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Abstract Background Community Heart Health Actions for Latinos at Risk (CHARLAR) is a promotora-led cardiovascular disease (CVD) risk-reduction program for socio-demographically disadvantaged Latinos and consists of 11 skill-building sessions. The COVID-19 pandemic has led to worsening health status in U.S. adults and necessitated transition to virtual implementation of the CHARLAR program. Methods A mixed-methods approach was used to evaluate virtual delivery of CHARLAR. Changes in health behaviors were assessed through a pre/post program survey. Results from virtual and historical (in-person delivery) were compared. Key informant interviews were conducted with promotoras and randomly selected participants and then coded and analyzed using a thematic approach. Results An increase in days of exercise per week (+ 1.52), daily servings of fruit (+ 0.60) and vegetables (+ 0.56), and self-reported general health (+ 0.38), were observed in the virtual cohort [all p

Takamasa Kinoshita, Junya Mori, Akira Hatanaka, Miho Shimizu, Hiroko Imaizumi Department of Ophthalmology, Sapporo City General Hospital, Sapporo, JapanCorrespondence: Takamasa KinoshitaDepartment of Ophthalmology, Sapporo City General Hospital, 1-1, N-11, W-13, Chuoku, Sapporo, 060-8604, JapanTel +81 11 726 2211Fax +81 11 726 9541Email knst129@gmail.comPurpose: To report the results of anti-vascular endothelial growth factor (VEGF) therapy using treat-and-extend (TAE) and treatment cessation regimens for exudative age-related macular degeneration (AMD) and pachychoroid neovasculopathy (PN).Methods: We retrospectively studied 101 treatment-naïve eyes of 101 patients with exudative AMD and PN that underwent anti-VEGF therapy using TAE and treatment cessation regimen with a follow-up period of ≥ 12 months. Best-corrected visual acuity (BCVA), treatment frequency, and number of eyes with successful treatment cessation were measured. Successful treatment cessation was defined as dry macula retention without treatment for > 16 weeks after the last injections. Factors related to the successful treatment cessation were evaluated.Results: BCVA was maintained at the last visit with a mean follow-up period of 49.9 ± 26.9 months. The injection number decreased from 6.8 ± 2.31 at the first year to 3.7 ± 3.64 at the fifth year. At the last visit, 48 (47.5%) eyes were being treated at an interval of ≥ 12 weeks or were under treatment cessation. Successful treatment cessation during the follow-up period and at the last visit were achieved in 56 (55.4%) and 27 (26.7%) eyes, with a median treatment-free period of 66 and 126 weeks, respectively. Good early treatment response and a small recurrence number were associated with successful treatment cessation at the last visit.Conclusion: Patients with good early response to treatment and fewer recurrences may achieve treatment cessation. This information could help physicians predict the achievement of treatment cessation for a considerable period.Keywords: age-related macular degeneration, pachychoroid neovasculopathy, anti-vascular endothelial growth factor, treat-and-extend regimen, treatment cessation

