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1.
Nat Mater ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831130

RESUMO

The coexistence of correlated electron and hole crystals enables the realization of quantum excitonic states, capable of hosting counterflow superfluidity and topological orders with long-range quantum entanglement. Here we report evidence for imbalanced electron-hole crystals in a doped Mott insulator, namely, α-RuCl3, through gate-tunable non-invasive van der Waals doping from graphene. Real-space imaging via scanning tunnelling microscopy reveals two distinct charge orderings at the lower and upper Hubbard band energies, whose origin is attributed to the correlation-driven honeycomb hole crystal composed of hole-rich Ru sites and rotational-symmetry-breaking paired electron crystal composed of electron-rich Ru-Ru bonds, respectively. Moreover, a gate-induced transition of electron-hole crystals is directly visualized, further corroborating their nature as correlation-driven charge crystals. The realization and atom-resolved visualization of imbalanced electron-hole crystals in a doped Mott insulator opens new doors in the search for correlated bosonic states within strongly correlated materials.

2.
Redox Biol ; 73: 103192, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38776754

RESUMO

BACKGROUND: In animals, dietary sulfur amino acid restriction (SAAR) improves metabolic health, possibly mediated by altering sulfur amino acid metabolism and enhanced anti-obesogenic processes in adipose tissue. AIM: To assess the effects of SAAR over time on the plasma and urine SAA-related metabolites (sulfurome) in humans with overweight and obesity, and explore whether such changes were associated with body weight, body fat and adipose tissue gene expression. METHODS: Fifty-nine subjects were randomly allocated to SAAR (∼2 g SAA, n = 31) or a control diet (∼5.6 g SAA, n = 28) consisting of plant-based whole-foods and supplemented with capsules to titrate contents of SAA. Sulfurome metabolites in plasma and urine at baseline, 4 and 8 weeks were measured using HPLC and LC-MS/MS. mRNA-sequencing of subcutaneous white adipose tissue (scWAT) was performed to assess changes in gene expression. Data were analyzed with mixed model regression. Principal component analyses (PCA) were performed on the sulfurome data to identify potential signatures characterizing the response to SAAR. RESULTS: SAAR led to marked decrease of the main urinary excretion product sulfate (p < 0.001) and plasma and/or 24-h urine concentrations of cystathionine, sulfite, thiosulfate, H2S, hypotaurine and taurine. PCA revealed a distinct metabolic signature related to decreased transsulfuration and H2S catabolism that predicted greater weight loss and android fat mass loss in SAAR vs. controls (all pinteraction < 0.05). This signature correlated positively with scWAT expression of genes in the tricarboxylic acid cycle, electron transport and ß-oxidation (FDR = 0.02). CONCLUSION: SAAR leads to distinct alterations of the plasma and urine sulfurome in humans, and predicted increased loss of weight and android fat mass, and adipose tissue lipolytic gene expression in scWAT. Our data suggest that SAA are linked to obesogenic processes and that SAAR may be useful for obesity and related disorders. TRIAL IDENTIFIER: https://clinicaltrials.gov/study/NCT04701346.

3.
J Chem Phys ; 160(9)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38450733

RESUMO

We review the GPAW open-source Python package for electronic structure calculations. GPAW is based on the projector-augmented wave method and can solve the self-consistent density functional theory (DFT) equations using three different wave-function representations, namely real-space grids, plane waves, and numerical atomic orbitals. The three representations are complementary and mutually independent and can be connected by transformations via the real-space grid. This multi-basis feature renders GPAW highly versatile and unique among similar codes. By virtue of its modular structure, the GPAW code constitutes an ideal platform for the implementation of new features and methodologies. Moreover, it is well integrated with the Atomic Simulation Environment (ASE), providing a flexible and dynamic user interface. In addition to ground-state DFT calculations, GPAW supports many-body GW band structures, optical excitations from the Bethe-Salpeter Equation, variational calculations of excited states in molecules and solids via direct optimization, and real-time propagation of the Kohn-Sham equations within time-dependent DFT. A range of more advanced methods to describe magnetic excitations and non-collinear magnetism in solids are also now available. In addition, GPAW can calculate non-linear optical tensors of solids, charged crystal point defects, and much more. Recently, support for graphics processing unit (GPU) acceleration has been achieved with minor modifications to the GPAW code thanks to the CuPy library. We end the review with an outlook, describing some future plans for GPAW.

