Shiga toxin-producing Escherichia coli-associated haemolytic uraemic syndrome (STEC-HUS) is one of the most important causes of acute kidney injury in patients of all ages, especially in children. It ...can occur sporadically or in outbreaks. STEC-HUS is a systemic illness caused by toxin-mediated injury to the vascular endothelium and a generalized inflammatory response. The kidney and the brain are the two primary target organs. Nearly 40% of patients with STEC-HUS require at least temporary renal replacement therapy and up to 20% will have permanent residual kidney dysfunction. Neurological injury can be sudden and severe and is the most frequent cause of acute mortality in patients with STEC-HUS. Over the past 30 years, a wide range of inflammatory mediators have been linked to the pathogenesis of STEC-HUS and associated renal and neurological complications. Recently, evidence has accumulated that abnormal activation of the alternative pathway of complement occurs in patients with STEC-HUS. In the large outbreak of STEC-HUS caused by E. coli O104:H4 that occurred in Germany in May 2011, a large number of patients received eculizumab, a monoclonal antibody directed against C5, in an open-label manner. We describe the experience with eculizumab under these emergent circumstances at one large centre.
In a randomized trial, 6545 patients with acute heart failure were assigned to either serelaxin or placebo in addition to standard care. There were no significant differences between the two groups ...in the incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days.
Abstract
Aims
Autophagy protects against the development of cardiac hypertrophy and failure. While aberrant Ca2+ handling promotes myocardial remodelling and contributes to contractile dysfunction, ...the role of autophagy in maintaining Ca2+ homeostasis remains elusive. Here, we examined whether Atg5 deficiency-mediated autophagy promotes early changes in subcellular Ca2+ handling in ventricular cardiomyocytes, and whether those alterations associate with compromised cardiac reserve capacity, which commonly precedes the onset of heart failure.
Methods and results
RT–qPCR and immunoblotting demonstrated reduced Atg5 gene and protein expression and decreased abundancy of autophagy markers in hypertrophied and failing human hearts. The function of ATG5 was examined using cardiomyocyte-specific Atg5-knockout mice (Atg5−/−). Before manifesting cardiac dysfunction, Atg5−/− mice showed compromised cardiac reserve in response to β-adrenergic stimulation. Consequently, effort intolerance and maximal oxygen consumption were reduced during treadmill-based exercise tolerance testing. Mechanistically, cellular imaging revealed that Atg5 deprivation did not alter spatial and functional organization of intracellular Ca2+ stores or affect Ca2+ cycling in response to slow pacing or upon acute isoprenaline administration. However, high-frequency stimulation exposed stunted amplitude of Ca2+ transients, augmented nucleoplasmic Ca2+ load, and increased CaMKII activity, especially in the nuclear region of hypertrophied Atg5−/− cardiomyocytes. These changes in Ca2+ cycling were recapitulated in hypertrophied human cardiomyocytes. Finally, ultrastructural analysis revealed accumulation of mitochondria with reduced volume and size distribution, meanwhile functional measurements showed impaired redox balance in Atg5−/− cardiomyocytes, implying energetic unsustainability due to overcompensation of single mitochondria, particularly under increased workload.
Conclusion
Loss of cardiac Atg5-dependent autophagy reduces mitochondrial abundance and causes subtle alterations in subcellular Ca2+ cycling upon increased workload in mice. Autophagy-related impairment of Ca2+ handling is progressively worsened by β-adrenergic signalling in ventricular cardiomyocytes, thereby leading to energetic exhaustion and compromised cardiac reserve.
Graphical Abstract
Androgens play an important role in women's health. They are responsible for the sexual well-being and for maintaining proper structure and function of genitourinary woman's tract. In menopausal ...period a relative increase in androgens level is observed as a result of dramatic demise of estrogens and increase of sex hormone-binding globulin (SHBG). However, the response of target tissue depends on its ability to control androgens availability. In menopausal women the symptoms of both hyperandrogenemia and of androgens deficiency may be observed. Hyperandrogenemia may result in discrete symptoms, such as slight terminal facial hair grow, or worsening of scalp hair loss. Those symptoms should not be belittled in any of the cases, especially when their severity increases one should seek possible causes of postmenopausal hyperandrogenemia. Ovarian and adrenal aging, leading to a progressive decline in androgen levels, may exert detrimental effects on the quality of life. During menopause, changes in activation of particular brain spheres are connected with low sex hormone concentration and correlate with loss of sexual arousability. Hypoactive sexual desire dysfunction (HSDD) may be the direct result of androgens deficiency in menopausal women. It is the only evidence-based indication for the use of testosterone in women. However, before treatment, other diseases must be excluded that might alternatively be the cause of HSDD.
