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Abstract Aims This study aimed to evaluate the impact of coronavirus disease 2019 (Covid‐19) outbreak on admissions for acute myocardial infarction (AMI) and related mortality, severity of presentation, major cardiac complications and outcome in a tertiary‐care university hospital in Berlin, Germany. Methods and results In a single‐centre cross‐sectional observational study, we included 355 patients with AMI containing ST‐elevation or non‐ST‐elevation myocardial infarction (STEMI or NSTEMI), admitted for emergency cardiac catheterization between January and April 2020 and the equivalent time in 2019. During the early phase of the Covid‐19 pandemic (e‐COV) in Berlin (March and April 2020), admissions for AMI halved compared with those in the pre‐Covid‐19 time (January and February 2020; pre‐COV) and with those in the corresponding months in 2019. However, mortality for AMI increased substantially from 5.2% pre‐COV to 17.7% (P 72 h +21% in STEMI, p = 0.04 and presentation > 72 h in NSTEMI +22%, p = 0.02). Door to balloon time was similar in STEMI patients, while time from first medical contact to revascularization was significantly delayed in NSTEMI patients (p = 0.02). Major cardiac complications after AMI occurred significantly more often, and cardiac recovery was worse in e‐COV than in pre‐COV, demonstrated by a significantly lower LVEF (39 ± 16 vs. 46 ± 16, p

Abstract Aims Heart failure with preserved ejection fraction (HFpEF) is associated with reduced exercise capacity elicited by skeletal muscle (SM) alterations. Up to now, no clear medical treatment advice for HFpEF is available. Identification of the ideal animal model mimicking the human condition is a critical step in developing and testing treatment strategies. Several HFpEF animals have been described, but the most suitable in terms of comparability with SM alterations in HFpEF patients is unclear. The aim of the present study was to investigate molecular changes in SM of three different animal models and to compare them with alterations of muscle biopsies obtained from human HFpEF patients. Methods and results Skeletal muscle tissue was obtained from HFpEF and control patients and from three different animal models including the respective controls—ZSF1 rat, Dahl salt‐sensitive rat, and transverse aortic constriction surgery/deoxycorticosterone mouse. The development of HFpEF was verified by echocardiography. Protein expression and enzyme activity of selected markers were assessed in SM tissue homogenates. Protein expression between SM tissue obtained from HFpEF patients and the ZSF1 rats revealed similarities for protein markers involved in muscle atrophy (MuRF1 expression, protein ubiquitinylation, and LC3) and mitochondrial metabolism (succinate dehydrogenase and malate dehydrogenase activity, porin expression). The other two animal models exhibited far less similarities to the human samples. Conclusions None of the three tested animal models mimics the condition in HFpEF patients completely, but among the animal models tested, the ZSF1 rat (ZSF1‐lean vs. ZSF1‐obese) shows the highest overlap to the human condition. Therefore, when studying therapeutic interventions to treat HFpEF and especially alterations in the SM, we suggest that the ZSF1 rat is a suitable model.

Abstract Aims Exercise intolerance is the leading manifestation of heart failure with preserved or mid‐range ejection fraction (HFpEF or HFmrEF), and left atrial (LA) function might contribute to modulating left ventricular filling and pulmonary venous pressures. We aim to assess the association between LA function and maximal exercise capacity in patients with HFpEF or HFmrEF. Methods and results Sixty‐five patients, prospectively enrolled in the German HFpEF Registry, were analysed. Inclusion criteria were New York Heart Association functional class ≥ II, left ventricular ejection fraction > 40%, structural heart disease or diastolic dysfunction, and elevated levels of N terminal pro brain natriuretic peptide (NT‐proBNP). LA function was evaluated through speckle‐tracking echocardiography by central reading in the Charité Academic Echocardiography core lab. All patients underwent maximal cardiopulmonary exercise test and were classified according to a peak VO2 cut‐off of prognostic value (14 mL/kg/min). NT‐pro‐BNP was measured. Twenty‐nine patients (45%) reached a peak VO2

