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Regeneration following spinal cord injury (SCI) is challenging in part due to the modified tissue composition and organization of the resulting glial and fibrotic scar regions. Inhibitory cell types and biochemical cues present in the scar have received attention as therapeutic targets to promote regeneration. However, altered Young's modulus of the scar as a readout for potential impeding factors for regeneration are not as well-defined, especially in vivo. Although the decreased Young's modulus of surrounding tissue at acute stages post-injury is known, the causation and outcomes at chronic time points remain largely understudied and controversial, which motivates this work. This study assessed the glial and fibrotic scar tissue's Young's modulus and composition (scar morphometry, cell identity, extracellular matrix (ECM) makeup) that contribute to the tissue's stiffness. The spatial Young's modulus of a chronic (~18-wks, post-injury) hemi-section, including the glial and fibrotic regions, were significantly less than naïve tissue (~200 Pa; p < 0.0001). The chronic scar contained cystic cavities dispersed in areas of dense nuclei packing. Abundant CNS cell types such as astrocytes, oligodendrocytes, and neurons were dysregulated in the scar, while epithelial markers such as vimentin were upregulated. The key ECM components in the CNS, namely sulfated proteoglycans (sPGs), were significantly downregulated following injury with concomitant upregulation of unsulfated glycosaminoglycans (GAGs) and hyaluronic acid (HA), likely altering the foundational ECM network that contributes to tissue stiffness. Our results reveal the Young's modulus of the chronic SCI scar as well as quantification of contributing elastic components that can provide a foundation for future study into their role in tissue repair and regeneration., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Timing of influenza spread across the United States is dependent on factors including local and national travel patterns and climate. Local epidemic intensity may be influenced by social, economic and demographic patterns. Data are needed to better explain how local socioeconomic factors influence both the timing and intensity of influenza seasons to result in national patterns., Methods: To determine the spatial and temporal impacts of socioeconomics on influenza hospitalization burden and timing, we used population-based laboratory-confirmed influenza hospitalization surveillance data from the CDC-sponsored Influenza Hospitalization Surveillance Network (FluSurv-NET) at up to 14 sites from the 2009/2010 through 2013/2014 seasons (n = 35,493 hospitalizations). We used a spatial scan statistic and spatiotemporal wavelet analysis, to compare temporal patterns of influenza spread between counties and across the country., Results: There were 56 spatial clusters identified in the unadjusted scan statistic analysis using data from the 2010/2011 through the 2013/2014 seasons, with relative risks (RRs) ranging from 0.09 to 4.20. After adjustment for socioeconomic factors, there were five clusters identified with RRs ranging from 0.21 to 1.20. In the wavelet analysis, most sites were in phase synchrony with one another for most years, except for the H1N1 pandemic year (2009-2010), wherein most sites had differential epidemic timing from the referent site in Georgia., Conclusions: Socioeconomic factors strongly impact local influenza hospitalization burden. Influenza phase synchrony varies by year and by socioeconomics, but is less influenced by socioeconomics than is disease burden., Competing Interests: Declaration of Competing Interest EJA declares the following competing interests: research grant with Novavax, research grant with Pfizer, Consultant for AbbVie, Research support from MedImmune, Research support from PaxVax, research support from Micron. The rest of the authors have no competing interests to disclose., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Cell surface receptors are the key contributors of macrophage function. Most macrophage cell surface receptors are glycoproteins with sialic acids at the terminal of their glycans. It is well recognized that lipopolysaccharide (LPS) induces cell surface sialylation changes that may in turn contribute to macrophage functions. In addition, cellular mechanics such as elasticity is also a major determinant of macrophage function, which in turn is modulated by LPS. In this report, we characterized the sialylation status of macrophages upon LPS stimulation and assessed the changes in its mechanical properties and function. Specifically, we confirmed that sialylation