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Abstract Periodontal disease presents a significant challenge in oral health due to its chronic inflammatory nature and subsequent degradation of tooth-supporting structures. Natural compounds have attracted attention for their potential therapeutic effects in alleviating symptoms of periodontitis (PD). In this study, we investigated the impact of Ganoderma lucidum spore oil (GLSO), a lipid component extracted from broken-walled GLS using the supercritical CO2 extraction method, on PD pathogenesis in vitro and in vivo. Treatment of human gingival fibroblasts with GLSO resulted in a significant reduction in the expression of inflammatory factors, including matrix metalloproteinase (MMP)-1 and interleukin (IL)-8, upregulated by lipopolysaccharide or IL-1β. Molecular mechanism studies revealed that the observed decrease in inflammatory factor expression may be attributed to the inhibition of phosphorylated c-Jun N-terminal kinase activity by GLSO. Furthermore, intraperitoneal injection of GLSO in a ligature-induced PD mouse model led to a notable reduction in periodontal inflammation and alveolar bone loss, accompanied by decreased levels of MMP-1 and IL-8. These in vivo results support the potential therapeutic efficacy of GLSO in alleviating PD symptoms. Overall, our study provides novel insights into the beneficial effects of GLSO in PD management. Further research is warranted to elucidate the underlying molecular mechanisms and explore the clinical applicability of GLSO as a promising therapeutic agent for PD treatment.

Background: Stress urinary incontinence (SUI) impacts the social, physical, and psychologi-cal well-being and quality of life of the patient. Several techniques exist for its management, including transcutaneous electrical stimulation (TES). Objects: We aimed to demonstrate the effects of TES on ultrasonographic variables and quality of life in women with SUI. Methods: This prospective study recruited 21 women who had been diagnosed with grade 1 or 2 SUI between July 2018 and March 2019. The exclusion criteria were pregnancy and a history of urogenital surgery. All participants were assessed at baseline and 8 weeks after intervention initiation. The bladder neck position (BNP), length of the urethra (LU), funneling index (FI), and rhabdosphincter thickness (RT) were measured. The Incontinence-Quality of Life (I-QOL) was used to assess incontinence-specific quality of life. Statistical significance level was set at p < 0.05. Results: Twenty-one patients with SUI used TES for 8 weeks. BNP and FI significantly de-creased after intervention (p < 0.05). LU, anterior and posterior RT (indicators of external sphincter hypertrophy) significantly increased post-intervention (p < 0.05). The total I-QOL score increased from 64.81 to 71.86 after the intervention (p < 0.05). Conclusion: This intervention improved BNP, LU, FI, RT, and subjective indicators such as quality of life in women with SUI. Therefore, TES can be an effective non-surgical treatment method for improving SUI symptoms and quality of life in these patients.

Background/Aims: A few studies have suggested the association between Helicobacter pylori (HP) infection and ischemic stroke. However, the impact of HP eradication on stroke risk has not been well evaluated. This study aimed to assess the influence of HP eradication on the incidence of ischemic stroke, considering the potential effect of sex. Methods: This prospective observational cohort study was conducted at Seoul National University Bundang Hospital, from May 2003 to February 2023, and involved gastroscopy-based HP testing. Propensity score (PS) matching was employed to ensure balanced groups by matching patients in the HP eradicated group (n=2,803) in a 3:1 ratio with patients in the HP non-eradicated group (n=960). Cox proportional hazard regression analysis was used to evaluate the risk of ischemic stroke. Results: Among 6,664 patients, multivariate analysis after PS matching indicated that HP eradication did not significantly alter the risk of ischemic stroke (hazard ratio, 0.531; 95% confidence interval, 0.221 to 1.270; p=0.157). Sex-specific subgroup analyses, both univariate and multivariate, did not yield statistically significant differences. However, Kaplan-Meier analysis revealed a potential trend: the females in the HP eradicated group exhibited a lower incidence of ischemic stroke than those in the HP non-eradicated group, although this did not reach statistical significance (p=0.057). Conclusion : s: This finding suggests that HP eradication might not impact the risk of ischemic stroke. However, there was a trend showing that females potentially had a lower risk of ischemic stroke following HP eradication, though further investigation is required to establish definitive evidence.

Abstract Light is a significant factor for living organisms with photosystems, like microbial rhodopsin—a retinal protein that functions as an ion pump, channel, and sensory transduction. Gloeobacter violaceus PCC7421, has a proton-pumping rhodopsin gene, the Gloeobacter rhodopsin (GR). The helix-turn-helix family of transcriptional regulators has various motifs, and they regulate gene expression in the presence of various metal ions. Here, we report that active proton outward pumping rhodopsin interacted with the helix-turn-helix transcription regulator and regulated gene expression. This interaction is confirmed using ITC analysis (K D of 8 μM) and determined the charged residues required. During in vitro experiments using fluorescent and luciferase reporter systems, ATP-binding cassette (ABC) transporters and the self-regulation of G. violaceus transcriptional regulator (GvTcR) are regulated by light, and gene regulation is observed in G. violaceus using the real-time polymerase chain reaction. These results expand our understanding of the natural potential and limitations of microbial rhodopsin function.

Abstract Heliorhodopsins (HeRs) have been hypothesized to have widespread functions. Recently, the functions for few HeRs have been revealed; however, the hypothetical functions remain largely unknown. Herein, we investigate light-modulation of heterodimeric multidrug resistance ATP-binding cassette transporters (OmrDE) mediated by Omithinimicrobium cerasi HeR. In this study, we classifiy genes flanking the HeR-encoding genes and identify highly conservative residues for protein–protein interactions. Our results reveal that the interaction between OcHeR and OmrDE shows positive cooperatively sequential binding through thermodynamic parameters. Moreover, light-induced OcHeR upregulates OmrDE drug transportation. Hence, the binding may be crucial to drug resistance in O. cerasi as it survives in a drug-containing habitat. Overall, we unveil a function of HeR as regulatory rhodopsin for multidrug resistance. Our findings suggest potential applications in optogenetic technology.

Background: Sleep accounts for approximately one-third of a person’s lifetime. It is a relaxing activity that relieves mental and physical fatigue. Pillows of different sizes, shapes, and materials have been designed to improve sleep quality by achieving an optimal sleep posture. Objects: This study aimed to determine which pillow provides the most comfortable and supports the head and neck during sleep, which may enhance sleep quality. Methods: Twenty-eight healthy adults (19 males and 9 females) with an average age of 29 years participated in this cross-sectional study. This experiment was conducted while the participants laid down for 5 minutes in four different pillow conditions: (1) no pillow (NP), (2) neck support foam pillow (NSFP), (3) standard microfiber filled pillow (SFP), and (4) hybrid foam pillow (HFP). The head-neck peak pressure, cranio-vertebral angle in supine (CVAs), cranio-horizontal angle in supine (CHAs), chin-sternum distance (CSD), and muscle tone of sternocleidomastoid were analyzed using one-way repeated measures analysis of variance (ANOVA). The significance level was set at p < 0.05. Results: The head-neck peak pressure was the highest in the NSFP condition, followed by the NP, SFP, and HFP conditions. The CVAs, CHAs, and CSD of the SFP were lower than those of the other pillows. Muscle tone was the highest in the NP condition, followed by the of NSFP, HFP, and SFP conditions. The participants subjective comfort level in both the supine and side-lying postures was highest in the HFP condition, followed by the SFP and NSFP conditions. Conclusion: This study can be used to establish the importance of pillow selection for highquality sleep. The results of this study, suggest that a hybrid pillow with a good supportive core and appropriate fluffiness can maintain comfort and correct cervical spine alignment during sleep.

