Metabolomic profiles of ovariectomized mice and their associations with body composition and frailty-related parameters in postmenopausal women.

BACKGROUND: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health. PURPOSE: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women. METHODS AND RESULTS: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk. CONCLUSIONS: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.

Comparing Rates of Undiagnosed Hypertension and Diabetes in Patients With and Without Substance Use Disorders.

BACKGROUND: Individuals with substance use disorders (SUDs) have increased risk for developing chronic conditions, though few studies assess rates of diagnosis of these conditions among patients with SUDs. OBJECTIVE: To compare rates of undiagnosed hypertension and diabetes among patients with and without an SUD. DESIGN: Cross-sectional analysis using electronic health record (EHR) data from 58 primary care clinics at a large, urban, healthcare system in New York. PARTICIPANTS: Patients who had at least two primary care visits from 2019-2022 were included in our patient sample. Patients without an ICD-10 hypertension diagnosis or prescribed hypertension medications and with at least two blood pressure (BP) readings ≥ 140/90 mm were labeled 'undiagnosed hypertension,' and patients without a diabetes diagnosis or prescribed diabetes medications and with A1C/hemoglobin ≥ 6.5% were labeled 'undiagnosed diabetes.' MAIN MEASURES: We calculated the mean number of patients with and without an ICD-10 SUD diagnosis who were diagnosed and undiagnosed for each condition. We used multivariate logistic regression to assess the association between being undiagnosed for each condition, and having an SUD diagnosis, patient demographic characteristics, clinical characteristics (body mass index, Elixhauser comorbidity count, diagnosed HIV and psychosis), the percentage of visits without a BP screening, and the total number of visits during the time period. KEY RESULTS: The percentage of patients with undiagnosed hypertension (2.74%) and diabetes (22.98%) was higher amongst patients with SUD than patients without SUD. In multivariate models, controlling for other factors, patients with SUD had significantly higher odds of having undiagnosed hypertension (OR: 1.81; 95% CI: 1.48, 2.20) and undiagnosed diabetes (OR: 1.93; 1.72, 2.16). Being younger, female, and having an HIV diagnosis was also associated with significantly higher odds for being undiagnosed. CONCLUSIONS: We found significant disparities in rates of undiagnosed chronic diseases among patients with SUDs, compared with patients without SUDs.

Initiatives to Support the Transition of Patients With Substance Use Disorders From Acute Care to Community-based Services Among a National Sample of Nonprofit Hospitals.

BACKGROUND: Hospitals are a key touchpoint to reach patients with substance use disorders (SUDs) and link them with ongoing community-based services. Although there are many acute care interventions to initiate SUD treatment in hospital settings, less is known about what services are offered to transition patients to ongoing care after discharge. In this study, we explore what SUD care transition strategies are offered across nonprofit US hospitals. METHODS: We analyzed administrative documents from a national sample of US hospitals that indicated SUD as a top 5 significant community need in their Community Health Needs Assessment reports (2019-2021). Data were coded and categorized based on the nature of described services. We used data on hospitals and characteristics of surrounding counties to identify factors associated with hospitals' endorsement of transition interventions for SUD. RESULTS: Of 613 included hospitals, 313 prioritized SUD as a significant community need. Fifty-three of these hospitals (17%) offered acute care interventions to support patients' transition to community-based SUD services. Most (68%) of the 53 hospitals described transition strategies without further detail, 23% described scheduling appointments before discharge, and 11% described discussing treatment options before discharge. No hospital characteristics were associated with offering transition interventions, but such hospitals were more likely to be in the Northeast, in counties with higher median income, and states that expanded Medicaid. CONCLUSIONS: Despite high need, most US hospitals are not offering interventions to link patients with SUD from acute to community care. Efforts to increase acute care interventions for SUD should identify and implement best practices to support care continuity.

Rural-urban disparities in the availability of hospital-based screening, medications for opioid use disorder, and addiction consult services.

