The Glucocorticoid Resistance Syndrome. Two Cases of a Novel Pathogenic Variant in the Glucocorticoid Receptor Gene.

Glucocorticoid resistance syndrome is a rare genetic condition characterized by generalized or partial target-tissue insensitivity to glucocorticoids and a consequent hyperactivation of the hypothalamic-pituitary-adrenal axis. Clinical manifestations may include mineralocorticoid and/or androgen excess without manifestations of Cushing syndrome. At a cellular level, glucocorticoid actions are mediated by the nuclear glucocorticoid receptor encoded by the NR3C1 gene. To date, only 33 glucocorticoid receptor loss-of-function pathogenic variants have been associated with glucocorticoid resistance syndrome. The NR3C1 gene has 2 known disease-causing mechanisms: haploinsufficiency and negative dominance. We describe a mother and her son with a mild hyperandrogenic phenotype and a novel genetic variant of the NR3C1 gene predicting a truncated protein and causing glucocorticoid resistance syndrome. To date, no accurate genotype-phenotype correlation has been found.

Unraveling the optoelectronic properties of CoSbx intrinsic selective solar absorber towards high-temperature surfaces.

The combination of the ability to absorb most of the solar radiation and simultaneously suppress infrared re-radiation allows selective solar absorbers (SSAs) to maximize solar energy to heat conversion, which is critical to several advanced applications. The intrinsic spectral selective materials are rare in nature and only a few demonstrated complete solar absorption. Typically, intrinsic materials exhibit high performances when integrated into complex multilayered solar absorber systems due to their limited spectral selectivity and solar absorption. In this study, we propose CoSbx (2 < x < 3) as a new exceptionally efficient SSA. Here we demonstrate that the low bandgap nature of CoSbx endows broadband solar absorption (0.96) over the solar spectral range and simultaneous low emissivity (0.18) in the mid-infrared region, resulting in a remarkable intrinsic spectral solar selectivity of 5.3. Under 1 sun illumination, the heat concentrates on the surface of the CoSbx thin film, and an impressive temperature of 101.7 °C is reached, demonstrating the highest value among reported intrinsic SSAs. Furthermore, the CoSbx was tested for solar water evaporation achieving an evaporation rate of 1.4 kg m-2 h-1. This study could expand the use of narrow bandgap semiconductors as efficient intrinsic SSAs with high surface temperatures in solar applications.

Atrial fibrillation and ischemic heart disease: (un)solved therapeutic dilemma?

Concomitant presence of atrial fibrillation and coronary artery disease requiring percutaneous coronary intervention is a frequent occurrence. The choice of optimal antithrombotic therapy, in this context, is still challenging. To offer the best protection both in terms of stroke and stent thrombosis, triple therapy with oral anticoagulation and dual antiplatelet therapy would be required. Several drug combinations have been tested in recent years, including direct oral anticoagulants, with the aim of balancing ischemic and bleeding risk. Both pharmacokinetic aspects of the molecules and patient's characteristics should be analyzed in choosing oral anticoagulation. Then, as suggested by guidelines, triple therapy should start with a seven-day duration and the aim to prolong to thirty days in high thrombotic risk patients. Dual therapy should follow to reach twelve months after coronary intervention. Even not fully discussed by the guidelines, in order to balance ischemic and bleeding risk it should also be considered: 1) integrated assessment of coronary artery disease and procedural complexity of coronary intervention; 2) appropriateness to maintain the anticoagulant drug dosage indicated in technical data sheet; the lack of data on the suspension of antiplatelet drugs one year after percutaneous intervention; 3) the possibility of combination therapy with ticagrelor; and 4) the need to treat the occurrence of paroxysmal atrial fibrillation during acute coronary syndrome. With data provided clinician should pursue a therapy as personalized as possible, both in terms of drug choice and treatment duration, in order to balance ischemic and bleeding risk.

Investigating the High-Temperature Water/MgCl2 Interface through Ambient Pressure Soft X-ray Absorption Spectroscopy.