Koichi Nishimura,1,2,* Jinichi Mori,1– 3,* Takahiro Sawada,1,2 Shuhei Nomura,1,4 Alexander Kouzmenko,1 Kaori Yamashita,5 Yoshiaki Kanemoto,1,2 Tomohiro Kurokawa,1,2 Akira Hayakawa,1 Suguru Tokiwa,5 Michihisa Ochi,5 Hiroaki Shimmura,5 Shigeaki Kato1,2 1Research Institute of Innovative Medicine, Tokiwa Foundation, Iwaki, Japan; 2Graduate School of Life Science and Engineering, Iryo Sosei University, Iwaki, Japan; 3Department of Hematology, Jyoban Hospital, Iwaki, Japan; 4Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 5Department of Urology, Jyoban Hospital, Iwaki, Japan*These authors contributed equally to this workCorrespondence: Shigeaki Kato Email uskato0525@gmail.comIntroduction: Although the ability of androgens to promote prostate cancer development has been known for decades, the molecular mechanisms of androgen receptor (AR) signaling in the tumorigenesis remain unclear. Enhancer RNAs (eRNAs) transcribed from strong enhancers, or super-enhancers (SEs), have recently emerged as a novel class of regulatory non-coding RNAs (ncRNAs) that facilitate transcription, including that of androgen target genes, through chromatin looping to position enhancers proximate to the promoters. The aim of this study was to assess androgen-dependent transcription in prostate tumors of eRNAs (designated as KLK3eRNAs) from the SE of the KLK3 gene encoding the prostate-specific antigen (PSA) protein, a clinical marker of prostate carcinogenesis.Materials and Methods: The androgen-induced KLK3eRNAs were identified in the LNCaP human prostate cancer cell line. The expressions of these KLK3eRNAs together with KLK3 and AR mRNA transcripts were assessed by qRT-PCR in prostate tumor samples from five prostate cancer patients.Results: Androgen-induced KLK3eRNAs have been identified in the LNCaP cells, and their expression was further analyzed in tumors of prostate cancer patients. Transcripts of the tested KLK3eRNAs have been detected in all clinical samples, but their expression patterns differed between individual tumor specimens. We found a statistically significant correlation between the levels of the KLK3 and AR mRNAs with those of the previously reported KLK3eRNAs, while such correlation was not observed for novel KLK3eRNAs described in our recent report.Conclusion: Presented data suggest that prostate tumor development may associate with epigenetic reorganization in the KLK3 genomic regulatory elements reflected by changes of the KLK3eRNA expression. Our findings support a potential of eRNAs profiling to be used as diagnostic marker.Keywords: enhancer RNA, prostate cancer, androgen receptor, PSA, non-coding RNA, epigenetic modification

Background Methadone is associated with a disproportionate risk of sudden death and ventricular tachyarrhythmia despite only modest inhibition of delayed rectifier K+ current (IKr), the principal mechanism of drug‐associated arrhythmia. Congenital defects of inward rectifier K+ current (IK1) have been linked to increased U‐wave amplitude on ECG and fatal arrhythmia. We hypothesized that methadone may also be a potent inhibitor of IK1, contributing to delayed repolarization and manifesting on surface ECGs as augmented U‐wave integrals. Methods and Results Using a whole‐cell voltage clamp, methadone inhibited both recombinant and native IK1 with a half‐maximal inhibitory concentration IC50) of 1.5 μmol/L, similar to that observed for IKr block (half‐maximal inhibitory concentration of 2.9 μmol/L). Methadone modestly increased the action potential duration at 90% repolarization and slowed terminal repolarization at low concentrations. At higher concentrations, action potential duration at 90% repolarization lengthening was abolished, but its effect on terminal repolarization rose steadily and correlated with increased fluctuations of diastolic membrane potential. In parallel, patient ECGs were analyzed before and after methadone initiation, with 68% of patients having a markedly increased U‐wave integral compared with premethadone (lead V3; mean +38%±15%, P=0.016), along with increased QT and TPeak to TEnd intervals, likely reflective of IKr block. Conclusions Methadone is a potent IK1 inhibitor that causes augmentation of U waves on surface ECG. We propose that increased membrane instability resulting from IK1 block may better explain methadone’s arrhythmia risk beyond IKr inhibition alone. Drug‐induced augmentation of U waves may represent evidence of blockade of multiple repolarizing ion channels, and evaluation of the effect of that agent on IK1 may be warranted.

