Influence of cardiac autonomic neuropathy on cardiac repolarisation during incremental adrenaline infusion in type 1 diabetes

Aims/hypothesis We examined the effect of a standardised sympathetic stimulus, incremental adrenaline (epinephrine) infusion on cardiac repolarisation in individuals with type 1 diabetes with normal autonomic function, subclinical autonomic neuropathy and established autonomic neuropathy. Methods Ten individuals with normal autonomic function and baroreceptor sensitivity tests (NAF), seven with subclinical autonomic neuropathy (SAN; normal standard autonomic function tests and abnormal baroreceptor sensitivity tests); and five with established cardiac autonomic neuropathy (CAN; abnormal standard autonomic function and baroreceptor tests) underwent an incremental adrenaline infusion. Saline (0.9% NaCl) was infused for the first hour followed by 0.01 μg kg−1 min−1 and 0.03 μg kg−1 min−1 adrenaline for the second and third hours, respectively, and 0.06 μg kg−1 min−1 for the final 30 min. High resolution ECG monitoring for QTc duration, ventricular repolarisation parameters (T wave amplitude, T wave area symmetry ratio) and blood sampling for potassium and catecholamines was performed every 30 min. Results Baseline heart rate was 68 (95% CI 60, 76) bpm for the NAF group, 73 (59, 87) bpm for the SAN group and 84 (78, 91) bpm for the CAN group. During adrenaline infusion the heart rate increased differently across the groups (p = 0.01). The maximum increase from baseline (95% CI) in the CAN group was 22 (13, 32) bpm compared with 11 (7, 15) bpm in the NAF and 10 (3, 18) bpm in the SAN groups. Baseline QTc was 382 (95% CI 374, 390) ms in the NAF, 378 (363, 393) ms in the SAN and 392 (367, 417) ms in the CAN groups (p = 0.31). QTc in all groups lengthened comparably with adrenaline infusion. The longest QTc was 444 (422, 463) ms (NAF), 422 (402, 437) ms (SAN) and 470 (402, 519) ms (CAN) (p = 0.09). T wave amplitude and T wave symmetry ratio decreased and the maximum decrease occurred earlier, at lower infused adrenaline concentrations in the CAN group compared with NAF and SAN groups. AUC for the symmetry ratio was different across the groups and was lowest in the CAN group (p = 0.04). Plasma adrenaline rose and potassium fell comparably in all groups. Conclusions/interpretation Participants with CAN showed abnormal repolarisation in some measures at lower adrenaline concentrations. This may be due to denervation adrenergic hypersensitivity. Such individuals may be at greater risk of cardiac arrhythmias in response to physiological sympathoadrenal challenges such as stress or hypoglycaemia

Ab initio molecular dynamics simulations of Aluminum solvation

The solvation of Al and its hydrolyzed species in water clusters has been studied by means of ab initio molecular dynamics simulations. The hexa-hydrate aluminum ion formed a stable complex in the finite temperature cluster simulation of one aluminum ion and 16 waters. The average dipole moment of strongly polarized hydrated water molecules in the first solvation shell of the hexa-hydrate aluminum ion was found to be 5.02 Debye. The deprotonated hexa-hydrate complex evolves into a tetra-coordinated aluminate ion with two water molecules in the second solvation shell forming hydrogen bonds to the hydroxyl groups in agreement with the observed coordination.Comment: 12 pages in Elsevier LaTeX, 5 figures in Postscript, 2 last figures are in color, submitted to Chemical Physics Letter

Nucleon-nucleon momentum correlation function for light nuclei

Nucleon-nucleon momentum correlation function have been presented for nuclear reactions with neutron-rich or proton-rich projectiles using a nuclear transport theory, namely Isospin-Dependent Quantum Molecular Dynamics model. The relationship between the binding energy of projectiles and the strength of proton-neutron correlation function at small relative momentum has been explored, while proton-proton correlation function shows its sensitivity to the proton density distribution. Those results show that nucleon-nucleon correlation function is useful to reflect some features of the neutron- or proton-halo nuclei and therefore provide a potential tool for the studies of radioactive beam physics.Comment: Talk given at the 18th International IUPAP Conference on Few-Body Problems in Physics (FB18), Santos, Brasil, August 21-26, 2006. To appear in Nucl. Phys.

Mid-to-Late Holocene environmental reconstruction on Pico Island (Azores, Portugal) based on multiproxy analysis of Lake Caveiro sediments

