Genetic Polymorphisms as Risk Stratification Tool in Primary Preventive ICD Therapy

More and more implantable cardioverter-defibrillators (ICDs) are implanted as primary prevention of sudden cardiac death (SCD). However, major problem in practice is to identify high-risk patients for SCD. Different methods for noninvasive risk stratification do not have a sufficient positive or negative predictive value. Since current approaches lead to implantation of ICDs in a large number of patients who will never suffer an arrhythmic event and simultaneously patients still die of SCD who currently did not seem eligible for primary preventive ICD implantation, there is a need for additional tools for risk stratification. Epidemiological studies point to a hereditary risk of SCD. Different susceptibility of each person concerning arrhythmogenic events might be explained by genetic polymorphisms. By obtaining an individual “pattern” of polymorphisms of genes encoding for proteins which are important in arrhythmogenesis in one patient, risk stratification in primary prevention of SCD might by improved

Narrow complex tachycardia with alternating R-R intervals during physical stress: Double ventricular excitation

A 44 year old man presented with recurrent symptomatic palpitations, always appearing during physical stress each with a similiar extent and never during resting periods. He also had fatigue and moderate dyspnoea during the episodes. The past medical history of the patient did not reveal any significant diseases. Findings of the attending physician including 12 lead ECG and echocardiography did not show any abnormality. As there was no electrocardiographic documentation of the episode, a 12-lead Holter evaluation was done

Unusual suppression of the superconducting energy gap and critical temperature in atomically thin NbSe2

It is well known that superconductivity in thin films is generally suppressed with decreasing thickness. This suppression is normally governed by either disorder-induced localization of Cooper pairs, weakening of Coulomb screening, or generation and unbinding of vortex-antivortex pairs as described by the Berezinskii-Kosterlitz-Thouless (BKT) theory. Defying general expectations, few-layer NbSe2 - an archetypal example of ultrathin superconductors - has been found to remain superconducting down to monolayer thickness. Here we report measurements of both the superconducting energy gap and critical temperature in high-quality monocrystals of few-layer NbSe2, using planar-junction tunneling spectroscopy and lateral transport. We observe a fully developed gap that rapidly reduces for devices with the number of layers N < 5, as does their ctitical temperature. We show that the observed reduction cannot be explained by disorder, and the BKT mechanism is also excluded by measuring its transition temperature that for all N remains very close to Tc. We attribute the observed behavior to changes in the electronic band structure predicted for mono- and bi- layer NbSe2 combined with inevitable suppression of the Cooper pair density at the superconductor-vacuum interface. Our experimental results for N > 2 are in good agreement with the dependences of the gap and Tc expected in the latter case while the effect of band-structure reconstruction is evidenced by a stronger suppression of the gap and the disappearance of its anisotropy for N = 2. The spatial scale involved in the surface suppression of the density of states is only a few angstroms but cannot be ignored for atomically thin superconductors.Comment: 21 pages, including supporting informatio

Early Postnatal Migration and Development of Layer II Pyramidal Neurons in the Rodent Cingulate/Retrosplenial Cortex

The cingulate and retrosplenial regions are major components of the dorsomedial (dm) limbic cortex and have been implicated in a range of cognitive functions such as emotion, attention, and spatial memory. While the structure and connectivity of these cortices are well characterized, little is known about their development. Notably, the timing and mode of migration that govern the appropriate positioning of late-born neurons remain unknown. Here, we analyzed migratory events during the early postnatal period from ventricular/subventricular zone (VZ/SVZ) to the cerebral cortex by transducing neuronal precursors in the VZ/SVZ of newborn rats/mice with Tomato/green fluorescent protein-encoding lentivectors. We have identified a pool of postmitotic pyramidal precursors in the dm part of the neonatal VZ/SVZ that migrate into the medial limbic cortex during the first postnatal week. Time-lapse imaging demonstrates that these cells migrate on radial glial fibers by locomotion and display morphological and behavioral changes as they travel through the white matter and enter into the cortical gray matter. In the granular retrosplenial cortex, these cells give rise to a Satb2+ pyramidal subtype and develop dendritic bundles in layer I. Our observations provide the first insight into the patterns and dynamics of cell migration into the medial limbic corte

