Immune Profiling of Peripheral Blood Mononuclear Cells at Pancreas Acute Rejection Episodes in Kidney-Pancreas Transplant Recipients

Profiling of circulating immune cells provides valuable insight to the pathophysiology of acute rejection in organ transplantation. Herein we characterized the peripheral blood mononuclear cells in simultaneous kidney-pancreas transplant recipients. We conducted a retrospective analysis in a biopsy-matched cohort (n = 67) and compared patients with biopsy proven acute rejection (BPAR; 41%) to those without rejection (No-AR). We observed that CD3+ T cells, both CD8+ and CD4+, as well as CD19+ B cells were increased in patients with BPAR, particularly in biopsies performed in the early post-transplant period (<3 months). During this period immune subsets presented a good discriminative ability (CD4+ AUC 0.79; CD8+ AUC 0.80; B cells AUC 0.86; p < 0.05) and outperformed lipase (AUC 0.62; p = 0.12) for the diagnosis of acute rejection. We further evaluated whether this could be explained by differences in frequencies prior to transplantation. Patients presenting with early post-transplant rejection (<3 months) had a significant increase in T-cell frequencies pre-transplant, both CD4+ T cells and CD8+ T cells (p < 0.01), which were associated with a significant inferior rejection-free graft survival. T cell frequencies in peripheral blood correlated with pancreas acute rejection episodes, and variations prior to transplantation were associated with pancreas early acute rejection.Copyright © 2022 Rovira, Ramirez-Bajo, Bañón-Maneus, Hierro-Garcia, Lazo-Rodriguez, Piñeiro, Montagud-Marrahi, Cucchiari, Revuelta, Cuatrecasas, Campistol, Ricart, Diekmann, Garcia-Criado and Ventura-Aguiar

VPS29 Is Not an Active Metallo-Phosphatase but Is a Rigid Scaffold Required for Retromer Interaction with Accessory Proteins

VPS29 is a key component of the cargo-binding core complex of retromer, a protein assembly with diverse roles in transport of receptors within the endosomal system. VPS29 has a fold related to metal-binding phosphatases and mediates interactions between retromer and other regulatory proteins. In this study we examine the functional interactions of mammalian VPS29, using X-ray crystallography and NMR spectroscopy. We find that although VPS29 can coordinate metal ions Mn2+ and Zn2+ in both the putative active site and at other locations, the affinity for metals is low, and lack of activity in phosphatase assays using a putative peptide substrate support the conclusion that VPS29 is not a functional metalloenzyme. There is evidence that structural elements of VPS29 critical for binding the retromer subunit VPS35 may undergo both metal-dependent and independent conformational changes regulating complex formation, however studies using ITC and NMR residual dipolar coupling (RDC) measurements show that this is not the case. Finally, NMR chemical shift mapping indicates that VPS29 is able to associate with SNX1 via a conserved hydrophobic surface, but with a low affinity that suggests additional interactions will be required to stabilise the complex in vivo. Our conclusion is that VPS29 is a metal ion-independent, rigid scaffolding domain, which is essential but not sufficient for incorporation of retromer into functional endosomal transport assemblies

Women’s, partners’ and healthcare providers’ views and experiences of assisted vaginal birth: a systematic mixed methods review

Background When certain complications arise during the second stage of labour, assisted vaginal delivery (AVD), a vaginal birth with forceps or vacuum extractor, can effectively improve outcomes by ending prolonged labour or by ensuring rapid birth in response to maternal or fetal compromise. In recent decades, the use of AVD has decreased in many settings in favour of caesarean section (CS). This review aimed to improve understanding of experiences, barriers and facilitators for AVD use. Methods Systematic searches of eight databases using predefined search terms to identify studies reporting views and experiences of maternity service users, their partners, health care providers, policymakers, and funders in relation to AVD. Relevant studies were assessed for methodological quality. Qualitative findings were synthesised using a meta-ethnographic approach. Confidence in review findings was assessed using GRADE CERQual. Findings from quantitative studies were synthesised narratively and assessed using an adaptation of CERQual. Qualitative and quantitative review findings were triangulated using a convergence coding matrix. Results Forty-two studies (published 1985–2019) were included: six qualitative, one mixed-method and 35 quantitative. Thirty-five were from high-income countries, and seven from LMIC settings. Confidence in the findings was moderate or low. Spontaneous vaginal birth was most likely to be associated with positive short and long-term outcomes, and emergency CS least likely. Views and experiences of AVD tended to fall somewhere between these two extremes. Where indicated, AVD can be an effective, acceptable alternative to caesarean section. There was agreement or partial agreement across qualitative studies and surveys that the experience of AVD is impacted by the unexpected nature of events and, particularly in high-income settings, unmet expectations. Positive relationships, good communication, involvement in decision-making, and (believing in) the reason for intervention were important mediators of birth experience. Professional attitudes and skills (development) were simultaneously barriers and facilitators of AVD in quantitative studies. Conclusions Information, positive interaction and communication with providers and respectful care are facilitators for acceptance of AVD. Barriers include lack of training and skills for decision-making and use of instruments

