Structure of the moiré exciton captured by imaging its electron and hole.

Interlayer excitons (ILXs) - electron-hole pairs bound across two atomically thin layered semiconductors - have emerged as attractive platforms to study exciton condensation1-4, single-photon emission and other quantum information applications5-7. Yet, despite extensive optical spectroscopic investigations8-12, critical information about their size, valley configuration and the influence of the moiré potential remains unknown. Here, in a WSe2/MoS2 heterostructure, we captured images of the time-resolved and momentum-resolved distribution of both of the particles that bind to form the ILX: the electron and the hole. We thereby obtain a direct measurement of both the ILX diameter of around 5.2 nm, comparable with the moiré-unit-cell length of 6.1 nm, and the localization of its centre of mass. Surprisingly, this large ILX is found pinned to a region of only 1.8 nm diameter within the moiré cell, smaller than the size of the exciton itself. This high degree of localization of the ILX is backed by Bethe-Salpeter equation calculations and demonstrates that the ILX can be localized within small moiré unit cells. Unlike large moiré cells, these are uniform over large regions, allowing the formation of extended arrays of localized excitations for quantum technology.

Interlayer engineering of Fe3GeTe2: From 3D superlattice to 2D monolayer.

The discoveries of ferromagnetism down to the atomically thin limit in van der Waals (vdW) crystals by mechanical exfoliation have enriched the family of magnetic thin films [C. Gong et al., Nature 546, 265-269 (2017) and B. Huang et al., Nature 546, 270-273 (2017)]. However, compared to the study of traditional magnetic thin films by physical deposition methods, the toolbox of the vdW crystals based on mechanical exfoliation and transfer suffers from low yield and ambient corrosion problem and now is facing new challenges to study magnetism. For example, the formation of magnetic superlattice is difficult in vdW crystals, which limits the study of the interlayer interaction in vdW crystals [M. Gibertini, M. Koperski, A. F. Morpurgo, K. S. Novoselov, Nat. Nanotechnol. 14, 408-419 (2019)]. Here, we report a strategy of interlayer engineering of the magnetic vdW crystal Fe3GeTe2 (FGT) by intercalating quaternary ammonium cations into the vdW spacing. Both three-dimensional (3D) vdW superlattice and two-dimensional (2D) vdW monolayer can be formed by using this method based on the amount of intercalant. On the one hand, the FGT superlattice shows a strong 3D critical behavior with a decreased coercivity and increased domain wall size, attributed to the co-engineering of the anisotropy, exchange interaction, and electron doping by intercalation. On the other hand, the 2D vdW few layers obtained by over-intercalation are capped with organic molecules from the bulk crystal, which not only enhances the ferromagnetic transition temperature (TC), but also substantially protects the thin samples from degradation, thus allowing the preparation of large-scale FGT ink in ambient environment.

Transcatheter or Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis and Small Aortic Annulus: A Randomized Clinical Trial.

BACKGROUND: The optimal treatment in patients with severe aortic stenosis and small aortic annulus (SAA) remains to be determined. This study aimed to compare the hemodynamic and clinical outcomes between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with a SAA. METHODS: This prospective multicenter international randomized trial was performed in 15 university hospitals. Participants were 151 patients with severe aortic stenosis and SAA (mean diameter <23 mm) randomized (1:1) to TAVR (n=77) versus SAVR (n=74). The primary outcome was impaired valve hemodynamics (ie, severe prosthesis patient mismatch or moderate-severe aortic regurgitation) at 60 days as evaluated by Doppler echocardiography and analyzed in a central echocardiography core laboratory. Clinical events were secondary outcomes. RESULTS: The mean age of the participants was 75.5±5.1 years, with 140 (93%) women, a median Society of Thoracic Surgeons predicted risk of mortality of 2.50% (interquartile range, 1.67%-3.28%), and a median annulus diameter of 21.1 mm (interquartile range, 20.4-22.0 mm). There were no differences between groups in the rate of severe prosthesis patient mismatch (TAVR, 4 [5.6%]; SAVR, 7 [10.3%]; P=0.30) and moderate-severe aortic regurgitation (none in both groups). No differences were found between groups in mortality rate (TAVR, 1 [1.3%]; SAVR, 1 [1.4%]; P=1.00) and stroke (TAVR, 0; SAVR, 2 [2.7%]; P=0.24) at 30 days. After a median follow-up of 2 (interquartile range, 1-4) years, there were no differences between groups in mortality rate (TAVR, 7 [9.1%]; SAVR, 6 [8.1%]; P=0.89), stroke (TAVR, 3 [3.9%]; SAVR, 3 [4.1%]; P=0.95), and cardiac hospitalization (TAVR, 15 [19.5%]; SAVR, 15 [20.3%]; P=0.80). CONCLUSIONS: In patients with severe aortic stenosis and SAA (women in the majority), there was no evidence of superiority of contemporary TAVR versus SAVR in valve hemodynamic results. After a median follow-up of 2 years, there were no differences in clinical outcomes between groups. These findings suggest that the 2 therapies represent a valid alternative for treating patients with severe aortic stenosis and SAA, and treatment selection should likely be individualized according to baseline characteristics, additional anatomical risk factors, and patient preference. However, the results of this study should be interpreted with caution because of the limited sample size leading to an underpowered study, and need to be confirmed in future larger studies. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03383445.