4.
Br J Nutr ; 131(10): 1678-1690, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38361451

RESUMO

Elevated plasma concentrations of several one-carbon metabolites are associated with increased CVD risk. Both diet-induced regulation and dietary content of one-carbon metabolites can influence circulating concentrations of these markers. We cross-sectionally analysed 1928 patients with suspected stable angina pectoris (geometric mean age 61), representing elevated CVD risk, to assess associations between dietary macronutrient composition (FFQ) and plasma one-carbon metabolites and related B-vitamin status markers (GC-MS/MS, LC-MS/MS or microbiological assay). Diet-metabolite associations were modelled on the continuous scale, adjusted for age, sex, BMI, smoking, alcohol and total energy intake. Average (geometric mean (95 % prediction interval)) intake was forty-nine (38, 63) energy percent (E%) from carbohydrate, thirty-one (22, 45) E% from fat and seventeen (12, 22) E% from protein. The strongest associations were seen for higher protein intake, i.e. with higher plasma pyridoxal 5'-phosphate (PLP) (% change (95 % CI) 3·1 (2·1, 4·1)), cobalamin (2·9 (2·1, 3·7)), riboflavin (2·4 (1·1, 3·7)) and folate (2·1 (1·2, 3·1)) and lower total homocysteine (tHcy) (-1·4 (-1·9, -0·9)) and methylmalonic acid (MMA) (-1·4 (-2·0, -0·8)). Substitution analyses replacing MUFA or PUFA with SFA demonstrated higher plasma concentrations of riboflavin (5·0 (0·9, 9·3) and 3·3 (1·1, 5·6)), tHcy (2·3 (0·7, 3·8) and 1·3 (0·5, 2·2)) and MMA (2·0 (0·2, 3·9) and 1·7 (0·7, 2·7)) and lower PLP (-2·5 (-5·3, 0·3) and -2·7 (-4·2, -1·2)). In conclusion, a higher protein intake and replacing saturated with MUFA and PUFA were associated with a more favourable metabolic phenotype regarding metabolites associated with CVD risk.


Assuntos
Angina Estável , Dieta , Complexo Vitamínico B , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Angina Estável/sangue , Complexo Vitamínico B/sangue , Complexo Vitamínico B/administração & dosagem , Nutrientes , Biomarcadores/sangue , Proteínas Alimentares/administração & dosagem , Fosfato de Piridoxal/sangue , Gorduras na Dieta/administração & dosagem , Carboidratos da Dieta/administração & dosagem , Ácido Metilmalônico/sangue , Vitamina B 12/sangue
5.
Nat Commun ; 15(1): 932, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38296946

RESUMO

Stacking of two-dimensional (2D) materials has emerged as a facile strategy for realising exotic quantum states of matter and engineering electronic properties. Yet, developments beyond the proof-of-principle level are impeded by the vast size of the configuration space defined by layer combinations and stacking orders. Here we employ a density functional theory (DFT) workflow to calculate interlayer binding energies of 8451 homobilayers created by stacking 1052 different monolayers in various configurations. Analysis of the stacking orders in 247 experimentally known van der Waals crystals is used to validate the workflow and determine the criteria for realisable bilayers. For the 2586 most stable bilayer systems, we calculate a range of electronic, magnetic, and vibrational properties, and explore general trends and anomalies. We identify an abundance of bistable bilayers with stacking order-dependent magnetic or electrical polarisation states making them candidates for slidetronics applications.

6.
J Transl Med ; 22(1): 40, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195568

RESUMO

BACKGROUND: Dietary sulfur amino acid restriction (SAAR) improves metabolic health in animals. In this study, we investigated the effect of dietary SAAR on body weight, body composition, resting metabolic rate, gene expression profiles in white adipose tissue (WAT), and an extensive blood biomarker profile in humans with overweight or obesity. METHODS: N = 59 participants with overweight or obesity (73% women) were randomized stratified by sex to an 8-week plant-based dietary intervention low (~ 2 g/day, SAAR) or high (~ 5.6 g/day, control group) in sulfur amino acids. The diets were provided in full to the participants, and both investigators and participants were blinded to the intervention. Outcome analyses were performed using linear mixed model regression adjusted for baseline values of the outcome and sex. RESULTS: SAAR led to a ~ 20% greater weight loss compared to controls (ß 95% CI - 1.14 (- 2.04, - 0.25) kg, p = 0.013). Despite greater weight loss, resting metabolic rate remained similar between groups. Furthermore, SAAR decreased serum leptin, and increased ketone bodies compared to controls. In WAT, 20 genes were upregulated whereas 24 genes were downregulated (FDR < 5%) in the SAAR group compared to controls. Generally applicable gene set enrichment analyses revealed that processes associated with ribosomes were upregulated, whereas processes related to structural components were downregulated. CONCLUSION: Our study shows that SAAR leads to greater weight loss, decreased leptin and increased ketone bodies compared to controls. Further research on SAAR is needed to investigate the therapeutic potential for metabolic conditions in humans. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04701346, registered Jan 8th 2021, https://www. CLINICALTRIALS: gov/study/NCT04701346.