status is closely related to macrophage biomechanical characteristics (elastic modulus, tether force, tether radius, adhesion force, and membrane tension) and thus directly involved in macrophage function. Further, we modulated macrophage sialylation status by feeding the cell with exogenous free sialic acid (Neu5Ac, Neu5Gc) and sialidase inhibitors, and examined the resulting effects on cellular mechanics and function. A systematic recognition of sialylation status related to cellular mechanics of macrophages will contribute to defining their phenotypes and elucidate macrophage functional diversity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To determine whether deficits in a key aspect of executive functioning, namely, initiation, were associated with current and future functional disabilities in intensive care unit survivors., Methods: A nested substudy within a 2-center prospective observational cohort. We used 3 tests of initiation at 3 and 12 months: the Ruff Total Unique Design, Controlled Oral Word Association, and Behavior Rating Inventory of Executive Function initiation. Disability in instrumental activities of daily living (IADL) was measured with the Functional Activities Questionnaire. We used a proportional odds logistic regression model to evaluate the association between initiation and disability. Covariates in the model included age, education, baseline Functional Activities Questionnaire, pre-existing cognitive impairment, comorbidities, admission severity of illness, episodes of hypoxia, and days of severe sepsis., Results: In 195 patients, after adjusting for covariates, only the Behavior Rating Inventory of Executive Function initiation was associated with disability at any time point. Comparing the 25th vs the 75th percentile scores (95% confidence interval) of the Behavior Rating Inventory of Executive Function initiation at 3 months, patients with worse initiation scores had 5.062 times the odds (95% confidence interval: 2.539, 10.092) of disability according to the Functional Activities Questionnaire at 3 months, with similar odds at 12 months (odds ratio: 3.476, 95% confidence interval: 1.943, 6.216). Worse Behavior Rating Inventory of Executive Function initiation scores at 3 months were associated with future disability at 12 months odds ratio (95% confidence interval) 5.079 (2.579, 10.000)., Conclusions: Executive function deficits acquired after a critical illness in the domain of initiation are common in intensive care unit survivors, and when they are identified via self-report tools, they are associated with current and future disability in instrumental activities of daily living., (Copyright © 2018 Academy of Consultation-Liaison Psychiatry. All rights reserved.)

Objective: We sought to determine how delirium subtyped by arousal affected 6-month function and cognition in acutely ill older patients., Methods: This was secondary analysis of a prospective cohort study which enrolled hospitalized patients ≥65 years old. Delirium and arousal were ascertained daily in the emergency department and the first 7 days of hospitalization using the modified Brief Confusion Assessment Method and Richmond Agitation Sedation Scale, respectively. For each day, patients were categorized as having no delirium, delirium with normal arousal, delirium with decreased arousal, or delirium with increased arousal. Preillness and 6-month functional status were determined using the Older American Resources and Services activities of daily living scale which ranges from 0 (completely dependent) to 28 (completely independent). Preillness and 6-month cognition were determined using the Informant Questionnaire on Cognitive Decline in the Elderly which ranges from 1 (markedly improved cognition) to 5 (severe cognitive impairment). Multiple linear regression was performed adjusted for preillness Older American Resources and Services activities of daily living and Informant Questionnaire on Cognitive Decline in the Elderly and other relevant confounders., Results: In 228 older patients, delirium with normal arousal was the only subtype independently associated with poorer 6-month function and cognition. For every day spent in this subtype, the 6-month Older American Resources and Services activities of daily living decreased by 0.84 points (95% confidence interval: -1.59 to -0.09) and the patient's 6-month Informant Questionnaire on Cognitive Decline in the Elderly significantly increased by 0.14 points (95% confidence interval: 0.06-0.23)., Conclusions: Delirium with normal arousal, as opposed to delirium with decreased or increased arousal, was the only arousal subtype significantly associated with worsening 6-month function