An uncommon case of inferior vena cava injury during atrial fibrillation ablation

A 64-year-old man underwent catheter ablation (CA) of atrial fibrillation with intracardiac echocardiography (ICE) assistance. As the probe was advanced toward the right atrium, sudden abdominal pain was felt by the patient with hypotension and tachycardia requiring fluids and vasopressors for hemodynamic stabilization. The inferior vena cava (IVC) was injured by the passing probe and open repair was then performed. To our knowledge, this is the first reported case of symptomatic IVC laceration by the probe used for ICE during CA

Cyclic dinucleotides bind the C-linker of HCN4 to control channel cAMP responsiveness

cAMP mediates autonomic regulation of heart rate by means of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which underlie the pacemaker current If. cAMP binding to the C-terminal cyclic nucleotide binding domain enhances HCN open probability through a conformational change that reaches the pore via the C-linker. Using structural and functional analysis, we identified a binding pocket in the C-linker of HCN4. Cyclic dinucleotides, an emerging class of second messengers in mammals, bind the C-linker pocket (CLP) and antagonize cAMP regulation of the channel. Accordingly, cyclic dinucleotides prevent cAMP regulation of If in sinoatrial node myocytes, reducing heart rate by 30%. Occupancy of the CLP hence constitutes an efficient mechanism to hinder β-adrenergic stimulation on If. Our results highlight the regulative role of the C-linker and identify a potential drug target in HCN4. Furthermore, these data extend the signaling scope of cyclic dinucleotides in mammals beyond their first reported role in innate immune system

Molecular Mechanisms Generating and Stabilizing Terminal 22q13 Deletions in 44 Subjects with Phelan/McDermid Syndrome

In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17–74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS

Soil degradation by land use change in an agropastoral area in Sardinia (Italy)

In recent decades the clearing of Mediterranean maquis along with the creation of new pastures has been a major factor of land degradation in Sardinia (Italy). This was due to an inadequate implementation of agricultural policies. Consequently, tillage and water erosion intensified over a wide area. The present work assesses the impacts of land use change on soil properties in a representative area of central-eastern Sardinia. Paired forest and pasture sampling sites were selected in relation to present land use, land suitability, and land use history. Different soil properties were considered: physical (sand, silt, clay, soil thickness, bulk density, and penetration resistance), chemical (pH, OC, N, C/N, Ca, Mg, Na, K, CEC, and BS), biological (BQI), and micromorphological (microporosity and microstructure). The comparison of forest and pasture soils showed a significant soil loss (in terms of soil thickness, −22%), and a clear decrease in organic carbon storage (−64% on average). An increase in bulk density (+ 44%) and a change in microporosity and its vertical distribution were also observed, respectively by field measurements and micromorphological quantification on digital images

Effects of land use and landscape on spatial distribution and morphological features of gullies in an agropastoral area in Sardinia (Italy)

According to the United Nations Convention to Combat Desertification (UNCCD), soil erosion is one of the main causes of desertification in the Northern Mediterranean. Recently, the role of channelled erosion in sediment delivery has been underlined by several studies. The aim of this paper is to describe a simplified experimental methodology settled up for studying the relationships between gully erosion and land use. The experimental site, which is wide about 720 ha, is located in a hilly area threatened by desertification in Central Eastern Sardinia (Italy). This area is characterised by irregular morphology with steep slopes, where agropastoral activities, particularly tillage with heavy machinery and overgrazing, are causing severe soil erosion and compromising agricultural productivity. Previous studies carried out in the same area highlighted the need to quantify and monitor soil erosion in order to outline management guidelines for farmers. In this study, an integrated methodology that uses aerial photographs and field surveys was applied to inventory the gullies of the area. The degree of activity and morphological characteristics of gullies were assessed in the field by measuring the position and shape of gully heads, and their width and depth. Total gully volume was also estimated. Relationships among distribution, density and morphological characteristics of gullies, and geomorphological features, land use and land use historical dynamics of the area have been studied. The results show the very significant impact of agricultural activities on gully activity and density

Modelling spatial uncertainty of soil erodibility factor using joint stochastic simulation

Soil erosion varies greatly over space and is commonly estimated using the revised universal soil loss equation (RUSLE). Neglecting information about estimation uncertainty, however, may lead to improper decision-making. One geostatistical approach to spatial analysis is joint stochastic simulation, which draws alternative, equally probable, joint realizations of a regionalized variable. Differences between the realizations provide a measure of spatial uncertainty and allow us to carry out an error propagation analysis. The objective of this paper was to assess spatial uncertainty of a soil erodibility factor (K) model resulting from the uncertainties in the input parameters (texture and organic matter). The 500 km2 study area was located in central-eastern Sardinia (Italy) and 152 samples were collected. A Monte Carlo analysis was performed where spatial cross-correlation information through joint turning bands simulation was incorporated. A linear coregionalization model was fitted to all direct and cross-variograms of the input variables, which included three different structures: a nugget effect, a spherical structure with a shorter range (3500 m) and a spherical structure with a longer range (10 000 m). The K factor was then estimated for each set of the 500 joint realizations of the input variables, and the ensemble of the model outputs was used to infer the soil erodibility probability distribution function. This approach permitted delineation of the areas characterized by greater uncertainty, to improve supplementary sampling strategies and K value predictions

Combining inkjet printing and chemical vapor deposition for fabricating low voltage, organic field-effect transistors on flexible substrates

A highly reliable fabrication process of low voltage organic field-effect transistors on plastic substrates by means of large area techniques is here reported. The proposed approach is based on the combination of two large-area techniques, inkjet printing and chemical vapor deposition for the fabrication of a thin dielectric layer. A printing process has been employed also for the fabrication of source and drain electrodes and for the organic active layer. The thorough optimization of the fabrication process allows obtaining transistors operated at voltages below 5 V. A morphological characterization is provided in order to demonstrate the effectiveness of the fabrication process and to quantify the impact of the device optimization in its final feasibility. Moreover, an analysis of a statistically relevant set of devices is reported to demonstrate the reproducibility of device performances. Bias and mechanical stress tests are provided to demonstrate the stability of the device performances during continuous polarization and for significant mechanical deformations of the substrate