Abstract Recycling of abandoned waste bottom ash has been a key issue in Republic of Korea in terms of environmental protection as well as economic concern. In this work, a method for recycling of abandoned bottom ash has been discussed based on the results from laboratory and industrial-scale experiments. Abandoned bottom ash was magnetically separated and properties of magnetically separated bottom ash samples as well as properties of mortar and masonry cement brick made of bottom ash were investigated. According to the experimental results, bulk and skeletal densities were ranked in the order of strongly magnetic > weakly magnetic > as-received > non-magnetic (from heavier to lighter) bottom ash. From laboratory-scale experiments, compressive strengths of mortars made of bottom ash samples (measured by ASTM C 109) were lower than that of mortar made of standard sand. Among bottom ash samples, mortar made of non-magnetic bottom ash (after removal of unburnt carbon) showed higher compressive strength with lower thermal conductivity (measured by ASTM C 1113) and weight than others. Masonry cement brick made of magnetic bottom ash showed lower weight and thermal conductivity than those made of standard sand, while meeting the KS strength guideline as a masonry cement brick. The results suggest the applicability of bottom ash as lightweight aggregate for production of masonry cement brick. However, considering the lower strength obtained from masonry cement brick made of as-received bottom ash (without removal of unburnt carbon), unburnt carbon content should be removed prior to its utilization as lightweight aggregate.

Abstract The Anthropocene has been framed around humanity's impact on atmospheric, biologic, and near‐surface processes, such as land use and vegetation change, greenhouse gas emissions, and the above‐ground hydrologic cycle. Groundwater extraction has lowered water tables in many key aquifers but comparatively little attention has been given to the impacts in the deeper subsurface. Here, we show that fluid fluxes from the extraction and injection of fluids associated with oil and gas production and inflow of water into mines likely exceed background flow rates in deep (>500 m) groundwater systems at a global scale. Projected carbon capture and sequestration (CCS), geothermal energy production, and lithium extraction to facilitate the energy transition will require fluid production rates exceeding current oil and co‐produced water extraction. Natural analogs and geochemical modeling indicate that subsurface fluid manipulation in the Anthropocene will likely appear in the rock record. The magnitude and importance of these changes are unclear, due to a lack of understanding of how deep subsurface hydrologic and geochemical cycles and associated microbial life interact with the rest of the Earth system.

Abstract Periodontitis is an infectious inflammation in the gums characterized by loss of periodontal ligaments and alveolar bone. Its persistent inflammation could result in tooth loss and other health issues. Ixeris dentata (IXD) and Lactobacillus gasseri media (LGM) demonstrated strong antioxidant activity, which may prevent oxidative and inflammatory periodontitis. Here, IXD and LGM extracts were investigated for antioxidative activity against oral discomfort and evaluated for their synergistic effect against oxidative and inflammatory periodontitis in a mouse model. IXD/LGM suppressed pro-inflammatory cytokines like interleukin (IL)-1β, IL-6, and TNF-α. Additionally, it reduced pro-inflammatory mediators, nitric oxide, iNOS (inducible nitric oxide synthase), and COX-2 (cyclooxygenase-2) and enhanced AKT, Nrf2, and HO-1 activation. Similarly, IXD/LGM treatment elevated osteogenic proteins and mRNAs; alkaline phosphatase, collagen type 1 (COL1), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2). Hematoxylin and Eosin (H&E) staining and micro-CT analysis confirm the positive impact of IXD/LGM on the periodontal structure and its associated inflammation. These findings demonstrate that IXD/LGM inhibits oxidative stress, periodontal inflammation, and its resultant alveolar bone loss in which Akt (also known as protein kinase B)-nuclear factor-erythroid 2-related factor 2 (Nrf2)-hemoxygenase-1 (HO-1) signaling is involved. Thus, IXD/LGM is a potential candidate against oxidative/inflammatory stress-associated periodontitis.

Varying risk-taking tendency is an important area of inquiry for the Carnegie perspective. Drawing on organizational learning literature, we develop a model to illuminate the mechanisms that can underlie time-varying risk taking tendency in entrepreneurship. In particular, we delineate conditions under which abrupt risk taking punctuates periods of risk-avoiding behaviors, a pattern that we call “intermittent risk taking.” We use serial entrepreneurs whose bouts with risk taking are often depicted as driven by an entrepreneurial itch to illustrate our model. In our conceptualization, decision makers engage in an interplay of experiential and vicarious learning as they move into and out of higher-risk self-employment (i.e., venture creation) with in-between stints in lower-risk wage-employment. Using a computational model to simulate the dynamics of this conceptualization, we find that vicarious learning from satisfied risk-avoiding peers can exert a pull that draws disappointed entrepreneurs into periods of risk avoidance (i.e., wage-employment). However, the moment that the satisfaction of these peers fails to convince, this pull wanes. In effect, the entrepreneur vicariously learns that the grass may not be greener on the other side which then leads them to return into self-employment. The itch for risk taking then recurs not necessarily because risky venture creation offers higher payoffs than risk-avoiding options but because decision makers come to see that risk avoidance may not be a satisfactory alternative either — a conceptualization that adds nuance to prior notions of varying risk tendencies and serial entrepreneurship.

Optimal medication management is important during hospitalization and at discharge because post-discharge adverse drug events (ADEs) are common, often preventable, and contribute to patient harms, healthcare utilization, and costs. Conduct a cost analysis of a comprehensive pharmacist-led transitions-of-care medication management intervention for older adults during and after hospital discharge. Twelve intervention components addressed medication reconciliation, medication review, and medication adherence. Trained, experienced pharmacists delivered the intervention to older adults with chronic comorbidities at 2 large U.S. academic centers. To quantify and categorize time spent on the intervention, we conducted a time-and-motion analysis of study pharmacists over 36 sequential workdays (14 519 min) involving 117 patients. For 40 patients’ hospitalizations, we observed all intervention activities. We used the median minutes spent and pharmacist wages nationally to calculate cost per hospitalization (2020 U.S. dollars) from the hospital perspective, relative to usual care. Pharmacists spent a median of 66.9 min per hospitalization (interquartile range 46.1-90.1), equating to $101 ($86 to $116 in sensitivity analyses). In unadjusted analyses, study site was associated with time spent (medians 111 and 51.8 min) while patient primary language, discharge disposition, number of outpatient medications, and patient age were not. In this cost analysis, comprehensive medication management around discharge cost about $101 per hospitalization, with variation across sites. This cost is at least an order of magnitude less than published costs associated with ADEs, hospital readmissions, or other interventions designed to reduce readmissions. Work is ongoing to assess the current intervention’s effectiveness.

Background: The utilization of herbal medicine has been noteworthy for treating cancer; however, there is not enough information regarding the characteristics of clinical trials of herbal medicine interventions. This study aimed to evaluate the characteristic of registered trials using herbal medicine interventions for cancer. Methods: A cross-sectional study was performed via the website ClinicalTrials.gov, ISRCTN registry, Chinese clinical trial registry, and international clinical trials registry platform to gather associated registered clinical trials using an advanced search with the developed keyword strategy as of March 26, 2023. All obtainable information from the trials was collected without any restrictions to conduct a comprehensive review. Results: A total of 169 registered trials were included for evaluation. Of all trials, 102 trials were eligible for this study. Countries from Asia registered the most trials (62.75%), and hospitals sponsored most of the trials (42.16%). Randomized, Phase 2, interventional trials were dominant, and approximately 64.71% of the trials anticipated recruiting less than 100 participants. More than half of the trials were from 2016 to 2023 (53.92%). While 45 trials were completed, only 16 trials had results for further analysis. According to the completed results, the types of herbal medicines from the trials mainly focused on lung, breast, and colorectal cancer. Conclusion: This study is the first to explore the characteristics of clinical trials of herbal medicine for cancer registered in large clinical databases. The acquired trials had relatively informative data; however, better-designed trials may be needed for health professionals to consider herbal medicine as an option when treating cancer patients.

