Comparison of three assays for total and free PSA using hybritech and WHO calibrations

Publisher Copyright: © 2021 International Institute of Anticancer Research. All rights reserved.Background/Aim: Lack of interchangeability between prostate-specific antigen (PSA) assays could have a clinical impact. We compared PSA assays from different manufacturers and calibrations. Patients and Methods: A total of 233 men who underwent prostate biopsy (PSA: 2-10 ng/ml; Beckman Coulter Access® Hybritech® as reference) were enrolled. Total (tPSA) and free PSA (fPSA) were also measured using the Roche cobas® and the Abbott Architect® methods. Results: Roche tPSA values were ≈ 1% higher than Beckman, while Abbott values were ~5% lower. Roche had the highest diagnostic sensitivity (92%) compared to Beckman Coulter (87%) and Abbott (85%). Roche fPSA was ≈3% lower and Abbott ≈17% higher than that of Beckman. For the percentage of fPSA, Roche had the highest sensitivity (98%). Conclusion: Roche cobas® and Beckman Coulter Access® Hybritech® tPSA were almost interchangeable. While the agreement was acceptable for tPSA, this did not happen with fPSA and greater efforts for harmonization are required.publishersversionpublishe

Self-passivating W-Cr-Y alloys: characterization and testing

The use of self-passivating tungsten alloys for the first wall armor of future fusion reactors is advantageous concerning safety issues in comparison with pure tungsten. Bulk W-10Cr-0.5Y alloy manufactured by mechanical alloying followed by HIP resulted in a fully dense material with grain size around 100 nm and a dispersion of Y-rich oxide nanoparticles located at the grain boundaries. An improvement in flexural strength and fracture toughness was observed with respect to previous works. Oxidation tests under isothermal and accident-like conditions revealed a very promising oxidation behavior for the W-10Cr-0.5Y alloy. Thermo-shock tests at JUDITH-1 to simulate ELM-like loads resulted in a crack network at the surface with roughness values lower than those of a pure W reference material. An additional thermal treatment at 1550 °C improves slightly the oxidation and thermo-shock resistance of the alloy

Numerical Modeling of physical-biological interactions in the Alboran Sea with a submesoscale-resolving model

Ageostrophic motion, such those associated to internal hydraulic jumps, propagating nonlinear internal waves, and submesoscale vortices, are recognized to efficiently supply nutrients to the euphotic zone and thereby fuel biological productivity. These processes are ubiquitous in the Strait of Gibraltar and the adjacent Alboran Sea, and therefore are expected to play an important role in the overall biomass budget of the basin. This has been investigated with a three-dimensional, tidally-forced, high-resolution model [O(1km)] ocean model embedded with an ecosystem NPZD module. We found that tidal mixing in the Strait of Gibraltar enhances remarkably local primary production and drive a net flow of biomass to the Alboran Sea. Additionally, tides also cause an inflow of nutrients confined to the photic layer, which increase further the Alboran Sea biomass through the enhancement of local primary productivity. Subinertial accelerations of the Atlantic flow are also found to temporary enhance biological productivity through the advection of shear vorticity (and submesoscale eddies) from the Strait to the Alboran Sea.JRC.H.1-Water Resource

Low-temperature transport in highly boron-doped nanocrystalline diamond

International audienceWe studied the transport properties of highly boron-doped nanocrystalline diamond thin films at temperatures down to 50 mK. The system undergoes a doping-induced metal-insulator transition with an interplay between intergranular conductance g and intragranular conductance g0, as expected for a granular system. The conduction mechanism in the case of the low-conductivity films close to the metal-insulator transition has a temperature dependence similar to Efros-Shklovskii type of hopping. On the metallic side of the transition, in the normal state, a logarithmic temperature dependence of the conductivity is observed, as expected for a metallic granular system. Metallic samples far away from the transition show similarities to heavily borondoped single-crystal diamond. Close to the transition, the behavior is richer. Global phase coherence leads in both cases to superconductivity also checked by ac susceptibility , but a peak in the low-temperature magnetoresistance measurements occurs for samples close to the transition. Corrections to the conductance according to superconducting fluctuations account for this negative magnetoresistance

Critical warm ischemia time point for cardiac donation after circulatory death.

