Silylenes with a small chalcogenide substituent: Tuning frontier orbital energies from O to Te.

The general synthesis of heteroleptic acyclic silylenes with a bulky carbazolyl substituent (dtbpCbz) is detailed and a series of compounds with a chalcogenide substituent of the type [(dtbpCbz)SiE16R] (E16R = OtBu, SEt, SePh, TePh) is reported. With the bulky carbazolyl substituent present, the chalcogenide moiety can be very small, as is shown by incorporating groups as small as ethyl, phenyl or tert-butyl. For the first time, the electronic properties of the silylene can be tuned along a complete series of chalcogenide substituents. The effects are clearly visible in the NMR and UV/vis spectra, and were rationalised by DFT computations. The reactivity of the heaviest chalcogenide-substituted silylenes was probed by reactions with trimethylphosphine selenide and the terphenyl azide TerN3 (Ter = 2,6-dimesitylphenyl).

Ureterorenoscopic stone removal without antibiotic prophylaxis.

Purpose To assess the feasibility of sparing routine antibiotic prophylaxis in patients without preoperative urinary tract infection (UTI) undergoing a ureterorenoscopy (URS) for stone removal. Patients and Methods A retrospective, monocentric study was conducted to evaluate the outcome of a modified perioperative antibiotic management strategy according to the principles of antibiotic stewardship (ABS). Patients with preoperative unremarkable urine culture received no antibiotic prophylaxis for ureterorenoscopic stone removal (NoPAP). The NoPAP group was compared to a historic URS cohort, when antibiotic prophylaxis was standard of care. Analysis focused on postoperative complications. Results Postoperative fever occurred in 1% of the NoPAP and 2% of the PAP patients (p= 0.589). Clavien 1-3 complications did not differ between groups with 9% in the NoPAP and 6.2% in the PAP (p= 0.159). No Clavien 4-5 complications were seen. We identified a residual stone (p=0.033) and an ASA-Score 3-4 (p=0.004) as significant risk factors for postoperative fever. By sparing routine antibiotic prophylaxis the overall antibiotic usage was reduced from 100% (PAP) to 8.3% (NoPAP). Conclusion Sparing a routine antibiotic prophylaxis during URS for stone removal seems feasible in patients with unremarkable preoperative urine culture for most of the patients. A prospective validation is warranted.

Sex-specific structural and functional cardiac remodeling during healthy aging assessed by cardiovascular magnetic resonance.

BACKGROUND: Aging as a major non-modifiable cardiac risk factor challenges future cardiovascular medicine and economic demands, which requires further assessments addressing physiological age-associated cardiac changes. OBJECTIVES: Using cardiovascular magnetic resonance (CMR), this study aims to characterize sex-specific ventricular adaptations during healthy aging. METHODS: The population included healthy volunteers who underwent CMR at 1.5 or 3 Tesla scanners applying cine-imaging with a short-axis coverage of the left (LV) and right (RV) ventricle. The cohort was divided by sex (female and male) and age (subgroups in years): 1 (19-29), 2 (30-39), 3 (40-49), and 4 (≥50). Cardiac adaptations were quantitatively assessed by CMR indices. RESULTS: After the exclusion of missing or poor-quality CMR datasets or diagnosed disease, 140 of 203 volunteers were part of the final analysis. Women generally had smaller ventricular dimensions and LV mass, but higher biventricular systolic function. There was a significant age-associated decrease in ventricular dimensions as well as a significant increase in LV mass-to-volume ratio (LV-MVR, concentricity) in both sexes (LV-MVR in g/ml: age group 1 vs. 4: females 0.50 vs. 0.57, p=0.016, males 0.56 vs. 0.67, p=0.024). LV stroke volume index decreased significantly with age in both sexes, but stronger for men than for women (in ml/m2: age group 1 vs. 4: females 51.76 vs. 41.94, p<0.001, males 55.31 vs. 40.78, p<0.001). Ventricular proportions (RV-to-LV-volume ratio) were constant between the age groups in both sexes. CONCLUSIONS: In both sexes, healthy aging was associated with an increase in concentricity and a decline in ventricular dimensions. Furthermore, relevant age-related sex differences in systolic LV performance were observed.