Partial replacement of mineral fertilisers with animal manures in an apple orchard: Effects on GHG emission.

Partial replacement of mineral fertilisers (MF) with animal manures is a good alternative to reduce MF use and increase both nutrient cycling in agriculture and soil organic matter. However, the adoption of this practice must not lead to increased environmental impacts. In this two-year study conducted in an apple orchard, MF were partially replaced with various animal manures, including cattle slurry (CS), acidified cattle slurry (ACS), solid cattle manure (CsM), or poultry manure (PM), and their impacts on greenhouse gas emission (GHG: CO2, N2O and CH4) were examined. A control (CTRL) receiving only MF served as the baseline, representing the conventional scenario in orchard fertilisation. Overall, replacing MF with manures increased GHG emissions, with the magnitude of the impacts depending on the specific characteristics of the manures and the amount of nutrients and organic matter applied. Comparing to the CTRL, application of ACS and CS led to higher CH4 and N2O emissions, while PM application increased both N2O and CO2 emissions. In contrast, replacement with PM and CsM decreased CH4 emissions. Nevertheless, results varied between the two years, influenced by several factors, including soil conditions. While acidification showed potential to mitigate CH4 emissions, it also led to increased N2O emissions compared to CS, particularly in 2022, suggesting the need for further investigation to avoid emission trade-offs. Replacement with CS (20.49 t CO2-eq ha-1) and CsM (20.30 t CO2-eq ha-1) showed comparable global warming potential (GWP) to the conventional scenario (CTRL, 19.49 t CO2-eq ha-1), highlighting their potential as viable MF substitutes.

Advanced Manufacturing, Formulation and Microencapsulation of Therapeutic Phages.

Manufacturing and formulation of stable, high purity, and high dose bacteriophage drug products (DPs) suitable for clinical usage would benefit from improved process monitoring and control of critical process parameters that affect product quality attributes. Chemistry, Manufacturing, and Controls (CMC) for both upstream (USP) and downstream processes (DSP) need mapping of critical process parameters (CPP) and linking these to critical quality attributes (CQA) to ensure quality and consistency of phage drug substance (DS) and DPs development. Single-use technologies are increasingly becoming the go-to manufacturing option with benefits both for phage bioprocess development at the engineering run research stage and for final manufacture of the phage DS. Future phage DPs under clinical development will benefit from implementation of process analytical technologies (PAT) for better process monitoring and control. These are increasingly being used to improve process robustness (to reduce batch-to-batch variability) and productivity (yielding high phage titers). Precise delivery of stable phage DPs that are suitably formulated as liquids, gels, solid-oral dosage forms, and so forth, could significantly enhance efficacy of phage therapy outcomes. Pre-clinical development of phage DPs must include at an early stage of development, considerations for their formulation including their characterization of physiochemical properties (size, charge, etc.), buffer pH and osmolality, compatibility with regulatory approved excipients, storage stability (packaging, temperature, humidity, etc.), ease of application, patient compliance, ease of manufacturability using scalable manufacturing unit operations, cost, and regulatory requirements.