Assuntos
Aminoácidos Sulfúricos , Sobrepeso , Feminino , Humanos , Masculino , Corpos Cetônicos , Leptina , Obesidade , Redução de Peso
7.
ACS Nano ; 17(16): 15441-15448, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37552585

RESUMO

Emergent quantum phenomena in two-dimensional van der Waal (vdW) magnets are largely governed by the interplay between exchange and Coulomb interactions. The ability to precisely tune the Coulomb interaction enables the control of spin-correlated flat-band states, band gap, and unconventional magnetism in such strongly correlated materials. Here, we demonstrate a gate-tunable renormalization of spin-correlated flat-band states and bandgap in magnetic chromium tribromide (CrBr3) monolayers grown on graphene. Our gate-dependent scanning tunneling spectroscopy (STS) studies reveal that the interflat-band spacing and bandgap of CrBr3 can be continuously tuned by 120 and 240 meV, respectively, via electrostatic injection of carriers into the hybrid CrBr3/graphene system. This can be attributed to the self-screening of CrBr3 arising from the gate-induced carriers injected into CrBr3, which dominates over the weakened remote screening of the graphene substrate due to the decreased carrier density in graphene. Precise tuning of the spin-correlated flat-band states and bandgap in 2D magnets via electrostatic modulation of Coulomb interactions not only provides effective strategies for optimizing the spin transport channels but also may exert a crucial influence on the exchange energy and spin-wave gap, which could raise the critical temperature for magnetic order.

8.
Diabetes Obes Metab ; 25(11): 3161-3170, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37435697

RESUMO

AIM: To investigate whether mesna-sodium-2-mercaptoethane sulfonate) can reduce diet-induced fat gain in mice, and to assess the safety of single ascending mesna doses in humans to find the dose associated with lowering of plasma tCys by at least 30%. METHODS: C3H/HeH mice were shifted to a high-fat diet ± mesna in drinking water; body composition was measured at weeks 0, 2 and 4. In an open, phase I, single ascending dose study, oral mesna (400, 800, 1200, 1600 mg) was administered to 17 men with overweight or obesity. Mesna and tCys concentrations were measured repeatedly for a duration of 48 hours postdosing in plasma, as well as in 24-hour urine. RESULTS: Compared with controls, mesna-treated mice had lower tCys and lower estimated mean fat mass gain from baseline (week 2: 4.54 ± 0.40 vs. 6.52 ± 0.36 g; week 4: 6.95 ± 0.35 vs. 8.19 ± 0.34 g; Poverall = .002), but similar lean mass gain. In men with overweight, mesna doses of 400-1600 mg showed dose linearity and were well tolerated. Mesna doses of 800 mg or higher decreased plasma tCys by 30% or more at nadir (4h post-dosing). With increasing mesna dose, tCys AUC0-12h decreased (Ptrend < .001), and urine tCys excretion increased (Ptrend = .004). CONCLUSIONS: Mesna reduces diet-induced fat gain in mice. In men with overweight, single oral doses of mesna (800-1600 mg) were well tolerated and lowered plasma tCys efficiently. The effect of sustained tCys-lowering by repeated mesna administration on weight loss in humans deserves investigation.