Donation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, the necessary period of warm ischemia is a concern. This study aims to determine the critical warm ischemia time based on in vivo biochemical changes. Sixteen DCD non-cardiac donors, without cardiovascular disease, underwent serial endomyocardial biopsies immediately before withdrawal of life-sustaining therapy (WLST), at circulatory arrest (CA) and every 2 min thereafter. Samples were processed into representative pools to assess calcium homeostasis, mitochondrial function and cellular viability. Compared to baseline, no significant deterioration was observed in any studied parameter at the time of CA (median: 9 min; IQR: 7-13 min; range: 4-19 min). Ten min after CA, phosphorylation of cAMP-dependent protein kinase-A on Thr197 and SERCA2 decreased markedly; and parallelly, mitochondrial complex II and IV activities decreased, and caspase 3/7 activity raised significantly. These results did not differ when donors with higher WLST to CA times (≥9 min) were analyzed separately. In human cardiomyocytes, the period from WLST to CA and the first 10 min after CA were not associated with a significant compromise in cellular function or viability. These findings may help to incorporate DCD into heart transplant programs.Fundación Mutua Madrileña.S

Aripiprazole as a Candidate Treatment of COVID-19 Identified Through Genomic Analysis

Background: Antipsychotics modulate expression of inflammatory cytokines and inducible inflammatory enzymes. Elopiprazole (a phenylpiperazine antipsychotic drug in phase 1) has been characterized as a therapeutic drug to treat SARS-CoV-2 infection in a repurposing study. We aim to investigate the potential effects of aripiprazole (an FDA approved phenylpiperazine) on COVID-19-related immunological parameters. Methods: Differential gene expression profiles of non-COVID-19 vs. COVID-19 RNA-Seq samples (CRA002390 project in GSA database) and drug-naïve patients with non-affective psychosis at baseline and after three months of aripiprazole treatment were identified. An integrative transcriptomic analyses of aripiprazole effects on differentially expressed genes in COVID-19 patients was performed. Findings: 82 out the 377 genes (21.7%) with expression significantly altered by aripiprazole have also their expression altered in COVID-19 patients and in 93.9% of these genes their expression is reverted by aripiprazole. The number of common genes with expression altered in both analyses is significantly higher than expected (Fisher?s Exact Test, two tail; p value = 3.2e-11). 11 KEGG pathways were significantly enriched with genes with altered expression both in COVID-19 patients and aripiprazole medicated non-affective psychosis patients (p adj<0.05). The most significant pathways were associated to immune responses and mechanisms of hyperinflammation-driven pathology (i.e.,?inflammatory bowel disease (IBD)? (the most significant pathway with a p adj of 0.00021), ?Th1 and Th2 cell differentiation? and ?B cell receptor signaling pathway?) that have been also associated with COVID19 clinical outcome. Interpretation: This exploratory investigation may provide further support to the notion that a protective effect is exerted by aripiprazole (phenylpiperazine) by modulating the expression of genes that have shown to be altered in COVID-19 patients. Along with many ongoing studies and clinical trials, repurposing available medications could be of use in countering SARS-CoV-2 infection, but require further studies and trials.Funding: The present study was part of a larger prospective longitudinal study, the “First Episode Psychosis Clinical Program 10” (PAFIP10) study. ClinicalTrials.gov Identifiers: NCT02200588, NCT03481465, and NCT03476473. No pharmaceutical industry or institutional sponsors participated in the study conception and design, data collection, analysis and interpretation of the results, or drafting of the manuscript. This work was supported by: SAF2016- 76046-R and SAF2013-46292-R (MINECO and FEDER) to B.C.F.Acknowledgments: We are highly indebted to the participants and their families for their cooperation in this study. We also thank IDIVAL biobank (Ines Santiuste and Jana Arozamena) for clinical samples and ́ data as well as the PAFIP members (Marga Corredera) for the data collection. We kindly thank all clinical staff at the Hospital Universitario Virgen del Rocio for support to collect clinical records and provide clinical care to COVID-19 patients. We also kindly thank Dra. Marisa Barrigon for helpful discussions regarding clinical data analysis, and Idalino Rocha for manuscript editing and formatting. This manuscript has been released as a pre-print at medRxiv. Available at: https://doi.org/ 10.1101/2020.12.05.20244590 (Crespo-Facorro et al., 2020)

Disrupted Peyer’s Patch Microanatomy in COVID-19 Including Germinal Centre Atrophy Independent of Local Virus

