enzymes formed sandwich structures. These particles were trapped on nickel (Ni) patterns of our sensor chip by an external magnetic field. Then, additional electrical signals from electrochemical markers generated by ALP enzymes were measured using the sensor, enabling the highly sensitive detection of target miRNA. The magnetic particles used on the sensor were easily removed by applying the opposite direction of external magnetic fields, which allowed us to repeat sensing measurements. As a proof of concept, we demonstrated the detection of miRNA-1254, one of the biomarkers for the H1N1 virus, with a high sensitivity down to 1 aM in real time. Moreover, our sensor could selectively detect the target from other miRNA samples. Importantly, our sensor chip showed reliable electrical signals even after six repeated miRNA sensing measurements. Furthermore, we achieved technical advances to utilize our sensor platform as part of an automated sensing system. In this regard, our reusable sensing platform could be utilized for versatile applications in the field of miRNA detection and basic research.

Expression and prognostic significance of microsomal triglyceride transfer protein in brain tumors: a retrospective cohort study.

Background: Glioblastoma (GBM) is the most common malignant brain tumor and has poor survival. An elevated cholesterol level is involved occurrence and progression of brain tumors. Microsomal triglyceride transfer protein (MTTP) is a target for lowering lipids, and its inhibition helps to improve hyperlipidemia. However, whether the altered expression of MTTP affects the development and prognosis of brain tumors is currently unidentified. The purpose of this study is to determine MTTP as a prognostic marker for brain tumors. Methods: Data for patients with brain cancers and control brain tissue were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The datasets were analyzed using Mann-Whitney U-test or t-test to compare the expression of MTTP in normal and brain tumor tissues. To examine whether MTTP affected the prognosis of patients with brain tumors, log-rank test and multivariable Cox proportional hazard regression were conducted. Results: The expression of MTTP was significantly upregulated in brain tumors and was correlated with age, tumor stage, and isocitrate dehydrogenase (IDH) mutation. Importantly, increased MTTP expression in brain tumors is associated with poor patient survival. Conclusions: High MTTP expression is associated with brain tumor development, tumor stage, and prognosis. Therefore, MTTP is an independent prognostic indicator for brain tumors, which can serve as one of the possible targets for adjuvant treatment of GBM.

Short-term aerobic exercise prevents development of glucocorticoid myopathic features in aged skeletal muscle in a sex-dependent manner.

Older adults are vulnerable to glucocorticoid-induced muscle atrophy and weakness, with sex potentially influencing their susceptibility to those effects. Aerobic exercise can reduce glucocorticoid-induced muscle atrophy in young rodents. However, it is unknown whether aerobic exercise can prevent glucocorticoid myopathy in aged muscle. The objectives of this study were to define the extent to which sex influences the development of glucocorticoid myopathy in aged muscle, and to determine the extent to which aerobic exercise training protects against myopathy development. Twenty-four-month-old female (n = 30) and male (n = 33) mice were randomized to either sedentary or aerobic exercise groups. Within their respective groups, mice were randomized to either daily treatment with dexamethasone (DEX) or saline. Upon completing treatments, the contractile properties of the triceps surae complex were assessed in situ. DEX marginally lowered muscle mass and soluble protein content in both sexes, which was attenuated by aerobic exercise only in females. DEX increased sub-tetanic force and rate of force development only in females, which was not influenced by aerobic exercise. Muscle fatigue was higher in both sexes following DEX, but aerobic exercise prevented fatigue induction only in females. The sex-specific differences to muscle function in response to DEX treatment coincided with sex-specific changes to the content of proteins related to calcium handling, mitochondrial quality control, reactive oxygen species production, and glucocorticoid receptor in muscle. These findings define several important sexually dimorphic changes to aged skeletal muscle physiology in response to glucocorticoid treatment and define the capacity of short-term aerobic exercise to protect against those changes. KEY POINTS: There are sexually dimorphic effects of glucocorticoids on aged skeletal muscle physiology. Glucocorticoid-induced changes to aged muscle contractile properties coincide with sex-specific differences in the content of calcium handling proteins. Aerobic exercise prevents glucocorticoid-induced fatigue only in aged females and coincides with differences in the content of mitochondrial quality control proteins and glucocorticoid receptors.