INTRODUCTION: Hospitals are an ideal setting to stage opioid-related interventions with patients who are hospitalized due to overdose or other substance use-related complications. Transitional opioid programs-which initiate care and provide linkages upon discharge, such as screening, initiation of medications for opioid use disorder, and addiction consult services-have become the gold standard, but implementation has been uneven. The purpose of this study was to assess disparities in the availability of hospital-based transitional opioid programs, across rural and urban hospital settings in the United States. METHODS: Using hospital administrative data paired with county-level demographic data, we conducted bivariate and regression analyses to assess rural-urban differences in the availability of transitional opioid services including screening, addiction consult services, and MOUD in U.S general medical centers, controlling for hospital- and community-level factors. Our sample included 2846 general medical hospitals that completed the 2021 American Hospital Association (AHA) Annual Survey of Hospitals. Our primary outcomes were five self-reported measures: whether the hospital provided screening in the ED; provided screening in the inpatient setting; whether the hospital provided addiction consult services in the ED; provided addiction consult services in the inpatient setting; and whether the hospital provided medications for opioid use disorder. RESULTS: Rural hospitals did not have lower odds of screening for OUD or other SUDs than urban hospitals, but both micropolitan rural counties and noncore rural counties had significantly lower odds of having addiction consult services in either the ED (OR: 0.74, 95 % CI: 0.58, 0.95; OR: 0.68, 95 % CI: 0.50, 0.91) or inpatient setting (OR: 0.76, 95 % CI: 0.59, 0.97; OR: 0.68, 95 % CI: 0.50, 0.93), respectively, or of offering MOUD (OR: 0.69, 95 % CI: 0.52, 0.90; OR: 0.52, 95 % CI: 0.37, 0.74). CONCLUSIONS: Our study suggests that evidence-based interventions, such as medications for opioid use disorder and addiction consult services, are less often available in rural hospitals, which may contribute to rural-urban disparities in health outcomes secondary to OUD. A priority for population health improvement should be developing implementation strategies to support rural hospital adoption of transitional opioid programs.

Comparison of different weight-based scalars of remimazolam tosylate for anesthesia induction in obese patients: study protocol for a prospective, controlled trial.

BACKGROUND: The physiologic and anthropometric characteristics changes associated with obesity may result in the alternation of pharmacologic management. Remimazolam tosylate is a new type of ultra-short-acting benzodiazepine with stable context-sensitive half-time (CSHT) and no lipid accumulation after long-time infusion. Although remimazolam tosylate has potential advantages for the induction and maintenance of anesthesia in obese patients, the appropriate induction dosing scalars among obese patients are unknown. Therefore, we aim to compare the different weight-based scalars for dosing remimazolam tosylate of anesthesia induction among obese patients. METHODS/DESIGN: The study will be performed as a prospective, single-center, double-blind, controlled clinical trial. The study design is a comparison of remimazolam tosylate requirements based on total body weight (TBW) or lean body weight (LBW) to reach a Modified Observer's Assessment of Alertness and Sedation (MOAA/S) score of 0 among obese subjects (BMI ≥ 35 kg/m2). Another twenty normal-weight subjects (18.5 kg/m2 ≤ BMI < 25 kg/m2) will be enrolled as a control group, whose induction dose is scaled based on TBW. The infusion rate of remimazolam tosylate during induction is 12 mg/kg/h in all groups. DISCUSSION: Results of the present study will provide evidence of dose scalar of remimazolam tosylate to guide the clinical practice of anesthesia induction in obese patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR220005664. Registered on 9 February 2022, https://www.chictr.org.cn/showproj.aspx?proj=151150 .

Strategies to support substance use disorder care transitions from acute-care to community-based settings: a scoping review and typology.

