Autonomic Innervation and Segmental Muscular Disconnections at the Human Pulmonary Vein-Atrial Junction Implications for Catheter Ablation of Atrial-Pulmonary Vein Junction

ObjectivesThis study sought to examine the muscle connections and autonomic nerve distributions at the human pulmonary vein (PV)-left atrium (LA) junction.BackgroundOne approach to catheter ablation of atrial fibrillation (AF) is to isolate PV muscle sleeves from the LA. Elimination of vagal response further improves success rates.MethodsWe performed immunohistochemical staining on 192 circumferential venoatrial segments (32 veins) harvested from 8 autopsied human hearts using antibodies to tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT).ResultsMuscular discontinuities of widths 0.1 to 5.5 mm (1.1 ± 1.0 mm) and abrupt 90° changes in fiber orientation were found in 70 of 192 (36%) and 36 of 192 (19%) of PV-LA junctions, respectively. Although these anisotropic features were more common in the anterosuperior junction (p < 0.01), they were also present around the entire PV-LA junction. Autonomic nerve density was highest in the anterosuperior segments of both superior veins (p < 0.05 versus posteroinferior) and inferior segments of both inferior veins (p < 0.05 vs. superior), highest in the LA within 5 mm of the PV-LA junction (p < 0.01), and higher in the epicardium than endocardium (p < 0.01). Adrenergic and cholinergic nerves were highly co-located at tissue and cellular levels. A significant proportion (30%) of ganglion cells expressed dual adrenocholinergic phenotypes.ConclusionsMuscular discontinuities and abrupt fiber orientation changes are present in >50% of PV-LA segments, creating significant substrates for re-entry. Adrenergic and cholinergic nerves have highest densities within 5 mm of the PV-LA junction, but are highly co-located, indicating that it is impossible to selectively target either vagal or sympathetic nerves during ablation procedures

Da doença ao milagre: etnografia de soluções terapêuticas entre evangélicos na cidade de Boa Vista, Roraima

São várias as possibilidades de articulação entre doença, religião e cura. O artigo em questão constitui uma análise de narrativas sobre doença e cura pela religião, realizada a partir de abordagem etnográfica em 10 bairros de Boa Vista, Roraima, com indivíduos que afirmaram terem sido curados através de intervenção divina. Os resultados mostram que a doença não se reduz aos sintomas físicos universais da realidade empírica. Rituais mágicos de cura são, também, caminhos abertos à sua interpretação

Fluorescence-suppressed time-resolved Raman spectroscopy of pharmaceuticals using complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) detector

In this work, we utilize a short-wavelength, 532-nm picosecond pulsed laser coupled with a time-gated complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) detector to acquire Raman spectra of several drugs of interest. With this approach, we are able to reveal previously unseen Raman features and suppress the fluorescence background of these drugs. Compared to traditional Raman setups, the present time-resolved technique has two major improvements. First, it is possible to overcome the strong fluorescence background that usually interferes with the much weaker Raman spectra. Second, using the high photon energy excitation light source, we are able to generate a stronger Raman signal compared to traditional instruments. In addition, observations in the time domain can be performed, thus enabling new capabilities in the field of Raman and fluorescence spectroscopy. With this system, we demonstrate for the first time the possibility of recording fluorescence-suppressed Raman spectra of solid, amorphous and crystalline, and non-photoluminescent and photoluminescent drugs such as caffeine, ranitidine hydrochloride, and indomethacin (amorphous and crystalline forms). The raw data acquired by utilizing only the picosecond pulsed laser and a CMOS SPAD detector could be used for identifying the compounds directly without any data processing. Moreover, to validate the accuracy of this time-resolved technique, we present density functional theory (DFT) calculations for a widely used gastric acid inhibitor, ranitidine hydrochloride. The obtained time-resolved Raman peaks were identified based on the calculations and existing literature. Raman spectra using non-time-resolved setups with continuous-wave 785- and 532-nm excitation lasers were used as reference data. Overall, this demonstration of time-resolved Raman and fluorescence measurements with a CMOS SPAD detector shows promise in diverse areas, including fundamental chemical research, the pharmaceutical setting, process analytical technology (PAT), and the life sciences.Peer reviewe

