Mildly Reduced Renal Function Is Associated With Increased Heart Failure Admissions in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: The association between renal dysfunction and cardiovascular outcomes has yet to be determined in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate whether mildly reduced renal function is associated with the prognosis in patients with HCM. METHODS: Patients with HCM were enrolled at two tertiary HCM centers. Patients who were on dialysis, or had a previous history of heart failure (HF) or stroke were excluded. Patients were categorized into 3 groups by estimated glomerular filtration rate (eGFR): stage I (eGFR ≥ 90 mL/min/1.73 m², n = 538), stage II (eGFR 60-89 mL/min/1.73 m², n = 953), and stage III-V (eGFR < 60 mL/min/1.73 m², n = 265). Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, hospitalization for HF (HHF), or stroke during median 4.0-year follow-up. Multivariable Cox regression model was used to adjust for covariates. RESULTS: Among 1,756 HCM patients (mean 61.0 ± 13.4 years; 68.1% men), patients with stage III-V renal function had a significantly higher risk of MACEs (adjusted hazard ratio [aHR], 2.71; 95% confidence interval [CI], 1.39-5.27; P = 0.003), which was largely driven by increased incidence of cardiovascular death and HHF compared to those with stage I renal function. Even in patients with stage II renal function, the risk of MACE (vs. stage I: aHR, 2.21' 95% CI, 1.23-3.96; P = 0.008) and HHF (vs. stage I: aHR, 2.62; 95% CI, 1.23-5.58; P = 0.012) was significantly increased. CONCLUSION: This real-world observation showed that even mildly reduced renal function (i.e., eGFR 60-89 mL/min/1.73 m²) in patients with HCM was associated with an increased risk of MACEs, especially for HHF.

Widening Disparities in COVID-19 Mortality and Life Expectancy Among 15 Major Racial and Ethnic Groups in the United States, 2020-2021.

Persistent and often widening racial/ethnic and socioeconomic inequalities in health have long existed in the US. Although racial/ethnic disparities in COVID-19 mortality are well documented, COVID-19 mortality risks and resultant reductions in life expectancy during the pandemic for detailed racial and ethnic groups in the US, including Asian and Hispanic subgroups, are not known. We used 2020-2021 US mortality data to estimate age-adjusted COVID-19 mortality rates, life expectancy, and the consequent declines in life expectancy due to COVID-19 overall and for the 15 largest racial/ethnic groups. We used standard life table methodology, cause-elimination life tables, and inequality indices to analyze trends in racial/ethnic disparities. The number of COVID-19 deaths increased from 350,827 in 2020 to 416,890 in 2021. COVID-19 death rates varied 7-fold among the racial/ethnic groups; Japanese and Chinese had the lowest mortality rates and Mexicans and American Indians/Alaska Natives (AIANs) had the highest rates. In 2021, life expectancy ranged from 70.3 years for Blacks and 70.6 years for AIANs to 85.2 years for Japanese and 87.7 years for Chinese. The life-expectancy gap was wide- 22.4 years in 2020 and 23.2 years in 2021. COVID-19 mortality had the greatest impact in reducing the life expectancy of Mexicans (3.53 years in 2020 and 3.78 years in 2021), Central/South Americans (4.86 years in 2020 and 3.50 years in 2021), and AIANs (2.51 years in 2020 and 2.38 years in 2021). Racial/ethnic inequalities in COVID-19 mortality, life expectancy, and resultant reductions in life expectancy during the pandemic widened between 2020 and 2021.

Absorption Distribution Metabolism Excretion and Toxicity Property Prediction Utilizing a Pre-Trained Natural Language Processing Model and Its Applications in Early-Stage Drug Development.