Assuntos
Cisteína , Mesna , Humanos , Masculino , Mesna/farmacologia , Camundongos Endogâmicos C3H , Obesidade/tratamento farmacológico , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Animais , Camundongos , Ensaios Clínicos Fase I como Assunto
9.
Europace ; 25(6)2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37345858

RESUMO

AIMS: Use of an absorbable antibacterial envelope during implantation prevents cardiac implantable electronic device infections in patients with a moderate-to-high infection risk. Previous studies demonstrated that an envelope is cost-effective in high-risk patients within German, Italian, and English healthcare systems, but these analyses were based on limited data and may not be generalizable to other healthcare settings. METHODS AND RESULTS: A previously published decision-tree-based cost-effectiveness model was used to compare the costs per quality-adjusted life year (QALY) associated with adjunctive use of an antibacterial envelope for infection prevention compared to standard-of-care intravenous antibiotics. The model was adapted using data from a Danish observational two-centre cohort study that investigated infection-risk patients undergoing cardiac resynchronization therapy (CRT) reoperations with and without an antibacterial envelope (n = 1943). We assumed a cost-effectiveness threshold of €34 125/QALY gained, based on the upper threshold used by the National Institute for Health and Care Excellence (£30 000). An antibacterial envelope was associated with an incremental cost-effectiveness ratio (ICER) of €12 022 per QALY in patients undergoing CRT reoperations, thus indicating that the envelope is cost-effective when compared with standard of care. A separate analysis stratified by device type showed ICERS of €6227 (CRT defibrillator) and €29 177 (CRT pacemaker) per QALY gained. CONCLUSIONS: Cost-effectiveness ratios were favourable for patients undergoing CRT reoperations in the Danish healthcare system, and thus are in line with previous studies. Results from this study can contribute to making the technology available to Danish patients and align preventive efforts in the pacemaker and ICD area.


Assuntos
Terapia de Ressincronização Cardíaca , Humanos , Reoperação , Terapia de Ressincronização Cardíaca/efeitos adversos , Análise Custo-Benefício , Estudos de Coortes , Antibacterianos/uso terapêutico , Dinamarca
10.
J Nutr ; 153(7): 2027-2040, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37164267

RESUMO

BACKGROUND: Plasma sulfur amino acids (SAAs), i.e., methionine, total cysteine (tCys), total homocysteine (tHcy), cystathionine, total glutathione (tGSH), and taurine, are potential risk factors for obesity and cardiometabolic disorders. However, except for plasma tHcy, little is known about how dietary intake modifies plasma SAA concentrations. OBJECTIVE: To investigate whether the intake of SAAs and proteins or diet quality is associated with plasma SAAs. METHODS: Data from a cross-sectional subset of The Maastricht Study (n = 1145, 50.5% men, 61 interquartile range: [55, 66] y, 22.5% with prediabetes and 34.3% with type 2 diabetes) were investigated. Dietary intake was assessed using a validated food frequency questionnaire. The intake of SAAs (total, methionine, and cysteine) and proteins (total, animal, and plant) was estimated from the Dutch and Danish food composition tables. Diet quality was assessed using the Dutch Healthy Diet Index, the Mediterranean Diet Score, and the Dietary Approaches to Stop Hypertension score. Fasting plasma SAAs were measured by liquid chromatography (LC) tandem mass spectrometry (MS) (LC/MS-MS). Associations were investigated with multiple linear regressions with tertiles of dietary intake measures (main exposures) and z-standardized plasma SAAs (outcomes). RESULTS: Intake of total SAAs and total proteins was positively associated with plasma tCys and cystathionine. Associations were stronger in women and in those with normal body weight. Higher intake of cysteine and plant proteins was associated with lower plasma tHcy and higher cystathionine. Higher methionine intake was associated with lower plasma tGSH, whereas cysteine intake was positively associated with tGSH. Higher intake of methionine and animal proteins was associated with higher plasma taurine. Better diet quality was consistently related to lower plasma tHcy concentrations, but it was not associated with the other SAAs. CONCLUSION: Targeted dietary modifications might be effective in modifying plasma concentrations of tCys, tHcy, and cystathionine, which have been associated with obesity and cardiometabolic disorders.


Assuntos
Aminoácidos Sulfúricos , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Cisteína , Cistationina , Estudos Transversais , Dieta , Metionina , Obesidade , Taurina , Homocisteína
11.
Cell Rep ; 42(5): 112499, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37178122

RESUMO

Physical activity is associated with beneficial adaptations in human and rodent metabolism. We studied over 50 complex traits before and after exercise intervention in middle-aged men and a panel of 100 diverse strains of female mice. Candidate gene analyses in three brain regions, muscle, liver, heart, and adipose tissue of mice indicate genetic drivers of clinically relevant traits, including volitional exercise volume, muscle metabolism, adiposity, and hepatic lipids. Although ∼33% of genes differentially expressed in skeletal muscle following the exercise intervention are similar in mice and humans independent of BMI, responsiveness of adipose tissue to exercise-stimulated weight loss appears controlled by species and underlying genotype. We leveraged genetic diversity to generate prediction models of metabolic trait responsiveness to volitional activity offering a framework for advancing personalized exercise prescription. The human and mouse data are publicly available via a user-friendly Web-based application to enhance data mining and hypothesis development.