An overview of metabolomic and proteomic profiling in bipolar disorder and its clinical value.

INTRODUCTION: Bipolar disorder (BD) is a complex psychiatric disease characterized by alternating mood episodes. As for any other psychiatric illness, currently there is no biochemical test that is able to support diagnosis or therapeutic decisions for BD. In this context, the discovery and validation of biomarkers are interesting strategies that can be achieved through proteomics and metabolomics. AREAS COVERED: In this descriptive review, a literature search including original articles and systematic reviews published in the last decade was performed with the objective to discuss the results of BD proteomic and metabolomic profiling analyses and indicate proteins and metabolites (or metabolic pathways) with potential clinical value. EXPERT OPINION: A large number of proteins and metabolites have been reported as potential BD biomarkers; however, most studies do not reach biomarker validation stages. An effort from the scientific community should be directed toward the validation of biomarkers and the development of simplified bioanalytical techniques or protocols to determine them in biological samples, in order to translate proteomic and metabolomic findings into clinical routine assays.

MS-Driven Metabolic Alterations Are Recapitulated in iPSC-Derived Astrocytes.

OBJECTIVE: Astrocytes play a significant role in the pathology of multiple sclerosis (MS). Nevertheless, for ethical reasons, most studies in these cells were performed using the Experimental Autoimmune Encephalomyelitis model. As there are significant differences between human and mouse cells, we aimed here to better characterize astrocytes from patients with MS (PwMS), focusing mainly on mitochondrial function and cell metabolism. METHODS: We obtained and characterized induced pluripotent stem cell (iPSC)-derived astrocytes from three PwMS and three unaffected controls, and performed electron microscopy, flow cytometry, cytokine and glutamate measurements, gene expression, in situ respiration, and metabolomics. We validated our findings using a single-nuclei RNA sequencing dataset. RESULTS: We detected several differences in MS astrocytes including: (i) enrichment of genes associated with neurodegeneration, (ii) increased mitochondrial fission, (iii) increased production of superoxide and MS-related proinflammatory chemokines, (iv) impaired uptake and enhanced release of glutamate, (v) increased electron transport capacity and proton leak, in line with the increased oxidative stress, and (vi) a distinct metabolic profile, with a deficiency in amino acid catabolism and increased sphingolipid metabolism, which have already been linked to MS. INTERPRETATION: Here we describe the metabolic profile of iPSC-derived astrocytes from PwMS and validate this model as a very powerful tool to study disease mechanisms and to perform non-invasive drug targeting assays in vitro. Our findings recapitulate several disease features described in patients and provide new mechanistic insights into the metabolic rewiring of astrocytes in MS, which could be targeted in future therapeutic studies. ANN NEUROL 2022;91:652-669.

Genome characterization of the novel lytic phage vB_AbaAut_ChT04 and the antimicrobial activity of its lysin peptide against Acinetobacter baumannii isolates from different time periods.

Acinetobacter baumannii is an important opportunistic pathogen, usually associated with immunocompromised individuals with a prolonged period of stay in a hospital. Currently, the incidence of multi-drug resistant A. baumannii (MDR-AB) and extensively drug-resistant A. baumannii (XDR-AB) is increasing rapidly in Thailand, mirroring the trend worldwide. Novel therapeutic approaches for the treatment of A. baumannii infection using bacteriophages are being evaluated, and the use of phage-derived peptides is being tested as alternative approach to fighting infection. In this study, we isolated and determined the biological features of a lytic A. baumannii phage called vB_AbaAut_ChT04 (vChT04). The vChT04 phage was classified as a member of the family Autographiviridae of the class Caudoviricetes. It showed a short latent period (10 min) and a large burst size (280 PFU cell-1), and it was able to infect 52 out of 150 clinical MDR-AB strains tested (34.67%). Most of the phage-sensitive strains were A. baumannii strains that had been isolated during the same year that the phage was isolated. The phage showed activity across a broad pH (pH 5.0-8.0) and temperature (4-37°C) range. Whole-genome analysis revealed that the vChT04 genome comprises 41,158 bp with a 39.3% GC content and contains 48 open reading frames (ORFs), 28 of which were assigned putative functions based on homology to previously identified phage genes. Comparative genomic analysis demonstrated that vChT04 had the highest similarity to phage vB_AbaP_WU2001, which was isolated in the southern part of Thailand. An endolysin gene found in the vChT04 genome was used to synthesize an antimicrobial peptide (designated as PLysChT04) and its antimicrobial activity was evaluated using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. The MIC and MBC values of peptide PLysChT04 against MDR-AB and XDR-AB were 312.5-625 µg/mL, and it was able to inhibit both phage-susceptible and phage-resistant isolates collected over different time periods. PLysChT04 showed good efficacy in killing drug-resistant A. baumannii and other bacterial strains, and it is a promising candidate for development as an alternative therapeutic agent targeting A. baumannii infections.

