Development of Biomimetic Models of Human Cardiac Tissue

The leading cause of death worldwide is cardiovascular disease (CVD). Myocardial infarction (MI) (i.e., heart attack) makes up ~8.5% of CVD and is a common cause of heart failure with a 40% five-year mortality after the first MI. This highlights a substantial patient population and an urgent need to develop new therapeutic strategies (e.g., regenerative cell therapies). Moreover, this also indicates that current models may not sufficiently recapitulate human cardiac tissue. To date, drug development strategies have largely depended on high throughput 2D cell models and pre-clinical testing in animal models of MI leading to minimal improvements in the heart failure treatment paradigm over the past 20 years. Relevant human cardiac models would provide insight into human cardiac tissue physiology and maturation while also providing an advanced in vitro screening tool to explore heart failure pathogenesis. Cardiac tissue engineering has allowed for advances in the development of cardiac constructs by combining developments in biomaterials, 3D microtissue culture, and human induced pluripotent stem cells (hiPSC) technology. Notably, approaches that mimic the natural processes in the body (i.e., biomimetic) have led to further insight into cardiac physiology. Here, I have pursued biomimetic strategies to create a biomimetic model of human cardiac tissue using hiPSC-derived cardiomyocytes (hiPSC-CMs). Throughout this development, I explored the role of the matrix microenvironment on cell behavior using functionalized alginate, the influence of pacemaker-like exogenous electrical stimulation on the maturation of hiPSC-CM spheroids with endogenous electrically conductive nanomaterials, and the development of vascularized, functional cardiac organoids by mimicking the coronary vasculogenesis stage of cardiac development. The research established here provided a biomimetic groundwork for future development into in vitro human cardiac tissue models for applications in basic research, drug discovery, and cell therapy

Differences in Antibiotic Resistance in Fresh-water Bacteria from Furman Lake and Feeder Streams

A one page summary by three Furman students describing their research on bacteria found in the Furman Lake.https://scholarexchange.furman.edu/lake-documents/1007/thumbnail.jp

Optical Sky Brightness at Cerro Tololo Inter-American Observatory from 1992 to 2006

We present optical UBVRI sky brightness measures from 1992 through 2006. The data are based on CCD imagery obtained with the CTIO 0.9-m, 1.3-m, and 1.5-m telescopes. The B- and V-band data are in reasonable agreement with measurements previously made at Mauna Kea, though on the basis of a small number of images per year there are discrepancies for the years 1992 through 1994. Our CCD-based data are not significantly different than values obtained at Cerro Paranal. We find that the yearly averages of V-band sky brightness are best correlated with the 10.7-cm solar flux taken 5 days prior to the sky brightness measures. This implies an average speed of 350 km/sec for the solar wind. While we can measure an enhancement of the night sky levels over La Serena 10 degrees above the horizon, at elevation angles above 45 degrees we find no evidence that the night sky brightness at Cerro Tololo is affected by artificial light of nearby towns and cities.Comment: 24 pages, 5 figures, to be published in the June, 2007, issue of the Publications of the Astron. Society of the Pacifi

Positive and Negative Emotions Predict Weight Loss Intentions and Behaviors beyond Theory of Planned Behavior Constructs

Acknowledgements: This study was funded by the ScienceCampus Tuebingen (TP7.1) awarded to Devin G. Ray and Kai Sassenberg.Peer reviewedPostprin

A comprehensive standardised data definitions set for acute coronary syndrome research in emergency departments in Australasia

Patients with chest discomfort or other symptoms suggestive of acute coronary syndrome are one of the most common categories seen in many Emergency Departments (EDs). Although the recognition of patients at high risk of acute coronary syndrome has improved steadily, identifying the majority of chest pain presentations who fall into the low-risk group remains a challenge. Research in this area needs to be transparent, robust, applicable to all hospitals from large tertiary centres to rural and remote sites, and to allow direct comparison between different studies with minimum patient spectrum bias. A standardized approach to the research framework using a common language for data definitions must be adopted to achieve this. The aim was to create a common framework for a standardized data definitions set that would allow maximum value when extrapolating research findings both within Australasian ED practice, and across similar populations worldwide. Therefore a comprehensive data definitions set for the investigation of non-traumatic chest pain patients with possible acute coronary syndrome was developed, specifically for use in the ED setting. This standardized data definitions set will facilitate‘knowledge translation’ by allowing extrapolation of useful findings into the real-life practice of emergency medicine

Common infections and neuroimaging markers of dementia in three UK cohort studies