BACKGROUND: Acute-care interventions that identify patients with substance use disorders (SUDs), initiate treatment, and link patients to community-based services, have proliferated in recent years. Yet, much is unknown about the specific strategies being used to support continuity of care from emergency department (ED) or inpatient hospital settings to community-based SUD treatment. In this scoping review, we synthesize the existing literature on patient transition interventions, and form an initial typology of reported strategies. METHODS: We searched Pubmed, Embase, CINAHL and PsychINFO for peer-reviewed articles published between 2000 and 2021 that studied interventions linking patients with SUD from ED or inpatient hospital settings to community-based SUD services. Eligible articles measured at least one post-discharge treatment outcome and included a description of the strategy used to promote linkage to community care. Detailed information was extracted on the components of the transition strategies and a thematic coding process was used to categorize strategies into a typology based on shared characteristics. Facilitators and barriers to transitions of care were synthesized using the Consolidated Framework for Implementation Research. RESULTS: Forty-five articles met inclusion criteria. 62% included ED interventions and 44% inpatient interventions. The majority focused on patients with opioid (71%) or alcohol (31%) use disorder. The transition strategies reported across studies were heterogeneous and often not well described. An initial typology of ten transition strategies, including five pre- and five post-discharge transition strategies is proposed. The most common strategy was scheduling an appointment with a community-based treatment provider prior to discharge. A range of facilitators and barriers were described, which can inform efforts to improve hospital-to-community transitions of care. CONCLUSIONS: Strategies to support transitions from acute-care to community-based SUD services, although critical for ensuring continuity of care, vary greatly across interventions and are inconsistently measured and described. More research is needed to classify SUD care transition strategies, understand their components, and explore which lead to the best patient outcomes.

Rural-urban disparities in health outcomes, clinical care, health behaviors, and social determinants of health and an action-oriented, dynamic tool for visualizing them.

While rural-urban disparities in health and health outcomes have been demonstrated, because of their impact on (and intervenability to improve) health and health outcomes, we sought to examine cross-sectional and longitudinal inequities in health, clinical care, health behaviors, and social determinants of health (SDOH) between rural and non-rural counties in the pre-pandemic era (2015 to 2019), and to present a Health Equity Dashboard that can be used by policymakers and researchers to facilitate examining such disparities. Therefore, using data obtained from 2015-2022 County Health Rankings datasets, we used analysis of variance to examine differences in 33 county level attributes between rural and non-rural counties, calculated the change in values for each measure between 2015 and 2019, determined whether rural-urban disparities had widened, and used those data to create a Health Equity Dashboard that displays county-level individual measures or compilations of them. We followed STROBE guidelines in writing the manuscript. We found that rural counties overwhelmingly had worse measures of SDOH at the county level. With few exceptions, the measures we examined were getting worse between 2015 and 2019 in all counties, relatively more so in rural counties, resulting in the widening of rural-urban disparities in these measures. When rural-urban gaps narrowed, it tended to be in measures wherein rural counties were outperforming urban ones in the earlier period. In conclusion, our findings highlight the need for policymakers to prioritize rural settings for interventions designed to improve health outcomes, likely through improving health behaviors, clinical care, social and environmental factors, and physical environment attributes. Visualization tools can help guide policymakers and researchers with grounded information, communicate necessary data to engage relevant stakeholders, and track SDOH changes and health outcomes over time.

An observational, sequential analysis of the relationship between local economic distress and inequities in health outcomes, clinical care, health behaviors, and social determinants of health.

