Connexin 43 mediated collective cell migration is independent of Golgi orientation.

Cell migration is vital for multiple physiological functions and is involved in the metastatic dissemination of tumour cells in various cancers. For effective directional migration, cells often reorient their Golgi apparatus and, therefore, the secretory traffic towards the leading edge. However, not much is understood about the regulation of Golgi's reorientation. Herein, we address the role of gap junction protein Connexin 43 (Cx43), which connects cells, allowing the direct exchange of molecules. We utilized HeLa WT cells lacking Cx43 and HeLa 43 cells, stably expressing Cx43, and found that functional Cx43 channels affected Golgi morphology and reduced the reorientation of Golgi during cell migration. Although the migration velocity of the front was reduced in HeLa 43, the front displayed enhanced coherence in movement, implying an augmented collective nature of migration. On BFA treatment, Golgi was dispersed and the high heterogeneity in inter-regional front velocity of HeLa WT cells was reduced to resemble the HeLa 43. HeLa 43 had higher vimentin expression and stronger basal F-actin. Furthermore, non-invasive measurement of basal membrane height fluctuations revealed a lower membrane tension. We, therefore, propose that reorientation of Golgi is not the major determinant of migration in the presence of Cx43, which induces collective-like coherent migration in cells.

Regulatory role of endoplasmic reticulum resident chaperone protein ERp29 in anti-murine ß-coronavirus host cell response.

Gap junctional intercellular communication (GJIC) involving astrocytes is important for proper CNS homeostasis. As determined in our previous studies, trafficking of the predominant astrocyte GJ protein, Connexin43 (Cx43), is disrupted in response to infection with a neurotropic murine ß-coronavirus (MHV-A59). However, how host factors are involved in Cx43 trafficking and the infection response is not clear. Here, we show that Cx43 retention due to MHV-A59 infection was associated with increased ER stress and reduced expression of chaperone protein ERp29. Treatment of MHV-A59-infected astrocytes with the chemical chaperone 4-sodium phenylbutyrate increased ERp29 expression, rescued Cx43 transport to the cell surface, increased GJIC, and reduced ER stress. We obtained similar results using an astrocytoma cell line (delayed brain tumor) upon MHV-A59 infection. Critically, delayed brain tumor cells transfected to express exogenous ERp29 were less susceptible to MHV-A59 infection and showed increased Cx43-mediated GJIC. Treatment with Cx43 mimetic peptides inhibited GJIC and increased viral susceptibility, demonstrating a role for intercellular communication in reducing MHV-A59 infectivity. Taken together, these results support a therapeutically targetable ERp29-dependent mechanism where ß-coronavirus infectivity is modulated by reducing ER stress and rescuing Cx43 trafficking and function.

Association of atrial fibrillation burden with in-hospital outcomes in patients with Takotsubo cardiomyopathy.

BACKGROUND: The effects of atrial fibrillation (AF) and its burden on in-hospital mortality in patients with Takotsubo cardiomyopathy (TCM) are unclear. Here, we examined the effect of AF and paroxysmal AF on in-hospital outcomes in patients with TCM. METHODS: We used ICD-10 codes to retrospectively identify patients with a primary diagnosis of TCM in the National Inpatient Sample database 2016-2018. We compared in-hospital outcomes in TCM patients with and without AF before and after propensity score matching. The effect of AF burden on outcomes was assessed in patients with paroxysmal AF and no AF. RESULTS: Of the 4,733 patients with a primary diagnosis of TCM, 650 (13.7%) had AF, and 4,083 (86.3%) did not. Of TCM patients with AF, 368 (56.6%) had paroxysmal AF. In-hospital mortality was higher in patients with AF before (3.4% vs 1.2%, P <  0.001) and after propensity matching (3.4% vs 1.7%, P = 0.021) but did not differ between the paroxysmal AF and the no AF groups (P = 0.205). In the matched cohorts, both AF and paroxysmal AF groups were associated with a higher rate of cardiogenic shock (AF, P < 0.001; paroxysmal AF, P < 0.001), ventricular arrhythmia (AF, P = 0.002; paroxysmal AF, P = 0.02), acute kidney injury (AF, P = 0.007; paroxysmal AF, P = 0.008), and acute respiratory failure (AF, P < 0.001; paroxysmal AF, P < 0.001) compared with the no AF group. CONCLUSIONS: Although AF was associated with increased in-hospital mortality, paroxysmal AF did not affect in-hospital mortality, suggesting a higher AF burden is associated with worse clinical outcome in patients with TCM.