The ICON Earth System Model Version 1.0

This work documents ICON-ESM 1.0, the first version of a coupled model based 19 on the ICON framework 20 • Performance of ICON-ESM is assessed by means of CMIP6 DECK experiments 21 at standard CMIP-type resolution 22 • ICON-ESM reproduces the observed temperature evolution. Biases in clouds, winds, 23 sea-ice, and ocean properties are larger than in MPI-ESM. Abstract 25 This work documents the ICON-Earth System Model (ICON-ESM V1.0), the first cou-26 pled model based on the ICON (ICOsahedral Non-hydrostatic) framework with its un-27 structured, icosahedral grid concept. The ICON-A atmosphere uses a nonhydrostatic dy-28 namical core and the ocean model ICON-O builds on the same ICON infrastructure, but 29 applies the Boussinesq and hydrostatic approximation and includes a sea-ice model. The 30 ICON-Land module provides a new framework for the modelling of land processes and 31 the terrestrial carbon cycle. The oceanic carbon cycle and biogeochemistry are repre-32 sented by the Hamburg Ocean Carbon Cycle module. We describe the tuning and spin-33 up of a base-line version at a resolution typical for models participating in the Coupled 34 Model Intercomparison Project (CMIP). The performance of ICON-ESM is assessed by 35 means of a set of standard CMIP6 simulations. Achievements are well-balanced top-of-36 atmosphere radiation, stable key climate quantities in the control simulation, and a good 37 representation of the historical surface temperature evolution. The model has overall bi-38 ases, which are comparable to those of other CMIP models, but ICON-ESM performs 39 less well than its predecessor, the Max Planck Institute Earth System Model. Problem-40 atic biases are diagnosed in ICON-ESM in the vertical cloud distribution and the mean 41 zonal wind field. In the ocean, sub-surface temperature and salinity biases are of con-42 cern as is a too strong seasonal cycle of the sea-ice cover in both hemispheres. ICON-43 ESM V1.0 serves as a basis for further developments that will take advantage of ICON-44 specific properties such as spatially varying resolution, and configurations at very high 45 resolution. 46 Plain Language Summary 47 ICON-ESM is a completely new coupled climate and earth system model that ap-48 plies novel design principles and numerical techniques. The atmosphere model applies 49 a non-hydrostatic dynamical core, both atmosphere and ocean models apply unstruc-50 tured meshes, and the model is adapted for high-performance computing systems. This 51 article describes how the component models for atmosphere, land, and ocean are cou-52 pled together and how we achieve a stable climate by setting certain tuning parameters 53 and performing sensitivity experiments. We evaluate the performance of our new model 54 by running a set of experiments under pre-industrial and historical climate conditions 55 as well as a set of idealized greenhouse-gas-increase experiments. These experiments were 56 designed by the Coupled Model Intercomparison Project (CMIP) and allow us to com-57 pare the results to those from other CMIP models and the predecessor of our model, the 58 Max Planck Institute for Meteorology Earth System Model. While we diagnose overall 59 satisfactory performance, we find that ICON-ESM features somewhat larger biases in 60 several quantities compared to its predecessor at comparable grid resolution. We empha-61 size that the present configuration serves as a basis from where future development steps 62 will open up new perspectives in earth system modellin

Radiation-induced cell transformation: transformation efficiencies of different types of ionizing radiation and molecular changes in radiation transformants and tumor cell lines

This study aims to compare the efficiencies of 5.4 keV soft X-rays, alpha-particles, and gamma-rays in transforming C3H 10T1/2 cells and to assess the sequence of cellular and molecular changes during the process of radiation-induced transformation of Syrian hamster embryo (SHE) cells. The somewhat more densely ionizing soft X-rays are more effective than gamma-rays both for cell inactivation and cell transformation. The relative biological effectiveness (RBE) appears to be independent of dose; it is approximately 1.3 for either end point. The RBE of alpha-particles versus gamma-rays, on the other hand, increases with decreasing dose; the dose dependence is somewhat more apparent for cell transformation than for cell inactivation. SHE cells transformed by different types of ionizing radiation and related tumor cell lines isolated from nude mice tumors were found to have a distinct growth advantage compared to primary SHE cells, documented by higher plating efficiencies, shorter doubling times, and higher cloning efficiencies in semisolid medium. Most transformed and tumor cell lines that were investigated have elevated mRNA levels for the H-ras gene, some of them show restriction fragment length polymorphisms of the H-ras gene, and some exhibit a substantially amplified c-myc gene. In a sequence analysis of the Syrian hamster H-ras gene of eight tumor cell lines from radiation transformants, we have not found any mutation in codons 12, 13, 59, 61, nor in the flanking regions of these codons. The transformed and tumor cell lines tend to have lower chromosome numbers than primary SHE cells

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