Functional Aspects of the Obesity Paradox in Patients with Severe Coronavirus Disease-2019: A Retrospective, Multicenter Study.

BACKGROUND: Results of studies investigating the association between body mass index (BMI) and mortality in patients with coronavirus disease-2019 (COVID-19) have been conflicting. METHODS: This multicenter, retrospective observational study, conducted between January 2020 and August 2021, evaluated the impact of obesity on outcomes in patients with severe COVID-19 in a Korean national cohort. A total of 1,114 patients were enrolled from 22 tertiary referral hospitals or university-affiliated hospitals, of whom 1,099 were included in the analysis, excluding 15 with unavailable height and weight information. The effect(s) of BMI on patients with severe COVID-19 were analyzed. RESULTS: According to the World Health Organization BMI classification, 59 patients were underweight, 541 were normal, 389 were overweight, and 110 were obese. The overall 28-day mortality rate was 15.3%, and there was no significant difference according to BMI. Univariate Cox analysis revealed that BMI was associated with 28-day mortality (hazard ratio, 0.96; p=0.045), but not in the multivariate analysis. Additionally, patients were divided into two groups based on BMI ≥25 kg/m2 and underwent propensity score matching analysis, in which the two groups exhibited no significant difference in mortality at 28 days. The median (interquartile range) clinical frailty scale score at discharge was higher in nonobese patients (3 [3 to 5] vs. 4 [3 to 6], p<0.001). The proportion of frail patients at discharge was significantly higher in the nonobese group (28.1% vs. 46.8%, p<0.001). CONCLUSION: The obesity paradox was not evident in this cohort of patients with severe COVID-19. However, functional outcomes at discharge were better in the obese group.

Asymmetric Polymer Additive for Morphological Regulation and Thermally Stable Organic Solar Cells.

High thermal stability is crucial for the commercialization of organic solar cells (OSCs). The thermal stability of OSCs has been improved using the tailoring blend morphology of bulk heterojunctions (BHJs). Herein, we demonstrated thermally stable OSCs in a ternary blended system containing low-crystalline semiconducting polymers (asy-PNDI1FTVT and PTB7-Th) and a non-fullerene acceptor (Y6). The asymmetric n-type semiconducting polymer (asy-PNDI1FTVT) differed from general symmetric semiconducting polymers as it randomly substituted fluorine atoms at the donor moiety (TVT), resulting in significantly lower crystallinity. asy-PNDI1FTVT in PTB7-Th:Y6 exhibited a well-mixed morphology at the BHJ and efficiently facilitated the charge dissociation process with an enhanced fill factor and power conversion efficiency. Furthermore, the ternary system of PTB7-Th:Y6:asy-PNDI1FTVT suppressed phase separation with negligible burn-in loss and performance degradation under thermal stress. The experiments showed that our devices without encapsulation retained over 90% of their initial efficiencies after 100 h at 65 °C. These results show significant potential for the development of thermally stable OSCs with reasonable efficiency.

Nanoscale Mapping of Carrier Mobilities in the Ballistic Transports of Carbon Nanotube Networks.

Much progress has been made in the nanoscale analysis of nanostructures, while the mapping of key charge transport properties such as a carrier mobility remains a challenge, especially for one-dimensional systems. Here, we report the nanoscale mapping of carrier mobilities in carbon nanotube (CNT) networks and show that charge transport behaviors varied depending on network structures. In this work, the spatial distribution of localized charge transport properties such as mobilities and charge trap densities in CNT networks were mapped via a scanning noise microscopy. The mobility map was obtained from the conductivity maps measured at different back-gate biases, showing up to two orders of mobility variations depending on localized network structures. Furthermore, from the maps, correlations between mobility/conductivity and charge trap density were analyzed to determine charge transport mechanisms. In metallic CNT networks, the regions with rather high (low) or low (high) charge trap densities (mobilities) exhibited a diffusive or ballistic transport behavior, respectively. Interestingly, semiconducting CNT networks also exhibited a gradual transition from a diffusive to a ballistic transport behavior as the CNT mobility was increased by reaching the on-state with negative gate biases. The mapping of the cross-patterned CNT network showed that metallic CNT electrodes could achieve a good electrical contact with semiconducting CNTs without high contact resistance regions. Since this method allowed one to map versatile charge transport properties such as mobility, conductivity, and charge trap density, it can be a powerful tool for basic research about charge transport phenomena and practical device applications.

