PTEN (Phosphatase and Tensin Homolog) Protects Against Ang II (Angiotensin II)-Induced Pathological Vascular Fibrosis and Remodeling-Brief Report.

OBJECTIVE: Pathological vascular remodeling and excessive perivascular fibrosis are major contributors to reduced vessel compliance that exacerbates cardiovascular diseases, for instance, promoting clinically relevant myocardial remodeling. Inflammation plays a significant role in both pathological vascular remodeling and fibrosis. We previously demonstrated that smooth muscle cell-specific PTEN depletion promotes significant vascular fibrosis and accumulation of inflammatory cells. In the current study, we aimed to determine the beneficial role of systemic PTEN elevation on Ang II (angiotensin II)-induced vascular fibrosis and remodeling. Approach and Results: Transgenic mice carrying additional copies of the wild-type Pten gene (super PTEN [sPTEN]) and WT littermates were subjected to Ang II or saline infusion for 14 or 28 days. Compared with WT, Ang II-induced vascular fibrosis was significantly blunted in sPTEN mice, as shown by histochemical stainings and label-free second harmonic generation imaging. The protection against Ang II was recapitulated in sPTEN mice bearing WT bone marrow but not in WT mice reconstituted with sPTEN bone marrow. Ang II-induced elevation of profibrotic and proinflammatory gene expression observed in WT mice was blocked in aortic tissue of sPTEN mice. Immunofluorescent staining and flow cytometry both indicated that perivascular infiltration of T cells and macrophages was significantly inhibited in sPTEN mice. In vitro induction of PTEN expression suppressed Ang II-induced Ccl2 expression in vascular smooth muscle cells. CONCLUSIONS: Systemic PTEN elevation mediates protection against Ang II-induced vascular inflammation and fibrosis predominantly through effects in resident vascular cells. Our data highly support that pharmacological upregulation of PTEN could be a novel and viable approach for the treatment of pathological vascular fibrosis.

Changes in paced signals may predict in-hospital cardiac arrest.

BACKGROUND: An increasing number of patients with chronic illnesses have implanted cardiac rhythm devices such as pacemakers and implantable cardioverter-defibrillators (ICDs). This study was conducted to identify potentially useful predictors of in-hospital cardiac arrest (I-HCA) within paced electrocardiogram (ECG) signals from cardiovascular patients with implanted medical devices. METHODS: In this retrospective study of 17 subjects, full-disclosure ECG traces prior to the time of documented I-HCA were analyzed to determine R-R intervals and QRS durations (QRSd). RESULTS: Ventricular paced QRSd prolongation was observed prior to I-HCA in 10/16 (63%) subjects. QRSd was significantly greater immediately preceding cardiac arrest than during each of the 8 hours prior to cardiac arrest (P < 0.05). Heart rate changes (measured using standard deviation) within 15 minutes of cardiac arrest were significantly greater in subjects with pulseless electrical activity (PEA)/asystolic arrest compared to those with cardiac arrests due to ventricular tachycardia/ventricular fibrillation (VT/VF) (10.13 vs 3.31; P  =  0.024). Significant differences over the 8 hours preceding cardiac arrest in heart rate (74 vs 86 beats/min; P  =  0.002) and QRS duration (172 ms vs 137 ms; P < 0.001) were observed between subjects with initial rhythms of VT/VF and those with initial rhythms of PEA/asystole. CONCLUSIONS: Patterns of diagnostic ECG features can be extracted from the telemetry data of patients with implanted medical devices prior to adverse events including I-HCA. The detection of these significant changes might have an immediate prognostic impact on the timely treatment of some patients at risk of adverse events.

Assessment of metal contamination in the biota of four rivers experiencing varying degrees of human impact.

