Swiss Survey on current practices and opinions on clinical constellations triggering the search for PNH clones.

This national survey investigated the current practice in Switzerland by collecting participants' opinions on paroxysmal nocturnal hemoglobinuria (PNH) clone assessment and clinical practice. Aim: This study aimed to investigate clinical indications prompting PNH clones' assessment and physician's accessibility of a flow cytometry facility, and also to understand clinical attitudes on the follow-up (FU) of patients with PNH clones. Methods: The survey includes 16 multiple-choice questions related to PNH and targets physicians with a definite level of experience in the topic using two screener questions. Opinion on clinical management was collected using hypothetical clinical situations. Each participant had the option of being contacted to further discuss the survey results. This was an online survey, and 264 physicians were contacted through email once a week for 5 weeks from September 2020. Results: In total, 64 physicians (24.2%) from 23 institutions participated (81.3% hematologists and 67.2% from university hospitals). All had access to flow cytometry for PNH clone testing, with 76.6% having access within their own institution. The main reasons to assess for PNH clones were unexplained thrombosis and/or hemolysis, and/or aplastic anemia (AA). Patients in FU for PNH clones were more likely to be aplastic anemia (AA) and symptomatic PNH. In total, 61% of the participants investigated PNH clones repetitively during FU in AA/myelodysplastic syndromes patients, even when there was no PNH clone found at diagnosis, and 75% of the participants tested at least once a year during FU. Opinions related to clinical management were scattered. Conclusion: The need to adhere to guidelines for the assessment, interpretation, and reporting of PNH clones emerges as the most important finding, as well as consensus for the management of less well-defined clinical situations. Even though there are several international guidelines, clear information addressing specific topics such as the type of anticoagulant to use and its duration, as well as the indication for treatment with complement inhibitors in some borderline situations are needed. The analysis and the discussion of this survey provide the basis for understanding the unmet needs of PNH clone assessment and clinical practice in Switzerland.

Impact of Molecular Orientation on Lateral and Interfacial Electron Transfer at Oxide Interfaces.

Molecular dyes, called sensitizers, with a cis-[Ru(LL)(dcb)(NCS)2] structure, where dcb is 4,4'-(CO2H)2-2,2'-bipyridine and LL is dcb or a different diimine ligand, are among the most optimal for application in dye-sensitized solar cells (DSSCs). Herein, a series of five sensitizers, three bearing two dcb ligands and two bearing one dcb ligand, were anchored to mesoporous thin films of conducting tin-doped indium oxide (ITO) or semiconducting TiO2 nanocrystallites. The number of dcb ligands impacts the surface orientation of the sensitizer; density functional theory (DFT) calculations revealed an ∼1.6 Å smaller distance between the oxide surface and the Ru metal center for sensitizers with two dcb ligands. Interfacial electron transfer kinetics from the oxide material to the oxidized sensitizer were measured as a function of the thermodynamic driving force. Analysis of the kinetic data with Marcus-Gerischer theory indicated that the electron coupling matrix element, Hab, was sensitive to distance and ranged from Hab = 0.23 to 0.70 cm-1, indicative of nonadiabatic electron transfer. The reorganization energies, λ, were also sensitive to the sensitizer location within the electric double layer and were smaller, with one exception, for sensitizers bearing two dcb ligands λ = 0.40-0.55 eV relative to those with one λ = 0.63-0.66 eV, in agreement with dielectric continuum theory. Electron transfer from the oxide to the photoexcited sensitizer was observed when the diimine ligand was more easily reduced than the dcb ligand. Lateral self-exchange "hole hopping" electron transfer between surface-anchored sensitizers was found to be absent for sensitizers with two dcb ligands, while those with only one were found to hop with rates similar to those previously reported in the literature, khh = 47-89 µs-1. Collectively, the kinetic data and analysis reveal that interfacial kinetics are highly sensitive to the surface orientation and sensitizers bearing two dcb ligands are most optimal for practical applications of DSSCs.

Adherence to thrombophilia testing guidelines and its influence on anticoagulation therapy: A single-center cross-sectional study.