Role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cryoballoon ablation outcomes for paroxysmal atrial fibrillation.

BACKGROUND: Cryoballoon ablation (CBA) is recommended for patients with paroxysmal atrial fibrillation (AF) refractory to antiarrhythmic drugs. However, only 80% of patients benefit from initial CBA. There is growing evidence that pretreatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) decreases the recurrence of AF postablation, particularly in nonparoxysmal AF undergoing radiofrequency ablation. The role of ACEIs and ARBs in patients with paroxysmal AF in CBA remains unknown. We decided to investigate the role of ACEIs and ARBs in preventing the recurrence of atrial arrhythmia (AA) following CBA for paroxysmal AF. AIM: To investigate the role of ACEIs and ARBs in preventing recurrence of AA following CBA for paroxysmal AF. METHODS: We followed 103 patients (age 60.6 ± 9.1 years, 29% women) with paroxysmal AF undergoing CBA 1-year post procedure. Recurrence was assessed by documented AA on electrocardiogram or any form of long-term cardiac rhythm monitoring. A multivariable Cox proportional hazard model was used to assess if ACEI or ARB treatment predicted the risk of AA recurrence. RESULTS: After a 1-year follow-up, 19 (18.4%) participants developed recurrence of AA. Use of ACEI or ARB therapy was noted in the study population. Patients on ACEI/ARB had a greater prevalence of hypertension and coronary artery disease. On a multivariate model adjusted for baseline demographics and risk factors for AF, ACEI or ARB therapy did not prevent recurrence of AA following CBA (P = 0.72). Similarly, on Kaplan-Meier analysis pretreatment with ACEI/ARB did not predict the time to first recurrence of AA (P = 0.2173). CONCLUSION: In our study population, preablation treatment with an ACEI or ARB had no influence on the recurrence of AA following CBA for paroxysmal AF.

Right Atrial Thrombus Mimicking a Myxoma: Synergism of Hormonal Contraceptives and Antiphospholipid Antibodies.

Cardiac thrombus, the most common intracardiac mass, is typically seen in the left side of the heart in the presence of atrial fibrillation, mitral stenosis, or impaired global wall motion. Right atrial thrombus, which is rarer, is usually associated with central venous catheter placement or pulmonary embolism. We present the case of a 24-year-old woman with a history of mitral valve prolapse who presented with fatigue and palpitations. Echocardiograms and cardiac magnetic resonance images revealed a right atrial mass compatible with a myxoma. However, after surgical excision of this and a second mass discovered intraoperatively, pathologic evaluation confirmed organized thrombus rather than myxoma. The patient's only risk factor was her use of oral contraceptive pills. Test results for hypercoagulable disorders revealed the presence of antiphosphatidylserine, an uncommon antiphospholipid antibody. The patient stopped taking the contraceptive. This case suggests the need to examine further the role of antiphosphatidylserine antibodies in the diagnosis of antiphospholipid syndrome.

Predictors and Rate of Progression of Aortic Root and Ascending Aorta Dilatation.