Machine learning techniques are extensively employed in drug discovery, with a significant focus on developing QSAR models that interpret the structural information of potential drugs. In this study, the pre-trained natural language processing (NLP) model, ChemBERTa, was utilized in the drug discovery process. We proposed and evaluated four core model architectures as follows: deep neural network (DNN), encoder, concatenation (concat), and pipe. The DNN model processes physicochemical properties as input, while the encoder model leverages the simplified molecular input line entry system (SMILES) along with NLP techniques. The latter two models, concat and pipe, incorporate both SMILES and physicochemical properties, operating in parallel and with sequential manners, respectively. We collected 5238 entries from DrugBank, including their physicochemical properties and absorption, distribution, metabolism, excretion, and toxicity (ADMET) features. The models' performance was assessed by the area under the receiver operating characteristic curve (AUROC), with the DNN, encoder, concat, and pipe models achieved 62.4%, 76.0%, 74.9%, and 68.2%, respectively. In a separate test with 84 experimental microsomal stability datasets, the AUROC scores for external data were 78% for DNN, 44% for the encoder, and 50% for concat, indicating that the DNN model had superior predictive capabilities for new data. This suggests that models based on structural information may require further optimization or alternative tokenization strategies. The application of natural language processing techniques to pharmaceutical challenges has demonstrated promising results, highlighting the need for more extensive data to enhance model generalization.

Identification of Peucedanum japonicum Thunb. extract components and their protective effects against dexamethasone-induced muscle atrophy.

BACKGROUND: Peucedanum japonicum Thunb. (PJ) is a vegetable widely consumed in East Asia and is known to have anticancer and anti-inflammatory effects. However, the effect of PJ on muscle atrophy remains elusive. PURPOSE: This study aimed to investigate the effect of PJ and its active compound on dexamethasone (DEX)-induced muscle atrophy. METHODS: We performed qualitative and quantitative analysis of PJ using ultra-performance liquid chromatography-mass spectrometry tandem mass spectrometry (UPLC-MS/MS) and high-performance liquid chromatography (HPLC), respectively. The efficacy of PJ and its main compound 4-caffeoylquinic acid (CQA) on muscle atrophy was evaluated in DEX-induced myotube atrophy and DEX-induced muscle atrophy in mouse myoblasts (C2C12) and C57BL/6 mice, in vitro and in vivo, respectively. RESULTS: The UPLC-MS/MS and HPLC data showed that the concentration of 4-CQA in PJ was 18.845 mg/g. PJ and 4-CQA treatments significantly inhibited DEX-induced myotube atrophy by decreasing protein synthesis and glucocorticoid translocation to the nucleus in C2C12 myotubes. In addition, PJ enhanced myogenesis by upregulating myogenin and myogenic differentiation 1 in C2C12 cells. PJ supplementation effectively increased muscle function and mass, downregulated atrogenes, and decreased proteasome activity in C57BL/6 mice. Additionally, PJ effectively decreased the nuclear translocation of forkhead transcription factor 3 alpha by inhibiting glucocorticoid receptor. CONCLUSION: Overall, PJ and its active compound 4-CQA alleviated skeletal muscle atrophy by inhibiting protein degradation. Hence, our findings present PJ as a potential novel pharmaceutical candidate for the treatment of muscle atrophy.

Factors contributing to differences in cervical cancer screening in rural and urban community health centers.

INTRODUCTION: Community health centers (CHCs) provide historically marginalized populations with primary care, including cancer screening. Previous studies have reported that women living in rural areas are less likely to be up to date with cervical cancer screening than women living in urban areas. However, little is known about rural-urban differences in cervical cancer screening in CHCs and the contributing factors, and whether such differences changed during the COVID-19 pandemic. METHODS: Using 8-year pooled Uniform Data System (2014-2021) data and Oaxaca-Blinder decomposition, the extent to which CHC- and catchment area-level characteristics explained rural-urban differences in up-to-date cervical cancer screening was estimated. RESULTS: Up-to-date cervical cancer screening was lower in rural CHCs than urban CHCs (38.2% vs 43.0% during 2014-2019), and this difference increased during the pandemic (43.5% vs 49.0%). The rural-urban difference in cervical cancer screening in 2014-2019 was mostly explained by differences in CHC-level proportions of patients with limited English proficiency (55.9%) or income below the poverty level (12.3%) and females aged 21 to 64 years (9.8%), and catchment area-level's unemployment (3.4%) and primary care physician density (3.2%). However, Medicaid (-48.5%) or no insurance (-19.6%) counterbalanced the differences between rural-urban CHCs. The contribution of these factors to rural-urban differences in cervical cancer screening generally increased in 2020-2021. CONCLUSIONS: Rural-urban differences in cervical cancer screening were mostly explained by multiple CHC-level and catchment area-level characteristics. The findings call for tailored interventions, such as providing resources and language services, to improve cancer screening utilization among uninsured, Medicaid, and patients with limited English proficiency in rural CHCs.