Abstract Aims Atrial contractile dysfunction contributes to worse prognosis in hypertensive heart disease (HHD), but the role of cardiomyocyte dysfunction in atrial remodelling in HHD is not well understood. We investigated and compared cellular mechanisms of left (LA) and right atrial (RA) contractile dysfunction in pigs with HHD. Methods and results In vivo electrophysiological and magnetic resonance imaging studies were performed in control and pigs treated with 11‐deoxycorticosterone acetate (DOCA)/high‐salt/glucose diet (12 weeks) to induce HHD. HHD leads to significant atrial remodelling and loss of contractile function in LA and a similar trend in RA (magnetic resonance imaging). Atrial remodelling was associated with a higher inducibility of atrial fibrillation but unrelated to changes in atrial refractory period or fibrosis (histology). Reduced atrial function in DOCA pigs was related to reduced contraction amplitude of isolated LA (already at baseline) and RA myocytes (at higher frequencies) due to reduced intracellular Ca release (Fura 2‐AM, field stimulation). However, Ca regulation differed in LA and RA cardiomyocytes: LA cardiomyocytes showed reduced sarcoplasmic reticulum (SR) [Ca], whereas in RA, SR [Ca] was unchanged and SR Ca2+‐ATPase activity was increased. Sodium–calcium exchanger (NCX) activity was not significantly altered. We used ORM‐10103 (3 μM), a specific NCX inhibitor to improve Ca availability in LA and RA cardiomyocytes from DOCA pigs. Partial inhibition of NCX increased Ca2+ transient amplitude and SR Ca in LA, but not RA cells. Conclusions In this large animal model of HHD, atrial remodelling in sinus rhythm in vivo was related to differential LA and RA cardiomyocyte dysfunction and Ca signalling. Selective acute inhibition of NCX improved Ca release in diseased LA cardiomyocytes, suggesting a potential therapeutic approach to improve atrial inotropy in HHD.

Communication skills of dentists have been demonstrated to be part of the good dental practice. The aim we set ourselves in this study was to review the literature related to the methods of teaching communication skills at dental faculties, and develop a handout in the Bulgarian language about leading a successful conversation with a patient.According to some authors, the most important principles for effective communication training include the use of practical exercises, clinically relevant scenarios, students’ self-assessment tools, videotapes, participation of patient actors, and training in small groups. Another communication training program is the so-called Miller pyramid. Using the method of objective structured clinical examina-tion (OSCE) can also be an effective way of teaching communication skills to dental students. The conclusion to be made is that communication skills should be taught across the entire dental curriculum as this leads to better understanding and sufficient outcome.

Abstract Background Sodium–glucose linked transporter type 2 (SGLT-2) inhibition has been shown to reduce cardiovascular mortality in heart failure independently of glycemic control and prevents the onset of atrial arrhythmias, a common co-morbidity in heart failure with preserved ejection fraction (HFpEF). The mechanism behind these effects is not fully understood, and it remains unclear if they could be further enhanced by additional SGLT-1 inhibition. We investigated the effects of chronic treatment with the dual SGLT-1&2 inhibitor sotagliflozin on left atrial (LA) remodeling and cellular arrhythmogenesis (i.e. atrial cardiomyopathy) in a metabolic syndrome-related rat model of HFpEF. Methods 17 week-old ZSF-1 obese rats, a metabolic syndrome-related model of HFpEF, and wild type rats (Wistar Kyoto), were fed 30 mg/kg/d sotagliflozin for 6 weeks. At 23 weeks, LA were imaged in-vivo by echocardiography. In-vitro, Ca2+ transients (CaT; electrically stimulated, caffeine-induced) and spontaneous Ca2+ release were recorded by ratiometric microscopy using Ca2+-sensitive fluorescent dyes (Fura-2) during various experimental protocols. Mitochondrial structure (dye: Mitotracker), Ca2+ buffer capacity (dye: Rhod-2), mitochondrial depolarization (dye: TMRE) and production of reactive oxygen species (dye: H2DCF) were visualized by confocal microscopy. Statistical analysis was performed with 2-way analysis of variance followed by post-hoc Bonferroni and student’s t-test, as applicable. Results Sotagliflozin ameliorated LA enlargement in HFpEF in-vivo. In-vitro, LA cardiomyocytes in HFpEF showed an increased incidence and amplitude of arrhythmic spontaneous Ca2+ release events (SCaEs). Sotagliflozin significantly reduced the magnitude of SCaEs, while their frequency was unaffected. Sotagliflozin lowered diastolic [Ca2+] of CaT at baseline and in response to glucose influx, possibly related to a ~ 50% increase of sodium sodium–calcium exchanger (NCX) forward-mode activity. Sotagliflozin prevented mitochondrial swelling and enhanced mitochondrial Ca2+ buffer capacity in HFpEF. Sotagliflozin improved mitochondrial fission and reactive oxygen species (ROS) production during glucose starvation and averted Ca2+ accumulation upon glycolytic inhibition. Conclusion The SGLT-1&2 inhibitor sotagliflozin ameliorated LA remodeling in metabolic HFpEF. It also improved distinct features of Ca2+-mediated cellular arrhythmogenesis in-vitro (i.e. magnitude of SCaEs, mitochondrial Ca2+ buffer capacity, diastolic Ca2+ accumulation, NCX activity). The safety and efficacy of combined SGLT-1&2 inhibition for the treatment and/or prevention of atrial cardiomyopathy associated arrhythmias should be further evaluated in clinical trials.