BACKGROUND: Socioeconomic status has long been associated with population health and health outcomes. While ameliorating social determinants of health may improve health, identifying and targeting areas where feasible interventions are most needed would help improve health equity. We sought to identify inequities in health and social determinants of health (SDOH) associated with local economic distress at the county-level. METHODS: For 3,131 counties in the 50 US states and Washington, DC (wherein approximately 325,711,203 people lived in 2019), we conducted a retrospective analysis of county-level data collected from County Health Rankings in two periods (centering around 2015 and 2019). We used ANOVA to compare thirty-three measures across five health and SDOH domains (Health Outcomes, Clinical Care, Health Behaviors, Physical Environment, and Social and Economic Factors) that were available in both periods, changes in measures between periods, and ratios of measures for the least to most prosperous counties across county-level prosperity quintiles, based on the Economic Innovation Group's 2015-2019 Distressed Community Index Scores. RESULTS: With seven exceptions, in both periods, we found a worsening of values with each progression from more to less prosperous counties, with least prosperous counties having the worst values (ANOVA p < 0.001 for all measures). Between 2015 and 2019, all except six measures progressively worsened when comparing higher to lower prosperity quintiles, and gaps between the least and most prosperous counties generally widened. CONCLUSIONS: In the late 2010s, the least prosperous US counties overwhelmingly had worse values in measures of Health Outcomes, Clinical Care, Health Behaviors, the Physical Environment, and Social and Economic Factors than more prosperous counties. Between 2015 and 2019, for most measures, inequities between the least and most prosperous counties widened. Our findings suggest that local economic prosperity may serve as a proxy for health and SDOH status of the community. Policymakers and leaders in public and private sectors might use long-term, targeted economic stimuli in low prosperity counties to generate local, community health benefits for vulnerable populations. Doing so could sustainably improve health; not doing so will continue to generate poor health outcomes and ever-widening economic disparities.

Substance Use Disorder Program Availability in Safety-Net and Non-Safety-Net Hospitals in the US.

Importance: Safety-net hospitals (SNHs) are ideal sites to deliver addiction treatment to patients with substance use disorders (SUDs), but the availability of these services within SNHs nationwide remains unknown. Objective: To examine differences in the delivery of different SUD programs in SNHs vs non-SNHs across the US and to determine whether these differences are increased in certain types of SNHs depending on ownership. Design, Setting, and Participants: This cross-sectional analysis used data from the 2021 American Hospital Association Annual Survey of Hospitals to examine the associations of safety-net status and ownership with the availability of SUD services at acute care hospitals in the US. Data analysis was performed from January to March 2022. Main Outcomes and Measures: This study used 2 survey questions from the American Hospital Association survey to determine the delivery of 5 hospital-based SUD services: screening, consultation, inpatient treatment services, outpatient treatment services, and medications for opioid use disorder (MOUD). Results: A total of 2846 hospitals were included: 409 were SNHs and 2437 were non-SNHs. The lowest proportion of hospitals reported offering inpatient treatment services (791 hospitals [27%]), followed by MOUD (1055 hospitals [37%]), and outpatient treatment services (1087 hospitals [38%]). The majority of hospitals reported offering consultation (1704 hospitals [60%]) and screening (2240 hospitals [79%]). In multivariable models, SNHs were significantly less likely to offer SUD services across all 5 categories of services (screening odds ratio [OR], 0.62 [95% CI, 0.48-0.76]; consultation OR, 0.62 [95% CI, 0.47-0.83]; inpatient services OR, 0.73 [95% CI, 0.55-0.97]; outpatient services OR, 0.76 [95% CI, 0.59-0.99]; MOUD OR, 0.6 [95% CI, 0.46-0.78]). With the exception of MOUD, public or for-profit SNHs did not differ significantly from their non-SNH counterparts. However, nonprofit SNHs were significantly less likely to offer all 5 SUD services compared with their non-SNH counterparts (screening OR, 0.52 [95% CI, 0.41-0.66]; consultation OR, 0.56 [95% CI, 0.44-0.73]; inpatient services OR, 0.45 [95% CI, 0.33-0.61]; outpatient services OR, 0.58 [95% CI, 0.44-0.76]; MOUD OR, 0.61 [95% CI, 0.46-0.79]). Conclusions and Relevance: In this cross-sectional study of SNHs and non-SNHs, SNHs had significantly lower odds of offering the full range of SUD services. These findings add to a growing body of research suggesting that SNHs may face additional barriers to offering SUD programs. Further research is needed to understand these barriers and to identify strategies that support the adoption of evidence-based SUD programs in SNH settings.

Strategies to support substance use disorder care transitions from acute-care to community-based settings: A Scoping review and typology.