High-throughput screening of small-molecules libraries identified antibacterials against clinically relevant multidrug-resistant A. baumannii and K. pneumoniae.

BACKGROUND: The current pipeline for new antibiotics fails to fully address the significant threat posed by drug-resistant Gram-negative bacteria that have been identified by the World Health Organization (WHO) as a global health priority. New antibacterials acting through novel mechanisms of action are urgently needed. We aimed to identify new chemical entities (NCEs) with activity against Klebsiella pneumoniae and Acinetobacter baumannii that could be developed into a new treatment for drug-resistant infections. METHODS: We developed a high-throughput phenotypic screen and selection cascade for generation of hit compounds active against multidrug-resistant (MDR) strains of K. pneumoniae and A. baumannii. We screened compound libraries selected from the proprietary collections of three pharmaceutical companies that had exited antibacterial drug discovery but continued to accumulate new compounds to their collection. Compounds from two out of three libraries were selected using "eNTRy rules" criteria associated with increased likelihood of intracellular accumulation in Escherichia coli. FINDINGS: We identified 72 compounds with confirmed activity against K. pneumoniae and/or drug-resistant A. baumannii. Two new chemical series with activity against XDR A. baumannii were identified meeting our criteria of potency (EC50 ≤50 µM) and absence of cytotoxicity (HepG2 CC50 ≥100 µM and red blood cell lysis HC50 ≥100 µM). The activity of close analogues of the two chemical series was also determined against A. baumannii clinical isolates. INTERPRETATION: This work provides proof of principle for the screening strategy developed to identify NCEs with antibacterial activity against multidrug-resistant critical priority pathogens such as K. pneumoniae and A. baumannii. The screening and hit selection cascade established here provide an excellent foundation for further screening of new compound libraries to identify high quality starting points for new antibacterial lead generation projects. FUNDING: BMBF and GARDP.

Pericardiocentesis versus window formation in malignant pericardial effusion: trends and outcomes.

OBJECTIVES: Malignant pericardial effusion (MPE) in patients with cancer is associated with poor prognosis. This study aimed to compare clinical outcomes in patients with cancer who underwent pericardiocentesis versus pericardial window formation. METHODS: In the present study, 765 consecutive patients with cancer (mean age 58.4 years, 395 men) who underwent pericardial drainage between 2003 and 2022 were retrospectively analysed. All-cause death and MPE recurrence were compared based on the drainage method (pericardiocentesis vs pericardial window formation) and time period (period 1: 2003-2012; period 2: 2013-2022). RESULTS: Pericardiocentesis was performed in 639 (83.5%) patients and pericardial window formation in 126 (16.5%). There was no difference in age, sex distribution, proportion of metastatic or relapsed cancer, and chemotherapy status between the pericardiocentesis and pericardial window formation groups. Difference was not found in all-cause death between the two groups (log-rank p=0.226) regardless of the period. The pericardial window formation group was associated with lower MPE recurrence than the pericardiocentesis group (6.3% vs 18.0%, log-rank p=0.001). This advantage of pericardial window formation was more significant in period 2 (18.1% vs 1.3%, log-rank p=0.005). In multivariate analysis, pericardial window formation was associated with lower MPE recurrence (HR: 0.31, 95% CI: 0.15 to 0.63, p=0.001); younger age, metastatic or relapsed cancer, and positive malignant cells in pericardial fluid were associated with increased recurrence. CONCLUSION: In patients undergoing pericardial drainage for MPE, pericardial window formation showed mortality outcomes comparable with pericardiocentesis and was associated with lower incidence of MPE recurrence.

Sunlight-Driven Self-Cleaning Ultrafine Particulate Matter Filter with Antibacterial Activity.