INTRODUCTION: The collected evidence on thrombophilia guidelines is scarce and data about their impact on clinical decisions are unknown. We aimed to investigate the adherence to thrombophilia testing guidelines, its therapeutic impact in patients with guideline-adherent and non-adherent testing and identify the patients' clinical characteristics mostly associated with treatment decisions. MATERIALS AND METHODS: We conducted a single-center cross-sectional study of patients referred for thrombophilia testing at the outpatient clinic of a tertiary hospital between 01/2010-10/2020. We systematically evaluated the adherence of thrombophilia testing to internal guidelines and the influence of test results on anticoagulation therapy. Using multivariable logistic regression, we evaluated the association between clinical characteristics and influence of thrombophilia tests on anticoagulation therapy in the entire cohort and by indication for referral. RESULTS: Of 3686 included patients, mostly referred for venous thromboembolism (2407, 65 %) or arterial thrombosis (591, 16 %), 3550 patients (96 %) underwent thrombophilia testing. Indication for testing was according to guidelines in 1208 patients (33 %). Test results influenced treatment decisions in 56 of 1102 work-ups (5.1 %) that were adherent to guidelines, and in 237 of 2448 (9.7 %) non-adherent work-ups (absolute difference, 4.3 %; 95 % confidence interval, 2.9-6.3 %). Age < 50 years, female sex, absence of risk factors and co-morbidities, weakly provoked venous thromboembolism and referral indication other than venous thromboembolism were associated with influence on anticoagulation therapy. CONCLUSIONS: Adherence to guidelines for thrombophilia testing was poor and did not have an impact on treatment decisions. Refinement of selection criteria is needed to increase the therapeutic impact of thrombophilia testing.

Spectroscopic and kinetic characterization of photogenerated charge carriers in photocatalysts.

The catastrophic consequences of increased power consumption, such as drastically rising CO2 levels, natural disasters, environmental pollution and dependence on fossil fuels supplied by countries with totalitarian regimes, illustrate the urge to develop sustainable technologies for energy generation. Photocatalysis presents eco-friendly means for fuels production via solar-to-chemical energy conversion. The conversion efficiency of a photocatalyst critically depends on charge carrier processes taking place in the ultrafast time regime. Transient absorption spectroscopy (TAS) serves as a perfect tool to track those processes. The spectral and kinetic characterization of charge carriers is indispensable for the elucidation of photocatalytic mechanisms and for the development of new materials. Hence, in this review, we will first present the basics of TAS and subsequently discuss the procedure required for the interpretation of the transient absorption spectra and transient kinetics. The discussion will include specific examples for charge carrier processes occurring in conventional and plasmonic semiconductors.

Reorganization Energies for Interfacial Proton-Coupled Electron Transfer to a Water Oxidation Catalyst.

The reorganization energy (λ) for interfacial electron transfer (ET) and proton-coupled ET (PCET) from a conductive metal oxide (In2O3:Sn, ITO) to a surface-bound water oxidation catalyst was extracted from kinetic data measured as a function of the thermodynamic driving force. Visible light excitation resulted in rapid excited-state injection (kinj > 108 s-1) to the ITO, which photo-initiated the two interfacial reactions of interest. The rate constants for both reactions increased with the driving force, -ΔG°, to a saturating limit, kmax, with rate constants consistently larger for ET than for PCET. Marcus-Gerischer analysis of the kinetic data provided the reorganization energy for interfacial PCET (0.90 ± 0.02 eV) and ET (0.40 ± 0.02 eV), respectively. The magnitude of kmax for PCET was found to decrease with pH, behavior that was absent for ET. Both the decrease in kmax and the larger reorganization energy for an unwanted competing PCET reaction from the ITO to the oxidized catalyst showcases a significant kinetic advantage for driving solar water oxidation at high pH. Computational analysis revealed a larger inner-sphere reorganization energy contribution for PCET than for ET arising from a more significant change in the Ru-O bond length for the PCET reaction. Extending the Marcus-Gerischer theory to PCET by including the excited electron-proton vibronic states and the proton donor-acceptor motion provided an apparent reorganization energy of 1.01 eV. This study demonstrates that the Marcus-Gerischer theory initially developed for ET can be reliably extended to PCET for quantifying and interpreting reorganization energies observed experimentally.

Characterization Methodology and Activity Evaluation of Solar-Driven Catalysts for Environmental Remediation.

Solar-driven photocatalysis mediated by semiconductors has been rapidly developed as a green and sustainable technology for environmental remediation. Continuous efforts have been devoted to novel semiconducting photocatalysts to boost the efficiency of the photocatalytic system. However, controversy has widely existed in materials characterization and photocatalytic activity evaluation. This review overviews the recent advances in characterization methodology and photocatalytic activity evaluation of solar-driven catalysts (SDCs) for environmental remediation. After a general and brief introduction of different SDCs, the compositional, structural, and optical characterizations of SDCs are summarized. Moreover, the characterization methods and challenges in the doped and coupled SDCs are discussed. Finally, the challenges in the evaluation of current evaluation methods for the photocatalytic activity of SDCs are highlighted.