and cognition. Subtyping delirium by arousal may have important prognostic value., (Copyright © 2018 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: The goal of this study was to develop and validate a dynamic risk model to predict daily changes in acute brain dysfunction (ie, delirium and coma), discharge, and mortality in ICU patients., Methods: Using data from a multicenter prospective ICU cohort, a daily acute brain dysfunction-prediction model (ABD-pm) was developed by using multinomial logistic regression that estimated 15 transition probabilities (from one of three brain function states [normal, delirious, or comatose] to one of five possible outcomes [normal, delirious, comatose, ICU discharge, or died]) using baseline and daily risk factors. Model discrimination was assessed by using predictive characteristics such as negative predictive value (NPV). Calibration was assessed by plotting empirical vs model-estimated probabilities. Internal validation was performed by using a bootstrap procedure., Results: Data were analyzed from 810 patients (6,711 daily transitions). The ABD-pm included individual risk factors: mental status, age, preexisting cognitive impairment, baseline and daily severity of illness, and daily administration of sedatives. The model yielded very high NPVs for "next day" delirium (NPV: 0.823), coma (NPV: 0.892), normal cognitive state (NPV: 0.875), ICU discharge (NPV: 0.905), and mortality (NPV: 0.981). The model demonstrated outstanding calibration when predicting the total number of patients expected to be in any given state across predicted risk., Conclusions: We developed and internally validated a dynamic risk model that predicts the daily risk for one of three cognitive states, ICU discharge, or mortality. The ABD-pm may be useful for predicting the proportion of patients for each outcome state across entire ICU populations to guide quality, safety, and care delivery activities., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: The study investigated effectiveness of transcatheter closure of post-myocardial infarction (MI) ventricular septal rupture (VSR) using atrial septal device (ASD) occluder in a cohort of patients admitted at our institute., Method: This was a retrospective, observational and single center study, which included patients who were treated with transcatheter closure for post-MI VSR at our tertiary care center between May 2000 and August 2014 depending upon inclusion and exclusion criteria. Primary outcome was all-cause mortality at 30-days follow-up. The MELD-XI (Model for End Stage Liver Disease) score was used as a predictor for poor outcome in these patients., Results: A total of 21 patients (mean age 66.4±5.9years) were included in the study. Study cohort predominantly included male patients (n=15; 71.4%) and patients with single vessel disease (n=15; 71.4%). Revascularization of the culprit lesion, before VSR closure, was attempted in 6 patients. Except one patient (treated with Cera ® occluder), all patients were treated with Amplatzer ® ASD occluders. Average diameter of VSR was 20.8±6.9mm. Diameter of the device used in the study ranged from 10mm to 30mm. Residual defect was detected in 13 patients (62%). All-cause mortality at 30-day follow-up was observed in 9 (42.9%) patients. Time to VSR closure, diameter of VSR, and serum creatinine levels were significantly related to the 30-day mortality. MELD-XI score was found to be strongly associated with increased risk of mortality., Conclusion: Primary transcatheter VSR closure using ASD occluders is a feasible approach which can provide reasonable survival outcomes along with equitable mortality rates., (Copyright © 2018. Published by Elsevier B.V.)

Background: Delirium during critical illness results from numerous insults, which might be interconnected and yet individually contribute to long-term cognitive impairment. We sought to describe the prevalence and duration of clinical phenotypes of delirium (ie, phenotypes defined by clinical risk factors) and to understand associations between these clinical phenotypes and severity of subsequent long-term cognitive impairment., Methods: In this multicentre, prospective cohort study, we included adult (≥18 years) medical or surgical ICU patients with respiratory failure, shock, or both as part of two parallel studies: the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study, and the Delirium and Dementia in Veterans Surviving ICU Care (MIND-ICU) study. We assessed patients at least once a day for delirium using the Confusion Assessment Method-ICU and identified a priori-defined, non-mutually exclusive phenotypes of delirium per the presence of hypoxia, sepsis, sedative exposure, or metabolic (eg, renal or hepatic) dysfunction. We considered delirium in the absence of hypoxia, sepsis, sedation, and metabolic dysfunction to be unclassified. 