In the absence of risk factors like bicuspid aortic valve, connective tissue disorder, or family history of aortic dissections, degenerative thoracic aortic aneurysm appears to be an indolent disease. Most American and European societies recommend yearly or biannual imaging of the thoracic aorta with computed tomographic (CT) imaging, magnetic resonance (MRI) imaging, and transthoracic echocardiographic (TTE) examination. We aimed to identify the rate of progression and predictors of early degenerative aortic root dilatation (ARD) and ascending aortic dilatation (AAD) over a period of 10 years on the basis of echocardiographic measurements. A retrospective chart analysis was performed on 340 patients (mean age 67.4 ± 11.6 years; 85.6% men; 83.8% White) with known ARD and AAD. Aortic root and ascending aorta measurements were followed by serial echocardiograms from the time of the first diagnosis for a total of 10 years. During this time, the mean change in ARD was 0.28 ± 0.71 mm and AAD was 0.15 ± 0.18 mm. On multivariate regression after adjusting for baseline demographics, risk factors, and medication use, there was no statistically significant increase in their unit change in mean ARD or AAD. In conclusion, mild to moderate degenerative thoracic aortic aneurysm has a minimal change in dimensions over time, and current guidelines recommending yearly surveillance imaging of ARD and AAD need to be revisited to allow a more liberal follow-up interval.

Presence of a left common pulmonary vein and pulmonary vein anatomical characteristics as predictors of outcome following cryoballoon ablation for paroxysmal atrial fibrillation.

PURPOSE: Pulmonary vein (PV) isolation using cryoballoon ablation (CBA) is a common therapy for patients with drug-refractory paroxysmal atrial fibrillation (PAF). However, initial CBA is successful in only 70-80% of patients. The role of an atypical left common PV (LCPV) and PV anatomical indices on CBA outcomes remains unclear. METHODS: We followed 80 patients (age 60.7 ± 9.7, 31 % women) with PAF undergoing CBA for 1-year post-procedure for the development of recurrent atrial arrhythmias (AA). Recurrence was assessed by documented AA on EKG or any form of long-term cardiac rhythm monitoring. The presence of an LCPV and individual PV diameters were evaluated using cardiac CT. Based on the maximum and minimum PV ostial diameters, the eccentricity index (EI), ovality index (OI), and PV ostial area (PVA) were calculated for all the veins. A multivariable Cox-proportional hazard model assessed whether the presence of an LCPV or PV anatomic indices (EI, OI, and PVA) predicted recurrence of AA following CBA. RESULTS: After 1-year follow-up, 19 (23.7%) participants developed recurrence of AA. On multivariable regression, the presence of an LCPV did not predict the recurrence of AA (p = 0.38). Among the PV anatomical indices, on univariate analysis, only the area of the left inferior PV showed a trend towards predicting recurrence, though this result was not significant on multivariate analysis (p = 0.09). CONCLUSIONS: In patients with PAF, neither the presence of an LCPV nor individual PV anatomical indices predicted recurrence of AA following CBA.

Amyloid-ß regulates gap junction protein connexin 43 trafficking in cultured primary astrocytes.

Altered expression and function of astroglial gap junction protein connexin 43 (Cx43) has increasingly been associated to neurotoxicity in Alzheimer disease (AD). Although earlier studies have examined the effect of increased ß-amyloid (Aß) on Cx43 expression and function leading to neuronal damage, underlying mechanisms by which Aß modulates Cx43 in astrocytes remain elusive. Here, using mouse primary astrocyte cultures, we have examined the cellular processes by which Aß can alter Cx43 gap junctions. We show that Aß25-35 impairs functional gap junction coupling yet increases hemichannel activity. Interestingly, Aß25-35 increased the intracellular pool of Cx43 with a parallel decrease in gap junction assembly at the surface. Intracellular Cx43 was found to be partly retained in the endoplasmic reticulum-associated cell compartments. However, forward trafficking of the newly synthesized Cx43 that already reached the Golgi was not affected in Aß25-35-exposed astrocytes. Supporting this, treatment with 4-phenylbutyrate, a well-known chemical chaperone that improves trafficking of several transmembrane proteins, restored Aß-induced impaired gap junction coupling between astrocytes. We further show that interruption of Cx43 endocytosis in Aß25-35-exposed astrocytes resulted in their retention at the cell surface in the form of functional gap junctions indicating that Aß25-35 causes rapid internalization of Cx43 gap junctions. Additionally, in silico molecular docking suggests that Aß can bind favorably to Cx43. Our study thus provides novel insights into the cellular mechanisms by which Aß modulates Cx43 function in astrocytes, the basic understanding of which is vital for the development of alternative therapeutic strategy targeting connexin channels in AD.