At depths of over 500 m, deep groundwater has long residence times and likely contributes less than 0.1% to global streamflow and only sporadically connects with the surface terrestrial water cycle on geological timescales, according to estimates derived from the chloride mass balance approach.

Abstract Objectives We evaluated the association between cardiovascular risk factors and the magnitude of the difference in systolic blood pressure (SBP) between office and ambulatory measurements (masked effect) in untreated individuals without apparent hypertension-mediated organ damage (HMOD). Methods The inclusion criteria were 1) age ≥ 20 years, 2) blood pressure ≥ 140/90 mmHg at the outpatient clinic, and 3) not receiving antihypertensive medications. The difference between office and ambulatory SBP was calculated by subtracting the ambulatory daytime SBP from the office SBP. The association between the masked effect and SBP variability was analyzed in individuals without HMOD (no electrocardiographic left ventricular hypertrophy, spot urine albumin-to-creatinine ratio -5 mmHg exhibited a higher SD and cv of 24-h SBP than those with a negative SBP difference ≤ -5 mmHg or a positive SBP difference. Conclusions The results of our study suggest that the magnitude of the negative difference in office and ambulatory SBP may be a potential risk factor, even in individuals without apparent HMOD. Trial registration This trial is registered with ClinicalTrials.gov ( NCT03855605 ).

Ulcerative colitis is a chronic inflammatory disease caused by abnormal immune responses in the intestinal mucosa and gut microorganisms. Unlike other mugworts, Artemisia argyi H. (A. argyi H.) enhances antioxidant, anti-inflammatory, and anticancer effects, but the improvement effects against gut inflammation have not yet been reported. Therefore, this study aimed to confirm the alleviation of the inflammatory state in the gut by A. argyi H. fermented with Lactobacillus plantarum (FAA), using lipopolysaccharide (LPS)-induced RAW 264.7 cells and dextran sulfate sodium (DSS)-induced colitis models. In vitro, FAA (10, 50, 100, and 200 μg/mL) was pretreated into RAW 264.7 cells, followed with LPS (100 ng/mL), which induced the cell damage. Meanwhile, in vivo, FAA (100, 200 mg/kg/day) was orally administered into 6-week-old C57BL/6N mice for 3 weeks. During the last week of FAA administration, 2.5% DSS was used to induce colitis. The results showed that FAA reduced the production of nitric oxide (p < 0.0001), tumor necrosis factor (TNF)-α, interleukin (IL)-6 (p < 0.0001), and IL-1β (p < 0.0001) in the LPS-induced RAW 264.7 cells. Moreover, in the DSS-induced colitis model, FAA alleviated clinical symptoms (p < 0.001), inhibited the inflammatory state by reducing the production of TNF-α (p < 0.0001) and interferon-γ in intestinal immune cells (p < 0.0001), and strengthened the intestinal barrier by increasing the number of goblet cells (p < 0.0001). Furthermore, the anti-inflammatory effects were confirmed by the alleviation of histological damage (p < 0.001) and down-regulation of the expression of inflammatory proteins (TLR4, p < 0.0001; MyD88, p < 0.0001; Cox-2, p < 0.0001). These results suggest the potential of FAA as a dietary ingredient for preventing inflammation in the gut.

IgE is a critical component of the allergic response and therapeutic targeting can alleviate symptomology. Here the authors propose the combined use of Bifidobacterium longum and a FcεRIα extracellular domain linked to a IgD/IgG4 hybrid Fc domain fusion protein called IgETRAP and show reduction of mast cell and IgE levels in models of food allergy.

Abstract How subsurface microbial life changed at the bottom of the kilometers‐deep (hypo) Critical Zone in response to evolving surface conditions over geologic time is an open question. This study investigates the burial and exhumation, biodegradation, and fluid circulation history of hydrocarbon reservoirs across the Colorado Plateau as a window into the hypo‐Critical Zone. Hydrocarbon reservoirs, in the Paradox and Uinta basins, were deeply buried starting ca. 100 to 60 Ma, reaching temperatures >80–140°C, likely sterilizing microbial communities present since the deposition of sediments. High salinities associated with evaporites may have further limited microbial activity. Upward migration of hydrocarbons from shale source rocks into shallower reservoirs during maximum burial set the stage for microbial re‐introduction by creating organic‐rich “hot spots.” Denudation related to the incision of the Colorado River over the past few million years brought reservoirs closer to the surface under cooler temperatures, enhanced deep meteoric water circulation and flushing of saline fluids, and likely re‐inoculated more permeable sediments up to several km depth. Modern‐ to paleo‐hydrocarbon reservoirs show molecular and isotopic evidence of anaerobic oxidation of hydrocarbons coupled to bacterial sulfate reduction in areas with relatively high SO4‐fluxes. Anaerobic oil biodegradation rates are high enough to explain the removal of at least some portion of postulated “supergiant oil fields” across the Colorado Plateau by microbial activity over the past several million years. Results from this study help constrain the lower limits of the hypo‐Critical Zone and how it evolved over geologic time, in response to changing geologic, hydrologic, and biologic forcings.

BackgroundBecause of the short half-life of non-vitamin K antagonist oral anticoagulants (NOACs), consistent drug adherence is crucial to maintain the effect of anticoagulants for stroke prevention in atrial fibrillation (AF). Considering the low adherence to NOACs in practice, we developed a mobile health platform that provides an alert for drug intake, visual confirmation of drug administration, and a list of medication intake history. This study aims to evaluate whether this smartphone app-based intervention will increase drug adherence compared with usual care in patients with AF requiring NOACs in a large population.MethodsThis prospective, randomized, open-label, multicenter trial (RIVOX-AF study) will include a total of 1,042 patients (521 patients in the intervention group and 521 patients in the control group) from 13 tertiary hospitals in South Korea. Patients with AF aged ≥19 years with one or more comorbidities, including heart failure, myocardial infarction, stable angina, hypertension, or diabetes mellitus, will be included in this study. Participants will be randomly assigned to either the intervention group (MEDI-app) or the conventional treatment group in a 1:1 ratio using a web-based randomization service. The intervention group will use a smartphone app that includes an alarm for drug intake, visual confirmation of drug administration through a camera check, and presentation of a list of medication intake history. The primary endpoint is adherence to rivaroxaban by pill count measurements at 12 and 24 weeks. The key secondary endpoints are clinical composite endpoints, including systemic embolic events, stroke, major bleeding requiring transfusion or hospitalization, or death during the 24 weeks of follow-up.DiscussionThis randomized controlled trial will investigate the feasibility and efficacy of smartphone apps and mobile health platforms in improving adherence to NOACs.Trial registrationThe study design has been registered in ClinicalTrial.gov (NCT05557123).

Structural alignment and molecular docking identifies a mutation on helix E and F of the opsin backbone of the Gloeobacteria rhodopsin, presenting more insight on the carotenoid-binding pocket.

Abstract Therapeutic dentin regeneration remains difficult to achieve, and a majority of the attention has been given to anabolic strategies to promote dentinogenesis directly, whereas, the available literature is insufficient to understand the role of inflammation and inflammatory complement system on dentinogenesis. The aim of this study is to determine the role of complement C5a receptor (C5aR) in regulating dental pulp stem cells (DPSCs) differentiation and in vivo dentin regeneration. Human DPSCs were subjected to odontogenic differentiation in osteogenic media treated with the C5aR agonist and C5aR antagonist. In vivo dentin formation was evaluated using the dentin injury/pulp-capping model of the C5a-deficient and wild-type mice. In vitro results demonstrate that C5aR inhibition caused a substantial reduction in odontogenic DPSCs differentiation markers such as DMP-1 and DSPP, while the C5aR activation increased these key odontogenic genes compared to control. A reparative dentin formation using the C5a-deficient mice shows that dentin regeneration is significantly reduced in the C5a-deficient mice. These data suggest a positive role of C5aR in the odontogenic DPSCs differentiation and tertiary/reparative dentin formation. This study addresses a novel regulatory pathway and a therapeutic approach for improving the efficiency of dentin regeneration in affected teeth.