Controllable synthesis and self-template phase transition of hydrous TiO2 colloidal spheres for photo/electrochemical applications.

Hydrous TiO2 colloidal spheres (HTCS) derived from the direct precipitation of titanium alkoxides have attracted continuous interests since 1982. Entering the 21st century, rapid progress in the development of structure-directing agents (SDAs) have enabled reproducible and size-controllable synthesis of highly uniform HTCS with diameters in the nano- to micro-meter range. The availability of various HTCS provides versatile self-templating platforms for the targeted synthesis of nanoporous TiO2 and titanate spheres with tunable composition, crystallographic phases, and internal structures for a variety of advanced photo/electrochemical applications. This review provides a historical overview for the evolution of HTCS, along with an insightful discussion for the formation mechanism of self-assembly of HTCS during the sol-gel process. Key synthetic parameters including SDA, solvent, reaction temperature and water dosage are discussed for the size and morphology control of HTCS with predictable textural properties. Then, we describe the synthetic strategies of nanoporous TiO2 and titanate spheres using various HTCS as self-templates. Here, the focus lies on the interactions between TiO2 nanobuilding blocks with precursors or media at the solid/liquid and solid/solid interfaces, the concurrent phase transitions, and the microstructural and morphological evolutions. Selective formation of crystal phase and internal structures (e.g., solid, hollow, core-shell, yolk-shell) are discussed by manipulating the crystallization kinetics. To further elucidate the composition-structure-property-performance relationship for the resulting nanoporous TiO2 and titanate spheres, their applications in photo(electro)catalysis, mesoscopic solar cells, and lithium-ion batteries are scrutinized. Finally, we share opinions on key challenges and perspectives for the future controllable preparation, formation mechanisms, and applications of HTCS and their crystalline derivatives.

The performance and accuracy of depression screening tools capable of self-administration in primary care: A systematic review and meta-analysis

Background and Objectives: The US Preventative Services Taskforce recommends screening adults for depression in primary care where adequate systems are established to ensure accurate diagnosis, effective treatment and follow-up. However, there is currently no consensus on which screening tool is most suitable for use in primary healthcare. We aim to systematically review the literature for operating characteristics of depression screening tools capable of self-administration in primary healthcare and meta-analyse the psychometric characteristics of these tools to determine their performance and accuracy.MethodsAn electronic literature search of EMBASE, Medline and CINAHL Complete was conducted from January 1982 to September 15, 2019 using the keywords: depression, screening, primary healthcare and adult. General and psychometric characteristics were extracted for screening tools studied in primary healthcare only when assessed against a ‘reference-standard’.ResultsEighty-one studies from 22 countries were included in the review. Forty unique depression screening tools suitable for self-administration were identified in studies yielding 138 psychometric data sets. Based on ease of administration, 18 screening tools were suitable for use in primary healthcare. Of the tools meta-analysed, only the PHQ-9 and WHO-5 displayed superior accuracy and were easily administered.ConclusionAlthough numerous depression screening tools are suitable for use in primary care based on ease of administration, the PHQ-9 was the most widely assessed tool and displayed superior DOR, a-ROC, specificity and LR + . Our review supports the use of the PHQ-9 as a brief, easily administered depression screening tool with superior discriminatory performance and robust psychometric characteristics in primary care settings. (AU)

Kinetic Evidence That the Solvent Barrier for Electron Transfer Is Absent in the Electric Double Layer.

Classical capacitance studies have revealed that the first layer of water present at an aqueous metal-electrolyte interface has a dielectric constant less than 1/10th of that of bulk water. Modern theory indicates that the barrier for electron transfer will decrease substantially in this layer; yet, this important prediction has not been tested experimentally. Here, we report the interfacial electron transfer kinetics for molecules positioned at variable distances within the electric double layer of a transparent conductive oxide as a function of the Gibbs free energy change. The data indicate that the solvent reorganization is indeed near zero and increases to bulk values only when the molecules are positioned greater than 15 Å from the conductive electrode. Consistent with this conclusion, lateral intermolecular electron transfer, parallel to a semiconducting oxide electrode, was shown to be more rapid when the molecules were within the electric double layer. The results provide much needed feedback for theoretical studies and also indicate a huge kinetic advantage for aqueous electron transfer and redox catalysis that takes place proximate to a solid interface.