3 and 12 months after discharge, we assessed cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We used multiple linear regression to separately analyse associations between the duration of each phenotype of delirium and RBANS global cognition scores at 3-month and 12-month follow-up, adjusting for potential confounders., Findings: Between March 14, 2007, and May 27, 2010, 1048 participants were enrolled, eight of whom could not be analysed. Of 1040 participants, 708 survived to 3 months of follow-up and 628 to 12 months. Delirium was common, affecting 740 (71%) of 1040 participants at some point during the study and occurring on 4187 (31%) of all 13 434 participant-days. A single delirium phenotype was present on only 1355 (32%) of all 4187 participant-delirium days, whereas two or more phenotypes were present during 2832 (68%) delirium days. Sedative-associated delirium was most common (present during 2634 [63%] delirium days), and a longer duration of sedative-associated delirium predicted a worse RBANS global cognition score 12 months later, after adjusting for covariates (difference in score comparing 3 days vs 0 days: -4·03, 95% CI -7·80 to -0·26). Similarly, longer durations of hypoxic delirium (-3·76, 95% CI -7·16 to -0·37), septic delirium (-3·67, -7·13 to -0·22), and unclassified delirium (-4·70, -7·16 to -2·25) also predicted worse cognitive function at 12 months, whereas duration of metabolic delirium did not (1·14, -0·12 to 3·01)., Interpretation: Our findings suggest that clinicians should consider sedative-associated, hypoxic, and septic delirium, which often co-occur, as distinct indicators of acute brain injury and seek to identify all potential risk factors that may impact on long-term cognitive impairment, especially those that are iatrogenic and potentially modifiable such as sedation., Funding: National Institutes of Health and the Department of Veterans Affairs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: To determine how delirium subtyped by level of arousal at initial presentation affects 6-month mortality., Design: This was a preplanned secondary analysis of two prospective cohort studies., Setting: Academic tertiary care emergency department (ED)., Participants: 1,084 ED patients who were 65 years old or older., Measurements: At the time of enrollment, trained research personnel performed the Confusion Assessment Method for the Intensive Care Unit and the Richmond Agitation Sedation Score to determine delirium and level of arousal, respectively. Patients were categorized as having no delirium, delirium with normal arousal, delirium with decreased arousal, or delirium with increased arousal. Death was ascertained by medical record review and the Social Security Death Index. Cox proportional hazard regression was used to analyze the association between delirium arousal subtypes and 6-month mortality., Results: Delirium with normal arousal was the only subtype that was significantly associated with increased 6-month mortality (hazard ratio [HR]: 3.1, 95% confidence interval [CI]: 1.3-7.4) compared with the no delirium group after adjusting for confounders. The HRs for delirium with decreased and increased arousal were 1.4 (95% CI: 0.9-2.1) and 1.3 (95% CI: 0.3-5.4), respectively., Conclusions: Delirious ED patients with normal arousal at initial presentation had a threefold increased hazard of death within 6 months compared with patients without delirium. There was a trend towards increased hazard of death in delirious ED patients with decreased arousal, but this relationship did not reach statistical significance. These data suggest that subtyping delirium by arousal may have prognostic value but requires confirmation with a larger study., (Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background and Rationale: Coronary artery disease (CAD) and its pathological atherosclerotic process are closely related to lipids. Lipids levels are in turn influenced by dietary oils and fats. Saturated fatty acids increase the risk for atherosclerosis by increasing the cholesterol level. This study was conducted to investigate the impact of cooking oil media (coconut oil and sunflower oil) on lipid profile, antioxidant mechanism, and endothelial function in patients with established CAD., Design and Methods: In a single center randomized study in India, patients with stable CAD on standard medical care were assigned to receive coconut oil (Group I) or sunflower oil (Group II) as cooking media for 2 years. Anthropometric