Background: Anorexia nervosa (AN) is associated with left ventricular (LV) atrophy and unexplained sudden death. Myocardial mechanics have not been well studied in adults with AN. Whether LV mass or illness duration, markers of AN severity, correlate with abnormal strain imaging is unknown. Methods: We performed a prospective study among patients hospitalized with severe AN (n = 29) [body mass index (BMI) < 14.5 kg/m2] and sex/age-matched controls (n = 16) (BMI > 18.5 kg/m2). LV ejection fraction (LVEF) was calculated via modified-biplane method and LV mass was derived using the truncated ellipsoid formula. Apical 2-, 3-, and 4-chamber images were used to generate regional strain mapping and global longitudinal strain (GLS). N-terminal brain natriuretic peptide (NT-proBNP) levels were measured and linear regression was used to determine independent predictors of strain. Results: Mean LVEF did not differ (65% ± 6.0 vs. 62% ± 4.4, p = 0.06), but LV mass was substantially reduced (61.6 ± 16.8 vs. 97.6 ± 19.1 g, p <.0001). GLS was similar (− 20.6 ± 3.8 vs. − 20.9 ± 2.8, p = 0.82), however, the basal strain was worse (-18.7 ± 4.8 vs. -21.9 ± 4.1, p = 0.03). Lower LV mass was associated with worsening GLS (r = − 0.40, p = 0.003), but not among controls (p = 0.89). Median (IQR) NT-proBNP (pg/ml) was higher in patients with AN [141 (59–257) vs. 35.5 (21–56.5) p = 0.0007]. Both increasing NT-proBNP and illness duration were associated with worsening strain patterns in AN (both p =.001). Conclusions: While LVEF and GLS did not differ, regional strain variation was noted among patients with AN. Elevated NT-proBNP may reflect increased wall tension from LV atrophy. Whether strain heterogeneity can identify patients with AN, at risk for sudden death, requires further study. [ABSTRACT FROM AUTHOR]

Vascular markers such as pulse-wave velocity and carotid intima-media thickness (CIMT) might improve the prediction of incident cardiovascular disease beyond traditional risk factors. These vascular markers have not been well characterized in minority populations and might be more useful than inflammatory biomarkers. We conducted a prospective, longitudinal cohort study among hypertensive patients in an urban safety-net hospital. We evaluated inflammatory biomarkers, arterial pulse-wave velocity, and carotid intima-media thickness at baseline, 1 year, and 2 years. The primary outcome variable was CIMT. Generalized linear mixed-effects models were used to evaluate associations between CIMT and predictive variables accounting for the correlation of multiple measurements within subjects over time. For our secondary outcome, we used administrative and National Death Index data to determine all-cause death, and univariate relationships were evaluated. Among 175 subjects, 117 were Latino (67%) and 117 were female (67%). Pulse-wave velocity and CIMT regressed over time (both P

BackgroundOmega-3 fatty acids prevent cardiovascular disease (CVD) events in patients with myocardial infarction or heart failure. Benefits in patients without overt CVD have not been demonstrated, though most studies did not use treatment doses (3.36 g) of omega-3 fatty acids. Arterial stiffness measured by pulse wave velocity (PWV) predicts CVD events independent of standard risk factors. However, no therapy has been shown to reduce PWV in a blood pressure-independent manner. We assessed the effects of esterified omega-3 fatty acids on PWV and serum markers of inflammation among patients with hypertension.Design and methodsWe performed a prospective, randomized; double-blinded pilot study of omega-3 fatty acids among 62 patients in an urban, safety net hospital. Patients received 3.36 g of omega-3 fatty acids vs. matched placebo daily for 3-months. The principal outcome measure was change in brachial-ankle PWV. Serum inflammatory markers associated with CVD risk were also assessed.ResultsThe majority (71 %) were of Latino ethnicity. After 3-months, mean change in arterial PWV among omega-3 and placebo groups was -97 cm/s vs. -33 cm/s respectively (p = 0.36 for difference, after multivariate adjustment for baseline age, systolic blood pressure, and serum adiponectin). Non-significant reductions in lipoprotein-associated phospholipase A2 (LpPLA2) mass and high sensitivity C-reactive protein (hsCRP) relative to placebo were also observed (p = 0.08, and 0.21, respectively).ConclusionHigh-dose omega-3 fatty acids did not reduce arterial PWV or markers of inflammation among patients within a Latino-predominant population with hypertension.Clinical trial registrationNCT00935766 , registered July 8 2009.

© 2015 Sakushima et al.; licensee BioMed Central.Background: Physician-scientists play key roles in biomedical research across the globe, yet prior studies have found that it is increasingly difficult to recruit and retain physician-scientists in research

Abstract Many volatile chemicals inhaled for a recreational high have a chemical structure similar to chloroform and may lead to Ikr blockade and subsequent torsades de pointes. This is one potential mechanism of action for huffing‐associated sudden death.