The New Plastic Flow Machining Process for Producing Thin Sheets

A new severe plastic deformation (SPD) process called plastic flow machining (PFM) was recently proposed to produce thin sheets with gradient structures. In the present paper, the role of the die geometry is investigated by studying the effects of the produced sheet thickness (h) on the material properties of commercial pure Aluminum (Al1050) processed by PFM. The obtained experimental results show that an increase of h in the range of 0.65 to 1.5 mm improved the formation efficiency of the sheet. Microstructures of the produced sheets show gradient structures with an average grain size varying from 0.8 to 3.81 µm across the sheet thickness. Both experiments and finite element (FE) simulations document that the degree of the gradient in the microstructure became more significant when h was increased. Sheets produced by PFM exhibited a better strength-ductility balance than sheets obtained in other SPD processes. Tensile strength of 160–175 MPa and total ductility of 18–25% were obtained for the processed samples after PFM. A rise of h from 0.65 to 1.5 mm lowered the strength but enhanced the ductility of the produced sheet, which is due to the coarser microstructure at larger values of h

Risk for life-threatening arrhythmia in newly diagnosed peripartum cardiomyopathy with low ejection fraction: a German multi-centre analysis

Introduction Peripartum cardiomyopathy (PPCM) is a rare cardiomyopathy characterized by an acute reduction in left ventricular ejection fraction (LVEF). Sudden deaths during the course of PPCM are reported to be elevated, the underlying mechanisms remains unknown. The aim of the present multi-centre study was to evaluate the arrhythmia burden in a multi-centre approach in patients with PPCM using a wearable cardioverter/defibrillator (WCD). Methods and results Forty-nine patients from 16 German centres with newly diagnosed PPCM and LVEF <= 35% receiving a WCD were included in this retrospective analysis. Mean follow-up was 15 +/- 10 months. At diagnosis, mean age was 33 +/- 5 years, parity was 2.1 +/- 1.6, LVEF was 21 +/- 7%, NYHA functional class was 3.4 +/- 0.7. Mean wear time was 120 +/- 106 days, mean wear time per day was 21.4 +/- 3.3 h. Six (12%) patients presented eight ventricular tachyarrhythmias during WCD period: five episodes of VF, two sustained ventricular tachycardia (VT) and one non-sustained VT occurred. Conclusion This multicentre study underpins the elevated risk for ventricular tachyarrhythmias in patients with newly diagnosed PPCM and reduced LVEF. A WCD should be considered for 3-6 months in these patients to prevent sudden cardiac death from ventricular tachyarrhythmias

Distinct EH domains of the endocytic TPLATE complex confer lipid and protein binding

Clathrin-mediated endocytosis (CME) is the gatekeeper of the plasma membrane. In contrast to animals and yeasts, CME in plants depends on the TPLATE complex (TPC), an evolutionary ancient adaptor complex. However, the mechanistic contribution of the individual TPC subunits to plant CME remains elusive. In this study, we used a multidisciplinary approach to elucidate the structural and functional roles of the evolutionary conserved N-terminal Eps15 homology (EH) domains of the TPC subunit AtEH1/Pan1. By integrating high-resolution structural information obtained by X-ray crystallography and NMR spectroscopy with all-atom molecular dynamics simulations, we provide structural insight into the function of both EH domains. Both domains bind phosphatidic acid with a different strength, and only the second domain binds phosphatidylinositol 4,5-bisphosphate. Unbiased peptidome profiling by mass-spectrometry revealed that the first EH domain preferentially interacts with the double N-terminal NPF motif of a previously unidentified TPC interactor, the integral membrane protein Secretory Carrier Membrane Protein 5 (SCAMP5). Furthermore, we show that AtEH/Pan1 proteins control the internalization of SCAMP5 via this double NPF peptide interaction motif. Collectively, our structural and functional studies reveal distinct but complementary roles of the EH domains of AtEH/Pan1 in plant CME and connect the internalization of SCAMP5 to the TPLATE complex. AtEH/Pan1 proteins contain two N-terminal Eps15 homology (EH) domains and are subunits of the endocytic TPLATE complex present in plants. Here, the authors combine X-ray crystallography, NMR and MD simulations with biochemical and in planta analysis to characterize the two AtEH1/Pan1 EH domains and reveal their structural differences and complementary functional roles

