OBESIDAD, ADIPOQUINAS Y LUPUS ERITEMATOSO SISTÉMICO

La obesidad es una estado pro-inflamatorio crónico en el cual participan una serie de procesos celulares incluyendo cambios fenotípicos de macrófagos, alteraciones en el  equilibrio de citoquinas, y un aumento en la expresión de moléculas reguladoras del sistema inmune derivadas de adipocitos y macrófagos residentes de tejido adiposo – también denominadas adipoquinas. Tales adipoquinas como la leptina, la adiponectina, y la resistina, son, entre otras, algunas de las más estudiadas hasta el momento. De igual manera, estas adipoquinas pueden tener un posible rol en la fisiopatología del lupus eritematoso sistémico, al promover diferentes procesos pro-inflamatorios; por lo tanto, representan también posibles dianas terapéuticas para el tratamiento de esta enfermedad.  AbstractObesity is a pro-inflammatory state characterized by phenotypic changes in macrophages, alterations on cytokines balance, and increasing expression of regulatory molecules of the immune system derived from adipocytes and adipose tissue macrophages – also known as adipokines. Currently, leptin, adiponectin and resistin are, among others, one of the most known adipokines. These adipokines might play a possible role in systemic lupus erythematosus pathogenesis, by promoting different pro-inflammatory conditions. Adipokines represent a possible treatment target in patients with lupus. </p

Sarcoidosis como espondiloartropatía seronegativa.

Two cases were presented with initial symptoms of inflammatory low back pain and alternate buttock pain. They developed a progressive dyspnea with bilateral mediastinal and hiliar lymphadenopathy and pulmonary interstitial disease as visualized with chest CT scan. Sarcoidosis diagnosis was confirmed by biopsy in both cases--in one case by skin biopsy and in the other by open lung biopsy. These clinical forms of spondyloarthropathy and sarcoidosis were unusual and were compared with similar cases present in the literature.Presentamos dos casos de dolor lumbar de tipo inflamatorio y dolor alternante en nalgas, que desarrollaron disnea progresiva con adenopatías mediastinales e hiliares y signos de enfermedad pulmonar intersticial a la tomografía de tórax. El diagnóstico de sarcoidosis se confirmó con biopsia cutánea en un caso y con biopsia pulmonar a cielo abierto en el otro. Se discute esta forma inusual de presentación de estas dos patologías y se revisan los casos similares de la literatura

Sucrose esters from Physalis peruviana calyces with anti-inflammatory activity

Physalis peruviana is a native plant from the South American Andes and is widely used in tra- ditional Colombian medicine of as an anti-inflam- matory medicinal plant, specifically the leaves, calyces, and small stems in poultice form. Pre- vious studies performed by our group on P. pe- ruviana calyces showed potent anti-inflamma- tory activity in an enriched fraction obtained from an ether total extract. The objective of the present study was to obtain and elucidate the ac- tive compounds from this fraction and evaluate their anti-inflammatory activity in vivo and in vi- tro. The enriched fraction of P. peruviana was pu- rified by several chromatographic methods to ob- tain an inseparable mixture of two new sucrose esters named peruviose A (1) and peruviose B (2). Structures of the new compounds were eluci- dated using spectroscopic methods and chemical transformations. The anti-inflammatory activity of the peruvioses mixture was evaluated using λ-carrageenan-induced paw edema in rats and lipopolysaccharide-activated peritoneal macro- phages. Results showed that the peruvioses did not produce side effects on the liver and kidneys and significantly attenuated the inflammation in- duced by λ-carrageenan in a dosage-dependent manner, probably due to an inhibition of nitric oxide and prostaglandin E2, which was demon- strated in vitro. To our knowledge, this is the first report of the presence of sucrose esters in P. pe- ruviana that showed a potent anti-inflammatory effect. These results suggest the potential of su- crose esters from the Physalis genus as a novel natural alternative to treat inflammatory diseases

Erythropoiesis-stimulating Agent Use among Patients with Lupus Nephritis Approaching End-stage Renal Disease