Integrated Ocean Drilling Program (IODP) Expedition 343, named the Japan Trench Fast Drilling Project (JFAST), drilled ocean floor boreholes through the fault zone of the 2011 Tōhoku-Oki earthquake (M9.0) to enhance understanding of the rupture process and tsunami generation. This project investigated the very large fault slip that caused the devastating tsunami by making borehole stress measurements, sampling the plate boundary fault zone, and taking temperature measurements across the fault zone. The results show that the earthquake rupture occurred in a narrow fault zone (< 5 m). Based on both laboratory experiments on fault zone material and temperature monitoring of the fault zone, we show that the fault had very low friction during the earthquake. The low friction properties of the fault zone might be attributed to high smectite clay content of the sediment. These physical and frictional characteristics contributed to the unusually large fault slip that occurred during the earthquake and generated the tsunami. © 2014 by The Oceanography Society. All rights reserved.

Purpose: Women and minorities with acute myocardial infarction (AMI) often fail to recognize prodromal symptoms leading to delays in care. The objective of this study was to conduct a mixed method assessment of the impact of ethnicity on symptom description, recognition, and treatment-seeking behavior in Hispanic and non-Hispanic women before hospitalization for AMI. Methods: We explored differences in symptomatology, treatment-seeking behavior, and delay patterns among a convenience sample of 43 women diagnosed with AMI (17 Hispanic women, 26 non-Hispanic women) in seven rural and urban Colorado hospitals. We performed in-depth interviews to establish patterns (typologies) of treatment-seeking behaviors. Chart abstraction provided delay times as a function of ethnicity. Results: Most (28/43) women reported prodromal symptoms in the weeks before their index AMI. Overall, fewer Hispanic women presented within 24?h of symptom onset (3/18, 17% vs. 15/18, 83%, p

The statewide Colorado Healthy Heart Solutions (CHHS) program provides cardiovascular disease (CVD) risk factor screening and education to the medically underserved and has been shown to improve CVD risk profiles. We aimed to enhance its effectiveness through addition of a mobile health (mHealth) intervention using SMS messaging (termed Cardio SMS). We conducted a prospective, non-randomized controlled pilot trial of this intervention implemented at 5 rural program sites (number of participants N = 204) compared with a contemporaneous propensity-score matched control group from 14 CHHS sites not receiving the intervention (N = 408) between 2012 and 2014. All participants were free of CVD at baseline, and follow-up time was 12-months. The primary outcome was program engagement, defined as the number of completed interactions with the program during the entire follow-up period. Secondary outcomes were program retention, defined as any interaction during the last two months of the study; change in self-reported healthy behaviors (physical activity, weight loss, smoking cessation, fat intake); and change in CVD risk factors. There were trends for differences between groups across multiple outcomes, but most did not reach statistical significance, except for a greater decrease in self-reported fat intake in the intervention vs. control groups (26.3% vs 10.6%, P = 0.001). In addition, a subset of surveyed participants who viewed the SMS messages as motivating showed greater program retention (P = 0.03). Given the relative ease and scalability of SMS interventions in rural underserved communities, further study of SMS as part of multicomponent strategies for CVD prevention is warranted. Keywords: Mobile health, Cardiovascular disease, Primary prevention

Background and objectivesSrc family kinases (SFKs) play a critical role in initiating and propagating signals in platelets. The aims of this study were to quantitate SFK members present in platelets and to analyze their contribution to platelet regulation using glycoprotein VI (GPVI) and intregrin αIIbβ3, and in vivo.Methods and resultsMouse platelets express four SFKs, Fgr, Fyn, Lyn and Src, with Lyn expressed at a considerably higher level than the others. Using mutant mouse models, we demonstrate that platelet activation by collagen-related peptide (CRP) is delayed and then potentiated in the absence of Lyn, but only marginally reduced in the absence of Fyn or Fgr, and unaltered in the absence of Src. Compound deletions of Lyn/Src or Fyn/Lyn, but not of Fyn/Src or Fgr/Lyn, exhibit a greater delay in activation relative to Lyn-deficient platelets. Fibrinogen-adherent platelets show reduced spreading in the absence of Src, potentiation in the absence of Lyn, but no change in the absence of Fyn or Fgr. In mice double-deficient in Lyn/Src or Fgr/Lyn, the inhibitory role of Lyn on spreading on fibrinogen is lost. Lyn is the major SFK-mediating platelet aggregation on collagen at arterial shear and its absence leads to a reduction in thrombus size in a laser injury model.ConclusionThese results demonstrate that SFKs share individual and overlapping roles in regulating platelet activation, with Lyn having a dual role in regulating GPVI signaling and an inhibitory role downstream of αIIbβ3, which requires prior signaling through Src.