Urbanization, agriculture, and other land transformations can affect water quality, decrease species biodiversity, and increase metal and nutrient concentrations in aquatic systems. Metal pollution, in particular, is a reported consequence of elevated anthropogenic inputs, especially from urbanized areas. The objectives of this study were to quantify metal (Cu, Al, Cd, Ni, and Pb) concentrations in the waters and biota of four streams in South Georgia, USA, and relate metal concentrations to land use and abiotic and biotic stream processes. Additionally, macrophytes, invertebrates, and fish were identified to assess biodiversity at each site. Metal concentrations in the three trophic levels differed among sites and species, correlating to differences in land use surrounding the rivers. The highest metal concentrations (except Al) were found in the streams most impacted by urbanization and development. Al concentrations were highest in streams surrounded by land dominated by forested areas. Metal content in macrophytes reflected metal concentrations in the water and was at least three orders of magnitude higher than any other trophic level. Despite metal concentration differences, all four streams contained similar water quality and were healthy based on macroinvertebrate community structure. This study provides insight into the impact of urbanization and the fate and effects of metals in river ecosystems with varying degrees of anthropogenic impact.

The nature of orthographic learning in self-teaching: Testing the extent of transfer.

The current study was designed to test how orthographic learning, or the learning of the spelling patterns of words, happens within the self-teaching paradigm. One possibility is that orthographic learning occurs on a word-specific basis. Two other possibilities are that orthographic learning transfers specifically to the processing of novel words that are morphologically related or that it transfers to novel words that are orthographically similar, regardless of morphological relationship. In an orthographic learning paradigm, we asked children in Grades 3 and 5 to read nonwords embedded in short stories. In a between-participants design, some children read nonwords that were base forms, others read nonwords that were morphologically complex forms, and others read nonwords that were orthographically complex forms (e.g., feap, feaper, and feaple, respectively). Children completed an orthographic choice task with the same items as in the stories. To evaluate transfer of learning, children also completed orthographic choices for the two forms of the nonwords not seen in the stories. Results indicated that children's orthographic learning affected processing of novel items that appeared to be morphologically related as well as those that shared only orthographic structure (e.g., both feaper and feaple). Additional analyses showed that these effects were held across cases when children did and did not successfully decode the novel words in the learning experience, although successful decoding did lead to higher levels of orthographic learning and transfer. Together, the findings suggest that children's prior experiences affect their processing of novel words that share orthographic similarity, likely reflecting a role for orthographic analogies in the self-teaching process.

High-dose IgG therapy mitigates bile duct-targeted inflammation and obstruction in a mouse model of biliary atresia.

BACKGROUND: A proposed etiology of biliary atresia (BA) entails a virus-induced, progressive immune-mediated injury of the biliary system. Intravenous Ig (IVIg) has demonstrated clinical benefit in several inflammatory diseases. The aim of this study was to determine the therapeutic effects of high-dose IgG treatment in the rhesus rotavirus (RRV)-induced mouse model of BA. METHODS: Newborn mice were infected with RRV, and jaundiced mice were given high-dose IgG or albumin control. Survival, histology, direct bilirubin, liver immune cell subsets, and cytokine production were analyzed. RESULTS: There was no difference in overall survival between RRV-infected groups, however high-dose IgG resulted in decreased bilirubin, bile duct inflammation, and increased extrahepatic bile duct patency. High-dose IgG decreased vascular cell adhesion molecule-1, resulting in limited migration of immune cells to portal tracts. High-dose IgG significantly decreased CD4(+) T cell production of interleukin (IL)-2, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α and CD8(+) T cell production of IFN-γ, as well as increased levels of regulatory T cells. CONCLUSION: High-dose IgG therapy in murine BA dramatically decreased Th1 cell-mediated inflammation and biliary obstruction. This study lends support for consideration of IVIg clinical trials in infants with BA, to diminish the progressive intrahepatic bile duct injury.

Integrative review of electrocardiographic characteristics in patients with reduced, mildly reduced, and preserved heart failure.