Synthesis and Reactivity of Base-Stabilized and Base-Free Silaimidoyl Bromides.

The reactivity of the base-free bromosilylene dtbpCbzSiBr (dtbpCbz = 1,8-bis(3,5-di-tert-butylphenyl)-3,6-di-tert-butylcarbazolyl) toward carbodiimides and azides was studied in order to generate base-stabilized and base-free silaimidoyl bromides, respectively. The steric bulk of carbodiimides and azides allows control over the reactivity. While with small substituents such as tert-butyl or adamantyl, the reactions cannot be stopped at the Si═N stage, with large substituents, they lead to C-H activation in the product. The Dipp substituent (Dipp = 2,6-diisopropylphenyl) allowed the isolation of the silaimidoyl bromide dtbpCbzSi(Br)NDipp and its CNDipp-coordinated analogue. The reactivity of the Si═N double bond species was studied with respect to cycloaddition and donor exchange reactions.

Erratum: Roadmap for phase change materials in photonics and beyond.

[This corrects the article DOI: 10.1016/j.isci.2023.107946.].

Roadmap for phase change materials in photonics and beyond.

Phase Change Materials (PCMs) have demonstrated tremendous potential as a platform for achieving diverse functionalities in active and reconfigurable micro-nanophotonic devices across the electromagnetic spectrum, ranging from terahertz to visible frequencies. This comprehensive roadmap reviews the material and device aspects of PCMs, and their diverse applications in active and reconfigurable micro-nanophotonic devices across the electromagnetic spectrum. It discusses various device configurations and optimization techniques, including deep learning-based metasurface design. The integration of PCMs with Photonic Integrated Circuits and advanced electric-driven PCMs are explored. PCMs hold great promise for multifunctional device development, including applications in non-volatile memory, optical data storage, photonics, energy harvesting, biomedical technology, neuromorphic computing, thermal management, and flexible electronics.

Multi-site comparison of parametric T1 and T2 mapping: healthy travelling volunteers in the Berlin research network for cardiovascular magnetic resonance (BER-CMR).

BACKGROUND: Parametric mapping sequences in cardiovascular magnetic resonance (CMR) allow for non-invasive myocardial tissue characterization. However quantitative myocardial mapping is still limited by the need for local reference values. Confounders, such as field strength, vendors and sequences, make intersite comparisons challenging. This exploratory study aims to assess whether multi-site studies that control confounding factors provide first insights whether parametric mapping values are within pre-defined tolerance ranges across scanners and sites. METHODS: A cohort of 20 healthy travelling volunteers was prospectively scanned at three sites with a 3 T scanner from the same vendor using the same scanning protocol and acquisition scheme. A Modified Look-Locker inversion recovery sequence (MOLLI) for T1 and a fast low-angle shot sequence (FLASH) for T2 were used. At one site a scan-rescan was performed to assess the intra-scanner reproducibility. All acquired T1- and T2-mappings were analyzed in a core laboratory using the same post-processing approach and software. RESULTS: After exclusion of one volunteer due to an accidentally diagnosed cardiac disease, T1- and T2-maps of 19 volunteers showed no significant differences between the 3 T sites (mean ± SD [95% confidence interval] for global T1 in ms: site I: 1207 ± 32 [1192-1222]; site II: 1207 ± 40 [1184-1225]; site III: 1219 ± 26 [1207-1232]; p = 0.067; for global T2 in ms: site I: 40 ± 2 [39-41]; site II: 40 ± 1 [39-41]; site III 39 ± 2 [39-41]; p = 0.543). CONCLUSION: Parametric mapping results displayed initial hints at a sufficient similarity between sites when confounders, such as field strength, vendor diversity, acquisition schemes and post-processing analysis are harmonized. This finding needs to be confirmed in a powered clinical trial. Trial registration ISRCTN14627679 (retrospectively registered).

Strain-Driven, Non-Catalysed Ring Expansion of Silicon Heterocycles.