Objectives: Little is known about erythropoiesis-stimulating agents (ESAs) utilization among lupus nephritis (LN) patients with incipient ESRD. We aimed to identify sociodemographic and clinical factors associated with ESA use among incident LN ESRD patients. Methods: Among all individuals age ≥18 with incident ESRD from 1995-2008 in the U.S. Renal Data System (USRDS), we identified those with systemic lupus erythematosus (ICD-9 code 710.0) as the cause of ESRD. ESA use at ESRD onset was ascertained from the Medical Evidence Report. Year of onset, age, sex, race/ethnicity, medical insurance, employment status, residential region, clinical factors and comorbidities were considered potentially associated with ESA use in multivariable-adjusted logistic regression analyses. Results: We identified 12,533 individuals with incident LN ESRD (1% of entire population). Of those, 4,288 (34%) received an ESA preceding ESRD. In multivariable-adjusted models, ESA users had higher serum albumin and hemoglobin concentrations, were more likely to be women, and to live in the Northeast. Conversely, Medicaid beneficiaries, the uninsured, unemployed, African Americans, Hispanics, and those with IV drug use, congestive heart failure and obesity had lower ESA use. Conclusion: Among all U.S. patients and those with LN who developed ESRD, approximately one third received ESAs. Patient sex, race, age, medical insurance, residential region and clinical factors were significantly associated with ESA therapy. While there are no guidelines for ESA use in LN patients approaching ESRD, there has been wide sociodemographic variation, raising questions about ESA prescription practices

The electronics of the energy plane of the NEXT-White detector

[EN] This paper describes the electronics of NEXT-White (NEW) detector PMT plane, a high pressure xenon TPC with electroluminescent amplification (HPXe-EL) currently operating at the Laboratorio Subterraneo de Canfranc (LSC) in Huesca, Spain. In NEXT-White the energy of the event is measured by a plane of photomultipliers (PMTs) located behind a transparent cathode. The PMTs are Hamamatsu R11410-10 chosen due to their low radioactivity. The electronics have been designed and implemented to fulfill strict requirements: an overall energy resolution below 1% and a radiopurity budget of 20 mBq unit(-1) in the chain of Bi-214. All the components and materials have been carefully screened to assure a low radioactivity level and at the same time meet the required front-end electronics specifications. In order to reduce low frequency noise effects and enhance detector safety a grounded cathode connection has been used for the PMTs. This implies an AC-coupled readout and baseline variations in the PMT signals. A detailed description of the electronics and a novel approach based on a digital baseline restoration to obtain a linear response and handle AC coupling effects is presented. The final PMT channel design has been characterized with linearity better than 0.4% and noise below 0.4mV.We acknowledge support from the following agencies and institutions: the European Research Council (ERC), Spain under the Advanced Grant 339787-NEXT; the Ministerio de Economia y Competitividad of Spain under grants FIS2014-53371-C04, the Severo Ochoa Program, Spain SEV-2014-0398 and the Maria de Maetzu Program, Spain MDM-2016-0692; the GVA of Spain under grants PROMETEO/2016/120 and SEJI/2017/011; the Portuguese FCT and FEDER, Spain through the program COMPETE, projects PTDC/FIS-NUC/2525/2014 and UID/FIS/04559/2013; the U.S. Department of Energy under contracts number DE-AC02-07CH11359 (Fermi National Accelerator Laboratory), DE-FG02-13ER42020 (Texas A&M) and de-sc0017721 (University of Texas at Arlington); and the University of Texas at Arlington. We acknowledge partial support from the European Union Horizon 2020 research and innovation programme, Spain under the Marie Sklodowska-Curie grant agreements No. 690575 and 674896. We also warmly acknowledge the Laboratorio Nazionale di Gran Sasso (LNGS) and the Dark Side collaboration for their help with TPB coating of various parts of the NEXT-White TPC. Finally, we are grateful to the Laboratorio Subterraneo de Canfranc for hosting and supporting the NEXT experiment.Álvarez-Puerta, V.; Herrero Bosch, V.; Esteve Bosch, R.; Laing, A.; Rodriguez-Samaniego, J.; Querol-Segura, M.; Monrabal, F.... (2019). The electronics of the energy plane of the NEXT-White detector. Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment. 917:68-76. https://doi.org/10.1016/j.nima.2018.11.126S687691