Abstract Clinical translation of pluripotent stem cell (PSC) derivatives is hindered by the tumorigenic risk from residual undifferentiated cells. Here, we identified salicylic diamines as potent agents exhibiting toxicity to murine and human PSCs but not to cardiomyocytes (CMs) derived from them. Half maximal inhibitory concentrations (IC50) of small molecules SM2 and SM6 were, respectively, 9- and 18-fold higher for human than murine PSCs, while the IC50 of SM8 was comparable for both PSC groups. Treatment of murine embryoid bodies in suspension differentiation cultures with the most effective small molecule SM6 significantly reduced PSC and non-PSC contamination and enriched CM populations that would otherwise be eliminated in genetic selection approaches. All tested salicylic diamines exerted their toxicity by inhibiting the oxygen consumption rate (OCR) in PSCs. No or only minimal and reversible effects on OCR, sarcomeric integrity, DNA stability, apoptosis rate, ROS levels or beating frequency were observed in PSC-CMs, although effects on human PSC-CMs seemed to be more deleterious at higher SM-concentrations. Teratoma formation from SM6-treated murine PSC-CMs was abolished or delayed compared to untreated cells. We conclude that salicylic diamines represent promising compounds for PSC removal and enrichment of CMs without the need for other selection strategies.

Reverse transcription polymerase chain reaction (RT-PCR) on respiratory tract swabs has become the gold standard for sensitive and specific detection of influenza virus, respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this retrospective analysis, we report on the successive implementation and routine use of multiplex RT-PCR testing for patients admitted to the Internal Medicine Emergency Department (ED) at a tertiary care center in Western Austria, one of the hotspots in the early coronavirus disease 2019 (COVID-19) pandemic in Europe. Our description focuses on the use of the Cepheid® Xpert® Xpress closed RT-PCR system in point-of-care testing (POCT). Our indications for RT-PCR testing changed during the observation period: From the cold season 2016/2017 until the cold season 2019/2020, we used RT-PCR to diagnose influenza or RSV infection in patients with fever and/or respiratory symptoms. Starting in March 2020, we used the RT-PCR for SARS-CoV-2 and a multiplex version for the combined detection of all these three respiratory viruses to also screen subjects who did not present with symptoms of infection but needed in-hospital medical treatment for other reasons. Expectedly, the switch to a more liberal RT-PCR test strategy resulted in a substantial increase in the number of tests. Nevertheless, we observed an immediate decline in influenza virus and RSV detections in early 2020 that coincided with public SARS-CoV-2 containment measures. In contrast, the extensive use of the combined RT-PCR test enabled us to monitor the re-emergence of influenza and RSV detections, including asymptomatic cases, at the end of 2022 when COVID-19 containment measures were no longer in place. Our analysis of PCR results for respiratory viruses from a real-life setting at an ED provides valuable information on the epidemiology of those infections over several years, their contribution to morbidity and need for hospital admission, the risk for nosocomial introduction of such infection into hospitals from asymptomatic carriers, and guidance as to how general precautions and prophylactic strategies affect the dynamics of those infections.