CD4 Deficiency Causes Poliomyelitis and Axonal Blebbing in Murine Coronavirus-Induced Neuroinflammation.

Mouse hepatitis virus (MHV) is a murine betacoronavirus (m-CoV) that causes a wide range of diseases in mice and rats, including hepatitis, enteritis, respiratory diseases, and encephalomyelitis in the central nervous system (CNS). MHV infection in mice provides an efficient cause-effect experimental model to understand the mechanisms of direct virus-induced neural-cell damage leading to demyelination and axonal loss, which are pathological features of multiple sclerosis (MS), the most common disabling neurological disease in young adults. Infiltration of T lymphocytes, activation of microglia, and their interplay are the primary pathophysiological events leading to disruption of the myelin sheath in MS. However, there is emerging evidence supporting gray matter involvement and degeneration in MS. The investigation of T cell function in the pathogenesis of deep gray matter damage is necessary. Here, we employed RSA59 (an isogenic recombinant strain of MHV-A59)-induced experimental neuroinflammation model to compare the disease in CD4-/- mice with that in CD4+/+ mice at days 5, 10, 15, and 30 postinfection (p.i.). Viral titer estimation, nucleocapsid gene amplification, and viral antinucleocapsid staining confirmed enhanced replication of the virions in the absence of functional CD4+ T cells in the brain. Histopathological analyses showed elevated susceptibility of CD4-/- mice to axonal degeneration in the CNS, with augmented progression of acute poliomyelitis and dorsal root ganglionic inflammation rarely observed in CD4+/+ mice. Depletion of CD4+ T cells showed unique pathological bulbar vacuolation in the brain parenchyma of infected mice with persistent CD11b+ microglia/macrophages in the inflamed regions on day 30 p.i. In summary, the current study suggests that CD4+ T cells are critical for controlling acute-stage poliomyelitis (gray matter inflammation), chronic axonal degeneration, and inflammatory demyelination due to loss of protective antiviral host immunity.IMPORTANCE The current trend in CNS disease biology is to attempt to understand the neural-cell-immune interaction to investigate the underlying mechanism of neuroinflammation, rather than focusing on peripheral immune activation. Most studies in MS are targeted toward understanding the involvement of CNS white matter. However, the importance of gray matter damage has become critical in understanding the long-term progressive neurological disorder. Our study highlights the importance of CD4+ T cells in safeguarding neurons against axonal blebbing and poliomyelitis from murine betacoronavirus-induced neuroinflammation. Current knowledge of the mechanisms that lead to gray matter damage in MS is limited, because the most widely used animal model, experimental autoimmune encephalomyelitis (EAE), does not present this aspect of the disease. Our results, therefore, add to the existing limited knowledge in the field. We also show that the microglia, though important for the initiation of neuroinflammation, cannot establish a protective host immune response without the help of CD4+ T cells.