Infiltrating CD16 +

Our aim was to characterize glomerular monocytes (Mo) infiltration and to correlate them with peripheral circulating Mo subsets and severity of lupus nephritis (LN). Methods. We evaluated 48 LN biopsy samples from a referral hospital. Recognition of Mo cells was done using microscopic view and immunohistochemistry stain with CD14 and CD16. Based on the number of cells, we classified LN samples as low degree of diffuse infiltration (<5 cells) and high degree of diffuse infiltration (≥5 cells). Immunophenotyping of peripheral Mo subsets was done using flow cytometry. Results. Mean age was 34.0±11.7 years and the mean SLEDAI was 17.5±6.9. The most common SLE manifestations were proteinuria (91%) and hypocomplementemia (75%). Severe LN was found in 70% of patients (Class III, 27%; Class IV, 43%). Severe LN patients and patients with higher grade of CD16+ infiltration had lower levels of nonclassical (CD14+CD16++) Mo in peripheral blood. Conclusions. Our results might suggest that those patients with more severe forms of LN had a higher grade of CD14+CD16+ infiltration and lower peripheral levels of nonclassical (CD14+CD16++) Mo and might reflect a recruitment process in renal tissues. However, given the small sample, our results must be interpreted carefully

Radiogenic backgrounds in the NEXT double beta decay experiment

[EN] Natural radioactivity represents one of the main backgrounds in the search for neutrinoless double beta decay. Within the NEXT physics program, the radioactivity- induced backgrounds are measured with the NEXT-White detector. Data from 37.9 days of low-background operations at the Laboratorio Subterraneo de Canfranc with xenon depleted in Xe-136 are analyzed to derive a total background rate of (0.84 +/- 0.02) mHz above 1000 keV. The comparison of data samples with and without the use of the radon abatement system demonstrates that the contribution of airborne-Rn is negligible. A radiogenic background model is built upon the extensive radiopurity screening campaign conducted by the NEXT collaboration. A spectral fit to this model yields the specific contributions of Co-60, K-40, Bi-214 and Tl-208 to the total background rate, as well as their location in the detector volumes. The results are used to evaluate the impact of the radiogenic backgrounds in the double beta decay analyses, after the application of topological cuts that reduce the total rate to (0.25 +/- 0.01) mHz. Based on the best-fit background model, the NEXT-White median sensitivity to the two-neutrino double beta decay is found to be 3.5 sigma after 1 year of data taking. The background measurement in a Q(beta beta)+/- 100 keV energy window validates the best-fit background model also for the neutrinoless double beta decay search with NEXT-100. Only one event is found, while the model expectation is (0.75 +/- 0.12) events.The NEXT collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the European Union's Framework Programme for Research and Innovation Horizon 2020 (2014-2020) under the Marie Sklodowska-Curie Grant Agreements No. 674896, 690575 and 740055; the Ministerio de Economia y Competitividad and the Ministerio de Ciencia, Innovacion y Universidades of Spain under grants FIS2014-53371-C04, RTI2018-095979, the Severo Ochoa Program SEV-2014-0398 and the Maria de Maetzu Program MDM-2016-0692; the GVA of Spain under grants PROMETEO/2016/120 and SEJI/2017/011; the Portuguese FCT under project PTDC/FIS-NUC/2525/2014, under project UID/FIS/04559/2013 to fund the activities of LIBPhys, and under grants PD/BD/105921/2014, SFRH/BPD/109180/2015 and SFRH/BPD/76842/2011; the U.S. Department of Energy under contracts number DE-AC02-06CH11357 (Argonne National Laboratory), DE-AC02-07CH11359 (Fermi National Accelerator Laboratory), DE-FG02-13ER42020 (Texas A&M) and DE-SC0019223/DE-SC0019054 (University of Texas at Arlington); and the University of Texas at Arlington. DGD acknowledges Ramon y Cajal program (Spain) under contract number RYC-2015-18820. We also warmly acknowledge the Laboratori Nazionali del Gran Sasso (LNGS) and the Dark Side collaboration for their help with TPB coating of various parts of the NEXT-White TPC. Finally, we are grateful to the Laboratorio Subterraneo de Canfranc for hosting and supporting the NEXT experiment.Novella, P.; Palmeiro, B.; Sorel, M.; Usón, A.; Ferrario, P.; Gómez-Cadenas, JJ.; Adams, C.... (2019). Radiogenic backgrounds in the NEXT double beta decay experiment. Journal of High Energy Physics (Online). (10):1-26. https://doi.org/10.1007/JHEP10(2019)051S12610KamLAND-Zen collaboration, Search for Majorana Neutrinos