measurements, serum, lipids, Lipoprotein a, apo B/A-1 ratio, antioxidants, flow-mediated vasodilation, and cardiovascular events were assessed at 3 months, 6 months, 1 year, and 2 years., Results: Hundred patients in each arm completed 2 years with 98% follow-up. There was no statistically significant difference in the anthropometric, biochemical, vascular function, and in cardiovascular events after 2 years., Conclusion: Coconut oil even though rich in saturated fatty acids in comparison to sunflower oil when used as cooking oil media over a period of 2 years did not change the lipid-related cardiovascular risk factors and events in those receiving standard medical care., (Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

We investigated the sensitivity of embryonic murine neural stem cells exposed to 10 pM-10 μM concentrations of three heavy metals (Cd, Hg, Pb), continuously for 14 days within 3D collagen hydrogels. Critical endpoints for neurogenesis such as survival, differentiation and neurite outgrowth were assessed. Results suggest significant compromise in cell viability within the first four days at concentrations ≥10 nM, while lower concentrations induced a more delayed effect. Mercury and lead suppressed neural differentiation at as low as 10 pM concentration within 7 days, while all three metals inhibited neural and glial differentiation by day 14. Neurite outgrowth remained unaffected at lower cadmium or mercury concentrations (≤100 pM), but was completely repressed beyond day 1 at higher concentrations. Higher metal concentrations (≥100 pM) suppressed NSC differentiation to motor or dopaminergic neurons. Cytokines and chemokines released by NSCs, and the sub-cellular mechanisms by which metals induce damage to NSCs have been quantified and correlated to phenotypic data. The observed degree of toxicity in NSC cultures is in the order: lead>mercury>cadmium. Results point to the use of biomimetic 3D culture models to screen the toxic effects of heavy metals during developmental stages, and investigate their underlying mechanistic pathways., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Poor cognitive function is associated with negative consequences across settings of care, but research instruments are arduous for routine clinical implementation. This study examined the association between impaired arousal, as measured using an ultra-brief screen, and risk of 2 adverse clinical outcomes: hospital length of stay and discharge to a skilled nursing facility (SNF)., Design, Setting, and Participants: A secondary data analysis was conducted using 2 separate groups of medical ward patients: a Veterans Affairs medical center in the northeast (N = 1487, between 2010 and 2012) 60 years and older and a large tertiary care, university-based medical center (N = 669, between 2007 and 2013) 65 years and older in the southeastern United States., Measurements: The impact of impaired arousal, defined by the Richmond Agitation Sedation Scale as anything other than "awake and alert," was determined using Cox Proportional Hazard Regression for time to hospital discharge and logistic regression for discharge to a SNF. Hazard ratios (HRs) and odds ratios (OR) with their 95% confidence intervals (CI) are reported, respectively. Both models were adjusted age, sex, and dementia., Results: The 2156 total patients included in these groups had a mean age of 76 years, of whom 16.4% in group 1 and 28.5% in group 2 had impaired arousal. In the first group, patients with normal arousal spent an average of 5.9 days (standard deviation 6.2) in the hospital, while those with impaired arousal spent 8.5 days (9.2). On any given day, patients with impaired arousal had 27% lower chance of being discharged (adjusted HR 0.73 (95% CI 0.63-0.84). In the second group, individuals with normal arousal spent 3.8 (4.1) days in the hospital compared with 4.7 (4.6) for those with impaired arousal; indicating a 21% lower chance of being discharged [adjusted HR 0.79 (95% CI 0.66-0.95). With regard to risk of discharge to SNF, those with impaired arousal in group 1 had a 65% higher risk than those without impaired arousal [adjusted OR 1.65 (95% CI 1.21-2.25)], and those in group 2 had a nonsignificant 27% higher risk [adjusted OR 1.27 (0.80-2.03)]. Because of the quality improvement nature, this analysis did not control for comorbidities, which is a significant limitation., Conclusions: In this study of over 2000 older hospitalized patients, the simple observation of an abnormal arousal level may be an independent predictor of a longer hospital stay and discharge to SNF., (Copyright © 2015 AMDA - The Society for Post-Acute and Long-Term Care Medicine. All rights reserved.)