Assuntos
Adaptação Fisiológica , Transcriptoma , Masculino , Pessoa de Meia-Idade , Humanos , Feminino , Camundongos , Animais , Transcriptoma/genética , Obesidade/metabolismo , Aclimatação , Tecido Adiposo/metabolismo , Músculo Esquelético/metabolismo
12.
Physiol Rep ; 11(7): e15658, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37020398

RESUMO

Whole-room indirect calorimeters (WRICs) provide accurate instruments for the measurement of respiratory exchange, energy expenditure, and macronutrient oxidation. Here, we aimed to determine the validity and reproducibility of a 7500 L WRIC for the measurement of ventilation rates and resting metabolic rate (RMR). Technical validation was performed with propane combustion tests (n = 10) whereas biological reproducibility was tested in healthy subjects (13 women, 6 men, mean ± SD age 39.6 ± 15.3) in two 60 min measurements separated by 24 h. Subjects followed a run-in protocol prior to measurements. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for ventilation rates of O2 (VO2), CO2 (VCO2), the respiratory quotient (RQ; VCO2/VO2), and RMR. Technical validation showed good validity with CVs ranging from 0.67% for VO2 to 1.00% for energy expenditure. For biological reproducibility, CVs were 2.89% for VO2 ; 2.67% for VCO2 ; 1.95% for RQ; and 2.68% for RMR. With the exception of RQ (74%), ICCs were excellent for VO2 (94%), VCO2 (96%) and RMR (95%). Excluding participants that deviated from the run-in protocol did not alter results. In conclusion, the 7500 L WRIC is technically valid and reproducible for ventilation rates and RMR.


Assuntos
Metabolismo Basal , Metabolismo Energético , Masculino , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Calorimetria Indireta/métodos , Taxa Respiratória , Consumo de Oxigênio , Dióxido de Carbono/metabolismo
14.
J Cataract Refract Surg ; 49(6): 556-557, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36753322

RESUMO

Improvement in biometry and formulas has raised the bar for accurate intraocular lens (IOL) power calculation. However, when we look closely at the performance of a specific IOL model, we often find that the prediction error varies with the implant power. This phenomenon has no explanation other than that the optic design of the IOL has shifted over the power range, thereby disrupting the assumptions of the calculations. By this report, we call the industry to be more transparent and disclose the basic information about the IOL design that is important for accurate IOL power calculation. The relevant information concerns the refractive index, the central optic thickness, the anterior and posterior curvature radii, the toricity location, the spherical aberration, and haptic angulation. The goal is to predict possible shifts in principal planes or IOL position over the power range causing a refractive surprise if not corrected for.


Assuntos
Lentes Intraoculares , Facoemulsificação , Cirurgiões , Humanos , Refração Ocular , Olho , Testes Visuais , Biometria , Óptica e Fotônica , Estudos Retrospectivos
15.
J Intern Med ; 293(4): 508-519, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36682040

RESUMO

BACKGROUND: Elevated plasma methylmalonic acid (MMA) is reported in patients with established coronary heart disease (CHD) and is considered a marker of vitamin B12 deficiency. Moreover, MMA-dependent reactions have been linked to alterations in mitochondrial energy metabolism and oxidative stress, key features in the pathophysiology of cardiovascular diseases (CVDs). OBJECTIVES: We examined whether plasma MMA prospectively predicted the long-term risk of acute myocardial infarction (AMI) and mortality. METHODS AND RESULTS: Using Cox modeling, we estimated hazard ratios (HRs) for endpoints according to per 1-SD increment of log-transformed plasma MMA in two independent populations: the Western Norway Coronary Angiography Cohort (WECAC) (patients evaluated for CHD; n = 4137) and the Norwegian Vitamin Trial (NORVIT) (patients hospitalized with AMI; n = 3525). In WECAC and NORVIT, 12.8% and 18.0% experienced an AMI, whereas 21.8% and 19.9% died, of whom 45.5% and 60.3% from CVD-related causes during follow-up (range 3-11 years), respectively. In WECAC, age- and gender-adjusted HRs (95% confidence interval) were 1.18 (1.09-1.28), 1.25 (1.18-1.33), and 1.28 (1.17-1.40) for future AMI, total mortality, and CVD mortality, respectively. Corresponding risk estimates were 1.19 (1.10-1.28), 1.22 (1.14-1.31), and 1.30 (1.19-1.42) in NORVIT. These estimates were only slightly attenuated after multivariable adjustments. Across both cohorts, the MMA-risk association was stronger in older adults, women, and non-smokers. CONCLUSIONS: Elevated MMA was associated with an increased risk of AMI and mortality in patients with suspected or verified CHD.