Confirmed SARS-coronavirus-2 infection with gastrointestinal symptoms and changes in microbiota associated with coronavirus disease 2019 (COVID-19) severity have been previously reported, but the disease impact on the architecture and cellularity of ileal Peyer’s patches (PP) remains unknown. Here we analysed post-mortem tissues from throughout the gastrointestinal (GI) tract of patients who died with COVID-19. When virus was detected by PCR in the GI tract, immunohistochemistry identified virus in epithelium and lamina propria macrophages, but not in lymphoid tissues. Immunohistochemistry and imaging mass cytometry (IMC) analysis of ileal PP revealed depletion of germinal centres (GC), disruption of B cell/T cell zonation and decreased potential B and T cell interaction and lower nuclear density in COVID-19 patients. This occurred independent of the local viral levels. The changes in PP demonstrate that the ability to mount an intestinal immune response is compromised in severe COVID-19, which could contribute to observed dysbiosis

Concurrent functional ultrasound imaging with graphene-based DC-coupled electrophysiology as a platform to study slow brain signals and cerebral blood flow under control and pathophysiological brain states

Current methodology used to investigate how shifts in brain states associated with regional cerebral blood volume (CBV) change in deep brain areas, are limited by either the spatiotemporal resolution of the CBV techniques, and/or compatibility with electrophysiological recordings; particularly in relation to spontaneous brain activity and the study of individual events. Additionally, infraslow brain signals (&lt;0.1 Hz), including spreading depolarisations, DC-shifts and infraslow oscillations (ISO), are poorly captured by traditional AC-coupled electrographic recordings; yet these very slow brain signals can profoundly change CBV. To gain an improved understanding of how infraslow brain signals couple to CBV we present a new method for concurrent CBV with wide bandwidth electrophysiological mapping using simultaneous functional ultrasound imaging (fUS) and graphene-based field effect transistor (gFET) DC-coupled electrophysiological acquisitions. To validate the feasibility of this methodology visually-evoked neurovascular coupling (NVC) responses were examined. gFET recordings are not affected by concurrent fUS imaging, and epidural placement of gFET arrays within the imaging window did not deteriorate fUS signal quality. To examine directly the impact of infra-slow potential shifts on CBV, cortical spreading depolarisations (CSDs) were induced. A biphasic pattern of decreased, followed by increased CBV, propagating throughout the ipsilateral cortex, and a delayed decrease in deeper subcortical brain regions was observed. In a model of acute seizures, CBV oscillations were observed prior to seizure initiation. Individual seizures occurred on the rising phase of both infraslow brain signal and CBV oscillations. When seizures co-occurred with CSDs, CBV responses were larger in amplitude, with delayed CBV decreases in subcortical structures. Overall, our data demonstrate that gFETs are highly compatible with fUS and allow concurrent examination of wide bandwidth electrophysiology and CBV. This graphene-enabled technological advance has the potential to improve our understanding of how infraslow brain signals relate to CBV changes in control and pathological brain states.</p

Distortion-free sensing of neural activity using graphene transistors

Graphene solution-gated field-effect transistors (g-SGFETs) are promising sensing devices to transduce electrochemical potential signals in an electrolyte bath. However, distortion mechanisms in g-SGFET, which can affect signals of large amplitude or high frequency, have not been evaluated. Here, a detailed characterization and modeling of the harmonic distortion and non-ideal frequency response in g-SGFETs is presented. This accurate description of the input-output relation of the g-SGFETs allows to define the voltage- and frequency-dependent transfer functions, which can be used to correct distortions in the transduced signals. The effect of signal distortion and its subsequent calibration are shown for different types of electrophysiological signals, spanning from large amplitude and low frequency cortical spreading depression events to low amplitude and high frequency action potentials. The thorough description of the distortion mechanisms presented in this article demonstrates that g-SGFETs can be used as distortion-free signal transducers not only for neural sensing, but also for a broader range of applications in which g-SGFET sensors are used

Metabolic and Functional Profile of Premenopausal Women With Metabolic Syndrome After Training With Elastics as Compared to Free Weights

The aim of this study was to compare the effects of a strength training program (STP) using free weights (FW) versus elastic tubing (ET) in 62 premenopausal, sedentary women diagnosed with metabolic syndrome (MS). Participants were randomly assigned to the FW or ET experimental group (EG) or a control group whose members remained sedentary. Members of each EG followed their assigned STP for 12 weeks, and biomarkers (BMs) related to MS and motor function (MF) parameters were evaluated. Both EGs showed a significant reduction in C-reactive protein level and a positive trend in the other BMs. Almost all MF parameters increased significantly in both EGs. No positive changes were found in the CG. These results indicate that the implementation of an STP, with either FW or ET, improves both metabolic health and MF and should be considered part of the basic approach to health care in women