Dose assessment to workers in a dicalcium phosphate production plant

The production of dicalcium phosphate (DCP) uses phosphate rock (PR) as a raw material. Sedimentary phosphate rocks are enriched with relevant concentrations of natural radionuclides from the 238U decay chain (around 103 Bq·kg-1), leading to the need of controlling potential exposures to radiation of workers and members of the public in accordance with IAEA safety standards. Indeed, phosphate industries are classified as Naturally Occurring Radioactive Material (NORM) industries. Thus, the aim of this work is to assess the radiological risk of the workers in a DCP production plant located in the Iberian Peninsula (South-West Europe), which digests PR with hydrochloric acid. In the present study 238U, 230Th, 222Rn, 210Pb and 210Po concentrations in aerosols (indoor and outdoor areas) are reported. Aerosols showed concentrations between 0.42–92 mBq·m-3 for 238U, 0.24–33 mBq·m-3 for 230Th, 0.67–147 mBq·m-3 for 210Pb and 0.09–34 mBq·m-3 for 210Po. Long-term exposure (four months) of passive 222Rn detectors provided concentrations that ranged from detection limit (< DL) to 121 Bq·m-3 in outdoor areas and from < DL to 211 Bq·m-3 in indoor areas, similar to concentrations obtained from short-term measurements with active detectors from < DL to 117 Bq·m-3 in outdoor areas and from < DL to 318 Bq·m-3 in indoor places. 226Ra accumulation in ebonite and pipe scales were the most important contributions to the ambient dose equivalent H*(10), resulting in 0.07 (background)–27 µSv·h-1 with a median value of 1.1 µSv·h-1. Average 222Rn air concentrations were lower than the 300 Bq·m-3 limit and therefore, according to European Directive 2013/59/EURATOM, 222Rn concentration is excluded from the worker operational annual effective dose. Thus, considering the inhalation of aerosols and the external dose sources, the total effective dose determined for plant operators was 0.37 mSv·y-1.Postprint (author's final draft

Dose assessment to workers in a dicalcium phosphate production plant

The production of dicalcium phosphate (DCP) uses phosphate rock (PR) as a raw material. Sedimentary phosphate rocks are enriched with relevant concentrations of natural radionuclides from the 238U decay chain (around 103 Bq·kg-1), leading to the need of controlling potential exposures to radiation of workers and members of the public in accordance with IAEA safety standards. Indeed, phosphate industries are classified as Naturally Occurring Radioactive Material (NORM) industries. Thus, the aim of this work is to assess the radiological risk of the workers in a DCP production plant located in the Iberian Peninsula (South-West Europe), which digests PR with hydrochloric acid. In the present study 238U, 230Th, 222Rn, 210Pb and 210Po concentrations in aerosols (indoor and outdoor areas) are reported. Aerosols showed concentrations between 0.42–92 mBq·m-3 for 238U, 0.24–33 mBq·m-3 for 230Th, 0.67–147 mBq·m-3 for 210Pb and 0.09–34 mBq·m-3 for 210Po. Long-term exposure (four months) of passive 222Rn detectors provided concentrations that ranged from detection limit (< DL) to 121 Bq·m-3 in outdoor areas and from < DL to 211 Bq·m-3 in indoor areas, similar to concentrations obtained from short-term measurements with active detectors from < DL to 117 Bq·m-3 in outdoor areas and from < DL to 318 Bq·m-3 in indoor places. 226Ra accumulation in ebonite and pipe scales were the most important contributions to the ambient dose equivalent H*(10), resulting in 0.07 (background)–27 µSv·h-1 with a median value of 1.1 µSv·h-1. Average 222Rn air concentrations were lower than the 300 Bq·m-3 limit and therefore, according to European Directive 2013/59/EURATOM, 222Rn concentration is excluded from the worker operational annual effective dose. Thus, considering the inhalation of aerosols and the external dose sources, the total effective dose determined for plant operators was 0.37 mSv·y-1

Wnt pathway activation in long term remnant rat model.