near the Inverted Mass Hierarchy Region with KamLAND-Zen, Phys. Rev. Lett.117 (2016) 082503 [arXiv:1605.02889] [INSPIRE].GERDA collaboration, Improved Limit on Neutrinoless Double-β Decay of76Ge from GERDA Phase II, Phys. Rev. Lett.120 (2018) 132503 [arXiv:1803.11100] [INSPIRE].NEXT collaboration, NEXT-100 Technical Design Report (TDR): Executive Summary, 2012JINST7 T06001 [arXiv:1202.0721] [INSPIRE].M. Redshaw, E. Wingfield, J. McDaniel and E.G. Myers, Mass and double-beta-decay Q value of Xe-136, Phys. Rev. Lett.98 (2007) 053003 [INSPIRE].EXO-200 collaboration, Improved measurement of the 2νββ half-life of136Xe with the EXO-200 detector, Phys. Rev.C 89 (2014) 015502 [arXiv:1306.6106] [INSPIRE].KamLAND-Zen collaboration, Measurement of the double-β decay half-life of136Xe with the KamLAND-Zen experiment, Phys. Rev.C 85 (2012) 045504 [arXiv:1201.4664] [INSPIRE].NEXT collaboration, Initial results on energy resolution of the NEXT-White detector, 2018JINST13 P10020 [arXiv:1808.01804] [INSPIRE].NEXT collaboration, Energy Calibration of the NEXT-White Detector with 1% Resolution Near Qββof136Xe, arXiv:1905.13110 [INSPIRE].NEXT collaboration, Near-Intrinsic Energy Resolution for 30 to 662 keV Gamma Rays in a High Pressure Xenon Electroluminescent TPC, Nucl. Instrum. Meth.A 708 (2013) 101 [arXiv:1211.4474] [INSPIRE].NEXT collaboration, Characterisation of NEXT-DEMO using xenon KαX-rays, 2014JINST9 P10007 [arXiv:1407.3966] [INSPIRE].NEXT collaboration, First proof of topological signature in the high pressure xenon gas TPC with electroluminescence amplification for the NEXT experiment, JHEP01 (2016) 104 [arXiv:1507.05902] [INSPIRE].NEXT collaboration, Demonstration of the event identification capabilities of the NEXT-White detector, arXiv:1905.13141 [INSPIRE].A.D. McDonald et al., Demonstration of Single Barium Ion Sensitivity for Neutrinoless Double Beta Decay using Single Molecule Fluorescence Imaging, Phys. Rev. Lett.120 (2018) 132504 [arXiv:1711.04782] [INSPIRE].P. Thapa et al., Barium Chemosensors with Dry-Phase Fluorescence for Neutrinoless Double Beta Decay, arXiv:1904.05901 [INSPIRE].NEXT collaboration, Ionization and scintillation response of high-pressure xenon gas to alpha particles, 2013 JINST8 P05025 [arXiv:1211.4508] [INSPIRE].NEXT collaboration, Initial results of NEXT-DEMO, a large-scale prototype of the NEXT-100 experiment, 2013 JINST8 P04002 [arXiv:1211.4838] [INSPIRE].NEXT collaboration, Operation and first results of the NEXT-DEMO prototype using a silicon photomultiplier tracking array, 2013 JINST8 P09011 [arXiv:1306.0471] [INSPIRE].NEXT collaboration, Description and commissioning of NEXT-MM prototype: first results from operation in a Xenon-Trimethylamine gas mixture, 2014 JINST9 P03010 [arXiv:1311.3242] [INSPIRE].NEXT collaboration, Ionization and scintillation of nuclear recoils in gaseous xenon, Nucl. Instrum. Meth.A 793 (2015) 62 [arXiv:1409.2853] [INSPIRE].NEXT collaboration, An improved measurement of electron-ion recombination in high-pressure xenon gas, 2015 JINST10 P03025 [arXiv:1412.3573] [INSPIRE].NEXT collaboration, Accurate γ and MeV-electron track reconstruction with an ultra-low diffusion Xenon/TMA TPC at 10 atm, Nucl. Instrum. Meth.A 804 (2015) 8 [arXiv:1504.03678] [INSPIRE].NEXT collaboration, The Next White (NEW) Detector, 2018 JINST13 P12010 [arXiv:1804.02409] [INSPIRE].NEXT collaboration, Sensitivity of NEXT-100 to Neutrinoless Double Beta Decay, JHEP05 (2016) 159 [arXiv:1511.09246] [INSPIRE].V. Alvarez et al., Radiopurity control in the NEXT-100 double beta decay experiment: procedures and initial measurements, 2013 JINST8 T01002 [arXiv:1211.3961] [INSPIRE].NEXT collaboration, Radiopurity assessment of the tracking readout for the NEXT double beta decay experiment, 2015 JINST10 P05006 [arXiv:1411.1433] [INSPIRE].NEXT collaboration, Radiopurity assessment of the energy readout for the NEXT double beta decay experiment, 2017 JINST12 T08003 [arXiv:1706.06012] [INSPIRE].NEXT collaboration, Measurement of radon-induced backgrounds in the NEXT double beta decay experiment, JHEP10 (2018) 112 [arXiv:1804.00471] [INSPIRE].NEXT collaboration, Electron drift properties in high pressure gaseous xenon, 2018 JINST13 P07013 [arXiv:1804.01680] [INSPIRE].NEXT collaboration, Calibration of the NEXT-White detector using83m Kr decays, 2018JINST13 P10014 [arXiv:1804.01780] [INSPIRE].NEXT collaboration, Background rejection in NEXT using deep neural networks, 2017JINST12 T01004 [arXiv:1609.06202] [INSPIRE].NEXT collaboration, Application and performance of an ML-EM algorithm in NEXT, 2017JINST12 P08009 [arXiv:1705.10270] [INSPIRE]