INTRODUCTION: Electrocardiographic (ECG) changes in heart failure with reduced, mildly reduced, and preserved ejection fractions can be critical in clinical assessment while waiting to perform echocardiograms or when it is unavailable. This integrative review aimed to identify ECG characteristics among hospitalized patients demonstrating three types of heart failure during acute decompensation. METHODS: We searched an electronic database of PubMed, Web of Science, EMBASE, Scopus, Google Scholar, and ClinicalTrials.gov using medical subject headings (MeSH) terms and keywords. Sixteen studies were synthesized and reported. RESULTS: Heart failure with reduced ejection fraction (HFrEF) was more common in men, comorbid with coronary artery diseases and diabetes mellitus, higher BNP/Pro-BNP, wide QRS, and left bundle branch block on ECG. On average, clients with heart failure with preserved ejection fraction (HFpEF) were older and more likely to have a history of atrial fibrillation, valvular heart diseases, hypertension, chronic obstructive pulmonary, and atrial fibrillation (AF) on ECG. Patients with mildly reduced (HFmrEF) were more similar to HFpEF in older patients, comorbid with hypertension, AF and valvular diseases, and AF on ECG. CONCLUSIONS: ECG characteristics might be related to left ventricular ejection fraction. Demographics, BNP/Pro-BNP, and ECG changes might help differentiate different heart failure types. Therefore, ECG might be a prognostic tool while caring for heart failure patients when highly skilled resources are unavailable. These identified ECG characteristics help generate research hypotheses and warrant validation in future research.

Estimating Ejection Fraction from the 12 Lead ECG among Patients with Acute Heart Failure.

Background: Identifying patients with low left ventricular ejection fraction (LVEF) in the emergency department using an electrocardiogram (ECG) may optimize acute heart failure (AHF) management. We aimed to assess the efficacy of 527 automated 12-lead ECG features for estimating LVEF among patients with AHF. Method: Medical records of patients >18 years old and AHF-related ICD codes, demographics, LVEF %, comorbidities, and medication were analyzed. Least Absolute Shrinkage and Selection Operator (LASSO) identified important ECG features and evaluated performance. Results: Among 851 patients, the mean age was 74 years (IQR:11), male 56% (n=478), and the median body mass index was 29 kg/m2 (IQR:1.8). A total of 914 echocardiograms and ECGs were matched; the time between ECG-Echocardiogram was 9 hours (IQR of 9 hours); ≤30% LVEF (16.45%, n=140). Lasso demonstrated 42 ECG features important for estimating LVEF ≤30%. The predictive model of LVEF ≤30% demonstrated an area under the curve (AUC) of 0.86, a 95% confidence interval (CI) of 0.83 to 0.89, a specificity of 54% (50% to 57%), and a sensitivity of 91 (95% CI: 88% to 96%), accuracy 60% (95% CI:60 % to 63%) and, negative predictive value of 95%. Conclusions: An explainable machine learning model with physiologically feasible predictors may be useful in screening patients with low LVEF in AHF.

Regulatory T cells inhibit Th1 cell-mediated bile duct injury in murine biliary atresia.

BACKGROUND & AIMS: Biliary atresia (BA) is a pediatric inflammatory disease of the biliary system which leads to cirrhosis and the need for liver transplantation. One theory regarding etiology is that bile duct injury is due to virus-induced autoreactive T cell-mediated inflammation. Regulatory T cell (Treg) abnormalities in BA could result in unchecked bystander inflammation and autoimmunity targeting bile ducts. The aim of this study was to determine if Tregs are dysfunctional in the rotavirus-induced mouse model of BA (murine BA). METHODS: Murine BA resulted from infection of BALB/c neonates with Rhesus rotavirus (RRV). RESULTS: Liver Tregs from BA mice were decreased in number, activation marker expression, and suppressive function. Adoptive transfer studies revealed that RRV-infected mice that received Tregs had significantly increased survival (84%) compared to controls (12.5%). In addition, ablation of Tregs in older mice, followed by RRV infection, resulted in increased bile duct injury. CONCLUSIONS: These studies demonstrate that dysregulation of Tregs is present in murine BA and that diminished Treg function may be implicated in the pathogenesis of human BA.

Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells.

UNLABELLED: Biliary atresia (BA) is a progressive, inflammatory cholangiopathy that culminates in fibrosis of extrahepatic and intrahepatic bile ducts. A leading theory on the pathogenesis of BA is that the bile duct damage is initiated by a virus infection, followed by a bile duct-targeted autoimmune response. One mechanism of autoimmunity entails a diminished number or function of regulatory T cells (Tregs). The aim of this study was to identify potential virus-specific liver T cells from infants with BA at the time of diagnosis, implicating the virus involved in early bile duct damage. A subaim was to determine if the presence of virus infection was associated with quantitative changes in Tregs. Liver T cells from BA and control patients were cultured with antigen-presenting cells in the presence of a variety of viral or control proteins. 56% of BA patients had significant increases in interferon-gamma-producing liver T cells in response to cytomegalovirus (CMV), compared with minimal BA responses to other viruses or the control group CMV response. In addition, a positive correlation between BA plasma CMV immunoglobulin M (IgM) and liver T-cell CMV reactivity was identified. Investigation of peripheral blood Tregs revealed significant deficits in Treg frequencies in BA compared with controls, with marked deficits in those BA patients who were positive for CMV. CONCLUSION: Liver T-cell responses to CMV were identified in the majority of BA patients at diagnosis, suggesting perinatal CMV infection as a plausible initiator of bile duct damage. Deficiency of Tregs in BA implies decreased inhibition of inflammation and autoreactivity, potentially allowing for exaggerated bile duct injury.

α-enolase autoantibodies cross-reactive to viral proteins in a mouse model of biliary atresia.

BACKGROUND & AIMS: Biliary atresia (BA) is a neonatal cholangiopathy of unknown etiology. The bile duct injury that occurs in patients with BA might result from a hepatobiliary viral infection followed by an autoimmune response against the bile duct epithelia. We aimed to identify autoantigens recognized by serum antibodies in the Rhesus rotavirus (RRV)-induced mouse model of BA; findings were correlated with BA in humans. METHODS: Bile duct epithelial proteins were screened for their reactivity with serum antibodies from the mouse model of BA using immunoblot assays. Unique proteins that reacted with sera antibodies were identified by mass spectrometry and verified using enzyme-linked immunosorbent assay (ELISA) and immunoblot analyses. Candidate autoantibodies in BA patient sera were analyzed by ELISA. RESULTS: A bile duct epithelial antigen that reacted strongly with serum immunoglobulin (Ig) G from the mouse model of BA was identified as α-enolase. α-Enolase autoantibody specificity was confirmed by ELISA and immunoblot analyses. Anti-RRV and anti-enolase antibodies cross-reacted with enolase and RRV proteins; we identified regions of sequence homology between RRV and enolase. Serum samples from patients with BA had increased levels of anti-enolase IgM and IgG. CONCLUSIONS: We have identified autoantibodies against α-enolase in a mouse model of BA (infected with RRV) and in serum samples from patients, indicating a role of humoral autoimmunity in disease pathogenesis. The cross-reactivity between an anti-enolase antibody and RRV proteins indicates that molecular mimicry might activate humoral autoimmunity in BA patients; further studies are required.

A Systematic Review Comparing Mineral Trioxide Aggregate to Other Commercially Available Direct Pulp Capping Agents in Dogs.