BackgroundPreventive cardiology has expanded beyond coronary heart disease towards prevention of a broader spectrum of cardiovascular diseases. Ethnic minorities are at proportionately greater risk for developing extracoronary vascular disease including heart failure and cerebrovascular disease.MethodsWe performed a cross sectional study of Latino and White hypertension patients in a safety-net healthcare system. Framingham risk factors, markers of inflammation (hsCRP, LPpLA2), arterial stiffness (Pulse wave velocity, augmentation index, and central aortic pressure), and endothelial function (brachial artery flow-mediated dilatation) were measured. Univariate and multivariable associations between these parameters and an index of extracoronary atherosclerosis (carotid intima media thickness) was performed.ResultsAmong 177 subjects, mean age was 62 years, 67% were female, and 67% were Latino. In univariate analysis, markers associated with carotid intima media thickness (IMT) at p.10). Only PWV retained a significant association with carotid IMT independent of the Framingham general risk profile parameters (p=.016). No statistically significant interactions between Framingham and other independent variables with ethnicity (all p>.05) were observed.ConclusionIn this safety net cohort, PWV is a potentially useful adjunctive atherosclerotic risk marker independent of traditional risk factors and irrespective of ethnicity.

BackgroundLatinos in the United States have a higher prevalence of type 2 diabetes than non-Latino whites, even after controlling for adiposity. Decreased adiponectin is associated with insulin resistance and predicts T2DM, and therefore may mediate this ethnic difference. We compared total and high-molecular-weight (HMW) adiponectin in Latino versus white individuals, identified factors associated with adiponectin in each ethnic group, and measured the contribution of adiponectin to ethnic differences in insulin resistance.MethodsWe utilized cross-sectional data from subjects in the Latinos Using Cardio Health Actions to reduce Risk study. Participants were Latino (n = 119) and non-Latino white (n = 60) men and women with hypertension and at least one other risk factor for CVD (age 61 ± 10 yrs, 49% with T2DM), seen at an integrated community health and hospital system in Denver, Colorado. Total and HMW adiponectin was measured by RIA and ELISA respectively. Fasting glucose and insulin were used to calculate the homeostasis model insulin resistance index (HOMA-IR). Variables independently associated with adiponectin levels were identified by linear regression analyses. Adiponectin's contribution to ethnic differences in insulin resistance was assessed in multivariate linear regression models of Latino ethnicity, with logHOMA-IR as a dependent variable, adjusting for possible confounders including age, gender, adiposity, and renal function.ResultsMean adiponectin levels were lower in Latino than white patients (beta estimates: -4.5 (-6.4, -2.5), p < 0.001 and -1.6 (-2.7, -0.5), p < 0.005 for total and HMW adiponectin), independent of age, gender, BMI/waist circumference, thiazolidinedione use, diabetes status, and renal function. An expected negative association between adiponectin and waist circumference was seen among women and non-Latino white men, but no relationship between these two variables was observed among Latino men. Ethnic differences in logHOMA-IR were no longer observed after controlling for adiponectin levels.ConclusionsAmong patients with CVD risk, total and HMW adiponectin is lower in Latinos, independent of adiposity and other known regulators of adiponectin. Ethnic differences in adiponectin regulation may exist and future research in this area is warranted. Adiponectin levels accounted for the observed variability in insulin resistance, suggesting a contribution of decreased adiponectin to insulin resistance in Latino populations.