Cardiac magnetic resonance in heart failure with preserved ejection fraction:myocyte, interstitium, microvascular, and metabolic abnormalities

Heart failure (HF) with preserved ejection fraction (HFpEF) is a chronic cardiac condition whose prevalence continues to rise, with high social and economic burden, but with no specific approved treatment. Patients diagnosed with HFpEF have a high prevalence of comorbidities and exhibit a high misdiagnosis rate. True HFpEF is likely to have multiple pathophysiological causes - with these causes being clinically ill-defined due to limitations of current measurement techniques. Myocyte, interstitium, microvascular, and metabolic abnormalities have been regarded as key components of the pathophysiology and potential therapeutic targets. Cardiac magnetic resonance (CMR) has the capability to look deeper with a number of tissue characterization techniques which are closer to the underlying specific abnormalities and which could be linked to personalized medicine for HFpEF. This review aims to discuss the potential role of CMR to better define HFpEF phenotypes and to infer measurable therapeutic targets

New middle Miocene (Langhian - Serravallian) vertebrate localities in northwestern Patagonia, Argentina: A contribution to high latitude south american land mammal ages sequence

The Miocene represents a key moment in the South American evolution, since meaningful geographic and climatic processes occurred, promoting the development of several biologic changes. The isolation of South America together with major global and regional climatic changes resulted in an enormous variety of biomes and endemic diversity of flora and fauna, especially of mammals diversity. Most of the best-known continental vertebrate fossil-bearing deposits correspond to the early and late Miocene, existing a deficient knowledge for the middle Miocene, which is poorly understood at high latitudes. This work examines four new middle Miocene fossiliferous localities from a North Patagonian foreland succession, through a multidisciplinary approach that combines stratigraphic and preliminary paleontological analyses within a previously defined high-resolution temporal scheme. Two localities are referred to the lower section of Collón Cura Formation, and were constrained to a range of 14.6–12.75 Ma, whereas the other two localities correspond to the upper section of Collón Cura Formation and were constrained to 12.75–12.05 Ma. A large variety of fossil vertebrates were recognized in the lower section, belonging to Teleostei, Testudinidae, Teiidae, Anura and Mammalia; whereas Teleostei, Testudinidae and Mammalia vertebrates were documented in the upper section. Our results indicate a Colloncuran and younger (e.g., Mayoan) South American Mammals Ages (SALMAs) for the lower and upper sections of Collón Cura Formation, respectively. However, data from this work support the idea of a continuum on the SALMAs sequence for the middle Miocene where overlap, at least partially, both in absolute dates and in the faunal assemblages.Fil: Bucher, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Pérez, María Emilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Museo Paleontológico Egidio Feruglio; ArgentinaFil: Gonzalez Ruiz, Laureano Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia San Juan Bosco. Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Laboratorio de Investigaciones en Evolución y Biodiversidad; ArgentinaFil: D'Elia, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Bilmes, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Geología y Paleontología; Argentin

Cell-Type-Specific Analysis of Molecular Pathology in Autism Identifies Common Genes and Pathways Affected Across Neocortical Regions

Despite its heterogeneity, autism is characterized by a defined behavioral phenotype, suggesting that the molecular pathology affects specific neural substrates to cause behavioral dysfunction. Previous studies identified genes dysregulated in autism cortex but did not address their cell-type specificity. Moreover, it is unknown whether there is a core of genes dysregulated across multiple neocortical regions. We applied RNA sequencing to postmortem brain tissue samples from autism patients and neurologically normal controls and combined our data with previously published datasets. We then identified genes, pathways, and alternative splicing events which are dysregulated in five neocortical regions in autism. To gain information about cell-type specificity of the dysregulated genes, we analyzed single-nuclei RNA sequencing data of adult human cortex and intersected cell-type-specific gene signatures with genes dysregulated in autism in specific cortical regions. We found that autism-associated gene expression changes across 4 frontal and temporal cortex regions converge on 27 genes related to immune response and enriched in human astrocytes, microglia, and brain endothelium. Shared splicing changes, however, are found in genes predominantly associated with synaptic function and adult interneurons and projection neurons. Finally, we demonstrate that regions of DNA differentially methylated in autism overlap genes associated with development and enriched in human cortical oligodendrocytes. Our study identifies signatures of autism molecular pathology shared across neocortical regions, as well as neural cell types enriched for common dysregulated genes, thus paving way for assessing cell-type-specific mechanisms of autism pathology