Background: Atrial fibrillation (AF) is promoted by various stimuli like angiotensin II, endothelin-1, epinephrine/norepinephrine, vagal activation, or mechanical stress, all of which activate receptors coupled to G-proteins of the Gαq/Gα11-family (Gq). Besides pro-fibrotic and pro-inflammatory effects, Gq-mediated signaling induces inositol trisphosphate receptor (IP3R)-mediated intracellular Ca2+ mobilization related to delayed after-depolarisations and AF. However, direct evidence of arrhythmogenic Gq-mediated signaling is absent. Methods and results: To define the role of Gq in AF, transgenic mice with tamoxifen-inducible, cardiomyocyte-specific Gαq/Gα11-deficiency (Gq-KO) were created and exposed to intracardiac electrophysiological studies. Baseline electrophysiological properties, including heart rate, sinus node recovery time, and atrial as well as AV nodal effective refractory periods, were comparable in Gq-KO and control mice. However, inducibility and mean duration of AF episodes were significantly reduced in Gq-KO mice—both before and after vagal stimulation. To explore underlying mechanisms, left atrial cardiomyocytes were isolated from Gq-KO and control mice and electrically stimulated to study Ca2+-mobilization during excitation–contraction coupling using confocal microscopy. Spontaneous arrhythmogenic Ca2+ waves and sarcoplasmic reticulum content-corrected Ca2+ sparks were less frequent in Gq-KO mice. Interestingly, nuclear but not cytosolic Ca2+ transient amplitudes were significantly decreased in Gq-KO mice. Conclusion: Gq-signaling promotes arrhythmogenic atrial Ca2+-release and AF in mice. Targeting this pathway, ideally using Gq-selective, biased receptor ligands, may be a promising approach for the treatment and prevention of AF. Importantly, the atrial-specific expression of the Gq-effector IP3R confers atrial selectivity mitigating the risk of life-threatening ventricular pro-arrhythmic effects.

We analyze TYPHOON long-slit-absorption line spectra of the starburst barred spiral galaxy NGC 1365 obtained with the Progressive Integral Step Method covering an area of 15 kpc ^2 . Applying a population synthesis technique, we determine the spatial distribution of ages and metallicities of the young and old stellar populations together with star formation rates, reddening, extinction, and the ratio R _V of extinction to reddening. We detect a clear indication of inside-out growth of the stellar disk beyond 3 kpc characterized by an outward increasing luminosity fraction of the young stellar population, a decreasing average age, and a history of mass growth, which was finished 2 Gyr later in the outermost disk. The metallicity of the young stellar population is clearly super solar but decreases toward larger galactocentric radii with a gradient of −0.02 dex kpc ^−1 . On the other hand, the metal content of the old population does not show a gradient and stays constant at a level roughly 0.4 dex lower than that of the young population. In the center of NGC 1365, we find a confined region where the metallicity of the young population drops dramatically and becomes lower than that of the old population. We attribute this to the infall of metal-poor gas, and additionally, to interrupted chemical evolution where star formation is stopped by active galactic nuclei and supernova feedback and then after several gigayears resumes with gas ejected by stellar winds from earlier generations of stars. We provide a simple model calculation as support for the latter.