Silacycles are ubiquitous building blocks. Small silacycles can typically be expanded catalytically. A silirane, silirene and phosphasilirene as well as a siletane and a silolene were prepared starting from the base-free bromosilylene [(dtbp Cbz)SiBr] (dtbp Cbz=1,8-bis(3,5-ditertbutylphenyl)-3,6-ditertbutylcarbazolyl). As these heterocycles were derived from a dicoordinated silylene, they are susceptible to reactions with an external base. The three-membered silacycles readily undergo non-catalysed ring expansion reactions with isonitriles yielding the related four-membered silacycles. Surprisingly, the ring-expanded derivatives of the silirane undergo up to two further isomerisation reactions, first by enamine formation and then by another ring expansion. DFT computations were utilised to gauge the scope of this reactivity pattern. Three-membered silacycles should essentially universally undergo a ring expansion with isonitriles, while for four-membered silacycles, only very few instances are predicted to accommodate more challenging kinetic requirements of this ring expansion. Larger silacycles lack the ring strain energy required for this ring expansion reaction and are not expected to be expanded.

Cardiac sarcoidosis presenting with complex conduction abnormalities as the first manifestation of widespread systemic sarcoidosis: a case report.

Background: Sarcoidosis is a granulomatous multi-organ disease of unknown aetiology. Despite being relatively rare, cardiac sarcoidosis constitutes a very important manifestation of sarcoidosis, as its symptoms regularly precede or occur in isolation of more prevalent ones, and as it is the main driver of mortality in systemic sarcoidosis. Case summary: We present the case of a 37-year-old woman, in which clinically isolated cardiac sarcoidosis revealed widespread systemic sarcoidosis. Apart from constitutional symptoms and strong recurrent dizziness (i.e. near-syncopes), which persisted for multiple years already, our patient initially presented with complex conduction abnormalities, including a right bundle branch block, left anterior hemi-block, and atrioventricular block °1. Following inconclusive endomyocardial biopsies, performed due to detection of focal septal scarring on cardiac magnetic resonance imaging, an 18F-FDG-PET-CT, performed upon admission to our clinic, showed distinct hypermetabolic lesions indicative of active inflammation in various organs and raised suspicion of systemic sarcoidosis. Eventually, histopathological evidence of non-caseating granulomas in affected lymph nodes, extracted by bronchoscopy, confirmed the diagnosis of systemic sarcoidosis after reasonable exclusion of other granulomatous diseases. Immediate initiation of long-term immunosuppressive therapy led to almost complete remission, as monitored by consequential 18F-FDG-PET-CT scans. Discussion: Unexplained complex conduction abnormalities in young patients may be a sign of sarcoidosis, even in isolation of more prevalent symptoms. Correct interpretation and prompt initiation of a structured interdisciplinary diagnostic workup, including 18F-FDG-PET-CT as the imaging modality of choice, are essential to initiate specific treatment and obviate the major risk of mortality resulting from cardiac sarcoidosis.

Highly tunable ß-relaxation enables the tailoring of crystallization in phase-change materials.

In glasses, secondary (ß-) relaxations are the predominant source of atomic dynamics. Recently, they have been discovered in covalently bonded glasses, i.e., amorphous phase-change materials (PCMs). However, it is unclear what the mechanism of ß-relaxations is in covalent systems and how they are related to crystallization behaviors of PCMs that are crucial properties for non-volatile memories and neuromorphic applications. Here we show direct evidence that crystallization is strongly linked to ß-relaxations. We find that the ß-relaxation in Ge15Sb85 possesses a high tunability, which enables a manipulation of crystallization kinetics by an order of magnitude. In-situ synchrotron X-ray scattering, dielectric functions, and ab-initio calculations indicate that the weakened ß-relaxation intensity stems from a local reinforcement of Peierls-like distortions, which increases the rigidity of the bonding network and decreases the dynamic heterogeneity. Our findings offer a conceptually new approach to tuning the crystallization of PCMs based on manipulating the ß-relaxations.

The illusion of stable fertility preferences.

Fertility preferences have long played a key role in models of fertility differentials and change. We examine the stability of preferences over time using rich panel data on Kenyan women's fertility desires, expectations, actual fertility, and recall of desires in three waves over a nine-year period, when respondents were in their 20s. We find that although desired fertility is quite unstable, most women perceive their desires to be stable. Under hypothetical future scenarios, few expect their desired fertility to increase over time but, in fact, such increases in fertility desires are common. Moreover, when asked to recall past desires, most respondents report previously wanting exactly as many children as they desire today. These patterns of bias are consistent with the emerging view that fertility desires are contextual, emotionally laden, and structured by identity.