The Azores constitutes the most remote archipelago of the North Atlantic Ocean. Both human colonization and natural changes have significantly modified its ecosystems. To assess the impacts of natural and anthropogenic changes over the last 8200 yr, elemental geochemistry on bulk organic matter, diatoms, Cladocera and chironomid remains were analyzed in a 952-cm long sediment (3.7m depth) from Lake Caveiro. From 8200 to 650 cal yr BP, climatic and volcanic forcing seem to have been the main drivers of biological change. Between 8200 and 6000 cal yr BP, the sedimentary sequence was characterized by dominance of volcaniclastic deposits and high abundance of aerophilic diatoms and sparse Cladocera and chironomid remains. This interval has been interpreted as indicative of unstable conditions because of intermittent renewal of lake bottom substratum owing to repetitive tephra sedimentation. Between 6000 and 3500 cal yr BP, fossil assemblages were dominated by benthic species, with an increasing trend of the planktonic/benthic (P:B) ratio, suggesting stable substratum and rising lake levels. An increase in planktonic taxa and the presence of deep-water chironomid species was found between 3500 and 1300 cal yr BP, suggesting a highstand phase. Between 1300 and 650 cal yr BP, a decreasing trend of the P:B ratio was recorded, implying a further lake shallowing. Moreover, the appearance of flowing water species suggests a period characterized by climate instability. From 650 cal yr BP to the present, a significant increase in primary production and a decline in species richness likely reflect anthropogenic impacts, such as forest clearance and the introduction of exotic species. These results highlight the impact that human, volcanic and climatic drivers have had on the environmental evolution of the ecosystems of Pico Island.This research is funded by Spanish projects PaleoNAO (CGL2010-15767), RapidNAO (CGL2013-40608-R) and PaleoModes (CGL2016-75281-C2).Peer Reviewe

Relativistic K shell decay rates and fluorescence yields for Zn, Cd and Hg

In this work we use the multiconfiguration Dirac-Fock method to calculate the transition probabilities for all possible decay channels, radiative and radiationless, of a K shell vacancy in Zn, Cd and Hg atoms. The obtained transition probabilities are then used to calculate the corresponding fluorescence yields which are compared to existing theoretical, semi-empirical and experimental results

Chemical Proteomic Analysis of Serine Hydrolase Activity in Niemann-Pick Type C Mouse Brain

The endocannabinoid system (ECS) is considered to be an endogenous protective system in various neurodegenerative diseases. Niemann-Pick type C (NPC) is a neurodegenerative disease in which the role of the ECS has not been studied yet. Most of the endocannabinoid enzymes are serine hydrolases, which can be studied using activity-based protein profiling (ABPP). Here, we report the serine hydrolase activity in brain proteomes of a NPC mouse model as measured by ABPP. Two ABPP methods are used: a gel-based method and a chemical proteomics method. The activities of the following endocannabinoid enzymes were quantified: diacylglycerol lipase (DAGL) α, α/β-hydrolase domain-containing protein 4, α/β-hydrolase domain-containing protein 6, α/β-hydrolase domain-containing protein 12, fatty acid amide hydrolase, and monoacylglycerol lipase. Using the gel-based method, two bands were observed for DAGL α. Only the upper band corresponding to this enzyme was significantly decreased in the NPC mouse model. Chemical proteomics showed that three lysosomal serine hydrolase activities (retinoid-inducible serine carboxypeptidase, cathepsin A, and palmitoyl-protein thioesterase 1) were increased in Niemann-Pick C1 protein knockout mouse brain compared to wild-type brain, whereas no difference in endocannabinoid hydrolase activity was observed. We conclude that these targets might be interesting therapeutic targets for future validation studies.Medical BiochemistryBio-organic SynthesisMolecular Physiolog

Machine Learning Framework to Identify Individuals at Risk of Rapid Progression of Coronary Atherosclerosis : From the PARADIGM Registry

Background Rapid coronary plaque progression (RPP) is associated with incident cardiovascular events. To date, no method exists for the identification of individuals at risk of RPP at a single point in time. This study integrated coronary computed tomography angiography-determined qualitative and quantitative plaque features within a machine learning (ML) framework to determine its performance for predicting RPP. Methods and Results Qualitative and quantitative coronary computed tomography angiography plaque characterization was performed in 1083 patients who underwent serial coronary computed tomography angiography from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry. RPP was defined as an annual progression of percentage atheroma volume 651.0%. We employed the following ML models: model 1, clinical variables; model 2, model 1 plus qualitative plaque features; model 3, model 2 plus quantitative plaque features. ML models were compared with the atherosclerotic cardiovascular disease risk score, Duke coronary artery disease score, and a logistic regression statistical model. 224 patients (21%) were identified as RPP. Feature selection in ML identifies that quantitative computed tomography variables were higher-ranking features, followed by qualitative computed tomography variables and clinical/laboratory variables. ML model 3 exhibited the highest discriminatory performance to identify individuals who would experience RPP when compared with atherosclerotic cardiovascular disease risk score, the other ML models, and the statistical model (area under the receiver operating characteristic curve in ML model 3, 0.83 [95% CI 0.78-0.89], versus atherosclerotic cardiovascular disease risk score, 0.60 [0.52-0.67]; Duke coronary artery disease score, 0.74 [0.68-0.79]; ML model 1, 0.62 [0.55-0.69]; ML model 2, 0.73 [0.67-0.80]; all P<0.001; statistical model, 0.81 [0.75-0.87], P=0.128). Conclusions Based on a ML framework, quantitative atherosclerosis characterization has been shown to be the most important feature when compared with clinical, laboratory, and qualitative measures in identifying patients at risk of RPP