Display omitted
•ZnO NCs as an interface layer improve the crystallinity and grain size of perovskite.•Increase in PCE of PSCs due to better charge extraction and lower recombination.•Interpretation ...of the ideality factor, EIS and IMVS for this PCE enhancement.
Hybrid perovskite solar cells (PSCs) have gained significant attention owing to their excellent physicochemical and photovoltaic properties. PSCs typically consist of a perovskite light absorber sandwiched between two carrier selective layers optimized with respect to optimal band alignment and low interfacial recombination. The quality of the perovskite layer and interfaces play major roles in the fabrication of high-performance PSCs. In the present work, we systematically investigate the planar structure PSCs based on TiO2 and TiO2/ZnO electron transport layers (ETLs), which provide deeper insight into the charge recombination and accumulation mechanisms. We show that the double-layer structure of TiO2/ZnO ETL improves the optical and morphology properties of perovskite film leading to superior device performance. From the ideality factor, EIS and IMVS results, a suppressed recombination in TiO2/ZnO PSCs is achieved, which is due to improved grain size of perovskite absorber layer grown on ZnO nanocrystals (NCs). Additionally, we find that the ZnO NCs improve the shunt resistance and quality of the perovskite and suppress the recombination. The present study provides a novel strategy to improve the device performance of PSCs along with a detail investigation procedure to understand the physical mechanism.
Display omitted
•Bio-safe ligand-free and easily dispersible ZnO QDs were prepared by a novel organometallic strategy.•The process involves transformation of a DMSO solution of Et2Zn upon air ...exposition.•DMSO acts both as a solvent and a low-molecular-weight l-type surface protector.•The resulting QDs display unique long-term colloidal stability.•The developed method leads to the rational-by-design ZnO-based functional materials.
Colloidal quantum dots (QDs) are of widespread importance for their unique combination of physicochemical properties and a number of prospective applications, and the search for efficient synthetic methods to produce readily dispersible, functionally stable and ligand-free quantum dot-based inks is a vital and timely area of research. We describe a convenient room-temperature and non-external-surfactant-assisted organometallic synthetic strategy for the reproducible preparation of solution-processable organic ligand-free zinc oxide (ZnO) QDs. The process involves the controlled transformation of a DMSO solution of commercially available diethylzinc upon exposition towards atmospheric air, where H2O and O2 act simultaneously as oxygen sources, and DMSO acts both as a solvent and a low-molecular-weight l-type surface protector. The resulting QDs with a narrow size distribution (4.7 ± 0.8 nm) were comprehensively characterized with a combination of various analytical techniques, which nicely documented their unique stabilities when dried, precipitated, re-dissolved or exposed to air. Moreover, to substantiate idealized surface passivation of the resulting QDs, we investigated their stability in the biological environment and nano-specific activity toward selected normal and cancer cell lines, and no significant toxic effect was revealed. Undoubtedly, the reported one-step-one-pot organometallic approach paves the way to high-quality and bio-stable ZnO QDs coated by an easily and reversibly removable organic shell, auguring applications in a vast array of devices and nanomedicine.
Oligomeric ladder silsesquioxanes (LPSQ-R) with side substituents (R = COOH, COOMe, OH) capable of acceptor/donor interactions through hydrogen bonds were used for the preparation of blends with ...polylactide (PLA). Depending on the strength of their interactions with the PLA, LPSQ-R were differently dispersed in the polyester matrix. The blends exhibited different properties and crystallization behaviour depending on the type and content of LPSQ-R. PLA/LPSQ-COOMe exhibited good transparency. Owing to very good dispersion of the modifier, PLA with 5 wt% of LPSQ-COOMe was ductile, which was reflected in nearly 230% elongation at break, retaining however relatively high yield strength of nearly 40 MPa. Moreover, the spherulite growth rate was accelerated in PLA/LPSQ-COOMe, which caused enhancement of the cold-crystallization. In turn, cold-crystallization of PLA/LPSQ-OH was enhanced by strong nucleation.