Perspectives on Dye Sensitization of Nanocrystalline Mesoporous Thin Films.

Recent advances in our mechanistic understanding of dye-sensitized electron transfer reactions occurring at metal oxide interfaces are described. These advances were enabled by the advent of mesoporous thin films, comprised of anatase TiO2 nanocrystallites, that are amenable to spectroscopic and electrochemical characterization in unprecedented molecular-level detail. The metal-to-ligand charge transfer (MLCT) excited states of Ru polypyridyl compounds serve as the dye sensitizers. Excited-state injection often occurs on ultrafast time scales with yields that can be tuned from unity to near zero through modification of the sensitizer or the electrolyte composition. Transport of the injected electron and the oxidized sensitizer (hole hopping) are both operative in the composite mechanism for charge recombination between the injected electron and the oxidized sensitizer. Sensitizers that contain a pendant electron donor, as well as core/shell SnO2/TiO2 nanostructures, often prolong the lifetime of the injected electron and provide fundamental insights into adiabatic and nonadiabatic electron transfer mechanisms. Regeneration of the oxidized sensitizer by iodide is enhanced through halogen bonding, orbital pathways, and ion pairing. A substantial ∼10 MV cm-1 electric field is created by electron injection into TiO2 nanocrystallites that induces ion migration, reports on the sensitizer dipole orientation, and (in some cases) reorients or flips the sensitizer. Dye-sensitized conductive oxides also promote long-lived charge separation with bias dependent kinetics that provide insights into the reorganization energies associated with electron and proton-coupled electron transfer in the electric double layer.

Hedgehog Signaling Regulates Epithelial Morphogenesis to Position the Ventral Embryonic Midline.

Despite much progress toward understanding how epithelial morphogenesis is shaped by intra-epithelial processes including contractility, polarity, and adhesion, much less is known regarding how such cellular processes are coordinated by extra-epithelial signaling. During embryogenesis, the coelomic epithelia on the two sides of the chick embryo undergo symmetrical lengthening and thinning, converging medially to generate and position the dorsal mesentery (DM) in the embryonic midline. We find that Hedgehog signaling, acting through downstream effectors Sec5 (ExoC2), an exocyst complex component, and RhoU (Wrch-1), a small GTPase, regulates coelomic epithelium morphogenesis to guide DM midline positioning. These effects are accompanied by changes in epithelial cell-cell alignment and N-cadherin and laminin distribution, suggesting Hedgehog regulation of cell organization within the coelomic epithelium. These results indicate a role for Hedgehog signaling in regulating epithelial morphology and provide an example of how transcellular signaling can modulate specific cellular processes to shape tissue morphogenesis.

Electron Transfer Reorganization Energies in the Electrode-Electrolyte Double Layer.

The total reorganization energy, λ, for interfacial electron transfer, ET, from a conductive electrode to redox-active molecules at fixed positions within the electric double layer, EDL, has been determined experimentally. Conductive indium-tin-oxide (ITO, In2O3:Sn) mesoporous films were functionalized with 4-[N,N-di(p-tolyl)-amino]benzylphosphonic acid (TPA) and/or [RuII(bpy)2(4,4'-(PO3H2)2-bpy)]2+ (RuP), where bpy is 2,2'-bipyridine. The small inner-sphere reorganizations, λi, for RuIII/IIP and TPA+/0 make them excellent probes of outer-sphere reorganization energy, λo, as λi ≪ λo such that λ = λi + λo ≈ λo. Consecutive layer-by-layer addition of ZrIV-bridged methylenediphosphonic acid enabled positioning at distances from 4 to 27 Å from the ITO. Excited-state injection into the ITO by RuP* generated ITO(e-)|RuIIIP. For ITO cofunctionalized with TPA and RuP, subnanosecond lateral ET yielded ITO(e-)|TPA+. The kinetics for ET from ITO to RuIIIP or TPA+ were quantified spectroscopically as a function of applied potential (Eapp) and hence driving force, -ΔG°. Marcus-Gerischer analysis of this data provided λ. Significantly, λo was near zero at close electrode proximity, λ = 0.11 eV at a distance of ∼4 Å, as manifest by kinetics largely insensitive to Eapp. In agreement with dielectric continuum theory, λ increased to values expected in CH3CN solution when the molecule was positioned at a distance of ∼27 Å (λ = 0.94 eV). The data reveal small intrinsic barriers for electron transfer proximate to conductive interfaces, which is an exploitable behavior in solar energy conversion and other applications that utilize transparent conductive oxides to accept or deliver electrons.