Efficacy and Safety of SID142 in Patients With Peripheral Arterial Disease: A Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group, Phase III Clinical Trial.

PURPOSE: Renexin® is a combination pill of cilostazol and Ginkgo biloba leaf extract that is used for the improvement of ischemic symptoms associated with peripheral arterial disease (PAD). SID142 is a controlled-release tablet of cilostazol (200 mg) and G biloba leaf extract (160 mg) that was developed to address the limitation of BID administration with Renexin. This study aimed to verify that SID142 was not inferior to Renexin in the treatment of patients with PAD. METHODS: This was a multicenter, randomized, double-blind, active-controlled, parallel-group, Phase III clinical trial. Study subjects were randomized to receive SID142 once daily or Renexin twice a day for 12 weeks. The primary end point was a change in the patient assessment of lower leg pain intensity with the use of a visual analog scale (VAS) after 12 weeks of treatment. If the lower limit of the two-sided 95% CI was greater than -10, the study drug was declared noninferior to the reference drug. Secondary efficacy end points included cold sensation, ankle-brachial index, ankle systolic pressure, maximum walking distance, pain-free walking distance, and investigator's global assessment. Study group results were compared 4, 8, and 12 weeks after treatment. Adverse events were assessed as a safety end point. FINDINGS: In total, 344 subjects from 19 medical centers were screened, and a total of 170 subjects were randomly assigned to either the SID142 (n = 86) or the Renexin (n = 84) group. Analysis of the change in lower extremity pain at 12 weeks compared with baseline revealed that SID142 was not inferior to Renexin (21.44 [19.23] vs 22.30 [17.75]; 95% CI, -7.70 to 5.97; P = 0.5942). No significant differences were found between groups in any secondary efficacy end point. However, the incidence of adverse reactions was significantly lower in the SID142 group (22.35% vs 39.29%; P = 0.0171). IMPLICATIONS: SID142 once daily was not inferior to Renexin twice a day for efficacy in patients with PAD. SID142 had a favorable safety profile. CLINICALTRIALS: gov identifier: NCT03318276.

A Case of Heart Transplantation for Fulminant Myocarditis After ChAdOx1 nCoV-19 Vaccination.

Vaccines have become the mainstay of management against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019; COVID-19) in the absence of effective antiviral therapy. Various adverse effects of COVID-19 vaccination have been reported, including cardiovascular complications such as myocarditis or pericarditis. Herein, we describe clinical records of a 63-year woman with fulminant myocarditis following ChAdOx1 nCoV-19 vaccination that was salvaged by heart transplantation. She complained chest pain, nausea, vomiting, and fever after the second vaccination. After the heart transplantation, the patient died due to necrotizing pneumonia on the 54th day of onset. Fulminant myocarditis is very rare after ChAdOx1 nCoV-19 vaccination but can be fatal.

The Short-Term Effect of Prunes in Improving Bone in Men.

Osteoporosis is a major health concern in aging populations, where 54% of the U.S. population aged 50 and older have low bone mineral density (BMD). Increases in inflammation and oxidative stress play a major role in the development of osteoporosis. Men are at a greater risk of mortality due to osteoporosis-related fractures. Our earlier findings in rodent male and female models of osteoporosis, as well as postmenopausal women strongly suggest the efficacy of prunes (dried plum) in reducing inflammation and preventing/reversing bone loss. The objective of this study was to examine the effects of two doses of prunes, daily, on biomarkers of inflammation and bone metabolism in men with some degree of bone loss (BMD; t-score between -0.1 and -2.5 SD), for three months. Thirty-five men between the ages of 55 and 80 years were randomized into one of three groups: 100 g prunes, 50 g prunes, or control. Consumption of 100 g prunes led to a significant decrease in serum osteocalcin (p < 0.001). Consumption of 50 g prunes led to significant decreases in serum osteoprotegerin (OPG) (p = 0.003) and serum osteocalcin (p = 0.040), and an increase in the OPG:RANKL ratio (p = 0.041). Regular consumption of either 100 g or 50 g prunes for three months may positively affect bone turnover.

Mapping the nanoscale effects of charge traps on electrical transport in grain structures of indium tin oxide thin films.