Assuntos
Doença das Coronárias , Infarto do Miocárdio , Humanos , Feminino , Idoso , Ácido Metilmalônico , Estudos de Coortes , Estudos Prospectivos , Biomarcadores , Fatores de Risco
16.
J Phys Condens Matter ; 35(10)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36595249

RESUMO

We present a plane wave implementation of the magnetic force theorem, which provides a first principles framework for extracting exchange constants parameterizing a classical Heisenberg model description of magnetic materials. It is shown that the full microscopic exchange tensor may be expressed in terms of the static Kohn-Sham susceptibility tensor and the exchange-correlation magnetic field. This formulation allows one to define arbitrary magnetic sites localized to predefined spatial regions, hence rendering the problem of finding Heisenberg parameters independent of any orbital decomposition of the problem. The susceptibility is calculated in a plane wave basis, which allows for systematic convergence with respect to unoccupied bands and spatial representation. We then apply the method to the well-studied problem of calculating adiabatic spin wave spectra for bulk Fe, Co and Ni, finding good agreement with previous calculations. In particular, we utilize the freedom of defining magnetic sites to show that the calculated Heisenberg parameters are robust towards changes in the definition of magnetic sites. This demonstrates that the magnetic sites can be regarded as well-defined and thus asserts the relevance of the Heisenberg model description despite the itinerant nature of the magnetic state.

18.
Amino Acids ; 55(3): 313-323, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36542145

RESUMO

People with high plasma total cysteine (tCys) have higher fat mass and higher concentrations of the atherogenic apolipoprotein B (apoB). The disulfide form, cystine, enhanced human adipogenesis and correlated with total fat mass in a Middle-Eastern cohort. In 35 European adults with overweight (88.6% women) and with dual-X-ray absorptiometry measurements of regional fat, we investigated how cystine compared to other free disulfides in their association with total regional adiposity, plasma lipid and glucose biomarkers, and adipose tissue lipid enzyme mRNA (n = 19). Most total plasma homocysteine (tHcy) (78%) was protein-bound; 63% of total glutathione (tGSH) was reduced. tCys was 49% protein-bound, 30% mixed-disulfide, 15% cystine, and 6% reduced. Controlling for age and lean mass, cystine and total free cysteine were the fractions most strongly associated with android and total fat: 1% higher cystine predicted 1.97% higher android fat mass (95% CI 0.64, 3.31) and 1.25% (0.65, 2.98) higher total fat mass (both p = 0.005). A positive association between tCys and apoB (ß: 0.64%; 95% CI 0.17, 1.12%, p = 0.009) was apparently driven by free cysteine and cystine; cystine was also inversely associated with the HDL-associated apolipoprotein A1 (ß: -0.57%; 95% CI -0.96, -0.17%, p = 0.007). No independent positive associations with adiposity were noted for tGSH or tHcy fractions. Plasma cystine correlated with CPT1a mRNA (Spearman's r = 0.68, p = 0.001). In conclusion, plasma cystine-but not homocysteine or glutathione disulfides-is associated with android adiposity and an atherogenic plasma apolipoprotein profile. The role of cystine in human adiposity and cardiometabolic risk deserves investigation. ClinicalTrials.gov identifiers: NCT02647970 and NCT03629392.