INTRODUCTION: We aimed to investigate associations between common infections and neuroimaging markers of dementia risk (brain volume, hippocampal volume, white matter lesions) across three population-based studies. METHODS: We tested associations between serology measures (pathogen serostatus, cumulative burden, continuous antibody responses) and outcomes using linear regression, including adjustments for total intracranial volume and scanner/clinic information (basic model), age, sex, ethnicity, education, socioeconomic position, alcohol, body mass index, and smoking (fully adjusted model). Interactions between serology measures and apolipoprotein E (APOE) genotype were tested. Findings were meta-analyzed across cohorts (Nmain  = 2632; NAPOE-interaction  = 1810). RESULTS: Seropositivity to John Cunningham virus associated with smaller brain volumes in basic models (β = -3.89 mL [-5.81, -1.97], Padjusted  < 0.05); these were largely attenuated in fully adjusted models (β = -1.59 mL [-3.55, 0.36], P = 0.11). No other relationships were robust to multiple testing corrections and sensitivity analyses, but several suggestive associations were observed. DISCUSSION: We did not find clear evidence for relationships between common infections and markers of dementia risk. Some suggestive findings warrant testing for replication

Nanowired human cardiac organoid transplantation enables highly efficient and effective recovery of infarcted hearts

Human cardiac organoids hold remarkable potential for cardiovascular disease modeling and human pluripotent stem cell–derived cardiomyocyte (hPSC-CM) transplantation. Here, we show cardiac organoids engineered with electrically conductive silicon nanowires (e-SiNWs) significantly enhance the therapeutic efficacy of hPSC-CMs to treat infarcted hearts. We first demonstrated the biocompatibility of e-SiNWs and their capacity to improve cardiac microtissue engraftment in healthy rat myocardium. Nanowired human cardiac organoids were then engineered with hPSC-CMs, nonmyocyte supporting cells, and e-SiNWs. Nonmyocyte supporting cells promoted greater ischemia tolerance of cardiac organoids, and e-SiNWs significantly improved electrical pacing capacity. After transplantation into ischemia/reperfusion–injured rat hearts, nanowired cardiac organoids significantly improved contractile development of engrafted hPSC-CMs, induced potent cardiac functional recovery, and reduced maladaptive left ventricular remodeling. Compared to contemporary studies with an identical injury model, greater functional recovery was achieved with a 20-fold lower dose of hPSC-CMs, revealing therapeutic synergy between conductive nanomaterials and human cardiac organoids for efficient heart repair

25-Hydroxyvitamin D concentration and Leukocyte telomere length in young adults: Findings from the Northern Finland birth cohort 1966

Higher vitamin D status, lower adiposity, and longer telomere length are each reportedly associated with lower risk of several chronic diseases and all-cause mortality. However, direct relationships between vitamin D status (measured by circulating 25-hydroxyvitamin D (25(OH)D) concentration), adiposity, and telomere length are not well established. We conducted a cross-sectional analysis of associations of 25(OH)D and body mass index (BMI; weight (kg)/height (m)2) with mean relative leukocyte telomere length (LTL) using data gathered on 5,096 participants from Northern Finland Birth Cohort 1966 at age 31 years (1997). 25(OH)D was not associated with LTL in either basic or confounder/mediator-adjusted models. BMI was inversely associated with LTL after adjustment for potential confounding by age, sex, socioeconomic position, physical activity, diet, smoking, alcohol intake, and use of oral contraceptives (per 1-unit increase in BMI, mean difference in LTL = −0.4%, 95% confidence interval: −0.6, −0.2). The BMI-LTL association was also independent of 25(OH)D and was attenuated slightly, but remained, after adjustment for C-reactive protein, a marker of low-grade inflammation (mean difference in LTL = −0.3%, 95% confidence interval −0.6, −0.1). These findings suggest that vitamin D status is unlikely to be an important determinant of LTL, at least by young adulthood. Inflammation may partly mediate associations of adiposity with LTL.This work was supported financially by the following institutions: the Academy of Finland (grants 104781, 120315, 129269, 1114194, 24300796, and 12926); University Hospital Oulu and Biocenter Oulu, University of Oulu (grant 75617); the European Commission (grant QLG1-CT-2000- 01643); the National Heart, Lung, and Blood Institute, US National Institutes of Health (grant 5R01HL087679-02); the National Institute of Mental Health, US National Institutes of Health (grant 5R01MH63706:02); the Medical Research Council (grants G0500539, G0600705, G0601653, and K014536); the Wellcome Trust (grant GR069224); and Diabetes UK (grant 08/0003775). J.L.B. was supported by a Wellcome Trust Fellowship grant (WT088431MA). D.M.W., S.S., and M.-R.J. were supported by the European Union’s Horizon 2020 research and innovation program under grant agreement DynaHEALTH (633595)

The Spatial Cross-Correlation Method for Dispersive Surface Waves

Dispersive surface waves are routinely used to estimate the subsurface shear-wave velocity distribution, at all length scales. In the well-known Spatial Autocorrelation method, dispersion information is gained from the correlation of seismic noise signals recorded on the vertical (or radial) components. We demonstrate practical advantages of including the cross-correlation between radial and vertical components of the wavefield in a spatial cross-correlation method. The addition of cross-correlation information increases the resolution and robustness of the phase velocity dispersion information, as demonstrated in numerical simulations and a near-surface field study with active seismic sources, where our method confirms the presence of a fault-zone conduit in a geothermal field