We report the mapping of the nanoscale effects of charge trap activities in the grain structures of an oxygen plasma-treated indium tin oxide (ITO) thin film. Here, a conducting Pt probe made direct contact with the surface of an ITO thin film and scanned the surface while measuring the maps of electrical currents and noises. The measured data were analyzed to obtain the maps of sheet conductance (G s) and charge trap density (N eff) in the grain structures of the ITO thin film. The results showed that grain boundaries exhibited a lower sheet conductance and a higher charge trap density than those of the regions inside grains. Interestingly, the scaling behavior of G s ∝ N eff -0.5 was observed in both grain and boundary regions, indicating diffusive charge transport. Furthermore, the sheet conductance increased by two times, and the density of charge traps decreased by ∼70% after an oxygen plasma treatment, presumably due to the enhanced crystallinity of the ITO film. Interestingly, in some boundary regions, the sheet conductance and the charge trap density exhibited the scaling behavior of G s ∝ N eff 0.5, which was attributed to the hopping conduction caused by the enhanced crystallinity and increased localized states in the boundary regions. Since our method provides valuable insights into charge transport and charge trap activities in transparent conducting thin films, it can be a powerful tool for basic research and practical optoelectronic device applications based on ITO thin films.

Reusable surface amplified nanobiosensor for the sub PFU/mL level detection of airborne virus.

We developed a reusable surface-amplified nanobiosensor for monitoring airborne viruses with a sub-PFU/mL level detection limit. Here, sandwich structures consisted of magnetic particles functionalized with antibodies, target viruses, and alkaline phosphatases (ALPs) were formed, and they were magnetically concentrated on Ni patterns near an electrochemical sensor transducer. Then, the electrical signals from electrochemical markers generated by ALPs were measured with the sensor transducer, enabling highly-sensitive virus detection. The sandwich structures in the used sensor chip could be removed by applying an external magnetic field, and we could reuse the sensor transducer chip. As a proof of concepts, the repeated detection of airborne influenza virus using a single sensor chip was demonstrated with a detection limit down to a sub-PFU/mL level. Using a single reusable sensor transducer chip, the hemagglutinin (HA) of influenza A (H1N1) virus with different concentrations were measured down to 10 aM level. Importantly, our sensor chip exhibited reliable sensing signals even after more than 18 times of the repeated HA sensing measurements. Furthermore, airborne influenza viruses collected from the air could be measured down to 0.01 PFU/mL level. Interestingly, the detailed quantitative analysis of the measurement results revealed the degradation of HA proteins on the viruses after the air exposure. Considering the ultrasensitivity and reusability of our sensors, it can provide a powerful tool to help preventing epidemics by airborne pathogens in the future.

Systemic delivery of a mitochondria targeted antioxidant partially preserves limb muscle mass and grip strength in response to androgen deprivation.

Muscle mass is important for health. Decreased testicular androgen production (hypogonadism) contributes to the loss of muscle mass, with loss of limb muscle being particularly debilitating. Androgen replacement is the only pharmacological treatment, which may not be feasible for everyone. Prior work showed that markers of reactive oxygen species and markers of mitochondrial degradation pathways were higher in the limb muscle following castration. Therefore, we tested whether an antioxidant preserved limb muscle mass in male mice subjected to a castration surgery. Subsets of castrated mice were treated with resveratrol (a general antioxidant) or MitoQ (a mitochondria targeted antioxidant). Relative to the non-castrated control mice, lean mass, limb muscle mass, and grip strength were partially preserved only in castrated mice treated with MitoQ. Independent of treatment, markers of mitochondrial degradation pathways remained elevated in all castrated mice. Therefore, a mitochondrial targeted antioxidant may partially preserve limb muscle mass in response to hypogonadism.

Sodium/glucose Co-Transporter 2 Inhibitor, Empagliflozin, Alleviated Transient Expression of SGLT2 after Myocardial Infarction.