Idiopathic Palmar Fasciitis with Polyarthritis Syndrome

A 31-yr-old Korean woman was presented with 4-month history of bilateral hand swelling and stiffness. On clinical examination, she had a painful synovitis of both hands, wrists, knees and ankles. The radiologic and histological examinations confirmed it with palmar fasciitis and polyarthritis syndrome (PFPAS). PFPAS is an uncommon disorder characterized by progressive flexion contractures of both hands, inflammatory fasciitiis, fibrosis, and a generalized inflammatory arthritis. Although most reported cases of PFPAS have been associated with various malignancies, our patient have not been associated with malignancy during 24 months follow up period from her first symptom onset. Her symptoms were improved with moderate dose of corticosteroid and she is currently taking prednisone 5 mg daily without any evidence for internal malignancy. We present here in a young Korean patient with idiopathic PFPAS who was successfully treated with administration of corticosteroid

Validation of plasma biomarker candidates for the prediction of eGFR decline in patients with type 2 diabetes

Objective: The decline of estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes is variable and early interventions would likely be cost effective. We elucidated the contribution of 17 plasma biomarkers to the prediction of eGFR loss on top of clinical risk factors. Research Design and Methods: We studied participants in PROVALID, a prospective multinational cohort study of patients with type 2 diabetes and a follow up of more than 24 months (n = 2560; baseline median eGFR 84 mL/min/1.73m2, UACR 8.1 mg/g). The 17 biomarkers were measured at baseline in 481 samples using Luminex technology and ELISA. The prediction of eGFR decline was evaluated by linear mixed modeling. Results: In univariable analyses nine of the 17 markers showed significant differences in median concentration between the two groups. A linear mixed model for eGFR obtained by variable selection exhibited an adjusted R2 of 62%. A panel of twelve biomarkers was selected by the procedure and accounted for 34% of the total explained variability, of which 32% were due to five markers. Each biomarker’s individual contribution to the prediction of eGFR decline on top of clinical predictors was generally low. When included into the model, baseline eGFR exhibited the largest explained variability of eGFR decline (R2 of 79%) and the contribution of each biomarker dropped below 1%. Conclusions: In this longitudinal study of patients with type 2 diabetes and maintained eGFR at baseline, 12 of the 17 candidate biomarkers were associated with eGFR decline, but their predictive power was low

Homogeneous analysis of globular clusters from the APOGEE survey with the BACCHUS code - III. omega Cen

We study the multiple populations of omega Cen by using the abundances of Fe, C, N, O, Mg, Al, Si, K, Ca, and Ce from the high-resolution, high signal-to-noise (S/N > 70) spectra of 982 red giant stars observed by the SDSS-IV/APOGEE-2 survey. We find that the shape of the Al-Mg and N-C anticorrelations changes as a function of metallicity, continuous for the metal-poor groups, but bimodal (or unimodal) at high metallicities. There are four Fe populations, similarly to previous literature findings, but we find seven populations based on Fe, Al, and Mg abundances. The evolution of Al in omega Cen is compared to its evolution in the Milky Way and in five representative globular clusters. We find that the distribution of Al in metal-rich stars of omega Cen closely follows what is observed in the Galaxy. Other alpha-elements and C, N, O, and Ce are also compared to the Milky Way, and significantly elevated abundances are observed over what is found in the thick disc for almost all elements. However, we also find some stars with high metallicity and low [Al/Fe], suggesting that omega Cen could be the remnant core of a dwarf galaxy, but the existence of these peculiar stars needs an independent confirmation. We also confirm the increase in the sum of CNO as a function of metallicity previously reported in the literature and find that the [C/N] ratio appears to show opposite correlations between Al-poor and Al-rich stars as a function of metallicity