A critical challenge to regenerating close mimics of native axonal pathways under chronic neurodegenerative disease or injury conditions is the inability to stimulate, sustain and steer neurite outgrowth over a long distance, until they reach their intended targets. Understanding neurite outgrowth necessitates quantitative determination of the role of molecular gradients on growth cone navigation under dynamic physiological conditions. High-fidelity biomimetic platforms are needed to computationally and experimentally acquire and analyze spatiotemporal molecular gradient evolution and the growth cone response across multiple conditions along this gradient pathway. In this study, we utilized a simple microfluidic platform in which diffusive gradients were generated within a 3-D porous scaffold in a defined and reproducible manner. The platform's characteristics (spatiotemporal gradient, steepness, diffusion time, etc.) were precisely quantified at every specified location within the scaffold. Using this platform, we show that the cortical neurite response within 3-D collagen scaffolds, at both the cellular and molecular level, is extremely sensitive to subtle changes in localized concentration and gradient steepness of IGF-1 within that region. This platform could also be used to study other biological processes such as morphogenesis and cancer metastasis, where chemogradients are expected to significantly regulate the outcomes. Results from this study might be of tremendous use in designing biomaterial scaffolds for neural tissue engineering, axonal pathway regeneration under injury or disease, and in formulating targeted drug-delivery strategies., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: To quantify the prevalence of prescribed opioid analgesics among pregnant women enrolled in Tennessee Medicaid from 1995 to 2009., Methods: Retrospective cohort study of 277,555 pregnancies identified from birth and fetal death certificates, and linked to previously validated, computerized pharmacy records. Poisson regression was used to estimate trends over time, rate ratios, and 95% confidence intervals (CI)., Results: During the study period, 29% of pregnant women filled a prescription for an opioid analgesic. From 1995 to 2009, any pregnancy-related use increased 1.90-fold (95% CI, 1.83-1.98), first trimester use increased 2.27-fold (95% CI, 2.14-2.41), and second or third trimester use increased 2.02-fold (95% CI, 1.93-2.12), after adjusting for maternal characteristics. Any pregnancy-related, first trimester, and second or third trimester use were each more likely among mothers who were at least 21 years old, white, non-Hispanic, prima gravid, resided in nonurban areas, enrolled in Medicaid owing to disability, and who had less than a high school education., Conclusions: Opioid analgesic use by Tennessee Medicaid-insured pregnant women increased nearly 2-fold from 1995 to 2009. Additional study is warranted to understand the implications of this increased use., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The childhood obesity epidemic disproportionately affects Hispanics. This paper reports on the design of the ongoing Healthy Families Study, a randomized controlled trial testing the efficacy of a community-based, behavioral family intervention to prevent excessive weight gain in Hispanic children using a community-based participatory research approach., Methods: The study will enroll 272 Hispanic families with children ages 5-7 residing in greater Nashville, Tennessee, United States. Families are randomized to the active weight gain prevention intervention or an alternative intervention focused on oral health. Lay community health promoters implement the interventions primarily in Spanish in a community center. The active intervention was adapted from the We Can! parent program to be culturally-targeted for Hispanic families and for younger children. This 12-month intervention promotes healthy eating behaviors, increased physical activity, and decreased sedentary behavior, with an emphasis on parental modeling and experiential learning for children. Families attend eight bi-monthly group sessions during four months then receive information and/or support by phone or mail each month for eight months. The primary outcome is change in children's body mass index. Secondary outcomes are changes in children's waist circumference, dietary behaviors, preferences for fruits and vegetables, physical activity, and screen time., Results: Enrollment and data collection are in progress., Conclusion: This study will contribute valuable evidence on efficacy of a childhood obesity prevention intervention targeting Hispanic families with implications for reducing disparities., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Persistent left superior vena cava (PLSVC) is the most common central venous anomaly in the thorax, which may remain asymptomatic throughout life. Indwelling catheters that are increasingly used in oncology practice may result in complications in the presence of PLSVC. The authors report an unusual case of recurrent ischemic attacks each time a portacath was accessed in a patient with breast cancer and PLSVC. This case highlights the importance of suspecting this condition in the presence of clinical and radiographic clues to prevent complications.

Elastin breakdown in vascular aneurysms is mediated by cytokines such as tumor necrosis factor alpha (TNF-alpha, which induces vascular smooth muscle cell (SMC) activation and regulates their deposition of matrix. We previously demonstrated that exogenous supplementation with TGF-beta1 (1 ng ml(-1)) and hyaluronan oligomers (0.786 kDa, 0.2 microg ml(-1)) cues the upregulation of elastin matrix synthesis by healthy cultured SMCs. Here, we determine whether these cues likewise enhance elastin matrix synthesis and assembly by TNF-alpha-stimulated SMCs, while restoring their healthy phenotype. Adult rat aortic SMCs were treated with TNF-alpha alone or together with TGF-beta1/hyaluronan oligomeric cues and the release of inflammatory markers were monitored during over a 21 day culture. Biochemical analysis was used to quantify cell proliferation, matrix protein synthesis and cross-linking efficiency, while immunofluorescence and electron microscopy were used to analyze the elastin matrix quality. It was observed that SMC activation with TNF-alpha (10 ng ml(-1)) induced matrix calcification and promoted production of elastolytic MMP-2 and MMP-9. However, these effects were attenuated by the addition of TGF-beta1 and HA oligomer cues to TNF-alpha-stimulated cultures, which also enhanced tropoelastin and collagen production, improved elastin matrix yield and cross-linking, promoted elastin fiber formation and suppressed elastase activity, although the release of MMP-2 and MMP-9 was not affected. Overall, the results suggest that TGF-beta1 and HA oligomers are potentially useful in suppressing SMC activation and inducing regenerative elastin repair within aneurysms.