Determination of Proton-Coupled Electron Transfer Reorganization Energies with Application to Water Oxidation Catalysts.

The reorganization energy, λ, for interfacial electron transfer (ET) and for proton-coupled electron transfer (PCET) between a water oxidation catalyst and a conductive In2O3:Sn (ITO) oxide were extracted from kinetic data by application of Marcus-Gerischer theory. Specifically, light excitation of the water oxidation catalyst [RuII(tpy)(4,4'-(PO3H2)2-bpy)OH2]2+ (RuII-OH2), where tpy is 2,2':6',2″-terpyridine and bpy is 2,2'-bipyridine, anchored to a mesoporous thin film of ITO nanocrystallites resulted in rapid excited-state injection ( kinj > 108 s-1). The subsequent reaction of the injected electron (ITO(e-)) and the oxidized catalyst was quantified spectroscopically on nanosecond and longer time scales. The metallic character of ITO allowed potentiostatic control of the reaction free energy change -Δ Go over a 1 eV range. At pH values below the p Ka = 1.7 of the oxidized catalyst, ET was the primary reaction. Within the pH range 2 ≤ pH ≤ 5, an interfacial PCET reaction (ITO(e-) + RuIII-OH + H+→ RuII-OH2) occurred with smaller rate constants. Plots of the rate constants versus -Δ Go provided a reorganization energy of λPCET = 0.9 eV and λET = 0.5 eV. A second water oxidation catalyst provided similar values and demonstrated generality. The utilization of conductive oxides is shown to be a powerful tool for quantifying PCET reorganization energies at oxide surfaces for the first time.

Photocatalytic activity and charge carrier dynamics of TiO2 powders with a binary particle size distribution.

The effects of the particle size distribution on the charge carrier dynamics and the photocatalytic activity of mixed titanium dioxide (TiO2) powder samples were investigated in this work. Instead of the synthesis of the small semiconductor particles, the binary particle size distributions of the powders were obtained by mixing commercially available TiO2 powders with different particle sizes. The pure anatase samples (average diameters: 7, 20, and 125 nm, respectively) were created via ultrasound treatment and discreet drying. The photocatalytic activity of the powder samples was assessed by the degradation of nitric oxide (NO) and acetaldehyde in the gas phase. Furthermore, the charge carrier kinetics was determined using transient absorption spectroscopy following pulsed laser excitation. Importantly, a recently published model based on fractal dimensions was used to fit the transient signals of the photo generated charge carriers in the TiO2 powder samples. The effects of the particle size on the acetaldehyde degradation could be explained by the formation of agglomerates, which reduce the available surface area of smaller particles. The fast oxidation of acetaldehyde on the surface of TiO2 by direct hole transfer was further independent of the observed charge carrier lifetimes on the microsecond time scale. The photocatalytic NO degradation, on the other hand, increased for samples containing larger amounts of small particles. The corresponding photonic efficiencies correlated well with the charge carrier lifetimes determined by the time-resolved studies. Hence, it was concluded that a long charge carrier lifetime generally leads to higher fractional conversions of NO. The employed fractal fit function was proved to be beneficial for the kinetic analysis of charge carrier recombination in TiO2, in direct comparison with a second order fit function.

New insights into the surface plasmon resonance (SPR) driven photocatalytic H2 production of Au-TiO2.

The Surface Plasmon Resonance (SPR) driven photocatalytic H2 production upon visible light illumination (≥500 nm) was investigated on gold-loaded TiO2 (Au-TiO2). It has been clearly shown that the Au-SPR can directly lead to photocatalytic H2 evolution under illumination (≥500 nm). However, there are still some open issues about the underlying mechanism for the SPR-driven photocatalytic H2 production, especially the explanation of the resonance energy transfer (RET) theory and the direct electron transfer (DET) theory. In this contribution, by means of the EPR and laser flash photolysis spectroscopy, we clearly showed the signals for different species formed by trapped electrons and holes in TiO2 upon visible light illumination (≥500 nm). However, the energy of the Au-SPR is insufficient to overcome the bandgap of TiO2. The signals of the trapped electrons and holes originate from two distinct processes, rather than the simple electron-hole pair excitation. Results obtained by Laser Flash Photolysis spectroscopy evidenced that, due to the Au-SPR effect, Au NPs can inject electrons to the conduction band of TiO2 and the Au-SPR can also initiate e-/h+ pair generation (interfacial charge transfer process) upon visible light illumination (≥500 nm). Moreover, the Density Functional Theory (DFT) calculation provided direct evidence that, due to the Au-SPR, new impurity energy levels occurred, thus further theoretically elaborating the proposed mechanisms.