COVID-19-associated pulmonary aspergillosis in immunocompetent patients: a virtual patient cohort study.

The opportunistic fungus Aspergillus fumigatus infects the lungs of immunocompromised hosts, including patients undergoing chemotherapy or organ transplantation. More recently however, immunocompetent patients with severe SARS-CoV2 have been reported to be affected by COVID-19 Associated Pulmonary Aspergillosis (CAPA), in the absence of the conventional risk factors for invasive aspergillosis. This paper explores the hypothesis that contributing causes are the destruction of the lung epithelium permitting colonization by opportunistic pathogens. At the same time, the exhaustion of the immune system, characterized by cytokine storms, apoptosis, and depletion of leukocytes may hinder the response to A. fumigatus infection. The combination of these factors may explain the onset of invasive aspergillosis in immunocompetent patients. We used a previously published computational model of the innate immune response to infection with Aspergillus fumigatus. Variation of model parameters was used to create a virtual patient population. A simulation study of this virtual patient population to test potential causes for co-infection in immunocompetent patients. The two most important factors determining the likelihood of CAPA were the inherent virulence of the fungus and the effectiveness of the neutrophil population, as measured by granule half-life and ability to kill fungal cells. Varying these parameters across the virtual patient population generated a realistic distribution of CAPA phenotypes observed in the literature. Computational models are an effective tool for hypothesis generation. Varying model parameters can be used to create a virtual patient population for identifying candidate mechanisms for phenomena observed in actual patient populations.

Visible Out-of-plane Polarized Luminescence and Electronic Resonance in Black Phosphorus.

Black phosphorus (BP) is unique among layered materials because of its homonuclear lattice and strong structural anisotropy. While recent investigations on few-layer BP have extensively explored the in-plane (a, c) anisotropy, much less attention has been given to the out-of-plane direction (b). Here, the optical response from bulk BP is probed using polarization-resolved photoluminescence (PL), photoluminescence excitation (PLE), and resonant Raman scattering along the zigzag, out-of-plane, and armchair directions. An unexpected b-polarized luminescence emission is detected in the visible, far above the fundamental gap. PLE indicates that this emission is generated through b-polarized excitation at 2.3 eV. The same electronic resonance is observed in resonant Raman with the enhancement of the Ag phonon modes scattering efficiency. These experimental results are fully consistent with DFT calculations of the permittivity tensor elements and demonstrate the remarkable extent to which the anisotropy influences the optical properties and carrier dynamics in black phosphorus.

Transcatheter Mitral Valve Replacement After Surgical Repair or Replacement: Comprehensive Midterm Evaluation of Valve-in-Valve and Valve-in-Ring Implantation From the VIVID Registry.

