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Bayer AG.

Aims This multicentre observational study aimed to prospectively assess the efficacy of left bundle branch area pacing (LBBAP) in heart failure patients with left bundle branch block (LBBB) and compare the 6-month outcomes between LBBAP and biventricular pacing (BVP). Methods and results Consecutive patients with LBBB and left ventricular ejection fraction (LVEF) ≤ 35% were prospectively recruited if they had undergone LBBAP as a primary or rescue strategy from three separate centres from March to December 2018. Patients who received BVP in 2018 were retrospectively selected by using 2 to 1 propensity score matching to minimize bias. Implant characteristics and echocardiographic parameters were assessed during the 6-month follow-up. LBBAP procedure succeeded in 81.1% (30/37) of patients, with selective LBBAP in 10 patients, and 3 of 20 patients combined non-selective LBBAP and LV lead pacing for further QRS narrowing. LBBAP resulted in significant QRS narrowing (from 178.2 ± 18.8 to 121.8 ± 10.8 ms, P < 0.001, paced QRS duration ≤ 130 ms in 27 patients) and improved LVEF (from 28.8 ± 4.5% to 44.3 ± 8.7%, P < 0.001) during the 6-month follow-up. The comparison between 27 patients with LBBAP alone and 54 of 130 matching patients with BVP showed that LBBAP delivered a greater reduction in the QRSd (58.0 vs. 12.5 ms, P < 0.001), a greater increase in LVEF (15.6% vs. 7.0%, P < 0.001), and greater echocardiographic (88.9% vs. 66.7%, P = 0.035) and super response (44.4% vs. 16.7%, P = 0.007) to cardiac resynchronization therapy. Conclusions LBBAP could deliver cardiac resynchronization therapy in most patients with heart failure and LBBB, and might be a promising alternative resynchronization approach to BVP.

Summary This manuscript explores cross‐cultural differences in reactions to perceived abusive supervision. Based on an integration of fairness heuristic theory with principles about cross‐cultural differences in the importance of hierarchical status, we theorize that subordinates from the Anglo culture perceive and react to abusive supervision more negatively than subordinates from the Confucian Asian culture. The predictions were tested within two field studies. Study 1 results show that culture moderated the direct effect of perceived abusive supervision on interpersonal justice and the indirect effects of perceived abusive supervision (via interpersonal justice) on subordinates' trust in the supervisor and work effort. The negative effects of perceived abusive supervision were stronger for subordinates within the Anglo versus the Confucian Asian culture; subordinates from Anglo culture compared with Confucian Asian culture perceived abusive supervision as less fair. Perceived abusive supervision indirectly and negatively influenced subordinates' trust in the supervisor and work effort. Study 2 replicated the findings from Study 1 and extended them to show culture (Anglo vs. Confucian culture) moderated the effects because it influences subordinates' power distance orientation. Copyright © 2014 John Wiley & Sons, Ltd.

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Poor survival of mesenchymal stem cells (MSCs) compromised the efficacy of stem cell therapy for myocardial infarction. The increase of exogenous reactive oxygen species (ROS) in infracted heart is one of the important factors that challenged the survival of donor MSCs. In the study we aimed to evaluate the effect of oxidative stress on the cell death of MSCs and investigate its mechanisms in order to help with the identification of new biological compounds to reduce donor cells damage. Apoptosis of MSCs were evaluated with Hoechst 33342 staining and flow cytometry analysis. The mitochondrial membrane potential of MSCs was analyzed with JC-1 staining. Signaling pathways involved in H(2)O(2) induced apoptosis were analyzed with Western blot. H(2)O(2) induced apoptosis of MSCs in a dose- and time-dependent manner. H(2)O(2) induced apoptosis of MSCs via both endoplasmic reticulum (ER) and mitochondrial pathways rather than extrinsic apoptosis pathway. H(2)O(2) caused transient rather than sustained activation of p38 and JNK with no effect on ERK1/2 pathway. P38 was involved in the regulation of early apoptosis of MSCs while JNK was involved in the late apoptosis. P38 directed both ER stress and mitochondria death pathway in the early apoptosis. In conclusion, exogenous ROS was a major factor to induce apoptosis of MSCs. Both ER stress and mitochondria death pathway were involved in the apoptosis of MSCs. H(2)O(2) activated p38 that directed the above two pathways in the regulation of early apoptosis of MSCs while JNK was involved in the late apoptosis of MSCs.

Derivation of cardiomyocytes from induced pluripotent stem cells (iPS-CMs) allowed us to probe the Ca2+-signaling parameters of human iPS-CMs from healthy- and catecholaminergic polymorphic ventricular tachycardia (CPVT1)-afflicted individuals carrying a novel point mutation p.F2483I in ryanodine receptors (RyR2). iPS-CMs were dissociated on day 30–40 of differentiation and patch-clamped within 3–6 days. Calcium currents (ICa) averaged ~8 pA/pF in control and mutant iPS-CMs. ICa-induced Ca2+-transients in control and mutant cells had bell-shaped voltage-dependence similar to that of ICa, consistent with Ca2+-induced Ca2+-release (CICR) mechanism. The ratio of ICa-activated to caffeine-triggered Ca2+-transients was ~0.3 in both cell types. Caffeine-induced Ca2+-transients generated significantly smaller Na+–Ca2+ exchanger current (INCX) in mutant cells, reflecting their smaller Ca2+-stores. The gain of CICR was voltage-dependent as in adult cardiomyocytes. Adrenergic agonists enhanced ICa, but differentially altered the CICR gain, diastolic Ca2+, and Ca2+-sparks in mutant cells. The mutant cells, when Ca2+-overloaded, showed longer and wandering Ca2+-sparks that activated adjoining release sites, had larger CICR gain at −30 mV yet smaller Ca2+-stores. We conclude that control and mutant iPS-CMs express the adult cardiomyocyte Ca2+-signaling phenotype. RyR2 F2483I mutant myocytes have aberrant unitary Ca2+-signaling, smaller Ca2+-stores, higher CICR gains, and sensitized adrenergic regulation, consistent with functionally altered Ca2+-release profile of CPVT syndrome.