Magnesium chloride is a prototypical deliquescent material whose surface properties, although central for Ziegler-Natta cataysis, have so far remained elusive to experimental characterization. In this work, we use surface-selective X-ray absorption spectroscopy (XAS) at ambient pressure in combination with multivariate curve resolution, molecular dynamics, and XAS theoretical methods to track in real time and accurately describe the interaction between water vapor and the MgCl2 surface. By exposing MgCl2 to water vapor at temperatures between 595 and 391 K, we show that water is preferentially adsorbed on five-coordinated Mg2+ sites in an octahedral configuration, confirming previous theoretical predictions, and find that MgCl2 is capable of retaining a significant amount of adsorbed water even under prolonged heating to 595 K. As a consequence, our work provides first experimental insights into the unique surface affinity of MgCl2 for atmospheric water. The developed technique is proven highly sensitive to the modifications induced by adsorbates on a given low-Z metal based surface and may be useful in the toolbox required to disentangle the mechanisms of interfacial chemical processes.

Hydrogen Production Mechanism in Low-Temperature Methanol Decomposition Catalyzed by Ni3Sn4 Intermetallic Compound: A Combined Operando and Density Functional Theory Investigation.

Hydrogen production from methanol decomposition to syngas (H2 + CO) is a promising alternative route for clean energy transition. One major challenge is related to the quest for stable, cost-effective, and selective catalysts operating below 400 °C. We illustrate an investigation of the surface reactivity of a Ni3Sn4 catalyst working at 250 °C, by combining density functional theory, operando X-ray absorption spectroscopy, and high-resolution transmission electron microscopy. We discovered that the catalytic reaction is driven by surface tin-oxide phases, which protects the underlying Ni atoms from irreversible chemical modifications, increasing the catalyst durability. Moreover, we found that Sn content plays a key role in enhancing the H2 selectivity, with respect to secondary products such as CO2. These findings open new perspectives for the engineering of scalable and low-cost catalysts for hydrogen production.

MOF-Derived CeO2 and CeZrOx Solid Solutions: Exploring Ce Reduction through FTIR and NEXAFS Spectroscopy.

The development of Ce-based materials is directly dependent on the catalyst surface defects, which is caused by the calcination steps required to increase structural stability. At the same time, the evaluation of cerium's redox properties under reaction conditions is of increasing relevant importance. The synthesis of Ce-UiO-66 and CeZr-UiO-66 and their subsequent calcination are presented here as a simple and inexpensive approach for achieving homogeneous and stable CeO2 and CeZrOx nanocrystals. The resulting materials constitute an ideal case study to thoroughly understand cerium redox properties. The Ce3+/Ce4+ redox properties are investigated by H2-TPR experiments exploited by in situ FT-IR and Ce M5-edge AP-NEXAFS spectroscopy. In the latter case, Ce3+ formation is quantified using the MCR-ALS protocol. FT-IR is then presented as a high potential/easily accessible technique for extracting valuable information about the cerium oxidation state under operating conditions. The dependence of the OH stretching vibration frequency on temperature and Ce reduction is described, providing a novel tool for qualitative monitoring of surface oxygen vacancy formation. Based on the reported results, the molecular absorption coefficient of the Ce3+ characteristic IR transition is tentatively evaluated, thus providing a basis for future Ce3+ quantification through FT-IR spectroscopy. Finally, the FT-IR limitations for Ce3+ quantification are discussed.

Caught while Dissolving: Revealing the Interfacial Solvation of the Mg2+ Ions on the MgO Surface.