Assuntos
Cisteína , Compostos de Sulfidrila , Adulto , Humanos , Feminino , Masculino , Composição Corporal , Cistina , Tecido Adiposo , Obesidade , Jejum , Biomarcadores , Lipídeos , Apolipoproteínas B/genética , Glutationa , Expressão Gênica , Índice de Massa Corporal
19.
Eur J Nutr ; 62(2): 891-904, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36322288

RESUMO

PURPOSE: Sulfur amino acids (SAAs) have been associated with obesity and obesity-related metabolic diseases. We investigated whether plasma SAAs (methionine, total cysteine (tCys), total homocysteine, cystathionine and total glutathione) are related to specific fat depots. METHODS: We examined cross-sectional subsets from the CODAM cohort (n = 470, 61.3% men, median [IQR]: 67 [61, 71] years) and The Maastricht Study (DMS; n = 371, 53.4% men, 63 [55, 68] years), enriched with (pre)diabetic individuals. SAAs were measured in fasting EDTA plasma with LC-MS/MS. Outcomes comprised BMI, skinfolds, waist circumference (WC), dual-energy X-ray absorptiometry (DXA, DMS), body composition, abdominal subcutaneous and visceral adipose tissues (CODAM: ultrasound, DMS: MRI) and liver fat (estimated, in CODAM, or MRI-derived, in DMS, liver fat percentage and fatty liver disease). Associations were examined with linear or logistic regressions adjusted for relevant confounders with z-standardized primary exposures and outcomes. RESULTS: Methionine was associated with all measures of liver fat, e.g., fatty liver disease [CODAM: OR = 1.49 (95% CI 1.19, 1.88); DMS: OR = 1.51 (1.09, 2.14)], but not with other fat depots. tCys was associated with overall obesity, e.g., BMI [CODAM: ß = 0.19 (0.09, 0.28); DMS: ß = 0.24 (0.14, 0.34)]; peripheral adiposity, e.g., biceps and triceps skinfolds [CODAM: ß = 0.15 (0.08, 0.23); DMS: ß = 0.20 (0.12, 0.29)]; and central adiposity, e.g., WC [CODAM: ß = 0.16 (0.08, 0.25); DMS: ß = 0.17 (0.08, 0.27)]. Associations of tCys with VAT and liver fat were inconsistent. Other SAAs were not associated with body fat. CONCLUSION: Plasma concentrations of methionine and tCys showed distinct associations with different fat depots, with similar strengths in the two cohorts.


Assuntos
Aminoácidos Sulfúricos , Hepatopatias , Masculino , Humanos , Feminino , Aminoácidos Sulfúricos/metabolismo , Estudos Transversais , Cromatografia Líquida , Espectrometria de Massas em Tandem , Tecido Adiposo/metabolismo , Obesidade , Cisteína , Metionina , Hepatopatias/metabolismo , Índice de Massa Corporal , Adiposidade , Gordura Intra-Abdominal/metabolismo
20.
J Interv Card Electrophysiol ; 66(4): 897-904, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35499775

RESUMO

PURPOSE: Cardiac surgery in patients with cardiac implantable electronic devices (CIEDs) has been associated with a higher risk of infective endocarditis, but how it influences risk of CIED-specific infections is not known. Our aim was to examine risk of systemic CIED infections after cardiac surgery in patients with CIEDs. METHODS: Based on data obtained from Danish administrative registries and the Danish Pacemaker and ICD Register, we conducted a case-control study nested within a nationwide cohort of patients who underwent a de novo CIED implantation in Denmark between 1998 and 2017. We defined cases as incident systemic CIED infections resulting in device system extraction. Controls were sampled 1:100 on time, age, sex and device type using risk set sampling. Exposure was defined as coronary artery bypass graft, or cardiac heart valve replacement or repair surgery. RESULTS: From a study cohort comprising 67,621 patients, we identified 170 cases and 16,788 controls. In the minimally adjusted model, the incidence rate ratio (IRR) for systemic CIED infection was 6.4 (95% confidence interval (CI) 3.8-10.7) with cardiac surgery, and after additional confounder adjustment, 5.4 (95% CI 3.2-9.2). IRRs were higher with restriction to heart valve replacement surgery (adjusted IRR 7.5, 95% CI 4.0-16.6), and when limiting our exposure time window to one year (adjusted IRR 10.1, 95% CI 4.5-22.3). CONCLUSION: Cardiac surgery in patients with de novo CIEDs was associated with a high risk of systemic CIED infections. Highest risk was observed after heart valve replacement surgery and within the first year of surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Desfibriladores Implantáveis , Marca-Passo Artificial , Infecções Relacionadas à Prótese , Humanos , Estudos de Casos e Controles , Desfibriladores Implantáveis/efeitos adversos , Fatores de Risco , Marca-Passo Artificial/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Estudos Retrospectivos , Infecções Relacionadas à Prótese/epidemiologia
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