BackgroundUntact cultures have rapidly spread around the world as a result of the prolongation of the COVID-19 pandemic, leading to various types of research and technological developments in the fields of medicine and health care, where digital health care refers to health care services provided in a digital environment. Previous studies relating to digital health care demonstrated its effectiveness in managing chronic diseases such as hypertension and diabetes. While many studies have applied digital health care to various diseases, daily health care is needed for healthy individuals before they are diagnosed with a disease. Accordingly, research on individuals who have not been diagnosed with a disease is also necessary. ObjectiveThis study aimed to identify the effects of using a customized digital health care service (CDHCS) on risk factors for metabolic syndrome (MS) and lifestyle improvement. MethodsThe population consisted of 63 adults who underwent a health checkup at the National Health Insurance Service Ilsan (NHIS) Hospital in 2020. Measured variables include basic clinical indicators, MS-related variables, and lifestyle variables. All items were measured at NHIS Ilsan Hospital before the use of the CDHCS and 3 months thereafter. The CDHCS used in this study is a mobile app that analyzes the health condition of the user by identifying their risk factors and provides appropriate health care content. For comparison between before and after CDHCS use (pre-post comparison), paired t test was used for continuous variables, and a chi-square test was used for nominal variables. ResultsThe study population included 30 (47.6%) male and 33 (52.4%) female participants, and the mean age was 47.61 (SD 13.93) years. The changes in clinical indicators before and after intervention results showed a decrease in weight, waist circumference, triglyceride, and high-density lipoprotein cholesterol and increases in systolic blood pressure and diastolic blood pressure. The distribution of the risk group increased from 32 (50.8%) to 34 (54%) and that of the MS group decreased from 18 (28.6%) to 16 (25.4%). The mean metabolic syndrome age–chronological age before the CDHCS was 2.20 years, which decreased to 1.72 years after CDHCS, showing a decrease of 0.48 years in the mean metabolic syndrome age–chronological age after the intervention. While all lifestyle variables, except alcohol consumption, showed a tendency toward improvement, the differences were not statistically significant. ConclusionsAlthough there was no statistical significance in the variables under study, this pilot study will provide a foundation for more accurate verification of CDHCS in future research.

Objectives The world is witnessing a sharp increase in its elderly population, accelerated by longer life expectancy and lower birth rates, which in turn imposes enormous medical burden on society. Although numerous studies have predicted medical expenses based on region, gender, and chronological age (CA), any attempt has rarely been made to utilize biological age (BA)—an indicator of health and aging—to ascertain and predict factors related to medical expenses and medical care use. Thus, this study employs BA to predict factors that affect medical expenses and medical care use. Materials and methods Referring to the health screening cohort database of the National Health Insurance Service (NHIS), this study targeted 276,723 adults who underwent health check-ups in 2009−2010 and kept track of the data on their medical expenses and medical care use up to 2019. The average follow-up period is 9.12 years. Twelve clinical indicators were used to measure BA, while the total annual medical expenses, total annual number of outpatient days, total annual number of days in hospital, and average annual increases in medical expenses were used as the variables for medical expenses and medical care use. For statistical analysis, this study employed Pearson correlation analysis and multiple regression analysis. Results Regression analysis of the differences between corrected biological age (cBA) and CA exhibited statistically significant increases (pConclusions This study quantified decreases in the variables for medical expenses and medical care use based on improved BA, thereby motivating people to become more health-conscious. In particular, this study is significant in that it is the first of its kind to predict medical expenses and medical care use through BA.

This study aims to investigate the protective effects and mechanisms of pectolinarin against oxidative stress-induced cell damage in SH-SY5Y cells. Neurodegenerative diseases—such as Alzheimer’s disease—are potentially associated with oxidative stress, which causes excessive production of reactive oxygen species (ROS) that damage DNA and proteins in neuronal cells. The results of this study demonstrate that pectolinarin can scavenge hydroxyl and nitric oxide radicals in a concentration-dependent manner. Moreover, pectolinarin significantly increased cell viability while reducing ROS production and LDH release in the hydrogen peroxide (H2O2)-induced control group. Additionally, Pectolinarin recovered protein expression from H2O2-altered levels back to close-to-normal SH-SY5Y cell levels for components of the oxidative stress, inflammation, and apoptosis pathways—such as nuclear factor erythroid 2-related factor 2 (Nrf2), kelch-like ECH-associated protein (Keap1), anti-heme oxygenase 1 (HO-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), B-cell lympho-ma-2 (Bcl-2) protein, and Bcl-2-associated X protein (Bax). These findings suggest that pectolinarin has the potential to be used as a plant material for functional foods to be applied in the treatment of neurodegenerative diseases, such as Alzheimer’s disease, by mitigating oxidative stress-induced damage to neuronal cells.

Abstract The authors developed and validated a diagnostic algorithm using the optimal upper and lower cut‐off values of office and home BP at which ambulatory BP measurements need to be applied. Patients presenting with high BP (≥140/90 mm Hg) at the outpatient clinic were referred to measure office, home, and ambulatory BP. Office and home BP were divided into hypertension, intermediate (requiring diagnosis using ambulatory BP), and normotension zones. The upper and lower BP cut‐off levels of intermediate zone were determined corresponding to a level of 95% specificity and 95% sensitivity for detecting daytime ambulatory hypertension by using the receiver operator characteristic curve. A diagnostic algorithm using three methods, OBP‐ABP: office BP measurement and subsequent ambulatory BP measurements if office BP is intermediate zone; OBP‐HBP‐ABP: office BP, subsequent home BP measurement if office BP is within intermediate zone and subsequent ambulatory BP measurement if home BP is within intermediate zone; and HBP‐ABP: home BP measurement and subsequent ambulatory BP measurements if home BP is within intermediate zone, were developed and validated. In the development population (n = 256), the developed algorithm yielded better diagnostic accuracies than 75.8% (95%CI 70.1–80.9) for office BP alone and 76.2% (95%CI 70.5–81.3) for home BP alone as follows: 96.5% (95%CI: 93.4–98.4) for OBP‐ABP, 93.4% (95%CI: 89.6–96.1) for OBP‐HBP‐ABP, and 94.9% (95%CI: 91.5–97.3%) for HBP‐ABP. In the validation population (n = 399), the developed algorithm showed similarly improved diagnostic accuracy. The developed algorithm applying ambulatory BP measurement to the intermediate zone of office and home BP improves the diagnostic accuracy for hypertension.

The odontoblastic differentiation of dental pulp stem cells (DPSCs) associated with caries injury happens in an inflammatory context. We recently demonstrated that there is a link between inflammation and dental tissue regeneration, identified via enhanced DPSC-mediated dentinogenesis in vitro. Brain-derived neurotrophic factor (BDNF) is a nerve growth factor-related gene family molecule which functions through tropomyosin receptor kinase B (TrkB). While the roles of BDNF in neural tissue repair and other regeneration processes are well identified, its role in dentinogenesis has not been explored. Furthermore, the role of BDNF receptor-TrkB in inflammation-induced dentinogenesis remains unknown. The role of BDNF/TrkB was examined during a 17-day odontogenic differentiation of DPSCs. Human DPSCs were subjected to odontogenic differentiation in dentinogenic media treated with inflammation inducers (LTA or TNFα), BDNF, and a TrkB agonist (LM22A-4) and/or antagonist (CTX-B). Our data show that BDNF and TrkB receptors affect the early and late stages of the odontogenic differentiation of DPSCs. Immunofluorescent data confirmed the expression of BDNF and TrkB in DPSCs. Our ELISA and qPCR data demonstrate that TrkB agonist treatment increased the expression of dentin matrix protein-1 (DMP-1) during early DPSC odontoblastic differentiation. Coherently, the expression levels of runt-related transcription factor 2 (RUNX-2) and osteocalcin (OCN) were increased. TNFα, which is responsible for a diverse range of inflammation signaling, increased the levels of expression of dentin sialophosphoprotein (DSPP) and DMP1. Furthermore, BDNF significantly potentiated its effect. The application of CTX-B reversed this effect, suggesting TrkB`s critical role in TNFα-mediated dentinogenesis. Our studies provide novel findings on the role of BDNF-TrkB in the inflammation-induced odontoblastic differentiation of DPSCs. This finding will address a novel regulatory pathway and a therapeutic approach in dentin tissue engineering using DPSCs.