Interfaces between water and materials are ubiquitous and are crucial in materials sciences and in biology, where investigating the interaction of water with the surface under ambient conditions is key to shedding light on the main processes occurring at the interface. Magnesium oxide is a popular model system to study the metal oxide-water interface, where, for sufficient water loadings, theoretical models have suggested that reconstructed surfaces involving hydrated Mg2+ metal ions may be energetically favored. In this work, by combining experimental and theoretical surface-selective ambient pressure X-ray absorption spectroscopy with multivariate curve resolution and molecular dynamics, we evidence in real time the occurrence of Mg2+ solvation at the interphase between MgO and solvating media such as water and methanol (MeOH). Further, we show that the Mg2+ surface ions undergo a reversible solvation process, we prove the dissolution/redeposition of the Mg2+ ions belonging to the MgO surface, and we demonstrate the formation of octahedral [Mg(H2O)6]2+ and [Mg(MeOH)6]2+ intermediate solvated species. The unique surface, electronic, and structural sensitivity of the developed technique may be beneficial to access often elusive properties of low-Z metal ion intermediates involved in interfacial processes of chemical and biological interest.

Computational NEXAFS Characterization of Molecular Model Systems for 2D Boroxine Frameworks.

The electronic properties of 2D boroxine networks are computationally investigated by simulating the NEXAFS spectra of a series of molecular models, with or without morphologic defects, with respect to the ideal honeycomb structure. The models represent portions of an irregular 2D boroxine framework obtained experimentally, as supported by the Au(111) surface. The B K-edge NEXAFS spectra are calculated within the transition potential (TP) approximation (DFT-TP). The role of the Au(111) supporting surface on the spectral features has also been investigated by comparing the calculated spectra of a defect-rich model in its free-standing and supported form. The calculated NEXAFS spectra differ from the experimental ones, as the position of the main resonance does not match in the two cases. This finding could suggest the presence of a strong interaction of the 2D boroxine network with the Au substrate, which is not captured in the model calculations. However, good agreement between measured and calculated B K-edge NEXAFS spectra is obtained for a model system, namely, trihydroxy boroxine, in which the B atoms are less screened by the valence electrons compared to the B-B linked boroxine network models considered here. These results suggest catalytic activity in the gold substrate in promoting a weakening or even the breaking of the B-B bond, which is not revealed by calculations.

Pushing Stoichiometries of Lithium-Rich Layered Oxides Beyond Their Limits.

Lithium-rich layered oxides (LRLOs) are opening unexplored frontiers for high-capacity/high-voltage positive electrodes in Li-ion batteries (LIBs) to meet the challenges of green and safe transportation as well as cheap and sustainable stationary energy storage from renewable sources. LRLOs exploit the extra lithiation provided by the Li1.2TM0.8O2 stoichiometries (TM = a blend of transition metals with a moderate cobalt content) achievable by a layered structure to disclose specific capacities beyond 200-250 mA h g-1 and working potentials in the 3.4-3.8 V range versus Li. Here, we demonstrate an innovative paradigm to extend the LRLO concept. We have balanced the substitution of cobalt in the transition-metal layer of the lattice with aluminum and lithium, pushing the composition of LRLO to unexplored stoichiometries, that is, Li1.2+x (Mn,Ni,Co,Al)0.8-x O2-δ. The fine tuning of the composition of the metal blend results in an optimized layered material, that is, Li1.28Mn0.54Ni0.13Co0.02Al0.03O2-δ, with outstanding electrochemical performance in full LIBs, improved environmental benignity, and reduced manufacturing costs compared to the state-of-the-art.

First Year Metabolic and Hormonal Behavior Define two Different Populations of SGA Newborn for Weight or Height.