Background: Our objective was to investigate the expression of survivin, Bcl-2, p53, Ki-67, and Src in thymic neoplasms and analyze their interrelationship with clinicopathologic variables., Methods: A series of 60 thymic neoplasms was reviewed and classified according to the World Health Organization (WHO) scheme. Key clinical information, including Masaoka stage, recurrence-free survival (RFS), and overall survival (OS) was obtained. The percentage and staining intensity of listed markers were recorded. The correlation of markers and clinicopathologic variables was statistically analyzed using the Fisher exact test and log-rank test., Results: There were 7 type A, 15 type AB, 8 type B1, 5 type B2, 17 type B3 thymomas, and 8 thymic carcinomas. Seven patients (11.7%) died of the disease. Tumors recurred in eight patients (13.3%). Although p53 expression alone was found to be correlated with RFS with borderline significance (p = 0.056), patients with Src-positive and p53-positive coexpression had a shorter OS time than the other groups (p < 0.008). Cytoplasmic expression of survivin was present in 5 of 60 thymic neoplasms (8.3%), 4 of which were thymic carcinomas that all recurred., Conclusions: Regardless of WHO type and/or tumor stage, although p53 expression may predict recurrence in thymomas, p53 and Src coexpression can predict shorter OS, and cytoplasmic localization of survivin may predict recurrence in thymic carcinoma. These findings make thymic tumors a prime target for newly developed anti-Src and anti-survivin therapies.

Elastin, a structural protein distributed in the extracellular matrix of vascular tissues, is critical to maintaining the elastic stability and mechanical properties of blood vessels, as well as regulating cell-signaling pathways involved in vascular injury response and morphogenesis. Pathological degradation of vascular elastin or its malformation within native vessels and the poor ability to tissue-engineer elastin-rich vascular replacements due to innately poor elastin synthesis by adult vascular cells can compromise vascular homeostasis, and must thus be addressed. Our recent studies attest to the utility of hyaluronan (HA) oligomers for elastin synthesis and organization by adult vascular smooth muscle cells (SMCs), though the elastin matrix yields in these cases were quite low relative to total elastin produced. Thus, in this study, we investigated the utility of copper (Cu(2+)) ions to enhance cellular elastin deposition, crosslinking and maturation into structural fibers. Copper nanoparticles (CuNPs; 80-100 nm) in the dose range of 1-100 ng ml(-1) were tested for Cu(2+) ion release, and based on mathematical modeling of their release profiles, CuNPs (1, 10, and 400 ng ml(-1)) were chosen for supplementation to adult SMC cultures. The 400 ng ml(-1) dose of CuNPs cumulatively delivered Cu(2+) doses in the range of 0.1 M, over the 21 day culture period. It was observed that while exogenous CuNP supplements do not up-regulate tropoelastin production by vascular SMCs, they promoted formation of crosslinked elastin matrices. The deposition of crosslinked matrix elastin was further improved by the additional presence of HA oligomers in these cultures. Immunofluorescence imaging and structural analysis of the isolated elastin matrices indicate that amorphous elastin clumps were formed within non-additive control cultures, while aggregating elastin fibrils were observed within SMC cultures treated with CuNPs (1-10 ng ml(-1)) alone or together with HA oligomers. The presence of 400 ng ml(-1) of CuNPs concurrent with HA oligomers furthered aggregation of these elastin fibrils into mature fibers with diameters ranging from 200 to 500 nm. Ultrastructural analysis of elastin matrix within cultures treated with HA oligomers and 400 ng ml(-1) of CuNPs suggest that elastin matrix deposition as stimulated by Cu(2+) ions proceeds via a fibrillin-mediated assembly process, with enhanced crosslinking occurring via stimulation of lysyl oxidase. Overall, the data suggest that CuNPs and HA oligomers are highly useful for regenerating crosslinked, fibrillar elastin matrices by adult vascular SMCs. These results have immense utility in tissue-engineering vascular replacements.