Vital pulp therapy (VPT) and direct pulp capping (DPC) are procedures regularly performed in dogs for the management of acute tooth fractures and as part of management for traumatic malocclusions. The purpose of this review is to apply an evidence-based medicine approach to systematically review and evaluate the scientific literature evaluating the efficacy of mineral trioxide aggregate (MTA) to other commercially available materials used for VPT in the permanent teeth of dogs. The 9 studies meeting inclusion criteria were reviewed and each studies evidence was classified using a grading system modified from the Oxford Centre for Evidence-Based Medicine. For the studies meeting inclusion criteria, MTA consistently performed as well or better than other commercially available products in terms of calcific barrier formation and biocompatibility. This review found a lack of consistency between the studies making a direct comparison of the results unreliable. Future studies would benefit from the implementation of a standard scoring system for histology, equivalent and longer study duration times and the correlation of histological and radiographic data.

Dissection of genetic mechanisms governing the expression of serum retroviral gp70 implicated in murine lupus nephritis.

The endogenous retroviral envelope glycoprotein, gp70, implicated in murine lupus nephritis is secreted by hepatocytes as an acute phase protein, and it has been thought to be a product of an endogenous xenotropic virus, NZB-X1. However, since endogenous polytropic (PT) and modified polytropic (mPT) viruses encode gp70s that are closely related to xenotropic gp70, these viruses can be additional sources of serum gp70. To better understand the genetic basis of the expression of serum gp70, we analyzed the abundance of xenotropic, PT, or mPT gp70 RNAs in livers and the genomic composition of corresponding proviruses in various strains of mice, including two different Sgp (serum gp70 production) congenic mice. Our results demonstrated that the expression of different viral gp70 RNAs was remarkably heterogeneous among various mouse strains and that the level of serum gp70 production was regulated by multiple structural and regulatory genes. Additionally, a significant contribution of PT and mPT gp70s to serum gp70 was revealed by the detection of PT and mPT, but not xenotropic transcripts in 129 mice, and by a closer correlation of serum levels of gp70 with the abundance of PT and mPT gp70 RNAs than with that of xenotropic gp70 RNA in Sgp3 congenic mice. Furthermore, the injection of lipopolysaccharides selectively up-regulated the expression of xenotropic and mPT gp70 RNAs, but not PT gp70 RNA. Our data indicate that the genetic origin of serum gp70 is more heterogeneous than previously thought, and that distinct retroviral gp70s are differentially regulated in physiological vs inflammatory conditions.

Evidence review to investigate the support for subtypes of children with difficulty processing and integrating sensory information.

We investigated the evidence for subtypes in children with difficulty processing and integrating sensory information. Fifty-seven articles were incorporated into a systematic literature review; only 4 articles provided direct evidence for subtypes. These studies did not provide a comprehensive assessment of all sensory functions and sensory-based motor functions (i.e., praxis) and included different diagnostic groups. Therefore, generalized conclusions about subtypes could not be drawn. The other 53 studies reviewed provided meaningful information about strengths and challenges that children with difficulty processing and integrating sensory information demonstrate, but these studies were limited in scope. A principal theme was the importance of conducting comprehensive assessments of sensory-based functions, including multiple measures of sensory integrative functions such as praxis, sensory modulation, and sensory discrimination in children and adolescents with various clinical disorders. In addition, more consistency in the use of specific assessment tools will allow for synthesis of data across studies.

Cholangiocytes as immune modulators in rotavirus-induced murine biliary atresia.