Context: Small-for-gestational-age (SGA) children have a particular metabolic and hormonal pattern at birth that changes rapidly. Objective: To evaluate the linear and weight growth in the first year of life in SGA children. Design: Prospective, monocentric cohort study. Setting: Real-world data collected from April 2012 to January 2016. Patients: SGA newborns uniformly defined by either growth or length lower than -2 SDs for gestational age. Interventions: All children were evaluated for 1 year after birth, at 3 days of life, then 3, 6, and 12 months after birth. Main outcome measures: Anthropometric parameters and biochemical variables, such as blood glucose, insulin, leptin, IGF-1, IGF binding protein-3 (IGFBP-3), and homeostasis model assessment - insulin resistance (HOMA-IR) index. Results: A total of 133 SGA children were enrolled. Length significantly improved 1 month after birth, whereas weight significantly increased only at 3 months after birth. Biochemical variables increased during the first year of life, showing a prediction by IGFBP-3 and HOMA-IR index. Then, the variables were divided considering either weight, length, or both, showing a different incidence. The biochemical variable changes recorded in the first step were maintained considering SGA children for weight or length, whereas they disappeared when weight and length were considered together. Conclusions: Our study shows a specific catchup growth for weight and length in SGA children. Moreover, we highlight that weight and length should be considered as independent parameters in SGA children, defining 2 different metabolic-hormonal populations with different conceivable predictive role in early catchup growth and in later growth and metabolic status.

Catching the Reversible Formation and Reactivity of Surface Defective Sites in Metal-Organic Frameworks: An Operando Ambient Pressure-NEXAFS Investigation.

In this work, we apply for the first time ambient pressure operando soft X-ray absorption spectroscopy (XAS) to investigate the location, structural properties, and reactivity of the defective sites present in the prototypical metal-organic framework HKUST-1. We obtained direct evidence that Cu+ defective sites form upon temperature treatment of the powdered form of HKUST-1 at 160 °C and that they are largely distributed on the material surface. Further, a thorough structural characterization of the Cu+/Cu2+ dimeric complexes arising from the temperature-induced dehydration/decarboxylation of the pristine Cu2+/Cu2+ paddlewheel units is reported. In addition to characterizing the surface defects, we demonstrate that CO2 may be reversibly adsorbed and desorbed from the surface defective Cu+/Cu2+ sites. These findings show that ambient pressure soft-XAS, combined with state-of-the-art theoretical calculations, allowed us to shed light on the mechanism involving the decarboxylation of the paddlewheel units on the surface to yield Cu+/Cu2+ complexes and their reversible restoration upon exposure to gaseous CO2.

Long-term percentage of ventricular pacing in patients requiring pacemaker implantation after transcatheter aortic valve replacement: A multicenter 10-year experience.

BACKGROUND: Recent studies suggest that atrioventricular (AV) conduction may recover after pacemaker (PM) implantation following transcatheter aortic valve replacement (TAVR), but little is known about long-term follow-up of such patients. OBJECTIVE: The purpose of this study was to evaluate the long-term percentage of right ventricular pacing in patients who underwent TAVR and required PM implantation stratified based on the indication for permanent pacing. METHODS: Retrospective analysis of all consecutive patients who underwent TAVR from February 2008 to August 2019 at 3 centers was performed. Patients already implanted with a PM/implantable cardioverter-defibrillator (ICD) before TAVR, implanted with a cardiac resynchronization therapy device, or implanted >30 days after TAVR were excluded. Eligible patients were divided into 2 groups based on the presence (persistent atrioventricular block [AVB] group) or absence (nonpersistent AVB group) of persistent third-degree AVB after TAVR. RESULTS: A total of 1594 patients underwent TAVR. Two hundred four patients were implanted with a PM or ICD after TAVR and 32 met exclusion criteria, so 172 patients were eligible (median time TAVR-PM implant 4 days) for a total of 352 follow-up visits analyzed. A significant difference in the percentage of ventricular pacing was observed at follow-up performed 7-90 days after implantation (98% persistent AVB group vs 8% nonpersistent AVB group; P <.001). This difference remained significant at follow-up performed 91-270 days (95% vs 3.5%; P <.001), 271-540 days (95.5% vs 3%; P = .006), and 541-900 days (97.4% vs 2.2%; P <.001) after implantation. CONCLUSION: Patients requiring PM implantation due to persistent third-degree AVB after TAVR were less likely to show AV conduction recovery, whereas patients implanted for other indications showed a low percentage of pacing during follow-up.