Air pollution by particulate matter (PM) and airborne pathogens causes severe health problems in the human body. Presently, popular disposable air filters yield huge waste and have a fatal impact on the environment. Postuse cleaning of air filters also leads to secondary air and water pollution. Here, we report a sunlight-driven self-cleaning PM filter by coupling a full-solar-spectrum-active photocatalyst comprising up-conversion nanoparticles (UCNPs) decorated with semiconductor iron(III) oxide (UCNP@α-Fe2O3) shells stabilized upon graphene functionalized borosilicate fibrous membrane (rGO-BF). While rGO-BF ensures high PM adsorption, UCNP@α-Fe2O3 (NP) enables self-photodegradation of adsorbed PM under abundant sunlight and subsequent membrane regeneration, while preventing secondary air or water pollution. Rational surface chemistry and optimal microstructure enable our filters to remove >99% of PM2.5 under deplorable air-quality conditions. Moreover, our filter shows excellent antibacterial activity toward E. coli and S. aureus, demonstrating its potential for practical utilization in face masks, air filtering devices, and protective medical wear. This work successfully suggests an intriguing design platform for self-sustainable zero-waste air filter membranes.

Novel Assessment of the Impact of Irritability on Physiological and Psychological Frustration Responses in Adolescents.

OBJECTIVE: Irritability, typically defined as a proneness to anger, particularly in response to frustration, falls at the intersection of emotion and disruptive behavior. Despite well-defined translational models, there are few convergent findings regarding the pathophysiology of irritability. Most studies utilize computer-based tasks to examine neural responses to frustration, with little work examining stress-related responding to frustration in social contexts. The present study is the first to utilize the novel Frustration Social Stressor for Adolescents (FSS-A) to examine associations between adolescent irritability and psychological and physiological responses to frustration. METHOD: The FSS-A was completed by a predominantly male, racially, ethnically, and socioeconomically diverse sample of 64 12- to 17-year-olds, who were originally recruited as children with varying levels of irritability. Current irritability was assessed using the Multidimensional Assessment Profiles-Temper Loss scale (MAP-TL-Youth). Adolescents rated state anger and anxiety before and after the FSS-A, and usable salivary cortisol data were collected from 43 participants. RESULTS: Higher MAP-TL-Youth scores were associated with greater increases in anger during the FSS-A, but not increases in anxiety, or alterations in cortisol. Pre-task state anger negatively predicted the slope of the rise in cortisol observed in anticipation of the FSS-A. CONCLUSIONS: Results provide support for unique associations between adolescent irritability and anger during, and in anticipation of, frustrating social interactions. Such findings lay a foundation for future work aimed at informing physiological models and intervention targets.

Social isolation and its influencing factors among age-related hearing loss patients: A cross-sectional study.

Hearing loss is considered one of the most common symptoms of aging worldwide, and age-related hearing loss is one of the three major chronic illnesses that affect older adults. This study examined social isolation among age-related hearing loss patients and its influencing factors. This cross-sectional descriptive study collected data from older adults with hearing loss from March 2019 to February 2020 at a university hospital. Social isolation, subjective hearing handicap, and communication-related life satisfaction were measured using a structured questionnaire. Objective hearing function was evaluated using an audiometer (Madsen Asterao 2). The independent t test, one-way analysis of variance, and multiple linear regression analysis were used to analyze the data. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used for reporting this study. Almost half (49.9%) of 203 age-related hearing loss patients aged 60 to 92, with a mean age of 71.6 ±â€…7.95 years, experienced social isolation. Factors predicting social isolation were communication-related life satisfaction (P < .001), religiosity (P = 001), experience using hearing aids (P = .006), and subjective hearing handicap (P = .047). The explanatory power of the model was 58.2%. Interventions to reduce social isolation among age-related hearing loss patients should be implemented in an effort to develop effective, appropriate, and comprehensive strategies targeting this high-risk group.

Gromwell ameliorates glucocorticoid-induced muscle atrophy through the regulation of Akt/mTOR pathway.