A case report of recurrent spontaneous coronary artery dissection and Takotsubo cardiomyopathy: a treatment dilemma.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an uncommon cause of acute coronary syndrome in younger females with no pre-existing history of coronary artery disease. Recurrent SCAD is common after a first episode and can involve the same coronary artery or present as a new dissection unrelated to the initial lesion. Current recommendations advise for a conservative approach in the absence of haemodynamic compromise and flow limitations. Conversely, there are no clear guidelines for the management of early recurrent SCAD. CASE SUMMARY: A 52-year-old woman with history of obesity, asthma, and prediabetes presented with chest pain and electrocardiogram (ECG) showing inferior wall ST-elevation myocardial infarction (STEMI). Coronary angiography revealed proximal right coronary artery (RCA) dissection and distal left anterior descending artery (LAD) dissection, while left ventriculogram showed Takotsubo cardiomyopathy (TC). Angiography revealed no flow limitations so conservative management was pursued. She returned within a couple of days with recurrent chest pain and ECG showing similar findings of inferior STEMI. Repeat angiography confirmed progression of the proximal RCA SCAD with resolution of distal LAD SCAD. Since flow through the distal RCA was still preserved, conservative medical management was continued. She presented a third time for palpitations only and another repeat coronary angiogram showed healing RCA SCAD. DISCUSSION: Management of early recurrent SCAD continues to be a clinical dilemma. In addition, our patient had features of TC which shares a similar clinical risk factor profile with SCAD thus it may be prudent to further investigate for TC in patients presenting with SCAD and have suggestive features of TC on history and echocardiography.

Bi-Linear Modeling of Data Manifolds for Dynamic-MRI Recovery.

This paper puts forth a novel bi-linear modeling framework for data recovery via manifold-learning and sparse-approximation arguments and considers its application to dynamic magnetic-resonance imaging (dMRI). Each temporal-domain MR image is viewed as a point that lies onto or close to a smooth manifold, and landmark points are identified to describe the point cloud concisely. To facilitate computations, a dimensionality reduction module generates low-dimensional/compressed renditions of the landmark points. Recovery of high-fidelity MRI data is realized by solving a non-convex minimization task for the linear decompression operator and affine combinations of landmark points which locally approximate the latent manifold geometry. An algorithm with guaranteed convergence to stationary solutions of the non-convex minimization task is also provided. The aforementioned framework exploits the underlying spatio-temporal patterns and geometry of the acquired data without any prior training on external data or information. Extensive numerical results on simulated as well as real cardiac-cine MRI data illustrate noteworthy improvements of the advocated machine-learning framework over state-of-the-art reconstruction techniques.

Impact of structured interdisciplinary bedside rounding on patient outcomes at a large academic health centre.

BACKGROUND: Effective communication between healthcare providers and patients and their family members is an integral part of daily care and discharge planning for hospitalised patients. Several studies suggest that team-based care is associated with improved length of stay (LOS), but the data on readmissions are conflicting. Our study evaluated the impact of structured interdisciplinary bedside rounding (SIBR) on outcomes related to readmissions and LOS. METHODS: The SIBR team consisted of a physician and/or advanced practice provider, bedside nurse, pharmacist, social worker and bridge nurse navigator. Outcomes were compared in patients admitted to a hospital medicine unit using SIBR (n=1451) and a similar control unit (n=770) during the period of October 2016 to September 2017. Multivariable negative binomial regression analysis was used to compare LOS and logistic regression analysis was used to calculate 30-day and 7-day readmission in patients admitted to SIBR and control units, adjusting for covariates. RESULTS: Patients admitted to SIBR and control units were generally similar (p≥0.05) with respect to demographic and clinical characteristics. Unadjusted readmission rates in SIBR patients were lower than in control patients at both 30 days (16.6% vs 20.3%, p=0.03) and 7 days (6.3% vs 9.0%, p=0.02) after discharge, while LOS was similar. After adjusting for covariates, SIBR was not significantly related to the odds of 30-day readmission (OR 0.81, p=0.07) but was lower for 7-day readmission (OR 0.70, p=0.03); LOS was similar in both groups (p=0.58). CONCLUSION: SIBR did not reduce LOS and 30-day readmissions but had a significant impact on 7-day readmissions.

Sex Differences in Risk Factors for Incident Atrial Fibrillation (from the Reasons for Geographic and Racial Differences in Stroke [REGARDS] Study).