Attempted reduction of a carbazolyl-diiodoalane.

We report details of our attempts to reduce the bulky carbazolyl diiodoalane [R-AlI2]. The reducing agents employed include KC8, Cp*2Co and the Mg(I) compound [(MesBDI)Mg]2. The use of KC8 allowed the spectroscopic observation of the alanediyl [R-Al]. With Cp*2Co as the reducing agent, the alanediyl [R-Al] was obtained as a crystalline material in low yield, but paramagnetic impurities remained. When diiodoalane [R-AlI2] was treated with [(MesBDI)Mg]2, no reduction but a 2 : 1 addition was observed.

The potential of chemical bonding to design crystallization and vitrification kinetics.

Controlling a state of material between its crystalline and glassy phase has fostered many real-world applications. Nevertheless, design rules for crystallization and vitrification kinetics still lack predictive power. Here, we identify stoichiometry trends for these processes in phase change materials, i.e. along the GeTe-GeSe, GeTe-SnTe, and GeTe-Sb2Te3 pseudo-binary lines employing a pump-probe laser setup and calorimetry. We discover a clear stoichiometry dependence of crystallization speed along a line connecting regions characterized by two fundamental bonding types, metallic and covalent bonding. Increasing covalency slows down crystallization by six orders of magnitude and promotes vitrification. The stoichiometry dependence is correlated with material properties, such as the optical properties of the crystalline phase and a bond indicator, the number of electrons shared between adjacent atoms. A quantum-chemical map explains these trends and provides a blueprint to design crystallization kinetics.

Short-term results of the combined application of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser and erbium-doped yttrium aluminum garnet (Er:YAG) laser in the treatment of periodontal disease: a randomized controlled trial.

OBJECTIVES: Nd:YAG and Er:YAG lasers have been previously used as an adjunct in periodontal therapy. The aim of this single-blinded randomized controlled clinical trial was to evaluate the efficacy of a combined application of Nd:YAG and Er:YAG laser irradiation in periodontal treatment. MATERIALS AND METHODS: Twenty-two patients with at least one site of ≥ 6 mm periodontal probing depth (PPD) after mechanical debridement with curettes and sonic instruments at periodontal reevaluation were included in the study. Patients were randomly allocated at a 1:1 ratio to either a combined Nd:YAG/Er:YAG laser therapy (test group) or a "turned off" laser therapy (control group). The Nd:YAG laser was used for periodontal pocket deepithelialization and to stabilize the resulting blood clot. The Er:YAG laser was primarily used for root surface modification. PPD (mm), clinical attachment level (CAL, mm), and bleeding on probing (BOP, +/-) at the site of laser treatment were evaluated at baseline and 2 months after treatment. RESULTS: The mean improvements from baseline to 2-month follow-up for PPD were significantly better in the laser group (2.05 ± 0.82 mm) compared to the control group (0.64 ± 0.90 mm; p = 0.001). Likewise, the gain in CAL was significantly better in the laser group (1.50 ± 1.10 mm) than in the control group (0.55 ± 1.01mm; p = 0.046). CONCLUSIONS: The combined application of Nd:YAG and Er:YAG laser irradiation as an adjunct to conventional non-surgical therapy showed a significant beneficial effect on periodontal treatment results. CLINICAL RELEVANCE: Combined Nd:YAG and Er:YAG laser irradiation could be a useful procedure additionally to conventional non-surgical periodontal therapy to improve periodontal treatment results. CLINICAL TRIAL REGISTRATION: ISRCTN registry #ISRCTN32132076.

Storm Event-Driven Occurrence and Transport of Dissolved and Sorbed Organic Micropollutants and Associated Effects in the Ammer River, Southwestern Germany.