BACKGROUND/AIMS: Biliary atresia (BA) is a progressive disease characterized by bile duct inflammation and fibrosis. The aetiology is unknown and may be due to a virus-induced, autoimmune-mediated injury of cholangiocytes. Cholangiocytes are not only targets of injury but may also modulate hepatic inflammation. The aim of this study was to determine the immune profile of murine cholangiocytes and the ability to function as antigen-presenting cells (APCs) in culture with Rhesus rotavirus (RRV), poly I:C (viral mimic) or interferon-gamma/tumour necrosis factor-alpha. METHODS/RESULTS: Both the cholangiocyte cell line (long-term culture) and fresh, ex vivo cholangiocytes expressed APC surface markers major histocompatibility complex (MHC)-class I and II and CD40, while only the cultured cell line expressed costimulatory molecules B7-1 and B7-2. Despite APC expression, cultured cholangiocytes were unable to function as competent APCs in T-cell proliferation assays. Furthermore, both cultured and ex vivo cholangiocytes expressed RNA transcripts for many pro-inflammatory cytokines and chemokines. CONCLUSIONS: Although cholangiocytes contain APC molecules, they are incompetent at antigen presentation and cannot elicit effective T-cell activation. Upregulation of MHC-class I and II found in BA mice may serve to prime the cholangiocyte as a target for immune-mediated injury. Cholangiocytes produced many pro-inflammatory cytokines and chemokines in the setting of RRV infection and T-helper type 1 cytokine milieu, suggesting a role of cholangiocytes as immune modulators promoting the ongoing inflammation that exists in RRV-induced BA.

PTEN deficiency promotes pathological vascular remodeling of human coronary arteries.

Phosphatase and tensin homolog (PTEN) is an essential regulator of the differentiated vascular smooth muscle cell (SMC) phenotype. Our goal was to establish that PTEN loss promotes SMC dedifferentiation and pathological vascular remodeling in human atherosclerotic coronary arteries and nonatherosclerotic coronary arteries exposed to continuous-flow left ventricular assist devices (CF-LVADs). Arteries were categorized as nonatherosclerotic hyperplasia (NAH), atherosclerotic hyperplasia (AH), or complex plaque (CP). NAH coronary arteries from CF-LVAD patients were compared to NAH coronaries from non-LVAD patients. Intimal PTEN and SMC contractile protein expression was reduced compared with the media in arteries with NAH, AH, or CP. Compared with NAH, PTEN and SMC contractile protein expression was reduced in the media and intima of arteries with AH and CP. NAH arteries from CF-LVAD patients showed marked vascular remodeling and reduced PTEN and α-smooth muscle actin (αSMA) in medial SMCs compared with arteries from non-LVAD patients; this correlated with increased medial collagen deposition. Mechanistically, compared with ApoE-/- mice, SMC-specific PTEN-null/ApoE-/- double-knockout mice exhibited accelerated atherosclerosis progression and increased vascular fibrosis. By microarray and validated quantitative RT-PCR analysis, SMC PTEN deficiency promotes a global upregulation of proinflammatory and profibrotic genes. We propose that PTEN is an antiinflammatory, antifibrotic target that functions to maintain SMC differentiation. SMC loss of PTEN results in pathological vascular remodeling of human arteries.

Progressive biliary destruction is independent of a functional tumor necrosis factor-alpha pathway in a rhesus rotavirus-induced murine model of biliary atresia.

Rhesus rotavirus (RRV)-inoculated neonatal BALB/c mice develop an immune-mediated inflammation of extra- and intrahepatic bile ducts that progresses to biliary obstruction and death by 3 wk of age. Livers of diseased animals demonstrate increased numbers of T lymphocytes with elevated expression of helper T cell type 1 (Th1) cytokines at 1 wk, which transitions to increased numbers of macrophages and high expression of the proinflammatory cytokine tumor necrosis factor (TNF)-alpha by 2 wk. We employed both pharmacologic and genetic approaches for attenuation of TNF-alpha to determine whether it plays a causal role in injury. First, RRV-inoculated BALB/c mice were subjected to multiple treatments with either the TNF receptor I (TNF-RI)-Fc fusion protein etanercept or neutralizing antibodies to mouse TNF-alpha. Also, TNF-RI(-/-) mice were injected with RRV in the same manner as wild-type mice. In all cases, TNF inhibition did not reduce the severity or incidence of disease. Survival curves of mice given blocking agents were similar to those of control RRV-inoculated mice, and survival of challenged TNF-RI(-/-) mice was worse than that of wild-type mice, likely because of the prolonged presence of infectious RRV. In all experimental groups, markers of disease were unchanged from those of control mice. In summary, although RRV-inoculated BALB/c mice have highly elevated expression of TNF-alpha, this cytokine does not play an obligate role in disease progression.