Background/Aims Ascertaining the prevalence of isolated nocturnal hypertension (INHT) in the general population and identifying the characteristics of patients with INHT may be important to determine patients who should receive 24- hour ambulatory blood pressure (BP) measurements. This study aimed to evaluate the prevalence and characteristics of INHT in the general population. Methods Of 1,128 participants (aged 20 to 70 years), we analyzed 823 who had valid 24-hour ambulatory BP measurements and were not on antihypertensive drug treatment. Results The prevalence of INHT in the study was 22.8%. Individuals with INHT had a higher office, 24-hour, and daytime and nighttime ambulatory systolic and diastolic BPs compared to individuals with sustained day-night normotension. INHT was more prevalent in individuals with masked hypertension (MH) than in those with sustained hypertension (59.8% vs. 15.6%, p < 0.001). Among individuals with INHT, 92.6% had MH. Among individuals with office BP-based prehypertension, 34.5% had both INHT and MH. The prevalence of INHT was highest in individuals with office BP-based prehypertension. INHT was an independent determinant of MH after adjustment for age, sex, body mass index, diabetes, low-density-lipoprotein cholesterol, 24-hour systolic and diastolic BP, systolic and diastolic BP dipping, and systolic and diastolic BP non-dipping. Conclusions The present study showed that INHT is not uncommon and is a major determinant of MH. Our findings strongly suggest the use of 24-hour ambulatory BP measurement for individuals within the prehypertension range of office BP owing to the high prevalence of INHT and MH in this population.

ABSTRACT Purpose: To identify an optimal self-expandable metallic stent (SEMS) and verify whether a mechanically superior SEMS would result in better clinical outcomes in the treatment of tracheal collapse. Methods: We selected three SEMS (n = 8 each), including an S-type stent with a wire diameter of 0.006 inches (S6) and two D-type stents with wire diameters of 0.006 (D6) and 0.007 inches (D7). Twenty-four New Zealand White rabbits were divided into three equal groups. After the stents were deployed, the clinical signs were recorded daily, and radiographic examinations were performed monthly. All rabbits were euthanized after three months. Results: Two rabbits with S6 stents and one rabbit with a D7 stent died within three months because of stent migration or pneumonia. All rabbits with D6 stents survived for three months. On histological examination, the D6 group had the lowest inflammation score. Conclusions: Both clinically and histopathologically, the results with D-type stents with a wire diameter of 0.006 inches were superior to those of the other groups (p = 0.001). The use of an optimal intraluminal stent may improve the long-term clinical outcomes in the treatment of tracheal collapse in dogs.

Amyloid beta (Aβ) is a neurotoxic peptide and a key factor causing Alzheimer’s disease. Cirsium japonicum var. maackii (CJM) has neuroprotective effects, but the protective effects of the flower from CJM (FCJM) on the neural system remain unclear. This study aimed to identify the fraction of FCJM with the highest neuroprotective potential and investigate its protective mechanisms against Aβ25–35-induced inflammation in C6 glial cells. The cell viability and generation of reactive oxygen species (ROS) were measured to investigate the positive effect of FCJM on oxidative stress. Treatment with the FCJM extract or fractions increased the cell viability to 60–70% compared with 52% in the Aβ25–35-treated control group and decreased ROS production to 84% compared with 100% in the control group. The ethyl acetate fraction of FCJM (EFCJM) was the most effective among all the extracts and fractions. We analyzed the protective mechanisms of EFCJM on Aβ25–35-induced inflammation in C6 glial cells using Western blot. EFCJM downregulated amyloidogenic pathway-related proteins, such as Aβ precursor protein, β-secretase, presenilin 1, and presenilin 2. Moreover, EFCJM attenuated the Bax/Bcl-2 ratio, an index of apoptosis, and upregulated the oxidative stress-related protein, heme oxygenase-1. Therefore, this study demonstrated that FCJM improves cell viability and inhibits ROS in Aβ25–35-treated C6 glial cells. Furthermore, EFCJM exhibits neuroprotective effects in Aβ25–35-induced inflammation in C6 glial cells by modulating oxidative stress and amyloidogenic and apoptosis signaling pathways. FCJM, especially EFCJM, can be a promising agent for neurodegenerative disease prevention.

Membrane-free stem cell extract (MFSCE) derived from adipose tissue has been reported to have anti-inflammatory activity. In the present study, we investigated the effects of MFSCE on atopic dermatitis (AD)-like skin inflammation using house-dust-mite-sensitized NC/Nga mice. Topical application of MFSCE significantly ameliorated AD-like clinical symptoms including erythema, dry skin, edema, excoriation, erosion, lichenification, and scratching. In addition, the levels of serum immunoglobulin E and inflammatory cytokines were decreased by MFSCE treatment. Furthermore, treatment with MFSCE inhibited the increase in epidermal thickness, infiltration of mast cells, expression of interleukin (IL)-4, IL-10, interferon-γ, tumor necrosis factor-α, thymus, and activation-regulated chemokines in the dorsal skin of NC/Nga mice. In conclusion, MFSCE effectively suppressed AD-like manifestations preclinically, systemically, and topically. Our study suggests that MFSCE may be a useful natural product for AD therapeutic strategies.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted primarily through droplets, and dental practitioners are at risk of occupational exposure to SARS-CoV-2 infection owing to direct contact with the patient’s mouth, aerosols from dental procedures, and saliva. Wearing a mask is believed to be the best method of protection against infection, and a systematic literature review was conducted on whether the dental masks used in dentistry are effective in preventing Coronavirus Infectious Disease-19 (COVID-19).Methods: We used PubMed, Google Scholar, DBpia, NDSL, and KISS databases for this study. Of the 917 documents narrowed down by the search terms “Coronavirus, COVID-19, and dental,” 83 documents were collected and studied. Ultimately, 42 of these papers were selected for analysis after considering duplication from the flow chart of the literature selection process.Results: While dental masks are often used when treating patients with unknown COVID-19 status, the Ministry of Food and Drug Safety stated that the use of dental masks is insufficient in preventing cross-transmission of COVID-19; instead, it was recommended that N95 masks, which correspond to KF94 masks, should be worn daily. On the other hand, wearing a dental mask and following precautions such as hand hygiene may not pose a significantly higher risk of infection than wearing an N95 mask when treating COVID-19 patients.Conclusion: There is an ongoing discussion regarding the use of dental masks when treating dental patients, and many argue that different types of masks should be selected according to the degree of infection and the individual's respiratory condition. By considering the safety and efficacy of dental masks in preventing infection, improvements can be made in the management of COVID-19 and dental-related infections.