BACKGROUND: Mitral valve-in-valve (ViV) and valve-in-ring (ViR) are alternatives to surgical reoperation in patients with recurrent mitral valve failure after previous surgical valve repair or replacement. Our aim was to perform a large-scale analysis examining midterm outcomes after mitral ViV and ViR. METHODS: Patients undergoing mitral ViV and ViR were enrolled in the Valve-in-Valve International Data Registry. Cases were performed between March 2006 and March 2020. Clinical endpoints are reported according to the Mitral Valve Academic Research Consortium (MVARC) definitions. Significant residual mitral stenosis (MS) was defined as mean gradient ≥10 mm Hg and significant residual mitral regurgitation (MR) as ≥ moderate. RESULTS: A total of 1079 patients (857 ViV, 222 ViR; mean age 73.5±12.5 years; 40.8% male) from 90 centers were included. Median STS-PROM score 8.6%; median clinical follow-up 492 days (interquartile range, 76-996); median echocardiographic follow-up for patients that survived 1 year was 772.5 days (interquartile range, 510-1211.75). Four-year Kaplan-Meier survival rate was 62.5% in ViV versus 49.5% for ViR (P<0.001). Mean gradient across the mitral valve postprocedure was 5.7±2.8 mm Hg (≥5 mm Hg; 61.4% of patients). Significant residual MS occurred in 8.2% of the ViV and 12.0% of the ViR patients (P=0.09). Significant residual MR was more common in ViR patients (16.6% versus 3.1%; P<0.001) and was associated with lower survival at 4 years (35.1% versus 61.6%; P=0.02). The rates of Mitral Valve Academic Research Consortium-defined device success were low for both procedures (39.4% total; 32.0% ViR versus 41.3% ViV; P=0.01), mostly related to having postprocedural mean gradient ≥5 mm Hg. Correlates for residual MS were smaller true internal diameter, younger age, and larger body mass index. The only correlate for residual MR was ViR. Significant residual MS (subhazard ratio, 4.67; 95% CI, 1.74-12.56; P=0.002) and significant residual MR (subhazard ratio, 7.88; 95% CI, 2.88-21.53; P<0.001) were both independently associated with repeat mitral valve replacement. CONCLUSIONS: Significant residual MS and/or MR were not infrequent after mitral ViV and ViR procedures and were both associated with a need for repeat valve replacement. Strategies to improve postprocedural hemodynamics in mitral ViV and ViR should be further explored.

Perivalvular Extension of Infective Endocarditis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Infective endocarditis (IE) following transcatheter aortic valve replacement (TAVR) has been associated with a dismal prognosis. However, scarce data exist on IE perivalvular extension (PEE) in such patients. METHODS: This multicenter study included 579 patients who had the diagnosis of definite IE at a median of 171 (53-421) days following TAVR. PEE was defined as the presence of an intracardiac abscess, pseudoaneurysm, or fistula. RESULTS: A total of 105 patients (18.1%) were diagnosed with PEE (perivalvular abscess, pseudoaneurysm, fistula, or a combination in 87, 7, 7, and 4 patients, respectively). A history of chronic kidney disease (adjusted odds ratio [ORadj], 2.08; 95% confidence interval [CI]: 1.27-3.41; P = .003) and IE secondary to coagulase-negative staphylococci (ORadj, 2.71; 95% CI: 1.57-4.69; P < .001) were associated with an increased risk of PEE. Surgery was performed at index IE episode in 34 patients (32.4%) with PEE (vs 15.2% in patients without PEE, P < .001). In-hospital and 2-year mortality rates among PEE-IE patients were 36.5% and 69.4%, respectively. Factors independently associated with an increased mortality were the occurrence of other complications (stroke post-TAVR, acute renal failure, septic shock) and the lack of surgery at index IE hospitalization (padj < 0.05 for all). CONCLUSIONS: PEE occurred in about one-fifth of IE post-TAVR patients, with the presence of coagulase-negative staphylococci and chronic kidney disease determining an increased risk. Patients with PEE-IE exhibited high early and late mortality rates, and surgery during IE hospitalization seemed to be associated with better outcomes.

Metabolomic and proteomic profiling in bipolar disorder patients revealed potential molecular signatures related to hemostasis.

INTRODUCTION: Bipolar disorder (BD) is a mood disorder characterized by the occurrence of depressive episodes alternating with episodes of elevated mood (known as mania). There is also an increased risk of other medical comorbidities. OBJECTIVES: This work uses a systems biology approach to compare BD treated patients with healthy controls (HCs), integrating proteomics and metabolomics data using partial correlation analysis in order to observe the interactions between altered proteins and metabolites, as well as proposing a potential metabolic signature panel for the disease. METHODS: Data integration between proteomics and metabolomics was performed using GC-MS data and label-free proteomics from the same individuals (N = 13; 5 BD, 8 HC) using generalized canonical correlation analysis and partial correlation analysis, and then building a correlation network between metabolites and proteins. Ridge-logistic regression models were developed to stratify between BD and HC groups using an extended metabolomics dataset (N = 28; 14 BD, 14 HC), applying a recursive feature elimination for the optimal selection of the metabolites. RESULTS: Network analysis demonstrated links between proteins and metabolites, pointing to possible alterations in hemostasis of BD patients. Ridge-logistic regression model indicated a molecular signature comprising 9 metabolites, with an area under the receiver operating characteristic curve (AUROC) of 0.833 (95% CI 0.817-0.914). CONCLUSION: From our results, we conclude that several metabolic processes are related to BD, which can be considered as a multi-system disorder. We also demonstrate the feasibility of partial correlation analysis for integration of proteomics and metabolomics data in a case-control study setting.