Combined Transcatheter Treatment of Severe Aortic Valve Stenosis and Infrarenal Abdominal Aortic Aneurysm in Increased Surgical Risk Patients.

The prevalence of combined severe aortic stenosis and abdominal aortic aneurysm is increasing with the aging of the population. Both conditions are associated with adverse outcome if not adequately managed. The choice of the optimal treatment of these patients is challenging and no clear recommendations are available. We report 2 cases of patients with concomitant severe symptomatic aortic stenosis and infrarenal abdominal aortic aneurysm successfully treated with combined transfemoral transcatheter aortic valve implantation (TAVI) and endovascular aortic aneurysm repair (EVAR). The reported cases demonstrate the versatility of transcatheter techniques and suggest that, in carefully selected patients, the combined procedure of TAVI plus EVAR, if performed by multidisciplinary expert operators, is safe and effective.

Dual antiplatelet therapy after TAVR: A drop in the bucket?

Current guidelines recommend a three- to six-months dual antiplatelet therapy (DAPT) in patients undergoing transcatheter aortic valve replacement (TAVR) or to continue with oral anticoagulant agents (OAC) if already indicated before procedure. However, recent studies showed that treatment with aspirin has the same efficacy of DAPT but it was associated with a significant reduction of major bleeding. Furthermore, half of cerebrovascular events, occurring >24 h after procedure, may be related to new onset of atrial fibrillation or to subclinical leaflets thrombosis and they may be prevented by use of OAC rather than antiplatelet therapy. In absence of very high bleeding risk and of recent percutaneous coronary intervention, the use of OAC over SAPT or DAPT might theoretically be considered in patients undergoing TAVR waiting for results of ongoing clinical trials.

[Bleeding risk in patients with acute coronary syndromes treated with antiplatelet agents: incidence, prognosis and clinical evaluation. From research to clinical practice]. / Il rischio di sanguinamento nei pazienti con sindrome coronarica acuta trattati con farmaci antiaggreganti: incidenza, impatto prognostico e metodi di valutazione, dagli studi alla pratica clinica.

Dual antiplatelet therapy (DAPT) including aspirin and a P2Y12 inhibitor is the cornerstone for the treatment of patients with acute coronary syndrome (ACS). The introduction of more potent drugs significantly reduced ischemic events, but with an associated increased risk of bleeding. Although appropriate estimation of bleeding risk by comparing the single drugs is challenging, mainly because of differences in definitions, it has been consistently shown that bleeding events are associated with an adverse outcome, both at short and long-term follow-up.Current guidelines recommend a short DAPT in patients at high bleeding risk, making appropriate risk estimation of crucial importance. Several numerical scores have been proposed for use in daily clinical practice. Although an objective risk assessment provides superior risk discrimination compared to physician's estimation, none of these scores appear free from limitations, nor have been obtained from cohorts of patients on short-tern treatment with prasugrel or ticagrelor. In the present review, we report the rates of major bleeding observed in the main randomized clinical trials and registries, their association with mortality, differences in definitions when used as safety endpoint, and finally the scores currently used for evaluation in daily clinical practice.

[Valve-in-valve treatment of a degenerated supra-annular stentless bioprosthesis using a balloon-expandable transcatheter valve in a patient at high risk for coronary occlusion]. / Trattamento valve-in-valve con protesi balloon-expandable di bioprotesi chirurgica stentless sovra-anulare degenerata con alto rischio di occlusione coronarica.

Transcatheter valve-in-valve treatment of degenerated supra-annular stentless bioprostheses may be challenging and associated with a high risk of coronary occlusion. Preprocedural imaging evaluation is a key step to assess feasibility and to minimize or prevent coronary occlusion. We report the case of a degenerated Freedom Solo valve, treated with a balloon-expandable valve and a previously deflated stent positioned at the level of both coronary ostia. The procedure was successful but stent inflation at the right coronary ostium was required due to slow flow that occurred after valve implantation.