In-Hospital Cardiac Arrest: An Update on Pulseless Electrical Activity and Asystole.

Nonshockable rhythms, including pulseless electrical activity (PEA) and asystole, precede more than 70% of in-hospital cardiac arrests (I-HCA). Compared with shockable rhythms (ventricular fibrillation and ventricular tachycardia), nonshockable rhythms have higher mortality and morbidity. Therefore, investigating the underlying mechanisms of these arrhythmias to improve the quality of care and outcome for patients who suffer cardiac arrest is a priority. As the first responders to I-HCA, nurses must have the proper knowledge and training to provide timely and efficient cardiopulmonary resuscitation therapy. This article provides an overview of nonshockable cardiac arrhythmias preceding I-HCA as a means of addressing the gap between science and clinical practice.

Kansas City Cardiomyopathy Questionnaire Administered to Hospitalized Patients With Heart Failure.

BACKGROUND AND PURPOSE: The psychometric properties of the Kansas City Cardiomyopathy Questionnaire (KCCQ) have been examined primarily in community-dwelling patients with heart failure (HF). The objective of this research was to examine the properties of the KCCQ administered to patients hospitalized with HF (N = 233). METHODS: Confirmatory factor analysis, Cronbach's alphas, and correlations were performed to examine the scale's dimensions, reliability, and validity. RESULTS: Confirmatory factor analysis indicated a 5-factor solution (63.6% of the variance). The Cronbach's alpha levels were greater than .70, except for the self-efficacy dimension (.60). Convergent validity was not verified between the KCCQ and several illness severity measures. CONCLUSIONS: The psychometric properties of the KCCQ may be different based on the population in which the KCCQ is administered, which may have clinical implications.

Psychometrics of the Kansas City Cardiomyopathy Questionnaire Adapted for Family Caregiver/Significant Other.

BACKGROUND AND PURPOSE: The Kansas City Cardiomyopathy Questionnaire (KCCQ) was adapted to be administered to the family caregiver/significant other (FC/SO) of hospitalized patients with heart failure (HF). The objective was to examine the psychometrics of the adapted scale (KCCQ-SO). METHODS: Factor analysis, Cronbach's alpha, and correlations were used. RESULTS: A 5-factor solution was found that explained 67.9% of the variance. The internal consistency of the KCCQ-SO factors were all greater than .70. Patient and FC/SO perceived health status scores were significantly related. CONCLUSIONS: Because the scores were found to have high internal consistency and correlated with patient scores on the KCCQ, there is evidence that the FC/SOs' reports may be used in circumstances when the patient is unable or unwilling to answer questions.

Nuclear PTEN functions as an essential regulator of SRF-dependent transcription to control smooth muscle differentiation.

Vascular disease progression is associated with marked changes in vascular smooth muscle cell (SMC) phenotype and function. SMC contractile gene expression and, thus differentiation, is under direct transcriptional control by the transcription factor, serum response factor (SRF); however, the mechanisms dynamically regulating SMC phenotype are not fully defined. Here we report that the lipid and protein phosphatase, PTEN, has a novel role in the nucleus by functioning as an indispensible regulator with SRF to maintain the differentiated SM phenotype. PTEN interacts with the N-terminal domain of SRF and PTEN-SRF interaction promotes SRF binding to essential promoter elements in SM-specific genes. Factors inducing phenotypic switching promote loss of nuclear PTEN through nucleo-cytoplasmic translocation resulting in reduced myogenically active SRF, but enhanced SRF activity on target genes involved in proliferation. Overall decreased expression of PTEN was observed in intimal SMCs of human atherosclerotic lesions underlying the potential clinical importance of these findings.