Temporal Trends, Characteristics, and Outcomes of Infective Endocarditis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Procedural improvements combined with the contemporary clinical profile of patients undergoing transcatheter aortic valve replacement (TAVR) may have influenced the incidence and outcomes of infective endocarditis (IE) following TAVR. We aimed to determine the temporal trends, characteristics, and outcomes of IE post-TAVR. METHODS: Observational study including 552 patients presenting definite IE post-TAVR. Patients were divided in 2 groups according to the timing of TAVR (historical cohort [HC]: before 2014; contemporary cohort [CC]: after 2014). RESULTS: Overall incidence rates of IE were similar in both cohorts (CC vs HC: 5.45 vs 6.52 per 1000 person-years; P = .12), but the rate of early IE was lower in the CC (2.29‰ vs 4.89‰, P < .001). Enterococci were the most frequent microorganism. Most patients presented complicated IE ( CC: 67.7%; HC: 69.6%; P = .66), but the rate of surgical treatment remained low (CC: 20.7%; HC: 17.3%; P = .32). The CC exhibited lower rates of in-hospital acute kidney injury (35.1% vs 44.6%; P = .036) and in-hospital (26.6% vs 36.4%; P = .016) and 1-year (37.8% vs 53.5%; P < .001) mortality. Higher logistic EuroScore, Staphylococcus aureus etiology, and complications (stroke, heart failure, and acute renal failure) were associated with in-hospital mortality in multivariable analyses (P < .05 for all). CONCLUSIONS: Although overall IE incidence has remained stable, the incidence of early IE has declined in recent years. The microorganism, high rate of complications, and very low rate of surgical treatment remained similar. In-hospital and 1-year mortality rates were high but progressively decreased over time.

Patients with COVID-19 who experience a myocardial infarction have complex coronary morphology and high in-hospital mortality: Primary results of a nationwide angiographic study.

OBJECTIVES: We aimed to explore angiographic patterns and in-hospital outcomes of patients with concomitant coronavirus disease-19 (COVID-19) and myocardial infarction (MI). BACKGROUND: Patients with COVID-19 may experience MI during the course of the viral infection. However, this association is currently poorly understood. METHODS: This is a multicenter prospective study of consecutive patients with concomitant COVID-19 and MI who underwent coronary angiography. Quantitative and qualitative coronary angiography were analyzed by two observers in an independent core lab. RESULTS: A total of 152 patients were included, of whom 142 (93.4%) had COVID-19 diagnosis confirmation. The median time between symptom onset and hospital admission was 5 (1-10) days. A total of 83 (54.6%) patients presented with ST-elevation MI. The median angiographic Syntax score was 16 (9.0-25.3) and 69.0% had multi-vessel disease. At least one complex lesion was found in 73.0% of patients, 51.3% had a thrombus containing lesion, and 57.9% had myocardial blush grades 0/1. The overall in-hospital mortality was 23.7%. ST-segment elevation MI presentation and baseline myocardial blush grades 0 or 1 were independently associated with a higher risk of death (HR 2.75, 95%CI 1.30-5.80 and HR 3.73, 95%CI 1.61-8.61, respectively). CONCLUSIONS: Patients who have a MI in the context of ongoing COVID-19 mostly present complex coronary morphologies, implying a background of prior atherosclerotic disease superimposed on a thrombotic milieu. The in-hospital prognosis is poor with a markedly high mortality, prompting further investigation to better clarify this newly described condition.