Previous studies have reported that deep neck flexor (DNF) exercise can improve neck problems, including neck pain, forward head posture, and headache, by targeting the deep and superficial muscles of the neck. Despite the prevailing opinion across studies, the benefits of DNF can vary according to the type of neck problems and the outcome measures adopted, ranging from positive outcomes to non-significant benefits. A meta-analysis was conducted in this study to assess conclusive evidence of the impact of DNF exercise on individuals with neck problems. We used PUBMED, MEDLINE, NDSL, EMBASE, and Web of Science to search for primary studies and the key terms used in these searches were “forward head posture (FHP),” “biofeedback,” “pressure biofeedback unit,” “stabilizer,” “headache,” and “neck pain.” Twenty- four eligible studies were included in this meta-analysis and were coded according to the type of neck problems and outcome measures described, such as pain, endurance, involvement of neck muscle, craniovertebral angle (CVA), neck disability index (NDI), cervical range of motion (CROM), radiographs of the neck, posture, strength, endurance, and headache disability index. The overall effect size of the DNF exercise was 0.489. The effect sizes of the neck problems were 0.556 (neck pain), –1.278 (FHP), 0.176 (headache), and 1.850 (mix). The effect sizes of outcome measures were 1.045 (pain), 0.966 (endurance), 0.894 (deep neck flexor), 0.608 (superficial neck flexor), 0.487 (CVA), 0.409 (NDI), and 0.252 (CROM). According to the results of this study, DNF exercise can effectively reduce neck pain. Thus, DNF exercise is highly recommend as an effective exercise method for individuals suffering from neck pain.

Background: The hamstring is a muscle that crosses two joints, that is the hip and knee, and its flexibility is an important indicator of physical health in its role in many activities of daily living such as sitting, walking, and running. Limited range of motion (ROM) due to hamstring tightness is strongly related to back pain and malfunction of the hip joint. High-frequency diathermy (HFD) therapy is known to be effective in relaxing the muscle and increasing ROM. Objects: To investigate the effects of HFD on active knee extension ROM and hamstring tone and stiffness in participants with hamstring tightness. Methods: Twenty-four participants with hamstring tightness were recruited, and the operational definition of hamstring tightness in this study was active knee extension ROM of below 160° at 90° hip flexion in the supine position. HFD was applied to the hamstring for 15 minutes using the WINBACK device. All participants were examined before and after the intervention, and the results were analyzed using a paired t-test. The outcome measures included knee extension ROM, the viscoelastic property of the hamstring, and peak torque for passive knee extension. Results: The active knee extension ROM significantly increased from 138.8° ± 9.9° (mean ± standard deviation) to 143.9° ± 10.4° after the intervention (p < 0.05), while viscoelastic property of the hamstring significantly decreased (p < 0.05). Also, the peak torque for knee extension significantly decreased (p < 0.05). Conclusion: Application of HFD for 15 minutes to tight hamstrings immediately improves the active ROM and reduces the tone, stiffness, and elasticity of the muscle. However, further experiments are required to examine the long-term effects of HFD on hamstring tightness including pain reduction, postural improvement around the pelvis and lower extremities, and enhanced functional movement.

Abstract The present study aims to investigate functional involvement of brain areas in consumers’ evaluation of brand extension that refers to the use of well-established brand for launching new offerings. During functional magnetic resonance imaging (fMRI) scanning, participants viewed a beverage brand name followed by an extension goods name selected from the beverage or household appliance categories. They responded acceptability to given brand extension. Both acceptability responses and reaction time revealed a noticeable pattern that participants responded to acceptable stimuli more carefully. General linear model (GLM) analyses revealed the involvement of insular activity in brand extension evaluation. Especially, insular activity was lateralized according to valence. Furthermore, its activity could explain behavioral response in parametric modulation model. According to these results, we speculate that insula activity is relevant to emotional processing. Finally, we divided neural activities during brand extension into separated clusters using a hierarchical clustering-based connectivity analysis. Excluding two of them related to sensorimotor functions for behavioral responses, the remaining cluster, including bilateral insula, was likely to reflect brand extension assessment. Hence, we speculate that consumers’ brand extension evaluation may involve emotional processes, shown as insular activity.

Laser scabbling is one of the options that can be used for removal of contaminated concrete when decommissioning and dismantling of nuclear power plant. Laser scabbling can be advantageous for such purpose because laser can transmit through long-distance and the system operates remotely in dry condition while minimizing the human access to the radioactively contaminated area. In order to investigate the applicability of laser scabbling on concrete, the experimental program was conducted on concrete with various moisture content, fine aggregate ratio with different paste content. According to the results, concrete in oven dry condition showed no efficiency on laser scabbling. The surface of the concrete was vitrified as a result. However, a 5 kW fiber laser with 900 mm stand-off distance was successfully applied for laser scabbling of air dry and saturated surface dry concretes. It was found that the moisture is a prerequisite requirement for successful laser scabbling of concrete. The changes in fine aggregate ratio and paste content did not affect the efficiency of laser scabbling.

Background This study assessed the proportion of risk-stratified Korean patients with dyslipidemia achieving their low-density lipoprotein cholesterol (LDL-C) targets as defined by the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) (2011) guidelines while receiving lipid-modifying treatments (LMTs). Methods In this multicenter, cross-sectional, observational study, we evaluated data from Korean patients aged ≥19 years who were receiving LMTs for ≥3 months and had an LDL-C value within the previous 12 months on the same LMT. Data were collected for demographics, cardiovascular (CV) risk factors, medical history, and healthcare consumption. Patients were risk-stratified according to the ESC Systematic COronary Risk Evaluation (SCORE) chart and LDL-C target achievement rate was assessed. Results Guideline-based risk-stratification of the 1,034 patients showed the majority (72.2%) to be in the very high-risk category. Investigators’ assessment of risk was underestimated in 71.6% compared to ESC/EAS guidelines. Overall LDL-C target achievement rate was 44.3%; target achievement was the highest (66.0%) in moderate-risk patients and the lowest (39.0%) in very high-risk patients. Overall 97.1% patients were receiving statin therapy, mostly as a single-agent (89.2%). High-intensity statins and the highest permissible dose of high-intensity statins had been prescribed to only 9.1% and 7.3% patients in the very high-risk group, respectively. Physician satisfaction with patients’ LDL-C levels was the primary reason for non-intensification of statin therapy. Conclusion Achievement of target LDL-C level is suboptimal in Korean patients with dyslipidemia, especially in those at very high-risk of CV events. Current practices in LMTs need to be improved based on precise CV risk evaluation posed by dyslipidemia.

Background: The gastrocnemius (GCM) is one of the lower extremity muscles that tend to tighten easily. GCM tightness results in limited ankle dorsi-flexion (DF), especially when the knee joint is fully extended. Joint flexibility is determined by the morphological and physiological characteristics of joints, muscles, tendons, and ligaments. Impaired joint flexibility can be attributed to increased susceptibility to muscle injury. High-frequency diathermy is clinically used to reduce pain and muscle tightness and to improve limited range of motion. Objects: This study aimed to investigate the immediate effects of high-frequency therapy in subjects with GCM tightness. Methods: The study was designed as a one-group before–after trial. The subjects included 28 volunteers with GCM tightness (an active ankle DF angle of less than 12°) without any known neurological and musculoskeletal pathologies in the ankle and calf areas. WINBACK Transfer Electrode Capacitive and Resistive Therapy equipment was used to apply high-frequency therapy to the subjects’ GCMs for 10–15 minutes. The pennation angle and the fascicle length of the GCM were measured using ultrasonography. The flexibility of the ankle joint, peak torque to the passive ankle DF (Biodex), and soft tissue stiffness (MyotonPRO) were also measured. Results: The pennation angle was significantly decreased following the treatment; however, no significant difference in the fascicle length was found (p < 0.05). The flexibility was significantly increased and both the passive peak torque to passive ankle DF and the soft tissue stiffness significantly decreased (p < 0.05). Conclusion: High-frequency therapy is immediately effective for improving the muscle’s architectural properties and functional factors in subjects with GCM tightness. Further longitudinal clinical studies are required to investigate the long-term effects of high-frequency therapy on subjects with GCM tightness from various causes.