Monte Carlo characterization of PETALO, a full-body liquid xenon-based PET detector

[EN] New detector approaches in Positron Emission Tomography imaging will play an important role in reducing costs, lowering administered radiation doses, and improving overall performance. PETALO employs liquid xenon as the active scintillating medium and UV-sensitive silicon photomultipliers for scintillation readout. The scintillation time in liquid xenon is fast enough to register time-of-flight information for each detected coincidence, and sufficient scintillation is produced with low enough fluctuations to obtain good energy resolution. The present simulation study examines a full-body-sized PETALO detector and evaluates its potential performance in PET image reconstruction.This work was supported by the European Research Council under grant ID 757829 and by Ministerio de Economia y Competitividad for grant FPA2016-78595-C3-1-R.Renner, J.; Romo-Luque, C.; Aliaga, RJ.; Álvarez-Puerta, V.; Ballester Merelo, FJ.; Benlloch-Rodríguez, J.; Carrión, J.... (2022). Monte Carlo characterization of PETALO, a full-body liquid xenon-based PET detector. Journal of Instrumentation. 17(5):1-14. https://doi.org/10.1088/1748-0221/17/05/P0504411417

Assessment of anti-malondialdehyde-acetaldehyde antibody frequencies in rheumatoid arthritis with new data from two independent cohorts, meta-analysis, and meta-regression

Autoantibodies are critical elements in RA pathogenesis and clinical assessment. The anti-malondialdehyde-acetaldehyde (anti-MAA) antibodies are potentially useful because of their claimed high sensitivity for all RA patients, including those lacking RF and anti-CCP antibodies. Therefore, we aimed to replicate these findings.The research done in Santiago was funded by Instituto de Salud Carlos III through the projects PI20/01268, PI17/01606 and RD21/0002/0003, co-funded by the European Union. L.R.-M. was supported by Xunta de Galicia (Spain) through a Gain pre-doctoral fellowship (IN606A-2017/015). The research in Barcelona was funded by the Spanish Ministry of Economy, Industry and Competitiveness and the European Regional Development Fund (Grant PID2021-122216OB-I00).Peer reviewe

Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis

Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: ≥ 2.9;P ≤ .03). Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P < .001), and might potentially be used as biomarkers for the identification of MGUS and MM patients, who are candidates for monitoring pre-symptomatic organ damage related to AL amyloidosis. Altogether, this study addressed the need for consensus on how to use flow cytometry in AL amyloidosis, and proposes a standardized MFC-based automated risk classification ready for implementation in clinical practice