Background: Acute-care interventions that identify patients with substance use disorders (SUDs), initiate treatment, and link patients to community-based services, have proliferated in recent years. Yet, much is unknown about the specific strategies being used to support continuity of care from emergency department (ED) or inpatient hospital settings to community-based SUD treatment. In this scoping review, we synthesize the existing literature on patient transition interventions, and form an initial typology of reported strategies. Methods: We searched Pubmed, Embase, CINAHL and PsychINFO for peer-reviewed articles published between 2000-2021 that studied interventions linking SUD patients from ED or inpatient hospital settings to community-based SUD services. Eligible articles measured at least one post-discharge treatment outcome and included a description of the strategy used to promote linkage to community care. Detailed information was extracted on the components of the transition strategies and a thematic coding process was used to categorize strategies into a typology based on shared characteristics. Facilitators and barriers to transitions of care were synthesized using the Consolidated Framework for Implementation Research. Results: Forty-five articles met inclusion criteria. 62% included ED interventions and 44% inpatient interventions. The majority focused on patients with opioid (71%) followed by alcohol (31%) use disorder. The transition strategies reported across studies were heterogeneous and often not well described. An initial typology of ten transition strategies, including five pre- and five post-discharge transition strategies is proposed. The most common strategy was scheduling an appointment with a community-based treatment provider prior to discharge. A range of facilitators and barriers were described, which can inform efforts to improve hospital-to-community transitions of care. Conclusions: Strategies to support transitions from acute-care to community-based SUD services, although critical for ensuring continuity of care, vary greatly across interventions and are inconsistently measured and described. More research is needed to classify SUD care transition strategies, understand their components, and explore which lead to the best patient outcomes.

Galangin alleviated myocardial ischemia-reperfusion injury by enhancing autophagic flux and inhibiting inflammation.

Autophagy is critically involved in myocardial ischemia-reperfusion (I/R). Autophagy inhibition exacerbates myocardial I/R injury. Few effective agents target autophagy to prevent myocardial I/R injury. Effective drugs that promote autophagy in myocardial I/R warrant further investigation. Galangin (Gal) enhances autophagy and alleviates I/R injury. Here we conducted both in vivo and in vitro experiments to observe the changes in autophagy after galangin treatment and investigated the cardioprotective effects of galangin on myocardial I/R. METHODS: After 45-min occlusion of the left anterior descending coronary artery, myocardial I/R was induced by slipknot release. One day before surgery and immediately after surgery, the mice were injected intraperitoneally with the same volume of saline or Gal. The effects of Gal were evaluated using echocardiography, 2,3,5-triphenyltetrazolium chloride staining (TTC staining), western blotting, and transmission electron microscopy. Primary cardiomyocytes and bone marrow-derived macrophages were extracted in vitro to measure the cardioprotective effects of Gal. RESULTS: Compared with the saline-treated group, Gal significantly improved cardiac function and limited infarct enlargement after myocardial I/R. In vivo and in vitro studies demonstrated that Gal treatment promoted autophagy during myocardial I/R. The anti-inflammatory effects of Gal were validated in bone marrow-derived macrophages. These results strongly suggest that Gal treatment can attenuate myocardial I/R injury. CONCLUSION: Our data demonstrated that Gal could improve left ventricular ejection fraction and reduce infarct size after myocardial I/R by promoting autophagy and inhibiting inflammation.

Factors associated with the adoption of evidence-based innovations by substance use disorder treatment organizations: A study of HIV testing.

INTRODUCTION: Though prior research shows that a range of important regulatory, market, community, and organizational factors influence the adoption of evidence-based practices (EBPs) among health care organizations, we have little understanding of how these factors relate to each other. To address this gap, we test a conceptual model that emphasizes indirect, mediated effects among key factors related to HIV testing in substance use disorder treatment organizations (SUTs), a critical EBP during the US opioid epidemic. METHODS: We draw on nationally representative data from the 2014 (n = 697) and 2017 (n = 657) National Drug Abuse Treatment System Survey (NDATSS) to measure the adoption of HIV testing among the nation's SUTs and their key organizational characteristics; we also draw on data from the US Census Bureau; Centers for Disease Control; and legislative sources to measure regulatory and community environments. We estimate cross-sectional and longitudinal structural equation models (SEM) to test the proposed model. RESULTS: Our longitudinal model of the adoption of HIV testing by SUTs in the United States identifies a pathway by which community and market characteristics (rurality and the number of other SUTs in the area) are related to key sociotechnical characteristics of these organizations (alignment of clients, staff, and harm-reduction culture) that, in turn, are related to the adoption of this EBP. CONCLUSIONS: Results also show the importance of developing conceptual models that include indirect effects to account for organizational adoption of EBPs.