We report high-quality H α /CO imaging spectroscopy of nine massive (log median stellar mass = 10.65 M _⊙ ) disk galaxies on the star-forming main sequence (henceforth SFGs), near the peak of cosmic galaxy evolution ( z ∼ 1.1–2.5), taken with the ESO Very Large Telescope, IRAM-NOEMA, and Atacama Large Millimeter/submillimeter Array. We fit the major axis position–velocity cuts with beam-convolved, forward models with a bulge, a turbulent rotating disk, and a dark matter (DM) halo. We include priors for stellar and molecular gas masses, optical light effective radii and inclinations, and DM masses from our previous rotation curve analysis of these galaxies. We then subtract the inferred 2D model-galaxy velocity and velocity dispersion maps from those of the observed galaxies. We investigate whether the residual velocity and velocity dispersion maps show indications for radial flows. We also carry out kinemetry, a model-independent tool for detecting radial flows. We find that all nine galaxies exhibit significant nontangential flows. In six SFGs, the inflow velocities ( v _r ∼ 30–90 km s ^−1 , 10%–30% of the rotational component) are along the minor axis of these galaxies. In two cases the inflow appears to be off the minor axis. The magnitudes of the radial motions are in broad agreement with the expectations from analytic models of gravitationally unstable, gas-rich disks. Gravitational torques due to clump and bar formation, or spiral arms, drive gas rapidly inward and result in the formation of central disks and large bulges. If this interpretation is correct, our observations imply that gas is transported into the central regions on ∼10 dynamical timescales.

The inner kiloparsec regions surrounding sub-Eddington (luminosity less than 10 ^−3 in Eddington units, L _Edd ) supermassive black holes (BHs) often show a characteristic network of dust filaments that terminate in a nuclear spiral in the central parsecs. Here we study the role and fate of these filaments in one of the least accreting BHs known, M31 (10 ^−7 L _Edd ) using hydrodynamical simulations. The evolution of a streamer of gas particles moving under the barred potential of M31 is followed from kiloparsec distance to the central parsecs. After an exploratory study of initial conditions, a compelling fit to the observed dust/ionized gas morphologies and line-of-sight velocities in the inner hundreds of parsecs is produced. After several million years of streamer evolution, during which friction, thermal dissipation, and self-collisions have taken place, the gas settles into a disk tens of parsecs wide. This is fed by numerous filaments that arise from an outer circumnuclear ring and spiral toward the center. The final configuration is tightly constrained by a critical input mass in the streamer of several 10 ^3 M _☉ (at an injection rate of 10 ^−4 ${M}_{\odot }\,{{\rm{yr}}}^{-1}$ ); values above or below this lead to filament fragmentation or dispersion respectively, which are not observed. The creation of a hot gas atmosphere in the region of ∼10 ^6 K is key to the development of a nuclear spiral during the simulation. The final inflow rate at 1 pc from the center is ∼1.7 × 10 ^−7 M _☉ yr ^−1 , consistent with the quiescent state of the M31 BH.

We study the relation between the metallicities of ionized and atomic gas in star-forming galaxies at z = 0–3 using the Evolution and Assembly of GaLaxies and their Environments (EAGLE) cosmological, hydrodynamical simulations. This is done by constructing a dense grid of sight lines through the simulated galaxies and obtaining the star formation rate- and H i column density-weighted metallicities, Z _SFR and Z _H I , for each sightline as proxies for the metallicities of ionized and atomic gas, respectively. We find Z _SFR ≳ Z _H I for almost all sight lines, with their difference generally increasing with decreasing metallicity. The stellar masses of galaxies do not have a significant effect on this trend, but the positions of the sight lines with respect to the galaxy centers play an important role: the difference between the two metallicities decreases when moving toward the galaxy centers, and saturates to a minimum value in the central regions of galaxies, irrespective of redshift and stellar mass. This implies that the mixing of the two gas phases is most efficient in the central regions of galaxies where sight lines generally have high column densities of H i . However, a high H i column density alone does not guarantee a small difference between the two metallicities. In galaxy outskirts, the inefficiency of the mixing of star-forming gas with H i seems to dominate over the dilution of heavy elements in H i through mixing with the pristine gas. We find good agreement between the available observational data and the Z _SFR – Z _H I relation predicted by the EAGLE simulations. Though, observed regions with a nuclear starburst mode of star formation appear not to follow the same relation.