Polarized Raman spectroscopy in low-symmetry 2D materials: angle-resolved experiments and complex number tensor elements.

In this perspective review, we discuss the power of polarized Raman spectroscopy to study optically anisotropic 2D materials, belonging to the orthorhombic, monoclinic and triclinic crystal families. We start by showing that the polarization dependence of the peak intensities is described by the Raman tensor that is unique for each phonon mode, and then we discuss how to determine the tensor elements from the angle-resolved polarized measurements by analyzing the intensities in both the parallel- and cross-polarized scattering configurations. We present specific examples of orthorhombic black phosphorus and monoclinic 1T'-MoTe2, where the Raman tensors have null elements and their principal axes coincide with the crystallographic ones, followed by a discussion on the results for triclinic ReS2 and ReSe2, where the axes of the Raman tensor do not coincide with the crystallographic axes and all elements are non-zero. We show that the Raman tensor elements are, in general, given by complex numbers and that phase differences between tensor elements are needed to describe the experimental results. We discuss the dependence of the Raman tensors on the excitation laser energy and thickness of the sample within the framework of the quantum model for the Raman intensities. We show that the wavevector dependence of the electron-phonon interaction is essential for explaining the distinct Raman tensor for each phonon mode. Finally, we close with our concluding remarks and perspectives to be explored using angle-resolved polarized Raman spectroscopy in optically anisotropic 2D materials.

Incidence, predictors, and clinical outcomes of coronary obstruction following transcatheter aortic valve replacement for degenerative bioprosthetic surgical valves: insights from the VIVID registry.

Aims: There are limited data on coronary obstruction following transcatheter valve-in-valve (ViV) implantation inside failed aortic bioprostheses. The objectives of this study were to determine the incidence, predictors, and clinical outcomes of coronary obstruction in transcatheter ViV procedures. Methods and results: A total of 1612 aortic procedures from the Valve-in-Valve International Data (VIVID) Registry were evaluated. Data were subject to centralized blinded corelab computed tomography (CT) analysis in a subset of patients. The virtual transcatheter valve to coronary ostium distance (VTC) was determined. A total of 37 patients (2.3%) had clinically evident coronary obstruction. Baseline clinical characteristics in the coronary obstruction patients were similar to controls. Coronary obstruction was more common in stented bioprostheses with externally mounted leaflets or stentless bioprostheses than in stented with internally mounted leaflets bioprostheses (6.1% vs. 3.7% vs. 0.8%, respectively; P < 0.001). CT measurements were obtained in 20 (54%) and 90 (5.4%) of patients with and without coronary obstruction, respectively. VTC distance was shorter in coronary obstruction patients in relation to controls (3.24 ± 2.22 vs. 6.30 ± 2.34, respectively; P < 0.001). Using multivariable analysis, the use of a stentless or stented bioprosthesis with externally mounted leaflets [odds ratio (OR): 7.67; 95% confidence interval (CI): 3.14-18.7; P < 0.001] associated with coronary obstruction for the global population. In a second model with CT data, a shorter VTC distance predicted this complication (OR: 0.22 per 1 mm increase; 95% CI: 0.09-0.51; P < 0.001), with an optimal cut-off level of 4 mm (area under the curve: 0.943; P < 0.001). Coronary obstruction was associated with a high 30-day mortality (52.9% vs. 3.9% in the controls, respectively; P < 0.001). Conclusion: Coronary obstruction following aortic ViV procedures is a life-threatening complication that occurred more frequently in patients with prior stentless or stented bioprostheses with externally mounted leaflets and in those with a short VTC.

Resistance training alone or combined with leucine supplementation improves the serum lipid profile of diabetic rats, whereas leucine alone does not.