Systematic transcriptome analysis associated with physiological and chronological aging in Caenorhabditis elegans.

Aging is associated with changes in a variety of biological processes at the transcriptomic level, including gene expression. Two types of aging occur during a lifetime: chronological and physiological aging. However, dissecting the difference between chronological and physiological ages at the transcriptomic level has been a challenge because of its complexity. We analyzed the transcriptomic features associated with physiological and chronological aging using Caenorhabditis elegans as a model. Many structural and functional transcript elements, such as noncoding RNAs and intron-derived transcripts, were up-regulated with chronological aging. In contrast, mRNAs with many biological functions, including RNA processing, were down-regulated with physiological aging. We also identified an age-dependent increase in the usage of distal 3' splice sites in mRNA transcripts as a biomarker of physiological aging. Our study provides crucial information for dissecting chronological and physiological aging at the transcriptomic level.

Gasdermin D mediates endoplasmic reticulum stress via FAM134B to regulate cardiomyocyte autophagy and apoptosis in doxorubicin-induced cardiotoxicity.

Cardiomyocyte pyroptosis and apoptosis play a vital role in the pathophysiology of several cardiovascular diseases. Our recent study revealed that gasdermin D (GSDMD) can promote myocardial I/R injury via the caspase-11/GSDMD pathway. We also found that GSDMD deletion attenuated myocardial I/R and MI injury by reducing cardiomyocyte apoptosis and pyroptosis. However, how GSDMD mediates cardiomyocyte apoptosis and protects myocardial function remains unclear. Here, we found that doxorubicin (DOX) treatment resulted in increased apoptosis and pyroptosis in cardiomyocytes and that caspase-11/GSDMD could mediate DOX-induced cardiotoxicity (DIC) injury. Interestingly, GSDMD overexpression promoted cardiomyocyte apoptosis, which was attenuated by GSDMD knockdown. Notably, GSDMD overexpression exacerbated DIC injury, impaired cardiac function in vitro and in vivo, and enhanced DOX-induced cardiomyocyte autophagy. Mechanistically, GSDMD regulated the activity of FAM134B, an endoplasmic reticulum autophagy receptor, by pore formation on the endoplasmic reticulum membrane via its N-terminus, thus activating endoplasmic reticulum stress. In turn, FAM134B interacted with autophagic protein LC3, thus inducing cardiac autophagy, promoting cardiomyocyte apoptosis, and aggravating DIC. These results suggest that GSDMD promotes autophagy and induces cardiomyocyte apoptosis by modulating the reaction of FAM134B and LC3, thereby promoting DIC injury. Targeted regulation of GSDMD may be a new target for the prevention and treatment of DIC.

Research Progress on Risk Factors of Preoperative Anxiety in Children: A Scoping Review.

BACKGROUND: Preoperative anxiety has adverse effects on children and negative impacts on postoperative rehabilitation. Anesthesiologists can accurately identify children with preoperative anxiety, and individualized intervention can effectively improve their psychological state and clinical prognosis. However, a comprehensive summary of the current available evidence has yet to be conducted. Searches were conducted in Medline databases from inception to March 2022. Primary studies that reported preoperative anxiety in children and its attendant effects on postoperative recovery and prognosis were screened and included. Among the 309 publications identified, 12 related studies (n = 3540 patients) met the eligibility criteria. The incidence of preoperative anxiety in children in the included studies ranged from 41.7% to 75.44%. While 16 influencing factors were identified, only 5 factors had a significant impact on preoperative anxiety in children: younger age (n = 8), parental anxiety (n = 7), negative previous hospitalizations (n = 3), less sociableness (n = 2), and surgical setting (n = 1). The current scoping review identified risk factors for preoperative anxiety in children. Healthcare workers should identify and manage preoperatively anxious children. There are still some factors that are controversial, and large-scale clinical studies are needed.