We examined whether the sex differences in atrial fibrillation (AF) is related to difference in risk factors leading to AF or due to a differential impact of the same risk factors in 11,806 participants (55.2 % women) from the REGARDS study. Incident AF was ascertained by electrocardiograms and medical history at a follow-up examination. Backwards elimination logistic regression was used to identify AF risk factors in men and women, separately. Over a median follow-up of 9.0years, 588 (11.1%) men and 428 (6.6%) women (p value <0.001) developed AF. Men had a higher risk of AF than women (age and race adjusted odds ratio [OR] [95% confidence interval (CI)]: 1.61 [1.26, 1.75]). Age, white race, height, weight, use of blood pressure lowering medications and history of cardiovascular disease were identified by backward elimination as AF risk factors shared by both sexes. On the other hand, diabetes was an AF risk factor in women but not in men. Among the shared risk factors between men and women, only age showed a stronger association in women than in men [Interaction p-value = 0.003]. Adjustment for the shared risk factors eliminated the sex difference in AF risk (OR [95% CI]: 0.90 [0.74, 1.09]), which was more noticeable in those younger than the median age (62 years) compared to those who were older (interaction p value 0.003). In conclusion, women and men share several AF risk factors, and these shared risk factors explain the sex differences. However, age association with AF differs by sex, and age modifies the associations between sex and other AF risk factors.

Loss of Cx43-Mediated Functional Gap Junction Communication in Meningeal Fibroblasts Following Mouse Hepatitis Virus Infection.

Mouse hepatitis virus (MHV) infection causes meningoencephalitis by disrupting the neuro-glial and glial-pial homeostasis. Recent studies suggest that MHV infection alters gap junction protein connexin 43 (Cx43)-mediated intercellular communication in brain and primary cultured astrocytes. In addition to astrocytes, meningeal fibroblasts also express high levels of Cx43. Fibroblasts in the meninges together with the basal lamina and the astrocyte endfeet forms the glial limitans superficialis as part of the blood-brain barrier (BBB). Alteration of glial-pial gap junction intercellular communication (GJIC) in MHV infection has the potential to affect the integrity of BBB. Till date, it is not known if viral infection can modulate Cx43 expression and function in cells of the brain meninges and thus affect BBB permeability. In the present study, we have investigated the effect of MHV infection on Cx43 localization and function in mouse brain meningeal cells and primary meningeal fibroblasts. Our results show that MHV infection reduces total Cx43 levels and causes its intracellular retention in the perinuclear compartments reducing its surface expression. Reduced trafficking of Cx43 to the cell surface in MHV-infected cells is associated with loss functional GJIC. Together, these data suggest that MHV infection can directly affect expression and cellular distribution of Cx43 resulting in loss of Cx43-mediated GJIC in meningeal fibroblasts, which may be associated with altered BBB function observed in acute infection.

Successful renal transplant in a pediatric patient with HIV-associated nephropathy.

HIV-associated nephropathy (HIVAN) is a pathological state of the kidneys due to longstanding, uncontrolled HIV infection. With the rapid progression of HIVAN to end-stage kidney failure, there is a significant potential for renal transplantation to improve the quality of life in these patients. Numerous studies have been recently published documenting renal transplantation as a primary treatment for HIVAN. With the use of highly active antiretroviral therapy, allograft and patient survival rates of HIV-infected persons are nearly identical to those who are HIV negative. Our case study documents the successful role of renal transplantation in treating HIVAN in a 9-year-old male child.

Microtubule-assisted altered trafficking of astrocytic gap junction protein connexin 43 is associated with depletion of connexin 47 during mouse hepatitis virus infection.