In this present study, we examined the anti-inflammatory and anti-oxidative properties of alcoholic lemon myrtle extract (LME). The total polyphenol and flavonoid content of LME were determined as 118.77 and 14.53 mg/g extract, respectively. LME showed anti-oxidative properties, such as 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2′-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid) (ABTS) radical scavenging activity. The anti-inflammatory activities of LME were investigated using the lipopolysaccharide-stimulated murine macrophage RAW 264.7 cells. Pretreatment with LME was performed at non-cytotoxic concentrations of 10–100 μg/mL. LME inhibited the production of inflammatory mediators such as nitric oxide (NO). Enzyme-linked immunosorbent assay and reverse-transcriptase polymerase chain reaction (RT-PCR) revealed that pretreatment with LME suppressed the protein expression and mRNA levels of pro-inflammatory cytokines such as interleukin IL-6, and tumor necrosis factor (TNF)-α in a concentration-dependent manner, respectively. These results suggest that LME could be used as a potential therapeutic agent having potent anti-inflammatory effects that could be used to treat inflammatory bowel disease.

A 4-year-old mixed breed dog and a 19-year-old English cocker spaniel dog were evaluated for fecal incontinence. The second dog’s fecal incontinence was associated with the anal mass. In both dogs, reconstruction of the external anal sphincter was required to gain fecal continence. Especially in the dog with an anal mass, the whole musculature involved in fecal continence was removed with the affected anorectum. Conventional surgical treatments for fecal incontinence have limitations in terms of muscle flap length and complexity of the surgical procedure. A modified surgical technique using the semitendinosus muscle was devised in the present study to overcome these limitations. The distal part of the semitendinosus muscle was bifurcated to make two muscle bundles, used to completely encircle the anorectum. These muscle bundles were sutured to the surrounding rectal muscle and the pelvic diaphragm to simulate the function of the external anal sphincter. Three months after surgery, both dogs showed significantly improved fecal continence without severe complications, such as infection, dehiscence, or lameness of the limb where the semitendinosus muscle was harvested. The outcomes of the two dogs supported the acceptability of the bifurcated muscle flap for anal sphincter augmentation. In addition, this report showed the possibility of more diverse applications of semitendinosus muscle in dogs.

Hair loss is a disease that requires accurate diagnosis and type-specific medical treatment. Many hair loss treatments have some side effects, such as hormone-related effects, so there is a need for safe and effective hair loss treatment. In this study, we investigated the effects of Lactobacillus paracasei HY7015 (HY7015) and Lycopus lucidus Turcz. (LT) extract on hair regrowth and protection. In vitro experiments were conducted to assess the effects of HY7015 and/or LT extract on human follicle dermal papilla cells (HFDPC) of cytoprotective functions such as proliferations, antioxidants, anti-inflammatory, and growth factor expressions. In animal experiments, we investigated hair regrowth rate, hair follicle formation and secretion of growth factors in telogenic C57BL/6 mice. We confirmed the cytoprotective effects of HY7015 and LT through regulations of proliferation, SOD and IL-1β in HFDPC. In mouse experiments, oral administration of HY7015 and LT promoted hair regrowth as well as hair follicle maturation in the dermal skin of C57BL/6 mice, and upregulated VEGF and IGF-1 growth factor levels in mouse serum. In summary, our data demonstrate that ingestions of HY7015 and LT can promote hair regrowth by enhancing cytoprotective effects and expressions of growth factors.

Abstract Global groundwater volumes in the upper 2 km of the Earth's continental crust—critical for water security—are well estimated. Beyond these depths, a vast body of largely saline and non‐potable groundwater exists down to at least 10 km—a volume that has not yet been quantified reliably at the global scale. Here, we estimate the amount of groundwater present in the upper 10 km of the Earth's continental crust by examining the distribution of sedimentary and crystalline rocks with depth and applying porosity‐depth relationships. We demonstrate that groundwater in the 2–10 km zone (what we call “deep groundwater”) has a volume comparable to that of groundwater in the upper 2 km of the Earth's crust. These new estimates make groundwater the largest continental reservoir of water, ahead of ice sheets, provide a basis to quantify geochemical cycles, and constrain the potential for large‐scale isolation of waste fluids.

While tactile sensation plays an essential role in interactions with the surroundings, relatively little is known about the neural processes involved in the perception of tactile information. In particular, it remains unclear how different intensities of tactile hardness are represented in the human brain during object manipulation. This study aims to investigate neural responses to various levels of tactile hardness using functional magnetic resonance imaging while people grasp objects to perceive hardness intensity. We used four items with different hardness levels but otherwise identical in shape and texture. A total of Twenty-five healthy volunteers participated in this study. Before scanning, participants performed a behavioral task in which they received a pair of stimuli and they were to report the perceived difference of hardness between them. During scanning, without any visual information, they were randomly given one of the four objects and asked to grasp it. We found significant blood oxygen-level-dependent (BOLD) responses in the posterior insula in the right hemisphere (rpIns) and the right posterior lobe of the cerebellum (rpCerebellum), which parametrically tracked hardness intensity. These responses were supported by BOLD signal changes in the rpCerebellum and rpIns correlating with tactile hardness intensity. Multidimensional scaling analysis showed similar representations of hardness intensity among physical, perceptual, and neural information. Our findings demonstrate the engagement of the rpCerebellum and rpIns in perceiving tactile hardness intensity during active object manipulation.

Background/Aims Efficacy and safety data of alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), is not yet well established in the Korean population. We assessed them in ODYSSEY-KT through the pre-specified Korean subanalysis. Methods In the ODYSSEY-KT study, South Korean and Taiwanese patients with hypercholesterolemia and high cardiovascular risks were randomized (1:1) to alirocumab or placebo. Alirocumab was self-administered subcutaneously at 75 mg every 2 weeks with a maximally tolerated statin dose with or without other lipid-modifying therapies. Alirocumab dose was increased to 150 mg every 2 weeks at week 12 if low density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dL at week 8. Primary endpoint was percent change in LDL-C from baseline to week 24. Results from Korean cohort (n = 83: 40 for alirocumab and 43 for placebo, respectively) analyses are reported here. Results In alirocumab group, the least square of mean change percent in LDL-C levels was –65.7% (placebo: 11.1%; p < 0.0001) and 92.0% of them achieved LDL-C < 70 mg/dL (placebo: 12.7%; p < 0.0001) at week 24. Alirocumab also showed significantly greater improvements in high density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol, lipoprotein(a), and apolipoprotein B than placebo (p < 0.05). Two consecutive calculated LDL-C values < 25 mg/dL were observed in 37.5% of alirocumab-treated patients. Overall, 45.0% alirocumab-treated and 51.2% placebo-treated patients experienced treatment-emergent adverse events (TEAEs) without discontinuation of treatment due to TEAEs. Conclusions Alirocumab has demonstrated to be effective in improvement of LDL-C and related lipid profiles in Korean cohort. Alirocumab was generally well tolerated with no significant safety signals.

Objective To compare a center-based cardiac rehabilitation (CR) program with a home-based CR program in terms of improving obesity related index and cardiopulmonary exercise capacity after the completing a phase II CR program. Methods In this study, there were seventy-four patients with acute myocardial infarction after percutaneous coronary intervention who were analyzed. Patients with mild to moderate risk (ejection fraction >40%) were included in the group. The patients underwent an exercise tolerance test by measurement of the modified Bruce protocol at three assessment points. Those in the center-based CR group participated in a 4-week training program with electrocardiography monitoring of the patient’s progress and results, while those patients who were in the home-based CR group underwent self-exercise training. We measured the obesity related indices such as body mass index, fat free mass index (FFMI), and cardiopulmonary exercise capacity including peak oxygen consumption (VO2max), metabolic equivalents (METs), heart rate, resting systolic blood pressure and the diastolic blood pressure of the participants and noted the results. Results Of the 74 patients, 25 and 49 participated in the center-based and home-based CR programs, respectively. Both groups showed significant improvement in VO2max and METs at 1-month and 6-month follow-up. However, FFMI was significantly improved only in the center-based CR group after 1 month of the phase II CR. Conclusion Both groups identified in the study showed significant improvement of VO2max and METs at 1-month and 6-month follow-up. However, there was no significant difference in the intergroup analysis. A significant improvement of FFMI was seen only in the center-based CR group after phase II CR.