BACKGROUND: Muscle atrophy is characterized by decreased muscle mass, function, and strength. Synthetic glucocorticoids, including dexamethasone (Dexa), are commonly used to treat autoimmune diseases. However, prolonged exposure of Dexa with high dose exerts severe side effects, including muscle atrophy. The purpose of this study was to investigate whether Gromwell root extract (GW) can prevent Dexa-induced muscle atrophy in C2C12 cells and mice and to characterize the composition of GW to identify bioactive compounds. METHODS: For in vitro experiments, GW (0.5 and 1 µg/mL) or lithospermic acid (LA, 5 and 10 µM) was added to C2C12 myotubes on day 4 of differentiation and incubated for 24 h, along with 50 µM Dexa. For in vivo experiment, four-week-old male C57BL/6 mice were randomly divided into the four following groups (n = 7/group): Con group, Dexa group, GW0.1 group, and GW0.2 group. Mice were fed experimental diets of AIN-93 M with or without 0.1 or 0.2% GW for 4 weeks. Subsequently, muscle atrophy was induced by administering an intraperitoneal injection of Dexa at a dose of 15 mg/kg/day for 38 days, in conjunction with dietary intake. RESULTS: In Dexa-induced myotube atrophy, treatment with GW increased myotube diameter, reduced the expression of muscle atrophy markers, and enhanced the expression of myosin heavy chain (MHC) isoforms in C2C12 cells. Supplementation with the GW improved muscle function and performance in mice with Dexa-induced muscle atrophy, evidenced in the grip strength and running tests. The GW group showed increased lean body mass, skeletal muscle mass, size, and myosin heavy chain isoform expression, along with reduced skeletal muscle atrophy markers in Dexa-injected mice. Supplementation with GW increased protein synthesis and decreased protein degradation through the Akt/mammalian target of rapamycin and glucocorticoid receptor/forkhead box O3 signaling pathways, respectively. We identified LA as a potential bioactive component of the GW. LA treatment increased myotube diameter and decreased the expression of muscle atrophy markers in Dexa-induced C2C12 cells. CONCLUSIONS: These findings underscore the potential of the GW in preventing Dexa-induced skeletal muscle atrophy and highlight the contribution of LA to its effects.

Differing Efficacy of Dapagliflozin Versus Empagliflozin on the Risk of Incident Atrial Fibrillation in Patients With Type 2 Diabetes: A Real-World Observation Using a Nationwide, Population-Based Cohort.

BACKGROUND: Meta-analyses of large clinical trials investigating SGLT2 (sodium-glucose cotransporter-2) inhibitors have suggested their protective effects against atrial fibrillation in patients with type 2 diabetes. However, the results were predominantly driven from trials involving dapagliflozin. METHODS AND RESULTS: We used a nationwide, population-based cohort of patients with type 2 diabetes who initiated either dapagliflozin or empagliflozin between May 2016 and December 2018. An active-comparator, new-user design was used, and the 2 groups of patients were matched using propensity scores. The primary outcome was incident nonvalvular atrial fibrillation, which was analyzed using both the main intention-to-treat and sensitivity analysis that censored patients who skipped their medications for ≥30 days. Men ≥55 years of age and women ≥60 years of age with ≥1 traditional risk factor or those with established cardiovascular disease were categorized as high cardiovascular risk group. Patients not included in the high-risk group were categorized as low risk. After 1:1 propensity-score matching, a total of 137 928 patients (mean age, 55 years; 58% men) were included and followed up for 2.2±0.6 years. The risk of incident atrial fibrillation was significantly lower in the dapagliflozin group in both the main (hazard ratio [HR], 0.885 [95% CI, 0.789-0.992]) and sensitivity analyses (HR, 0.835 [95% CI, 0.719-0.970]). Notably, this was consistent in both the low and high cardiovascular risk groups. There was no effect modification by age, sex, body mass index, duration of diabetes, or renal function. CONCLUSIONS: This real-world, population-based study demonstrates that patients with type 2 diabetes using dapagliflozin may have a lower risk of developing nonvalvular atrial fibrillation than those using empagliflozin.

Gromwell (Lithospermum erythrorhizon) Attenuates High-Fat-Induced Skeletal Muscle Wasting by Increasing Protein Synthesis and Mitochondrial Biogenesis.