OBJECTIVES: Diabetes mellitus is associated with dyslipidemia, which contributes to a higher risk of thrombosis, atherosclerosis and cardiovascular disease. This study evaluated the effects of leucine and resistance training on the serum lipid profile in rats with streptozotocin-induced diabetes for 8 weeks. METHODS: Wistar rats with neonatal streptozotocin-induced diabetes were treated with leucine supplementation (5%) and/or resistance training (3 days per week) for 8 weeks, and divided in DL (diabetic and leucine), DT (diabetic and resistance training group) and DLT (diabetic, leucine and resistance training) groups. Others 2 groups of animals received isonitrogen AIN-93M diet that was defined as a control diet: group D (diabetic untreated) and group C (non-diabetic). RESULTS: The decrease in serum total cholesterol and increase in high-density lipoprotein cholesterol (HDL-C) was observed in the resistance training-induced diabetic rats when compared with diabetic rats. There was no change in serum lipid profile in leucine-supplemented diabetic rats and no synergistic effect of leucine and resistance training. The fasting glucose levels were reduced in all animals treated compared to D group. CONCLUSION: The diabetic trained rats demonstrate a protective effect of resistance training on the serum lipid profile.

Leucine and resistance training improve hyperglycemia, white adipose tissue loss, and inflammatory parameters in an experimental model of type 1 diabetes.

BACKGROUND: Loss of white adipose tissue (WAT), associated with type 1 diabetes (DM1), contributes to increased chronic systemic inflammation. AIM: The aim of this study was to investigate the effects of leucine supplementation and resistance training (RT) in attenuating WAT loss and improving inflammatory parameters and glucose metabolism in DM1 rats. METHODS: Thirty-two male Wistar rats were distributed into four groups: DA (sedentary and supplemented with non-essential amino acids (NEAA)), DL (sedentary and supplemented with leucine), DTA (submitted to RT and supplemented with NEAA) and DTL (submitted to RT and supplemented with leucine). DM1 was induced by streptozotocin (STZ). An 8-week period of RT consisted of climbing a ladder with a progressively increased load, and supplementation was offered in the feed. RESULTS: Glycemia, polyphagia and polydipsia were lower in DL, DTA and DTL groups compared with the DA group by approximately 20% ( p<.0001), 28% ( p=.004) and 64% ( p<.0001), respectively. Weight of total WAT and retroperitoneal adipose tissue (RPAT) were higher by approximately 21% ( p=.01) and 54% ( p=.0004), respectively, in DL, DTA and DTL groups compared with DA. However, gene expression of adiponectin and leptin in RPAT was only increased by RT (DTA and DTL) compared with DA and DL by approximately 93% ( p<.0001) and 78% ( p=.0002), respectively. Similarly, the levels of adiponectin in the serum, tissue IL-10 (RPAT) and serum IL-10 were only increased in DTA and DTL compared with DA and DL by approximately 31% ( p=.03), 45% ( p=.0009) and 35% ( p=.003), respectively. CONCLUSIONS: Both interventions, isolated or together, reduced hyperglycemia and excessive loss of WAT, but RT was the main factor responsible for attenuating inflammation.

Effects of a physical activity and nutritional intervention in overweight and obese children through an educational and recreational camp.

BACKGROUND:: Educational camps have hosted millions of children around the world. However, few studies have described their benefits on weight control and health promotion for overweight and obese children. AIM:: To investigate the impact of a health educational program for children composed of 5 days of camp and a 12-week follow up on the physical activity level, sedentary behaviour, anthropometric data and food intake in overweight and obese children. METHODS:: 12 children attended the Health Educational Program for Children divided into two phases. Phase 1 consisted of pre-assessments and Phase 2 corresponded to 12 weeks of follow up. Physical activity level, sedentary behaviour and food intake were assessed throughout the questionnaire. RESULTS:: After the follow up, 25% of the children became active (>1500 and <3000 Metabolic Equivalent of Tasks per week). In contrast, the number of sedentary children (<600 Metabolic Equivalent of Tasks per week) decreased by 15% and insufficiently active (600-1500 Metabolic Equivalent of Tasks per week) increased by 15%. The physical activity level of leisure time increased significantly throughout weekdays (26.0%) and weekends (14.1%) after the follow up compared to before the camp. Sedentary behaviour showed a significant reduction of 177.14 and 41.43 minutes on weekdays and weekends, respectively. Before the camp, the consumption of sugar and sweets was out of control (100% inadequate), and after the intervention, 58.4% started to consume these foods in a balanced way. CONCLUSIONS:: The Health Educational Program for Children (5-day camp and the 12 weeks of follow up) contributed to an increase in the physical activity level and a reduction in the sedentary behaviour and anthropometric measures in overweight and obese children.