BACKGROUND AND OBJECTIVES: Large clinical studies of sodium/glucose cotransporter 2 (SGLT2) inhibitors have shown a significant beneficial effect on heart failure-associated hospitalization and cardiovascular events. As SGLT2 is known to be absent in heart cells, improved cardiovascular outcomes are thought to be accounted for by the indirect effects of the drug. We sought to confirm whether such benefits were mediated through SGLT2 expressed in the heart using myocardial infarction (MI) model. METHODS: Mice pre-treated with empagliflozin (EMPA), an SGLT2 inhibitor, showed a significantly reduced infarct size compared with the vehicle group three days post-MI. Interestingly, we confirmed SGLT2 localized in the infarct zone. The sequential changes of SGLT2 expression after MI were also evaluated. RESULTS: One day after MI, SGLT2 transiently appeared in the ischemic areas in the vehicle group and increased until 72 hours. The appearance of SGLT2 was delayed and less in amount compared with the vehicle group. Additionally, there was a significant difference in metabolites, including glucose and amino acids in the ¹H nuclear magnetic resonance analysis between groups. CONCLUSIONS: Our work demonstrates that SGLT2 is transiently expressed in heart tissue early after MI and EMPA may directly operate on SGLT2 to facilitate metabolic substrates shifts.

Pharmacodynamic Profile and Prevalence of Bleeding Episode in East Asian Patients with Acute Coronary Syndromes Treated with Prasugrel Standard-Dose versus De-escalation Strategy: A Randomized A-MATCH Trial.

Compared with Caucasian patients, East Asian patients have the unique risk-benefit trade-off and different responsiveness to antithrombotic regimens. The aim of this study was to compare pharmacodynamic profile in East Asian patients with acute coronary syndromes (ACSs) treated with prasugrel standard-dose versus a de-escalation strategy. Before discharge, ACS patients with age <75 years or weight ≥60 kg (n = 255) were randomly assigned to the standard-dose (10-mg group) or de-escalation strategy (5-mg group or platelet function test [PFT]-guided group). After 1 month, VerifyNow P2Y12 assay-based platelet reactivity (P2Y12 reaction unit [PRU]) and bleeding episodes were evaluated. Primary endpoint was the percentage of patients with the therapeutic window (85 ≤ PRU ≤ 208). The 250 patients completed 1-month treatment. The percentage of patients within the therapeutic window was significantly lower in the 10-mg group (n = 85) compared with the 5-mg (n = 83) and PFT-guided groups (n = 82) (35.3 vs. 67.5 vs. 65.9%) (odds ratio [OR]: 3.80 and 3.54; 95% confidence interval [CI]: 2.01-7.21 and 1.87-6.69, respectively). Compared with the 10-mg group, the bleeding rate was tended to be lower with de-escalation strategies (35.3 vs. 24.1% vs. 23.2%) (hazard ratio [HR]: 0.58 and 0.55; 95% CI: 0.30-1.14 and 0.28-1.09, respectively). "PRU < 127" was the optimal cut-off for predicting 1-month bleeding events (area under the curve: 0.616; 95% CI: 0.543-0.689; p = 0.005), which criteria was significantly associated with early discontinuation of prasugrel treatment (HR: 2.00; 95% CI: 1.28-3.03; p = 0.001). In conclusion, compared with the standard-dose prasugrel, the prasugrel de-escalation strategy in East Asian patients presented with ACS showed a higher chance within the therapeutic window and a lower tendency toward bleeding episodes. REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier:NCT01951001.

Progerinin, an optimized progerin-lamin A binding inhibitor, ameliorates premature senescence phenotypes of Hutchinson-Gilford progeria syndrome.

Previous work has revealed that progerin-lamin A binding inhibitor (JH4) can ameliorate pathological features of Hutchinson-Gilford progeria syndrome (HGPS) such as nuclear deformation, growth suppression in patient's cells, and very short life span in an in vivo mouse model. Despite its favorable effects, JH4 is rapidly eliminated in in vivo pharmacokinetic (PK) analysis. Thus, we improved its property through chemical modification and obtained an optimized drug candidate, Progerinin (SLC-D011). This chemical can extend the life span of LmnaG609G/G609G mouse for about 10 weeks and increase its body weight. Progerinin can also extend the life span of LmnaG609G/+ mouse for about 14 weeks via oral administration, whereas treatment with lonafarnib (farnesyl-transferase inhibitor) can only extend the life span of LmnaG609G/+ mouse for about two weeks. In addition, progerinin can induce histological and physiological improvement in LmnaG609G/+ mouse. These results indicate that progerinin is a strong drug candidate for HGPS.