Storm events lead to agricultural and urban runoff, to mobilization of contaminated particulate matter, and to input from combined sewer overflows into rivers. We conducted time-resolved sampling during a storm event at the Ammer River, southwest Germany, which is representative of small river systems in densely populated areas with a temperate climate. Suspended particulate matter (SPM) and water from 2 sampling sites were separately analyzed by a multi-analyte liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for 97 environmentally relevant organic micropollutants and with 2 in vitro bioassays. Oxidative stress response (AREc32) may become activated by various stressors covering a broad range of physicochemical properties and induction of aryl hydrocarbon receptor-chemical-activated luciferase gene expression (AhR-CALUX) by hydrophobic compounds such as dioxins and dioxin-like molecules. Compound numbers, concentrations, their mass fluxes, and associated effect fluxes increased substantially during the storm event. Micropollutants detected in water and on SPM pointed toward inputs from combined sewer overflow (e.g., caffeine, paracetamol), urban runoff (e.g., mecoprop, terbutryn), and agricultural areas (e.g., azoxystrobin, bentazone). Particle-facilitated transport of triphenylphosphate and tris(1-chloro-2-propyl) phosphate accounted for up to 34 and 33% of the total mass flux even though SPM concentrations were <1 g L-1 . Effect fluxes attributed to SPM were similar or higher than in the water phase. The important role of SPM-bound transport emphasizes the need to consider not only concentrations but also mass and effect fluxes for surface water quality assessment and wastewater/stormwater treatment options. Environ Toxicol Chem 2021;40:88-99. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Influence of Emission Sources and Tributaries on the Spatial and Temporal Patterns of Micropollutant Mixtures and Associated Effects in a Small River.

Organic micropollutants of anthropogenic origin in river waters may impair aquatic ecosystem health and drinking water quality. To evaluate micropollutant fate and turnover on a catchment scale, information on input source characteristics as well as spatial and temporal variability is required. The influence of tributaries from agricultural and urban areas and the input of wastewater were investigated by grab and Lagrangian sampling under base flow conditions within a 7.7-km-long stretch of the Ammer River (southwest Germany) using target screening for 83 organic micropollutants and 4 in vitro bioassays with environmentally relevant modes of action. In total, 9 pesticides and transformation products, 13 pharmaceuticals, and 6 industrial and household chemicals were detected. Further, aryl hydrocarbon receptor induction, peroxisome proliferator-activated receptor activity, estrogenicity, and oxidative stress response were measured in the river. The vast majority of the compounds and mixture effects were introduced by the effluent of a wastewater-treatment plant, which contributed 50% of the total flow rate of the river on the sampling day. The tributaries contributed little to the overall load of organic micropollutants and mixture effects because of their relatively low discharge but showed a different chemical and toxicological pattern from the Ammer River, though a comparison to effect-based trigger values pointed toward unacceptable surface water quality in the main stem and in some of the tributaries. Chemical analysis and in vitro bioassays covered different windows of analyte properties but reflected the same picture. Environ Toxicol Chem 2020;39:1382-1391. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Emerging therapies in transthyretin amyloidosis - a new wave of hope after years of stagnancy?

Transthyretin amyloidosis (ATTR) is a rare, yet underdiagnosed disease characterized by progressive impairment of neurologic and cardiac function due to deposition of misfolded transthyretin. Despite great efforts, such as the introduction of orthotopic liver transplant, the devastating prognosis for both variant and wild-type ATTR patients remained unchanged over the last decades, mainly due to a lack of specific therapies. Fortunately, recent years saw the introduction of promising targeted therapies, which aim to interfere with the deposition of misfolded transthyretin (TTR) at various stages of the cascade underlying ATTR progression. These include TTR tetramer stabilizers (tafamidis, diflunisal, epigallocatechin-3-gallate), TTR silencers (inotersen, patisiran) and fibril disruptors (monoclonal antibodies, doxycycline and tauroursodeoxycholic acid). In the context of this review we explain their mechanisms of action, analyse their efficacy on neurologic and cardiac function based on all clinical trials conducted to date and discuss their clinical applicability. Eventually suggestions for future clinical research into the field are provided.

Aberrant brain network topology in fronto-limbic circuitry differentiates euthymic bipolar disorder from recurrent major depressive disorder.