Determinants of functional capacity after mitral valve annuloplasty or replacement for ischemic mitral regurgitation

International audienceOBJECTIVE:To identify the exercise echocardiographic determinants of long-term functional capacity, in patients with chronic ischemic mitral regurgitation, after restrictive mitral valve annuloplasty (RMA) or mitral valve replacement (MVR).METHODS:We retrospectively analyzed 121 patients with significant chronic ischemic mitral regurgitation, who underwent RMA (n = 62) or MVR (n = 59), between 2005 and 2011. Preoperatively, all patients underwent a resting echocardiographic examination, and a 6-minute walking test (6-MWT) to measure distance. Resting and exercise stress echocardiography, and the 6-MWT were repeated at 41 ± 16.5 months.RESULTS:After surgery, the 6-MWT distance significantly improved in the MVR group, and decreased in the RMA group (+37 ± 39 m vs -24 ± 49 m, respectively; P < .0001). Exercise indexed effective orifice area was significantly higher in the MVR, versus the RMA, group (MVR: change from 1.3 ± 0.2 cm(2)/m(2) to 1.5 ± 0.3 cm(2)/m(2); RMA: change from 1.1 ± 0.3 cm(2)/m(2) to 1.2 ± 0.3 cm(2)/m(2); P = .001). The mean mitral gradients significantly increased from rest to exercise, in both groups, but to a greater extent in the RMA group (change from 4.4 ± 1.4 to 11 ± 3.6 mm Hg; MVR: change from 4.3 ± 1.8 to 9 ± 3.5 mm Hg; P = .006). On multivariate analysis, MVR and exercise indexed effective orifice area were the main independent determinants of postoperative 6-MWT. In the RMA group, 25 patients experienced late mitral regurgitation recurrence, severe in 9 (14%) of them. The rate of postoperative cardiovascular events was significantly higher in the RMA group (21% vs MVR: 8%; P = .03). Follow-up survival was 83% in the RMA group and 88% in the MVR group (P = .54).CONCLUSIONS:For chronic ischemic mitral regurgitation, MVR versus RMA was associated with better postoperative exercise hemodynamic performance and long-term functional capacity

How should I treat a challenging case of MitraClip implantation?

BACKGROUND: A 71-year-old woman affected by idiopathic dilated cardiomyopathy with normal coronary arteries and permanent atrial fibrillation was found to have severe mitral regurgitation at transthoracic echocardiography (TTE), due to annular dilatation and restricted motion of the posterior leaflet. Because of poor quality of life, high functional class (NYHA Class III) and the high risk of surgery, the patient agreed to undergo the implantation of a MitraClip device. During the procedure, the transoesophageal echocardiographic (TEE) images were of a poor quality since the view of the mitral valve in the mid-oesophageal and transgastric projections did not accurately show the valve leaflets and the convergence area of the regurgitation at colour Doppler, which is indispensable for the correct positioning of the clip. INVESTIGATION: Physical examination, transthoracic echocardiography, transoesophageal echocardiography. DIAGNOSIS: Severe mitral regurgitation suitable for MitraClip implantation. MANAGEMENT: Transthoracic, and not transoesophageal, echocardiography approach during MitraClip procedure