Drug-Induced Autoimmune Hepatitis following Treatment with Zoledronic Acid.

Adverse drug reactions are among the most frequent side effects of synthetic and complementary alternative drugs and represent the premier causes of license revocations and acute liver failure. Drug-induced liver injury can resemble literally any other genuine liver disease and usually responds well to drug dechallenge. However, in some cases autoimmune-like hepatitis can evolve, requiring short- and sometimes long-term immunosuppression. Here, we present the hitherto first case of autoimmune-like hepatitis following treatment with zoledronic acid.

Cold sprayed WO3 and TiO2 electrodes for photoelectrochemical water and methanol oxidation in renewable energy applications.

Films prepared by cold spray have potential applications as photoanodes in electrochemical water splitting and waste water purification. In the present study cold sprayed photoelectrodes produced with WO3 (active under visible light illumination) and TiO2 (active under UV illumination) on titanium metal substrates were investigated as photoanodes for the oxidation of water and methanol, respectively. Methanol was chosen as organic model pollutant in acidic electrolytes. Main advantages of the cold sprayed photoelectrodes are the improved metal-semiconductor junctions and the superior mechanical stability. Additionally, the cold spray method can be utilized as a large-scale electrode fabrication technique for photoelectrochemical applications. Incident photon to current efficiencies reveal that cold sprayed TiO2/WO3 photoanodes exhibit the best photoelectrochemical properties with regard to the water and methanol oxidation reactions in comparison with the benchmark photocatalyst Aeroxide TiO2 P25 due to more efficient harvesting of the total solar light irradiation related to their smaller band gap energies.

Laser-flash-photolysis-spectroscopy: a nondestructive method?

Herein, we report the effect of the laser illumination during the diffuse-reflectance laser-flash-photolysis measurements on the morphological and optical properties of TiO2 powders. A grey-blue coloration of the TiO2 nanoparticles has been observed after intense laser illumination. This is explained by the formation of nonreactive trapped electrons accompanied by the release of oxygen atoms from the TiO2 matrix as detected by means of UV-vis and EPR spectroscopy. Moreover, in the case of the pure anatase sample a phase transition of some TiO2 nanoparticles located in the inner region from anatase to rutile occurred. It is suggested that these structural changes in TiO2 are caused by an energy and charge transfer to the TiO2 lattice.

DNA methylation profiling reveals differences in the 3 human monocyte subsets and identifies uremia to induce DNA methylation changes during differentiation.

Human monocytes are a heterogeneous cell population consisting of 3 subsets: classical CD14++CD16-, intermediate CD14++CD16+ and nonclassical CD14+CD16++ monocytes. Via poorly characterized mechanisms, intermediate monocyte counts rise in chronic inflammatory diseases, among which chronic kidney disease is of particular epidemiologic importance. DNA methylation is a central epigenetic feature that controls hematopoiesis. By applying next-generation Methyl-Sequencing we now tested how far the 3 monocyte subsets differ in their DNA methylome and whether uremia induces DNA methylation changes in differentiating monocytes. We found that each monocyte subset displays a unique phenotype with regards to DNA methylation. Genes with differentially methylated promoter regions in intermediate monocytes were linked to distinct immunological processes, which is in line with results from recent gene expression analyses. In vitro, uremia induced dysregulation of DNA methylation in differentiating monocytes, which affected several transcription regulators important for monocyte differentiation (e.g., FLT3, HDAC1, MNT) and led to enhanced generation of intermediate monocytes. As potential mediator, the uremic toxin and methylation inhibitor S-adenosylhomocysteine induced shifts in monocyte subsets in vitro, and associated with monocyte subset counts in vivo. Our data support the concept of monocyte trichotomy and the distinct role of intermediate monocytes in human immunity. The shift in monocyte subsets that occurs in chronic kidney disease, a proinflammatory condition of substantial epidemiological impact, may be induced by accumulation of uremic toxins that mediate epigenetic dysregulation.