INTRODUCTION: Previous studies have established graph theoretical analysis of functional network connectivity (FNC) as a potential tool to detect neurobiological underpinnings of psychiatric disorders. Despite the promising outcomes in studies that examined FNC aberrancies in bipolar disorder (BD) and major depressive disorder (MDD), there is still a lack of research comparing both mood disorders, especially in a nondepressed state. In this study, we used graph theoretical network analysis to compare brain network properties of euthymic BD, euthymic MDD and healthy controls (HC) to evaluate whether these groups showed distinct features in FNC. METHODS: We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 BD patients, 15 patients with recurrent MDD as well as 30 age- and gender-matched HC. Graph theoretical analyses were then applied to investigate functional brain networks on a global and regional network level. RESULTS: Global network analysis revealed a significantly higher mean global clustering coefficient in BD compared to HC. We further detected frontal, temporal and subcortical nodes in emotion regulation areas such as the limbic system and associated regions exhibiting significant differences in network integration and segregation in BD compared to MDD patients and HC. Participants with MDD and HC only differed in frontal and insular network centrality. CONCLUSION: In conclusion, our findings indicate that a significantly altered brain network topology in the limbic system might be a trait marker specific to BD. Brain network analysis in these regions may therefore be used to differentiate euthymic BD not only from HC but also from patients with MDD.

Mitochondrial Toxicity of Selected Micropollutants, Their Mixtures, and Surface Water Samples Measured by the Oxygen Consumption Rate in Cells.

Some environmental pollutants impair mitochondria, which are of vital importance as energy factories in eukaryotic cells. Mitochondrial toxicity was quantified by measuring the change of the oxygen consumption rate (OCR) of HepG2 cells with the Agilent Seahorse XFe 96 Analyzer. Various mechanisms of mitochondrial toxicity, including inhibition of the electron transport chain or adenosine triphosphate (ATP) synthase as well as uncoupling of oxidative phosphorylation, were differentiated by dosing the sample in parallel with reference compounds following the OCR over time. These time-OCR traces were used to derive effect concentrations for 10% inhibition of the electron transport chain or 10% of uncoupling. The low effect level of 10% was necessary because environmental mixtures contain thousands of chemicals; only few of them interfere with mitochondria, but the others cause cytotoxicity. The OCR bioassay was validated with environmental pollutants of known mechanism of mitochondrial toxicity. Binary mixtures of uncouplers or inhibitors acted according to the mixture model of concentration addition. Uncoupling and/or inhibitory effects were detected in extracts of river water samples without apparent cytotoxicity. Uncoupling effects could only be quantified in water samples if inhibitory effects occurred at lower concentrations because no uncoupling can be detected without an appreciable membrane potential built up. The OCR bioassay can thus complement chemical analysis and in vitro bioassays for monitoring micropollutants in water. Environ Toxicol Chem 2019;00:1-12. © 2019 SETAC.

Recurrences of Pituitary Adenomas or Second De Novo Tumors: Comparisons with First Tumors.

BACKGROUND: Recurrences of pituitary adenomas are not so rare. METHODS: In the German Registry of Pituitary Tumors, more than 12,000 surgical specimens were collected between 1967 and 2012, of which 312 patients with altogether 334 recurrences (n = 646 specimens) were included in our study. RESULTS: The histopathology of 162 recurrent adenomas could be compared with the original tumor and 37 second recurrences could be compared with the first recurrence. Comparing the proliferation index (Ki-67) of the original and the first recurrent tumor (n = 162), we found an unchanged index in 43 cases (26%), whereas in 69 cases (43%) the index increased and in 50 cases (31%) it decreased. Comparing the first with the second recurrence (n = 37), we found an unchanged index in 8 cases (22%), an increased index in 15 cases (40%), and a decreased index in 14 cases (38%). The third recurrence showed an unchanged index in 1 case (20%), an increased index in 2 cases (40%), and a decreased index in 2 cases (40%). p53 was unchanged in recurrences in 44% of cases, increased in 33%, and decreased in 22%. In 4 cases, adenomas developed into adenomas with strongly increased proliferation (formerly atypical adenomas, now aggressive adenomas) for the first recurrence, and 9 recurrences became aggressive adenomas. A change of tumor type without change of the common transcription factor occurred in 82 cases. CONCLUSIONS: A second independent de novo adenoma was present in 10 cases, probably due to changes of transcription factors.