High Estimated 24-Hour Urinary Sodium Excretion Is Related to Symptomatic Knee Osteoarthritis: A Nationwide Cross-Sectional Population-Based Study.

OBJECTIVES: High salt intake results in various harmful effects on human health including hypertension, cardiovascular disease, and reduced bone density. Despite this, there are very few studies in the literature that have investigated the association between sodium intake and osteoarthritis (OA). Therefore, we aimed to explore these associations in a Korean population. METHODS: This study used cross-sectional data from adult subjects aged 50-75 years from two consecutive periods of the Korean National Health and Nutrition Examination Survey V-VII (2010-2011 and 2014-2016). The estimated 24-hour urinary sodium excretion (24HUNa) was used as a surrogate marker of salt intake. In the 2010-2011 dataset, knee OA (KOA) was defined as the presence of the radiographic features of OA and knee pain. The association between KOA and salt intake was analysed using univariable and multivariable logistic regression methods. For the sensitivity analysis, the same procedures were conducted on subjects with self-reported OA (SR-OA) with knee pain in the 2010-2011 dataset and any site SR-OA in the 2014-2016 dataset. RESULTS: Subjects with KOA had significantly lower energy intake, but higher 24HUNa than those without KOA. The restricted cubic spline plots demonstrated a J-shaped distribution between 24HUNa and prevalent KOA. When 24HUNa was stratified into five groups (<2, 2-3, 3-4, 4-5 and ≥5 g/day), subjects with high sodium intake (≥5 g/day) had a higher risk of KOA (odds ratio [OR] = 1.64, 95% confidence interval [CI] 1.03-2.62) compared to the reference group (3-4 g/day) after adjusting for covariates. The sensitivity analysis based on SR-OA with knee pain showed that high sodium intake was also significantly associated with increased prevalence of OA (OR = 1.84, 95% CI 1.10-3.10) compared with the reference group. Regarding SR-OA at any site in the 2014-2016 dataset, estimated 24HUNa showed a significantly positive association with the presence of SR-OA after adjusting for potential confounders. CONCLUSIONS: This nationwide Korean representative study showed a significant association between symptomatic KOA and high sodium intake (≥5 g/day). Avoidance of a diet high in salt might be beneficial as a non-pharmacologic therapy for OA.

Aldehyde Dehydrogenase 2 (ALDH2) Elicits Protection against Pulmonary Hypertension via Inhibition of ERK1/2-Mediated Autophagy.

Pulmonary hypertension (PH) is caused by chronic hypoxia that induces the migration and proliferation of pulmonary arterial smooth muscle cells (PASMCs), eventually resulting in right heart failure. PH has been related to aberrant autophagy; however, the hidden mechanisms are still unclear. Approximately 40% East Asians, equivalent to 8% of the universal population, carry a mutation in Aldehyde dehydrogenase 2 (ALDH2), which leads to the aggregation of noxious reactive aldehydes and increases the propensity of several diseases. Therefore, we explored the potential aspect of ALDH2 in autophagy associated with PH. In vitro mechanistic studies were conducted in human PASMCs (HPASMCs) after lentiviral ALDH2 knockdown and treatment with platelet-derived growth factor-BB (PDGF-BB). PH was induced in wild-type (WT) and ALDH2-knockout (ALDH2-/-) mice using vascular endothelial growth factor receptor inhibitor SU5416 under hypoxic conditions (HySU). Right ventricular function was assessed using echocardiography and invasive hemodynamic monitoring. Histological and immunohistochemical analyses were performed to evaluate pulmonary vascular remodeling. EdU, transwell, and wound healing assays were used to evaluate HPASMC migration and proliferation, and electron microscopy and immunohistochemical and immunoblot assays were performed to assess autophagy. The findings demonstrated that ALDH2 deficiency exacerbated right ventricular pressure, hypertrophy, fibrosis, and right heart failure resulting from HySU-induced PH. ALDH2-/- mice exhibited increased pulmonary artery muscularization and 4-hydroxynonenal (4-HNE) levels in lung tissues. ALDH2 knockdown increased PDGF-BB-induced PASMC migration and proliferation and 4-HNE accumulation in vitro. Additionally, ALDH2 deficiency increased the number of autophagosomes and autophagic lysosomes together with autophagic flux and ERK1/2-Beclin-1 activity in lung tissues and PASMCs, indicating enhanced autophagy. In conclusion, the study shows that ALDH2 has a protective role against the migration and proliferation of PASMCs and PH, possibly by regulating autophagy through the ERK1/2-Beclin-1 pathway.