Modesta o il romanzo che ancora deve essere scritto

Il volume ha origine da un convegno della Società Italiana delle Letterate che ha avuto luogo a Genova nel 2011 e dedicato alle figure femminili protagoniste della letteratura e di altre forme della narrazione culturale, per le quali si è voluto coniare il neologismo "personagge". Il saggio è dedicato alla protagonista del romanzo di Goliarda Sapienza, L'arte della gioia, che ha nome Modesta, e al rapporto che intrattiene con la tradizione letteraria a firma di scrittrici del Novecento italiano. In particolare si riattraversano le opere di Sibilla Aleramo, Alba de Céspedes, Paola Masino, per arrivare fino a Alice Ceresa e Carla Lonzi, tutte antecedenti a Goliarda Sapienza

Comorbidities, Cardiovascular Therapies, and COVID-19 Mortality: A Nationwide, Italian Observational Study (ItaliCO)

Background: Italy has one of the world's oldest populations, and suffered one the highest death tolls from Coronavirus disease 2019 (COVID-19) worldwide. Older people with cardiovascular diseases (CVDs), and in particular hypertension, are at higher risk of hospitalization and death for COVID-19. Whether hypertension medications may increase the risk for death in older COVID 19 inpatients at the highest risk for the disease is currently unknown. Methods: Data from 5,625 COVID-19 inpatients were manually extracted from medical charts from 61 hospitals across Italy. From the initial 5,625 patients, 3,179 were included in the study as they were either discharged or deceased at the time of the data analysis. Primary outcome was inpatient death or recovery. Mixed effects logistic regression models were adjusted for sex, age, and number of comorbidities, with a random effect for site. Results: A large proportion of participating inpatients were >= 65 years old (58%), male (68%), non-smokers (93%) with comorbidities (66%). Each additional comorbidity increased the risk of death by 35% [adjOR = 1.35 (1.2, 1.5) p = 65 years old, indicates that there is a linear direct relationship between the number of comorbidities and the risk of death. Among CVDs, hypertension and pre-existing cardiomyopathy were significantly associated with risk of death. The use of hypertension medications reported to be safe in younger cohorts, do not contribute significantly to increased COVID-19 related deaths in an older population that suffered one of the highest death tolls worldwide.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Comorbidities, Cardiovascular Therapies, and COVID-19 Mortality: A Nationwide, Italian Observational Study (ItaliCO)

Background: Italy has one of the world's oldest populations, and suffered one the highest death tolls from Coronavirus disease 2019 (COVID-19) worldwide. Older people with cardiovascular diseases (CVDs), and in particular hypertension, are at higher risk of hospitalization and death for COVID-19. Whether hypertension medications may increase the risk for death in older COVID 19 inpatients at the highest risk for the disease is currently unknown. Methods: Data from 5,625 COVID-19 inpatients were manually extracted from medical charts from 61 hospitals across Italy. From the initial 5,625 patients, 3,179 were included in the study as they were either discharged or deceased at the time of the data analysis. Primary outcome was inpatient death or recovery. Mixed effects logistic regression models were adjusted for sex, age, and number of comorbidities, with a random effect for site. Results: A large proportion of participating inpatients were 6565 years old (58%), male (68%), non-smokers (93%) with comorbidities (66%). Each additional comorbidity increased the risk of death by 35% [adjOR = 1.35 (1.2, 1.5) p &lt; 0.001]. Use of ACE inhibitors, ARBs, beta-blockers or Ca-antagonists was not associated with significantly increased risk of death. There was a marginal negative association between ARB use and death, and a marginal positive association between diuretic use and death. Conclusions: This Italian nationwide observational study of COVID-19 inpatients, the majority of which 6565 years old, indicates that there is a linear direct relationship between the number of comorbidities and the risk of death. Among CVDs, hypertension and pre-existing cardiomyopathy were significantly associated with risk of death. The use of hypertension medications reported to be safe in younger cohorts, do not contribute significantly to increased COVID-19 related deaths in an older population that suffered one of the highest death tolls worldwide