Ventricular Geometry From Non-contrast Non-ECG-gated CT Scans:An Imaging Marker of Cardiopulmonary Disease in Smokers

Cardiovascular disease is a major cause of morbidity in smokers, and as much as 50% of the estimated 24 million patients in the United States with chronic obstructive pulmonary disease (COPD) die of cardiovascular causes (1,2). Although echocardiography and cardiac magnetic resonance imaging (MRI) are often used to study cardiac structure and function in COPD (3), these are not routinely deployed in all smokers. Computed tomographic (CT) imaging of the chest is broadly used in clinical care and is increasingly used for lung cancer screening in high-risk smokers (4). Assessment of cardiac structure on those CT scans may help identify patients with COPD at greater risk of developing cardiac dysfunction. Rapid, noninvasive assessments of cardiac morphology and a better understanding of the functional interdependence of heart and lung may improve healthcare outcomes through early detection and initiation of treatment

Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration

Age-related macular degeneration (AMD) remains a major cause of blindness, with dysfunction and loss of retinal pigment epithelium (RPE) central to disease progression. We engineered an RPE patch comprising a fully differentiated, human embryonic stem cell (hESC)-derived RPE monolayer on a coated, synthetic basement membrane. We delivered the patch, using a purpose-designed microsurgical tool, into the subretinal space of one eye in each of two patients with severe exudative AMD. Primary endpoints were incidence and severity of adverse events and proportion of subjects with improved best-corrected visual acuity of 15 letters or more. We report successful delivery and survival of the RPE patch by biomicroscopy and optical coherence tomography, and a visual acuity gain of 29 and 21 letters in the two patients, respectively, over 12 months. Only local immunosuppression was used long-term. We also present the preclinical surgical, cell safety and tumorigenicity studies leading to trial approval. This work supports the feasibility and safety of hESC-RPE patch transplantation as a regenerative strategy for AMD

Species concepts for conservation - reply to Russello and Amato

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Implications of different species concepts for conserving biodiversity

The ~26 definitions of species often yield different numbers of species and disparate groupings, with financial, legal, biological and conservation implications. Using conservation genetic considerations, we demonstrate that different species concepts have a critical bearing on our ability to conserve species. Many species of animals and plants persist as small isolated populations suffering inbreeding depression, loss of genetic diversity, and elevated extinction risks. Such small populations usually can be rescued by restoring gene flow, but substantial genetic drift effects can lead them to be classified as distinct species under the diagnostic phylogenetic species concept. Minimum harm to fitness is done and maximum potential fitness and evolutionary potential benefits accrue when reproductive isolation (pre- and/or post-zygotic) is used as the criterion to define distinct species. For sympatric populations, distinct species are diagnosed by very limited gene flow. For allopatric populations, both minimal gene flow and evidence of reduced reproductive fitness in crosses (or effects predicted from adaptive differentiation among populations and/or fixed chromosomal differences) are required to satisfy conservation issues. Species delineations based upon the biological and differential fitness species concepts meet the above requirements. Conversely, if species are delineated using the diagnostic phylogenetic species concept, genetic rescue of small genetically isolated populations may require crosses between species, with consequent legal and regulatory ramifications that could preclude actions to prevent extinction. Consequently, we conclude that the diagnostic phylogenetic species concept is unsuitable for use in conservation contexts, especially for classifying allopatric populations.7 page(s

Chloroform extract of hog barn dust modulates skeletal muscle ryanodine receptor calcium-release channel (RyR1)

Skeletal muscle weakness is a reported ailment in individuals working in commercial hog confinement facilities. To date, specific mechanisms responsible for this symptom remain undefined. The purpose of this study was to assess whether hog barn dust (HBD) contains components that are capable of binding to and modulating the activity of type 1 ryanodine receptor Ca2+-release channel (RyR1), a key regulator of skeletal muscle function. HBD collected from confinement facilities in Nebraska were extracted with chloroform, filtered, and rotary evaporated to dryness. Residues were resuspended in hexane-chloroform (20:1) and precipitates, referred to as HBDorg, were air-dried and studied further. In competition assays, HBDorg dose-dependently displaced [3H]ryanodine from binding sites on RyR1 with an IC50 of 1.5 ± 0.1 μg/ml (Ki = 0.4 ± 0.0 μg/ml). In single-channel assays using RyR1 reconstituted into a lipid bilayer, HBDorg exhibited three distinct dose-dependent effects: first it increased the open probability of RyR1 by increasing its gating frequency and dwell time in the open state, then it induced a state of reduced conductance (55% of maximum) that was more likely to occur and persist at positive holding potentials, and finally it irreversibly closed RyR1. In differentiated C2C12 myotubes, addition of HBD triggered a rise in intracellular Ca2+ that was blocked by pretreatment with ryanodine. Since persistent activation and/or closure of RyR1 results in skeletal muscle weakness, these new data suggest that HBD is responsible, at least in part, for the muscle ailment reported by hog confinement workers