Scaffolds comprising poly(lactic acid) and nano-hydroxyapatite (HA) were prepared using the solvent-casting/salt-leaching technique. NaCl was used as the leaching agent. Nano-sized HA was synthesized by a hydrothermal method at 170 degrees C and autogenous pressure. High-resolution TEM imaging revealed that the HA particles were ellipsoidal-shaped with needle-like morphologies. The particles had an average size of approximately 25 nm in width and 150 nm in length with aspect ratios ranging from 6 to 8. As the HA content increased in the scaffold from 0 to 50 wt%, the compression modulus of the scaffolds increased from 4.72+/-1.2 to 9.87+/-1.8 MPa, while the yield strength from 0.29+/-0.03 to 0.44+/-0.01 MPa. Such polymeric scaffolds should be suitable materials for non-load sharing tissue-engineering applications.

Objectives: The purpose of this study was to report the safety, efficacy, and predictors of recurrence of circumferential pulmonary vein (PV) catheter ablation in patients with atrial fibrillation (AF)., Background: Circumferential PV ablation has been described as an alternate ablation strategy for AF., Methods: Seventy consecutive patients (age 56 +/- 10 years) with symptomatic drug refractory paroxysmal (n = 21), persistent (n = 22), and permanent (n = 27) AF underwent catheter ablation. The catheter ablation procedure was performed by creating circular lesions encircling right- and left-side PV ostia guided by an electroanatomic (CARTO) mapping system. Linear ablation lesions also were created in the cavotricuspid isthmus, the mitral isthmus, and in the posterior left atrium. In 42 patients (60%), additions linear lesions were created between superior and inferior PVs in a "figure-of-eight" fashion., Results: At 6 +/- 2.5 months of follow-up, 53 patients (76%) were AF free, including 39 patients (56%) not taking and 14 patients (20%) taking antiarrhythmic drugs. Among various variables, only early recurrence of AF was a predictor of long-term recurrence. Significant complications included one pericardial tamponade, one stroke, and two PV occlusions. Both patients with PV occlusion received radiofrequency delivery in a figure-of-eight fashion., Conclusions: Circumferential PV catheter ablation of AF is associated with moderate efficacy and risk of complications. The absence of a difference in efficacy combined with the risk of PV stenosis associated with figure-of-eight lesion lead us to conclude that the figure-of-eight lesion should not be a routine component of circumferential PV AF ablation procedures.

Cardiovascular disease (CVD) is the leading cause of death in the United States, resulting in increased awareness of the preventive importance of regular physical activity. Because athletes are considered physically fit, occurrence of sudden athlete death from CVD is perplexing. Regular intense physical activity can cause changes to the cardiovascular system that mimic known CVD processes. Therefore, screening of athletes for conditions that may increase risk for sudden cardiac death (SCD) is challenging. This article focuses on this problem, discussing the athlete's heart, SCD and associated CV conditions, and preparticipation screening. We also review recommendations of the 26th Bethesda Conference on determining eligibility for competition in athletes with known CV abnormalities, and how the recommendations relate to individual disease processes.

Favorable results of circumferential pulmonary vein (PV) ostial ablation guided by electroanatomic mapping (Carto) have fueled great enthusiasm for this technique. The lesion set for this ablation procedure as described by Pappone et al.(1,2) involves a figure of 8 lesions encompassing the 2 right and 2 left PV ostia with 2 additional linear lesions. Pulmonary vein stenosis/or occlusion has not previously been reported as a complication of this procedure. We describe PV occlusion after this procedure. Based on the occurrence of this previously unreported complication, we no longer create a figure '8' lesion around the right superior and inferior PVs. We anticipate that this complication can be avoided by creating a circular lesion encompassing the 2 PV ostia, while avoiding the linear lesion between the 2 PV ostia.