Progression of chronic kidney disease (CKD) is characterized by deposition of extracellular matrix. This is an irreversible process that leads to tubulointerstitial fibrosis and finally loss of kidney function. Wnt/beta-catenin pathway was reported to be aberrantly activated in the progressive damage associated with chronic organ failure. Extensive renal ablation is an experimental model widely used to gain insight into the mechanisms responsible for the development of CKD, but it was not evaluated for Wnt/beta-catenin pathway. This study aimed to elucidate if the rat 5/6 renal mass reduction model (RMR) is a good model for the Wnt/beta-catenin activation and possible next modulation. RMR model was evaluated at 12 and 18 weeks after the surgery, when CKD is close to end-stage kidney disease demonstrated by molecular and histological studies. Wnt pathway components were analyzed at mRNA and protein level. Our results demonstrate that Wnt pathway is active by increase of beta-catenin at mRNA level and nuclear translocation in tubular epithelium as well as some target genes. These results validate the RMR model for future modulation of Wnt pathway, starting at shorter time after the surgery

The 2022 Magneto-Optics Roadmap

International audienceMagneto-optical effects, viz. magnetically induced changes in light intensity or polarization upon reflection from or transmission through a magnetic sample, were discovered over a century and a half ago. Initially they played a crucially relevant role in unveiling the fundamentals of electromagnetism and quantum mechanics. A more broad-based relevance and wide-spread use of magneto-optical methods, however, remained quite limited until the 1960s due to a lack of suitable, reliable and easy- to-operate light sources. The advent of Laser technology and the availability of other novel light sources led to an enormous expansion of magneto-optical measurement techniques and applications that continues to this day (see Section 1). The here-assembled roadmap article is intended to provide a meaningful survey over many of the most relevant recent developments, advances, and emerging research directions in a rather condensed form, so that readers can easily access a significant overview about this very dynamic research field. While light source technology and other experimental developments were crucial in the establishment of today’s magneto-optics, progress also relies on an ever-increasing theoretical understanding of magneto-optical effects from a quantum mechanical perspective (see Section 2), as well as using electromagnetic theory and modelling approaches (see Section 3) to enable quantitatively reliable predictions for ever more complex materials, metamaterials, and device geometries. The latest advances in established magneto-optical methodologies and especially the utilization of the magneto-optical Kerr effect (MOKE) are presented in effect in 2D materials). In addition, magneto-optical effects are now being investigated and utilized in spectral ranges, to which they originally seemed completely foreign, as those of synchrotron radiation X-rays (see Section 14 on 3D magnetic characterization and Section 16 on light beams carrying orbital angular momentum) and, very recently, the terahertz regime (see Section 18 on THz MOKE and Section 19 on THz ellipsometry for electron paramagnetic resonance detection). Magneto-optics also demonstrates its strength in a unique way when combined with femtosecond laser pulses (see Section 10 on ultrafast MOKE and Section 15 on magneto-optics using X-ray free electron lasers), facilitating the very active field of time- resolved magneto-optical spectroscopy that enables investigations of phenomena like spin relaxation of nonequilibrium photoexcited carriers, transient modifications of ferromagnetic order, and photo- induced dynamic phase transitions, to name a few. Recent progress in nanoscience and nanotechnology, which is intimately linked to the achieved impressive ability to reliably fabricate materials and functional structures at the nanoscale, now enables the exploitation of strongly enhanced magneto-optical effects induced by light-matter interaction at the nanoscale (see Section 12 on magnetoplasmonics and Section 13 on magneto- optical metasurfaces). Magneto-optical effects are also at the very heart of powerful magnetic characterization techniques like Brillouin light scattering and time-resolved pump-probe measurements for the study of spin waves (see Section 7), their interactions with acoustic waves (see Section 11), and ultra-sensitive magnetic field sensing applications based on Nitrogen-vacancy centers in diamond (see Section 17). Despite our best attempt to represent the field of magneto-optics accurately and do justice to all its novel developments and its diversity, the research area is so extensive and active that there remains great latitude in deciding what to include in an article of this sort, which in turn means that some areas might not be adequately represented here. However, we feel that the 20 sections that form this 2022 Magneto-Optics Roadmap article, each written by experts in the field and addressing a specific subject on only two pages, provide an accurate snapshot of where this research field stands today. Correspondingly, it should act as a valuable reference point and guideline for emerging research directions in modern magneto-optics, as well as illustrate the directions this research field might take in the foreseeable future