Display omitted
•Polylactide blends with novel oligomeric ladder silsesquioxanes were studied.•Spherulite growth was accelerated in blends of polylactide with LPSQ-COOMe.•Cold-crystallization was enhanced in blends of PLA with LPSQ-COOMe and LPSQ-OH.•Polylactide with 5 wt% of LPSQ-COOMe exhibited very good drawability.
Zinc oxide (ZnO) is a promising electron‐transport layer (ETL) in thin‐film photovoltaics. However, the poor chemical compatibility between commonly used sol–gel‐derived ZnO nanostructures and ...organo–metal halide perovskites makes it highly challenging to obtain efficient and stable perovskite solar cells (PSCs). Here, a novel approach is reported for low‐temperature processed pure ZnO ETLs for planar heterojunction PSCs based on ZnO quantum dots (QDs) stabilized by dimethyl sulfoxide (DMSO) as easily removable solvent molecules. With no need for the ETL doping or surface modification, the champion PSC comprising the mixed‐cation and mixed‐halide Cs5(MA0.17FA0.83)95Pb(I0.83Br0.17)3 absorber layer reaches a maximum power conversion efficiency of 20.05%, which is significantly higher than that obtained for a reference device based on a standard sol–gel‐derived ZnO nanostructured layer (17.78%). Thus, along with the observed better operational stability in ambient conditions and elevated temperature, the champion device achieves the state‐of‐the‐art performance among reported non‐passivated pure ZnO ETL‐based PSCs. The improved photovoltaic performance is attributed to both a higher uniformity of the surface morphology and a lower defects density of films based on the organometallic‐derived QDs that are likely to ensure the enhanced stability of the ZnO/perovskite interface.
High quality colloidal ZnO quantum dots (ZnO OM) are synthesized using a new wet‐organometallic approach. The use of ZnO OM as an electron transfer layer (ETL) in planar perovskite solar cells improves the ETL/perovskite interface stability and reduces charge carrier recombination pathways. Consequently, the performance and stability of the ZnO OM‐based device is improved compared to the control device fabricated on the sol–gel processed ZnO ETL.
The aim of this cross-sectional study was to identify important biopsychosocial correlates of major depression. Biological mechanisms, including the inflammatory and the tryptophan-serotonin ...deficiency hypotheses of major depression, were investigated alongside health-related quality of life, life satisfaction, and social support.
The concentrations of plasma tryptophan, plasma kynurenine, plasma kynurenic acid, serum quinolinic acid, and the tryptophan breakdown to kynurenine were determined alongside health-related quality of life (Medical Outcome Study Form, SF-36), life satisfaction (Life Satisfaction Questionnaire, FLZ), and social support (Social Support Survey, SSS) in 71 depressive patients at the time of their in-patient admittance and 48 healthy controls.
Corresponding with the inflammatory hypothesis of major depression, our study results suggest a tryptophan breakdown to kynurenine in patients with major depression, and depressive patients had a lower concentration of neuroprotective kynurenic acid in comparison to the healthy controls (Mann-Whitney-U: 1315.0;
= 0.046). Contradicting the inflammatory theory, the concentrations of kynurenine (
: -0.945;
= 116;
= 0.347) and quinolinic acid (Mann-Whitney-U: 1376.5;
= 0.076) in depressive patients were not significantly different between depressed and healthy controls. Our findings tend to support the tryptophan-serotonin deficiency hypothesis of major depression, as the deficiency of the serotonin precursor tryptophan in depressive patients (
: -3.931;
= 116;
< 0.001) suggests dysfunction of serotonin neurotransmission. A two-step hierarchical linear regression model showed that low tryptophan concentrations, low social support (SSS), occupational requirements (FLZ), personality traits (FLZ), impaired physical role (SF-36), and impaired vitality (SF-36) predict higher Beck Depression Inventory (BDI-II) scores.
Our study results argue for the validity of a biopsychosocial model of major depression with multiple pathophysiological mechanisms involved.
Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the ...other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure.
•Inotropes increase cardiac output mainly by enhancing cardiac contractility.•Inotropes indicated for heart failure are beta-agonists, milrinone, levosimendan.•Inotropes should only be used in low-output acute or advanced heart failure.•Identifying patients with low-output heart failure is often challenging.•Inotrope selection should be individually tailored.
PDF
