Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy

It is generally believed that increase in adult contractile cardiac mass can be accomplished only by hypertrophy of existing myocytes. Documentation of myocardial regeneration in acute stress has challenged this dogma and led to the proposition that myocyte renewal is fundamental to cardiac homeostasis. Here we report that in human aortic stenosis, increased cardiac mass results from a combination of myocyte hypertrophy and hyperplasia. Intense new myocyte formation results from the differentiation of stem-like cells committed to the myocyte lineage. These cells express stem cell markers and telomerase. Their number increased >13-fold in aortic stenosis. The finding of cell clusters with stem cells making the transition to cardiogenic and myocyte precursors, as well as very primitive myocytes that turn into terminally differentiated myocytes, provides a link between cardiac stem cells and myocyte differentiation. Growth and differentiation of these primitive cells was markedly enhanced in hypertrophy, consistent with activation of a restricted number of stem cells that, through symmetrical cell division, generate asynchronously differentiating progeny. These clusters strongly support the existence of cardiac stem cells that amplify and commit to the myocyte lineage in response to increased workload. Their presence is consistent with the notion that myocyte hyperplasia significantly contributes to cardiac hypertrophy and accounts for the subpopulation of cycling myocytes

Ex vivo model predicted in vivo efficacy of CFTR modulator therapy in a child with rare genotype

Background: New drugs that target the basic defect in cystic fibrosis (CF) patients may now be used in a large number of patients carrying responsive mutations. Nevertheless, further research is needed to extend the benefit of these treatments to patients with rare mutations that are still uncharacterized in vitro and that are not included in clinical trials. For this purpose, ex vivo models are necessary to preliminary assessing the effect of CFTR modulators in these cases. Method: We report the clinical effectiveness of lumacaftor/ivacaftor therapy prescribed to a CF child with a rare genetic profile (p.Phe508del/p.Gly970Asp) after testing the drug on nasal epithelial cells. We observed a significant drop of the sweat chloride value, as of the lung clearance index. A longer follow-up period is needed to define the effects of therapy on pancreatic status, although an increase of the fecal elastase values was found. Conclusion: Drug response obtained on nasal epithelial cells correlates with changes in vivo therapeutic endpoints and can be a predictor of clinical efficacy of novel drugs especially in pediatric patients

Internal Carotid Artery Redundancy is Significantly Associated With Dissection.

BACKGROUND AND PURPOSE: Redundant internal carotid arteries have been considered a risk factor in tonsillectomy, adenoidectomy, and surgical treatment of peritonsillar abscess and also a potentially treatable cause of stroke. However, an association between internal carotid artery redundancy and spontaneous dissection has not yet been clearly demonstrated. METHODS: We reviewed, for spontaneous carotid artery dissection, records of all patients admitted to our institution during the period from 1986 through 1992 with the diagnosis of stroke or transient ischemic attack. We also reviewed 108 percutaneous cerebral arteriograms performed between September 1992 and December 1992 for presence of carotid artery redundancies. RESULTS: Thirteen patients exhibited spontaneous dissection. Of these, 8 of 13 (62%) patients and 13 of 20 (65%) internal carotid arteries, viewed to the siphon, had significant redundancies, kinks, coils, or loops. Of 108 consecutive arteriograms of patients without dissection, in which 187 internal carotid arteries were viewed to the siphon, there were 20 (19%) patients and 22 (12%) of 187 vessels with significant redundancy. Five patients in the dissection group and 2 in the nondissection group had bilateral internal carotid artery redundancy (P = .0019 and P = .0001, respectively). CONCLUSIONS: We found a significant correlation between internal carotid artery redundancy and dissection, particularly if redundancy is present bilaterally

Detection of melatonin-onset in real settings via wearable sensors and artificial intelligence : a pilot study

Circadian rhythms modulate physiological and behavioral processes of approximately 24-h periodicity. Alterations in the circadian timing system may lead to cardiovascular, metabolic or neurological diseases, cancers and sleep disorders, as well as to disruption of quality of life. Circadian rhythms can be tracked via laboratory tests measuring hormones in salivary, urinary or blood samples, which are collected in controlled environments. These tests are unsuitable for continuous monitoring in real-life, being expensive and time consuming, producing discrete information (i.e., few values per day) and requiring controlled environmental conditions (e.g., exposure to light can alter the samples). Thus, there is a need to develop non-invasive methods and tools to track circadian rhythms in real-life conditions