Gromwell (Lithospermum erythrorhizon, LE) can mitigate obesity-induced skeletal muscle atrophy in C2C12 myotubes and high-fat diet (HFD)-induced obese mice. The purpose of this study was to investigate the anti-skeletal muscle atrophy effects of LE and the underlying molecular mechanism. C2C12 myotubes were pretreated with LE or shikonin, and active component of LE, for 24 h and then treated with 500 µM palmitic acid (PA) for an additional 24 h. Additionally, mice were fed a HFD for 8 weeks to induced obesity, and then fed either the same diet or a version containing 0.25% LE for 10 weeks. LE attenuated PA-induced myotubes atrophy in differentiated C2C12 myotubes. The supplementation of LE to obese mice significantly increased skeletal muscle weight, lean body mass, muscle strength, and exercise performance compared with those in the HFD group. LE supplementation not only suppressed obesity-induced skeletal muscle lipid accumulation, but also downregulated TNF-α and atrophic genes. LE increased protein synthesis in the skeletal muscle via the mTOR pathway. We observed LE induced increase of mitochondrial biogenesis and upregulation of oxidative phosphorylation related genes in the skeletal muscles. Furthermore, LE increased the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and the phosphorylation of adenosine monophosphate-activated protein kinase. Collectively, LE may be useful in ameliorating the detrimental effects of obesity-induced skeletal muscle atrophy through the increase of protein synthesis and mitochondrial biogenesis of skeletal muscle.

Performance of 2020 AHA/ACC HCM Guidelines and Incremental Value of Myocardial Strain for Predicting SCD.

Background: The 2020 American Heart Association (AHA)/American College of Cardiology (ACC) guidelines for sudden cardiac death (SCD) risk stratification in hypertrophic cardiomyopathy (HCM) need further international validation. Objectives: Performance of the guidelines and the incremental value of myocardial strain for predicting SCD in HCM were investigated. Methods: In 1,416 HCM patients, SCD risk was stratified according to the 2020 AHA/ACC and 2014 European Society of Cardiology (ESC) guidelines. Left ventricular (LV) global longitudinal strain (GLS) and left atrial reservoir strain (LARS) were measured. The main outcome consisted of SCD events. Results: Overall, 29.1% had major risk factors (RFs), and 14.7% had nonmajor RFs in the absence of major RFs; estimated 5-year SCD event rates were 6.8% and 2.3%, respectively. SCD risk was significantly increased in the former group but not in the latter. When stratified by the number of RFs, 5-year SCD event rates were 1.9%, 3.0%, 4.9%, and 18.4% for patients with 0, 1, 2, and 3 or more RFs, respectively. SCD risk was elevated in patients with multiple RFs but not in those with a single RF. Performance of the AHA/ACC and ESC guidelines did not differ significantly over 10 years (5-year time-dependent area under the curve: 0.677 vs 0.724; P = 0.235). Decreased LV GLS and LARS were independently associated with SCD events with optimal cutoffs of LV GLS <13% and LARS <21%. Adding LV GLS and LARS to the guidelines had incremental predictive value. Conclusions: The 2020 AHA/ACC guidelines were predictive of SCD events with modest power in a large Asian HCM cohort. Implantable cardioverter-defibrillators are reasonable in patients with multiple RFs, and consideration of myocardial strain can improve SCD prediction.

Government Housing Assistance and Cancer Screening Among Adults With Low Income.

INTRODUCTION: Access to affordable housing may support cancer control for adults with low income by alleviating financial barriers to preventive care. This study examines relationships between cancer screening and receipt of government housing assistance among adults with low income. METHODS: Data are from the 2019 and 2021 National Health Interview Survey. Eligible respondents were classified as up-to-date or not with breast cancer (BC), cervical cancer (CVC) and colorectal cancer (CRC) screening guidelines. Multivariable logistic regression was used to model guideline-concordant screening by receipt of government housing assistance, overall and stratified by urban-rural status, race/ethnicity, and age. Analyses were performed in 2023. RESULTS: Analyses for BC, CVC and CRC screening included 2,258, 3,132, and 3,233 respondents, respectively. There was no difference in CVC screening by housing assistance status, but screening for BC and CRC was higher among those who received assistance compared to those who did not (59.7% vs. 50.8%, p<0.01 for BC; 57.1% vs. 44.1%, p<0.01 for CRC). In models adjusted for sociodemographic characteristics, health status and insurance, these differences were not statistically significant for either BC or CRC screening. In stratified adjusted models, housing assistance was statistically significantly associated with increased BC screening in urban areas (aOR=1.35, 95% CI=1.00-1.82) and among Hispanic women (aOR=2.20, 95% CI=1.01-4.78) and women 45-54 years of age (aOR=2.10, 95% CI=1.17-3.75). CONCLUSIONS: Policies that address housing affordability may enhance access to BC screening for some subgroups, including women in urban areas, Hispanic women, and younger women. More research on the mechanisms that link housing assistance to BC screening is needed.