A novel conservative system with hidden flows evolved from the simplest memristive circuit.

Over the past few decades, the research of dissipative chaotic systems has yielded many achievements in both theory and application. However, attractors in dissipative systems are easily reconstructed by the attacker, which leads to information security problems. Compared with dissipative systems, conservative ones can effectively avoid these reconstructing attacks due to the absence of attractors. Therefore, conservative systems have advantages in chaos-based applications. Currently, there are still relatively few studies on conservative systems. For this purpose, based on the simplest memristor circuit in this paper, a non-Hamiltonian 3D conservative system without equilibria is proposed. The phase volume conservatism is analyzed by calculating the divergence of the system. Furthermore, a Kolmogorov-type transformation suggests that the Hamiltonian energy is not conservative. The most prominent property in the conservative system is that it exhibits quasi-periodic 3D tori with heterogeneous coexisting and different amplitude rescaling trajectories triggered by initial values. In addition, the results of Spectral Entropy analysis and NIST test show that the system can produce pseudo-random numbers with high randomness. To the best of our knowledge, there is no 3D conservative system with such complex dynamics, especially in a memristive conservative system. Finally, the analog circuit of the system is designed and implemented to test its feasibility as well.

The selective STING inhibitor H-151 preserves myocardial function and ameliorates cardiac fibrosis in murine myocardial infarction.

BACKGROUND: During myocardial infarction (MI), the stimulation of the cGAS-STING-IRF3 pathway in infiltrated macrophages can induce the apoptosis of cardiomyocytes and the fibrosis of cardiac fibroblasts, while H-151 is reported as a selective STING inhibitor. We intended to use H-151 to alleviate MI injury. METHODS: Male C57BL/6J mice were subjected to induce MI, while H-151 (750 nmol) were used for treatment. Myocardial function was assessed through echocardiology and cardiac fibrosis was evaluated by Masson's Trichrome-staining. The stimulation of the STING pathway and the aggravation of inflammation was assessed by levels of protein and mRNA. BMDMs were stimulated by dsDNA extracted from the murine heart, while H-151 was used as treatment. After co-culturing adult cardiomyocytes and cardiac fibroblasts with supernatant of BMDMs, the apoptosis of adult cardiomyocytes and the fibrosis of cardiac fibroblasts was assessed. RESULTS: H-151 treatment showed significant function in preserving myocardial function and decreasing cardiac fibrosis 28 days after MI. H-151 treatment showed significant function in inhibiting the cGAS-STING-IRF3 pathway and inflammation, especially type I interferon response. H-151 could alleviate the type I interferon response in BMDMs elicited by cardiac dsDNA, and thus H-151 could attenuate the apoptosis of adult cardiomyocytes and fibrosis of cardiac fibroblasts after co-culturing them with the supernatant of BMDMs. CONCLUSIONS: H-151, a selective inhibitor of the cGAS-STING-IRF3 pathway, can preserve myocardial function and alleviate cardiac fibrosis after MI by inhibiting the type I interferon response in infiltrated macrophages triggered by cardiac dsDNA which increase the apoptosis of adult cardiomyocytes and fibrosis of cardiac fibroblasts.