From Surveillance to Witnessing: Revanche, Red Road, and the Anti-Revenge Film

This essay examines recent European art films that reinterpret the revenge plot and radically challenge the possibility of legitimized violence. I argue that what I term “anti-revenge” films, in particular Andrea Arnold’s Red Road (2006), and Götz Spielmann’s Revanche (2008), frustrate the desire for vengeance (both the protagonist’s and the spectator’s), replacing violent spectacle with uneasy engagement that inhibits revenge, gesturing instead toward the possibility, however remote, of forgiveness. In both films prolonged surveillance, surveillance ostensibly in the service of retribution, inadvertently becomes a means for ethical engagement that actually prohibits violence. In their failure to conform to generic conventions and their depiction of the collapse of the retributive drive, these films challenge the moral legitimacy of revenge, substituting uneasy, often inconclusive moments of potential forgiveness for violent spectacle

Heating, current drive and energetic particle studies on JET in preparation of ITER operation

This paper summarizes the recent work on JET in the three areas of heating, current drive and energetic particles. The achievements have extended the possibilities of JET, have a direct connection to ITER operation and provide new and interesting physics. Toroidal rotation profiles of plasmas heated far off axis with little or no refuelling or momentum input are hollow with only small differences on whether the power deposition is located on the low field side or on the high field side. With LH current drive the magnetic shear was varied from slightly positive to negative. The improved coupling (through the use of plasma shaping and CD4) allowed up to 3.4 MW of PLH in internal transport barrier (ITB) plasmas with more than 15 MW of combined NBI and ICRF heating. The q-profile with negative magnetic shear and the ITB could be maintained for the duration of the high heating pulse (8 s). Fast ions have been produced in JET with ICRF to simulate alpha particles: by using third harmonic 4He heating, beam injected 4He at 120 kV were accelerated to energies above 2 MeV, taking advantage of the unique capability of JET to use NBI with 4He and to confine MeV class ions. ICRF heating was used to replicate the dynamics of alpha heating and the control of an equivalent Q = 10 `burn' was simulated

COMADRE: A global data base of animal demography

This is the final version. Available on open access from Wiley via the DOI in this recordData accessibility: The data associated with this manuscript can be accessed at www.comadre-db.orgThe open-data scientific philosophy is being widely adopted and proving to promote considerable progress in ecology and evolution. Open-data global data bases now exist on animal migration, species distribution, conservation status, etc. However, a gap exists for data on population dynamics spanning the rich diversity of the animal kingdom world-wide. This information is fundamental to our understanding of the conditions that have shaped variation in animal life histories and their relationships with the environment, as well as the determinants of invasion and extinction. Matrix population models (MPMs) are among the most widely used demographic tools by animal ecologists. MPMs project population dynamics based on the reproduction, survival and development of individuals in a population over their life cycle. The outputs from MPMs have direct biological interpretations, facilitating comparisons among animal species as different as Caenorhabditis elegans, Loxodonta africana and Homo sapiens. Thousands of animal demographic records exist in the form of MPMs, but they are dispersed throughout the literature, rendering comparative analyses difficult. Here, we introduce the COMADRE Animal Matrix Database, an open-data online repository, which in its version 1.0.0 contains data on 345 species world-wide, from 402 studies with a total of 1625 population projection matrices. COMADRE also contains ancillary information (e.g. ecoregion, taxonomy, biogeography, etc.) that facilitates interpretation of the numerous demographic metrics that can be derived from its MPMs. We provide R code to some of these examples. Synthesis: We introduce the COMADRE Animal Matrix Database, a resource for animal demography. Its open-data nature, together with its ancillary information, will facilitate comparative analysis, as will the growing availability of databases focusing on other aspects of the rich animal diversity, and tools to query and combine them. Through future frequent updates of COMADRE, and its integration with other online resources, we encourage animal ecologists to tackle global ecological and evolutionary questions with unprecedented sample size.Australian Research Council (ARC)Evolutionary Demography Laboratory at the Max Planck Institute for Demographic Research (MPIDR)Natural Environment Research Council (NERC