Irreversible myocardial injury attenuates the benefits of sacubitril/valsartan in heart failure patients.

BACKGROUND: Despite the established benefits of angiotensin receptor-neprilysin inhibitor (ARNI) in heart failure with reduced ejection fraction (HFrEF) across various etiologies, there are controversies regarding the effects of ARNI in patients with irreversible myocardial injury. The aim of this study is to investigate the impact of irreversible myocardial injury on the benefits of ARNI treatment in patients with HFrEF, consisted of both ischemic and non-ischemic etiologies. METHODS AND RESULTS: We conducted a retrospective single-center study including 409 consecutive patients with HFrEF treated with ARNI between March 2017 and May 2020. Irreversible myocardial injury was defined as nonviable myocardium without contractile reserve, which suggests a limited potential for recovery of left ventricular function and geometry. At baseline, irreversible myocardial injury was observed in 129 (31.5%) patients. Composite outcome was cardiovascular death or hospitalization for heart failure, which occurred in 56 (43.4%) and 61 (21.8%) patients with and without irreversible myocardial injury, respectively. On multivariable analysis, irreversible injury presence, but not ischemic etiology, was an independent predictor of composite outcome (hazard ratio 2.16, 95% confidence interval 1.33-3.49). Mediation analysis revealed that the increased risk of the composite outcome due to irreversible myocardial injury was mediated by attenuated LV reverse remodeling (Z value = 2.02, P = 0.043). CONCLUSIONS: The presence of irreversible myocardial injury was significantly associated with the response to ARNI treatment in patients with HFrEF, regardless of etiology.

Living alone and cancer mortality by race/ethnicity and socioeconomic status among US working-age adults.

BACKGROUND: Previous studies have shown an association between living alone and cancer mortality; however, findings by sex and race/ethnicity have generally been inconsistent, and data by socioeconomic status are sparse. The association between living alone and cancer mortality by sex, race/ethnicity, and socioeconomic status in a nationally representative US cohort was examined. METHODS: Pooled 1998-2019 data for adults aged 18-64 years at enrollment from the National Health Interview Survey linked to the National Death Index (N = 473,648) with up to 22 years of follow-up were used to calculate hazard ratios (HRs) for the association between living alone and cancer mortality. RESULTS: Compared to adults living with others, adults living alone were at a higher risk of cancer death in the age-adjusted model (HR, 1.32; 95% CI, 1.25-1.39) and after additional adjustments for multiple sociodemographic characteristics and cancer risk factors (HR, 1.10; 95% CI, 1.04-1.16). Age-adjusted models stratified by sex, poverty level, and educational attainment showed similar associations between living alone and cancer mortality, but the association was stronger among non-Hispanic White adults (HR, 1.33; 95% CI, 1.25-1.42) than non-Hispanic Black adults (HR, 1.18; 95% CI, 1.05-1.32; p value for difference < .05) and did not exist in other racial/ethnic groups. These associations were attenuated but persisted in fully adjusted models among men (HR, 1.13; 95% CI, 1.05-1.23), women (HR, 1.09; 95% CI, 1.01-1.18), non-Hispanic White adults (HR, 1.13; 95% CI, 1.05-1.20), and adults with a college degree (HR, 1.22; 95% CI, 1.07-1.39). CONCLUSIONS: In this nationally representative study in the United States, adults living alone were at a higher risk of cancer death in several sociodemographic groups.

Age-dependent association of metabolic dyslipidemia with clinical expression of hypertrophic cardiomyopathy.