Gap junctions (GJs) are important for maintenance of CNS homeostasis. GJ proteins, connexin 43 (Cx43) and connexin 47 (Cx47), play a crucial role in production and maintenance of CNS myelin. Cx43 is mainly expressed by astrocytes in the CNS and forms gap junction intercellular communications between astrocytes-astrocytes (Cx43-Cx43) and between astrocytes-oligodendrocytes (Cx43-Cx47). Mutations of these connexin (Cx) proteins cause dysmyelinating diseases in humans. Previously, it has been shown that Cx43 localization and expression is altered due to mouse hepatitis virus (MHV)-A59 infection both in vivo and in vitro; however, its mechanism and association with loss of myelin protein was not elaborated. Thus, we explored potential mechanisms by which MHV-A59 infection alters Cx43 localization and examined the effects of viral infection on Cx47 expression and its association with loss of the myelin marker proteolipid protein. Immunofluorescence and total internal reflection fluorescence microscopy confirmed that MHV-A59 used microtubules (MTs) as a conduit to reach the cell surface and restricted MT-mediated Cx43 delivery to the cell membrane. Co-immunoprecipitation experiments demonstrated that Cx43-ß-tubulin molecular interaction was depleted due to protein-protein interaction between viral particles and MTs. During acute MHV-A59 infection, oligodendrocytic Cx47, which is mainly stabilized by Cx43 in vivo, was down-regulated, and its characteristic staining remained disrupted even at chronic phase. The loss of Cx47 was associated with loss of proteolipid protein at the chronic stage of MHV-A59 infection.

Relation Between Estimated Cardiorespiratory Fitness and Atrial Fibrillation (from the Reasons for Geographic and Racial Differences in Stroke Study).

Estimated cardiorespiratory fitness (e-CRF) based on readily available clinical and self-reported data is a promising alternative to the costly traditional assessment of CRF using exercise equipment, but its role as a predictor for incident atrial fibrillation (AF) is unclear. This study included 10,126 participants (54.5% women, 35% African-American, mean age 63.2 years) from the Reasons for Geographic and Racial Differences in Stroke study who were free of AF at baseline. Baseline (2003 to 2007) e-CRF was determined using a previously validated nonexercise algorithm. Incident AF cases were identified at a follow-up examination by electrocardiogram and self-reported medical history of previous physician diagnosis. After a median follow-up of 9.4 years, 906 participants (8.9%) developed AF. In a multivariable logistic regression model adjusted for sociodemographics and baseline cardiovascular disease risk factors as well as incident coronary heart disease, heart failure, and stroke, each 1-metabolic equivalent of task increase in e-CRF was associated with a 5% lower risk of AF development (odds ratio [95% CI] 0.95 [0.92 to 0.99]; p = 0.0129). This association was stronger in women (OR [95% CI] 0.85 (0.79, 0.92) than in men (OR (95% CI) 0.88 (0.84, 0.93), interaction p value = 0.05. No significant interactions by age, race, history of cardiovascular disease, or physical limitations were observed. In conclusion, e-CRF using a nonexercise algorithm is a useful predictor of incident AF, which is consistent with previous reports using traditional CRF. This suggests that e-CRF using nonexercise algorithms may serve as a useful alternative to CRF measured by costly and time-consuming exercise testing.

Bi-Linear Modeling of Manifold-Data Geometry for Dynamic-MRI Recovery.

This paper establishes a modeling framework for data located onto or close to (unknown) smooth manifolds, embedded in Euclidean spaces, and considers its application to dynamic magnetic resonance imaging (dMRI). The framework comprises several modules: First, a set of landmark points is identified to describe concisely a data cloud formed by highly under-sampled dMRI data, and second, low-dimensional renditions of the landmark points are computed. Searching for the linear operator that decompresses low-dimensional data to high-dimensional ones, and for those combinations of landmark points which approximate the manifold data by affine patches, leads to a bi-linear model of the dMRI data, cognizant of the intrinsic data geometry. Preliminary numerical tests on synthetically generated dMRI phantoms, and comparisons with state-of-the-art reconstruction techniques, underline the rich potential of the proposed method for the recovery of highly under-sampled dMRI data.