We present a high-resolution kinematic study of the massive main-sequence star-forming galaxy (SFG) SDSS J090122.37+181432.3 (J0901) at z = 2.259, using ∼0.″36 Atacama Large Millimeter/submillimeter Array CO(3–2) and ∼0.″1–0.″5 SINFONI/VLT H α observations. J0901 is a rare, strongly lensed but otherwise normal massive ( $\mathrm{log}({M}_{\star }/{M}_{\odot })\sim 11$ ) main-sequence SFG, offering a unique opportunity to study a typical massive SFG under the microscope of lensing. Through forward dynamical modeling incorporating lensing deflection, we fit the CO and H α kinematics in the image plane out to about one disk effective radius ( R _e ∼ 4 kpc) at an ∼600 pc delensed physical resolution along the kinematic major axis. Our results show high intrinsic dispersions of the cold molecular and warm ionized gas ( σ _0,mol. ∼ 40 km s ^−1 and σ _0,ion. ∼ 66 km s ^−1 ) that remain constant out to R _e ; a moderately low dark matter fraction ( f _DM ∼ 0.3–0.4) within R _e ; and a centrally peaked Toomre Q parameter—agreeing well with the previously established σ _0 versus z , f _DM versus Σ _baryon , and Q 's radial trends using large-sample non-lensed main-sequence SFGs. Our data further reveal a high stellar mass concentration within ∼1–2 kpc with little molecular gas, and a clumpy molecular gas ring-like structure at R ∼ 2–4 kpc, in line with the inside-out quenching scenario. Our further analysis indicates that J0901 had assembled half of its stellar mass only ∼400 Myr before its observed cosmic time, and the cold gas ring and dense central stellar component are consistent with signposts of a recent wet compaction event of a highly turbulent disk found in recent simulations.

We analyze H α or CO rotation curves extending out to several galaxy effective radii for 100 massive, large, star-forming disk galaxies (SFGs) across the peak of cosmic galaxy star formation ( z ∼ 0.6–2.5), more than doubling the previous sample presented by Genzel et al. and Price et al. The observations were taken with SINFONI and KMOS integral-field spectrographs at the ESO-Very Large Telescope, LUCI-LBT, NOEMA-IRAM, and Atacama Large Millimeter/submillimeter Array. We fit the major-axis kinematics with beam-convolved, forward models of turbulent rotating disks with bulges embedded in dark matter (DM) halos, including the effects of pressure support. The fraction of dark to total matter within the disk effective radius ( R _e ∼ 5 kpc), f _DM ( R _e ) = V ^2 _DM ( R _e )/ V ^2 _circ ( R _e ) decreases with redshift: at z ∼ 1 ( z ∼ 2) the median DM fraction is 0.38 ± 0.23 (0.27 ± 0.18), and a third (half) of all galaxies are maximal disks with f _DM ( R _e ) < 0.28. DM fractions correlate inversely with the baryonic surface density, and the low DM fractions can be explained with a flattened, or cored, inner DM density distribution. At z ∼ 2, there is ≈40% less DM mass on average within R _e compared to expected values based on cosmological stellar-mass–halo-mass relations. The DM deficit is more evident at high star formation rate surface densities (≳2.5 M _⊙ yr ^−1 kpc ^2 ) and galaxies with massive bulges (≥10 ^10 M _⊙ ). A combination of stellar or active galactic nucleus feedback, and/or heating due to dynamical friction, may drive the DM from cuspy into cored mass distributions, pointing to an efficient buildup of massive bulges and central black holes at z ∼ 2 SFGs.

How does the complexity of executive compensation contracts affect firm performance? With unknown consequences, the compensation complexity of executives has been rising. We define and measure executive compensation complexity and relate it to accounting; market; and environmental, social, and governance metrics of firm performance. Chief executive officer (CEO) compensation complexity negatively affects all three types of firm performance. We explore theoretical explanations for this relationship and find that cognitively complex CEOs can better deal with complex contracts. The negative complexity effects disappear if firms use only financial goals. Complexity is more harmful in unstable and munificent industries. Complexity also mitigates the negative effect of CEO tenure on long-term performance. In addition, firm performance suffers if the top management team members have heterogeneously complex contracts. Robustness checks support these findings. We conclude that the trend of adding more metrics to executive compensation contracts is not a generally preferable solution to the new and more intense agency problems that firms encounter. [ABSTRACT FROM AUTHOR]