BACKGROUND: Previous studies have shown that the clinical expression of hypertrophic cardiomyopathy (HCM) can be determined by obesity and metabolic syndrome. The present study aimed to investigate the association between triglyceride and high-density lipoprotein cholesterol (HDLC) level, the two dyslipidemia-related components of metabolic syndrome, and the incidence of HCM. We also explored an age-dependent association between them. METHODS: Individuals without previous HCM diagnosis who underwent a designated national health examination in 2009 were recruited. Individuals who used lipid-lowering medications within 1-year of the baseline were excluded. The outcome of interest was a newly diagnosed HCM. RESULTS: Our cohort consisted of 8,652,709 individuals (mean 46 years, 55.6% men). During the median 9.3 years of follow-up, 5932 (0.07%) individuals were newly diagnosed with HCM. There was a gradual increase in the incidence of HCM towards higher triglyceride and lower HDL-C levels (log-rank p < 0.001). When stratified by age, the incidence of HCM was highest in individuals aged ≥65 years, followed by those aged 40-64 and 20-39 years (0.22% vs. 0.07% vs. 0.03%, log-rank p < 0.001). In individuals aged 20-39 years, a higher triglyceride level was associated with a higher incidence of HCM (i.e., ≥200 vs. <100 mg/dL: adjusted hazard ratio 2.28, 95% confidence interval 1.89-2.75), whereas there was no significant association in older groups (p-for-interaction<0.001). Similarly, a lower HDL-C level was associated with a higher incidence of HCM, particularly in individuals aged 20-39 years (p-for-interaction = 0.001). CONCLUSIONS: High triglyceride and low HDL-C levels are associated with a higher incidence of HCM, particularly in young individuals.

Nutrition and health challenges among low-income families of young children in the post COVID-19 era: a qualitative study.

BACKGROUND/OBJECTIVES: In the United States, one in every 5 children is obese with greater likelihood in low-income households. The coronavirus disease 2019 (COVID-19) pandemic may have accelerated disparities in child obesity risk factors, such as poor dietary intake and increased sedentary behaviors, among low-income families because of financial difficulties, social isolation and other struggles. This study reveals insights into nutrition and health challenges among low-income families of young children in West Texas to better understand needs and develop interventions. SUBJECTS/METHODS: In-depth individual interviews were performed via Zoom among 11 families of children under the age of 3. A semi-structured interview guide was developed to explore 3 areas: changes in (1) dietary intake and (2) sedentary behaviors and (3) families' preferences regarding a parent nutrition education program. Each interview was audio-recorded, transcribed, and coded using MaxQDA software. RESULTS: Eating together as a family become challenging because of irregular work schedules during the COVID-19 pandemic. Most parents stated that their children's dietary habits shifted with an increased consumption of processed foods. Many parents are unable to afford healthful foods and have utilized food and nutrition assistance programs to help feed their families. All families reported that their children's screen time substantially increased compared to the pre-pandemic times. Moreover, the majority of parents did not associate child screen time with an obesity risk, so this area could be of particular interest for future interventions. Meal preparation ideas, remote modality, and early timing were identified as key intervention strategies. CONCLUSIONS: Online nutrition interventions that emphasize the guidelines for child screen time and regular meal routines will be effective and promising tools to reach low-income parents for early childhood health promotion and obesity prevention.

Effects of Post Traumatic Growth on Successful Aging in Breast Cancer Survivors in South Korea: The Mediating Effect of Resilience and Intolerance of Uncertainty.

This study aimed to identify post-traumatic growth and successful aging and the mediating effects of resilience and intolerance of uncertainty in breast cancer survivors. This study employed a descriptive survey approach. Data were collected from 143 breast cancer survivors between 27 January and 10 December 2021, at a cancer center in Gyeongsangnam-do, South Korea. SPSS/WIN 25.0 and PROCESS Macro version 3.5 were used for data analysis. Descriptive statistics were analyzed with SPSS. PROCESS was used to conduct a mediation analysis and the significance of the mediating effect was evaluated using 95% confidence intervals. Successful aging was significantly associated with post-traumatic growth, resilience, and the intolerance of uncertainty. The impact of post-traumatic growth on successful aging was mediated by resilience in breast cancer survivors. Resilience should be considered when developing nursing interventions to enhance post-traumatic growth and promote successful aging in breast cancer survivors.