β2-Adrenergic receptor (β2-AR) is implicated in muscle metabolic activities such as glycogen metabolism, glucose uptake, lipolysis and muscle growth. However, the functional role of β2-AR in the differentiation of skeletal muscle is largely unknown. Here, we examined the functional role of β2-AR in L6 myoblast differentiation using the long-term-acting β2-AR-specific agonist formoterol. We observed that formoterol treatment strongly suppressed L6 myoblast differentiation and the expression of myosin heavy chain (MHC) in a dose- and time-dependent manner. Showing that both long-acting agonist (formoterol) and short-acting agonist (terbutaline) inhibited the induction of MHC protein, whereas β2-AR antagonist (ICI-118,551) upregulated MHC expression, we clearly demonstrated that β2-AR is involved in L6 myoblast differentiation. Furthermore, our pharmacological inhibition study revealed that the PI3K–AKT pathway is the main signaling pathway for myotube formation. Formoterol inhibited the activation of PI3K–AKT signaling, but not that of ERK signaling. Moreover, formoterol selectively inhibited AKT activation by IGF-I, but not by insulin. Collectively, our findings reveal a previously undocumented role of β2-AR activation in modulating the differentiation of L6 myoblasts.

Herein, we present a qualitative and quantitative analysis of the compositions of plasmalogens and phospholipids (PLs) in dried big head shrimp (Solenocera melantho), opossum shrimp (Neomysis awatschensis), mussel (Mytilus galloprovincialis), and sea cucumber (Apostichopus japonicus). We also analyze the fatty acid composition of the extracted lipids, phosphatidyl choline (PtdCho), and plasmalogen choline (PlsCho) from each sample. In big head shrimp, opossum shrimp, and mussel, phosphatidyl choline (PtdCho) was the most abundant PL at 1677.9, 1603, and 1661.6 mg/100 g of dried sample, respectively, whereas the most abundant PL in sea cucumber was PlsCho (206.9 mg/100 g of dried sample). In all four samples, plasmalogen ethanolamine (PlsEtn) was higher than phosphatidyl ethanolamine (PtdEtn). The content (mg/100 g of dried sample) of PlsCho was highest in mussel (379.0), and it was higher in big head shrimp (262.3) and opossum shrimp (245.6) than sea cucumber (206.9). The contents (mg/100 g of dried sample) of PlsEtn were in the order of mussel (675.4) > big head shrimp (629.5) > opossum shrimp (217.9) > sea cucumber (51.5). For analyzing the fatty acids at the sn-2 position of PlsCho, the consecutive treatment with phospholipase A1, solid phase extraction, thin-layer chromatography (TLC), and GC-FID were applied. The most abundant fatty acid was eicosapentaenoic acid (EPA, C20:5, n-3) in big head shrimp and sea cucumber, palmitoleic acid (C16:1, n-7) in opossum shrimp, and docosadienoic acid (C22:2, n-6) in mussel.

Summary: Microbial rhodopsin is a retinal protein that functions as an ion pump, channel, and sensory transducer, as well as a light sensor, as in biosensors and biochips. Tara76 rhodopsin is a typical proton-pumping rhodopsin that exhibits strong stability against extreme pH, detergent, temperature, salt stress, and dehydration stress and even under dual and triple conditions. Tara76 rhodopsin has a thermal stability approximately 20 times higher than that of thermal rhodopsin at 80°C and is even stable at 85°C. Tara76 rhodopsin is also stable at pH 0.02 to 13 and exhibits strong resistance in detergent, including Triton X-100 and SDS. We tested the current flow that electrical current flow across dried proteins on the paper at high temperatures using an electrode device, which was measured stably from 25°C up to 120°C. These properties suggest that this Tara76 rhodopsin is suitable for many applications in the fields of bioengineering and biotechnology.

Microbial rhodopsin is a simple solar energy-capturing molecule compared to the complex photosynthesis apparatus. Light-driven proton pumping across the cell membrane is a crucial mechanism underlying microbial energy production. Actinobacteria is one of the highly abundant bacterial phyla in freshwater habitats, and members of this lineage are considered to boost heterotrophic growth via phototrophy, as indicated by the presence of actino-opsin (ActR) genes in their genome. However, it is difficult to validate their function under laboratory settings because Actinobacteria are not consistently cultivable. Based on the published genome sequence of Candidatus aquiluna sp. strain IMCC13023, actinorhodopsin from the strain (ActR-13023) was isolated and characterized in this study. Notably, ActR-13023 assembled with natively synthesized carotenoid/retinal (used as a dual chromophore) and functioned as a light-driven outward proton pump. The ActR-13023 gene and putative genes involved in the chromophore (retinal/carotenoid) biosynthetic pathway were detected in the genome, indicating the functional expression ActR-13023 under natural conditions for the utilization of solar energy for proton translocation. Heterologous expressed ActR-13023 exhibited maximum absorption at 565 nm with practical proton pumping ability. Purified ActR-13023 could be reconstituted with actinobacterial carotenoids for additional light-harvesting. The existence of actinorhodopsin and its chromophore synthesis machinery in Actinobacteria indicates the inherent photo-energy conversion function of this microorganism. The assembly of ActR-13023 to its synthesized chromophores validated the microbial community’s importance in the energy cycle.

Alzheimer’s disease (AD) is caused by abnormal metabolism of amyloid beta (Aβ), leading to cognitive dysfunction. Carthamus tinctorius L. seed (CTS) and Taraxacum coreanum (TC) are attracted wide attention because of their potential property of alleviation of neurotoxicity; however, their combination therapy for synergistic effects have not yet been evaluated. We investigated the synergistic effects of CTS, TC, and their combination on the Aβ25-35-infused mice. In the T-maze test and novel object recognition test, the combination improved the spatial memory and object recognitive capacity compared with their single treatments. In Morris water maze test, the combination groups performed better spatial memory, indicating a synergistically effect on improving learning and memory ability in Aβ25-35-infused mice. We also investigated the Aβ-related protein expressions, suggesting the combination administration attenuated amyloidogenesis by regulating the metabolism of Aβ. Therefore, the combination might provide a positive synergistic effect on AD protection by metabolism of Aβ.

According to the variance hypothesis, variety-seeking or exploration is a critical condition for improving learning and performance over time. Extant computational learning models support this hypothesis by showing how individuals who are exposed to diverse knowledge sources are more likely to find superior solutions to a particular problem. Yet this research provides no precise guidelines about how broadly individuals should search. Our goal in this paper is to elucidate the conditions under which variety-seeking in organizations is beneficial. To this end, we developed a computational model in which individuals learn as they interact with other individuals, and update their knowledge as a result of this interaction. The model reveals how the type of learning environment (performance landscape) in which the learning dynamic unfolds determines when the benefits of variety-seeking outweigh the costs. Variety-seeking is performance-enhancing only when the knowledge of the chosen learning targets (i.e., individuals to learn from) provide useful information about the features of the performance landscape. The results further suggest that superior knowledge might be available locally, i.e., in the proximity of an individual's current location. We also identify the point beyond which variety-seeking causes a sharp performance decline and show how this point depends on the type of landscape in which the learning dynamic unfolds and the degree of specialization of individual knowledge. The presence of this critical point explains why exploration becomes very costly. The implications of our findings for establishing the boundaries of exploration are discussed.