Método de calibración para interrogadores de redes de Bragg en fibra óptica

Se ha desarrollado un método de calibración de interrogadores de redes de Bragg en fibra óptica que compara la respuesta del equipo de prueba con un simulador de red de Bragg compuesto por un filtro sintonizable unido a un espejo de fibra óptica. La longitud de onda simulada obtenida se mide con un interferómetro de referencia calibrado en el Instituto de Óptica del Consejo Superior de Investigaciones Científicas (IO?CSIC). Este método de calibración ha sido aplicado para calibrar varios tipos de interrogadores de redes de Bragg: estáticos y dinámicos. La incertidumbre en la calibración absoluta de los interrogadores es de ±88 pm, y es debida principalmente a la anchura espectral del filtro que simula la red de Bragg. Sin embrago, en calibraciones relativas la incertidumbre baja a ±3 pm, dominado por la incertidumbre en la calibración del interferómetro de referencia

MXRA5 is a TGF-β1-regulated human protein with anti-inflammatory and anti-fibrotic properties

Current therapy for chronic kidney disease (CKD) is unsatisfactory because of an insufficient understanding of its pathogenesis. Matrix remodelling-associated protein 5 (MXRA5, adlican) is a human protein of unknown function with high kidney tissue expression, not present in rodents. Given the increased expression of MXRA5 in injured tissues, including the kidneys, we have suggested that MXRA5 may modulate kidney injury. MXRA5 immunoreactivity was observed in tubular cells in human renal biopsies and in urine from CKD patients. We then explored factors regulating MXRA5 expression and MXRA5 function in cultured human proximal tubular epithelial cells and explored MXRA5 expression in kidney cancer cells and kidney tissue. The fibrogenic cytokine transforming growth factor-β1 (TGFβ1) up-regulated MXRA5 mRNA and protein expression. TGFβ1-induced MXRA5 up-regulation was prevented by either interference with TGFβ1 activation of the TGFβ receptor 1 (TGFBR1, ALK5) or by the vitamin D receptor agonist paricalcitol. By contrast, the pro-inflammatory cytokine TWEAK did not modulate MXRA5 expression. MXRA5 siRNA-induced down-regulation of constitutive MXRA5 expression resulted in higher TWEAK-induced expression of chemokines. In addition, MXRA5 down-regulation resulted in a magnified expression of genes encoding extracellular matrix proteins in response to TGFβ1. Furthermore, in clear cell renal cancer, von Hippel–Lindau (VHL) regulated MXRA5 expression. In conclusion, MXRA5 is a TGFβ1- and VHL-regulated protein and, for the first time, we identify MXRA5 functions as an anti-inflammatory and anti-fibrotic molecule. This information may yield clues to design novel therapeutic strategies in diseases characterized by inflammation and fibrosis.This work was supported by grants from the Instituto de Salud Carlos III (FEDER funds ISCIII RETIC REDINREN RD12/0021, PI13/00047, PI15/00298, PIE13/00051, Comunidad de Madrid (CIFRA S2010/BMD-2378), Sociedad Española de Nefrología. Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) to AO, ISCIII Joan Rodes JR14/00028 to BFF and Miguel Servet MS12/03262, MS14/00133, MECD to JP, and Biobanco IIS-FJD PT13/0010/001

A mechanobiological model for tumor spheroid evolution with application to glioblastoma: A continuum multiphysics approach

Background: Spheroids are in vitro quasi-spherical structures of cell aggregates, eventually cultured within a hydrogel matrix, that are used, among other applications, as a technological platform to investigate tumor formation and evolution. Several interesting features can be replicated using this methodology, such as cell communication mechanisms, the effect of gradients of nutrients, or the creation of realistic 3D biological structures. The main objective of this work is to link the spheroid evolution with the mechanical activity of cells, coupled with nutrient consumption and the subsequent cell dynamics. Method: We propose a continuum mechanobiological model which accounts for the most relevant phenomena that take place in tumor spheroid evolution under in vitro suspension, namely, nutrient diffusion in the spheroid, kinetics of cellular growth and death, and mechanical interactions among the cells. The model is qualitatively validated, after calibration of the model parameters, versus in vitro experiments of spheroids of different glioblastoma cell lines. Results: Our model is able to explain in a novel way quite different setups, such as spheroid growth (up to six times the initial configuration for U-87 MG cell line) or shrinking (almost half of the initial configuration for U-251 MG cell line); as the result of the mechanical interplay of cells driven by cellular evolution. Conclusions: Glioblastoma tumor spheroid evolution is driven by mechanical interactions of the cell aggregate and the dynamical evolution of the cell population. All this information can be used to further investigate mechanistic effects in the evolution of tumors and their role in cancer disease

Penning-trap eigenfrequency measurements with optical radiofrequency detectors

We use an electric-dipole laser-driven transition to precisely measure the cyclotron-frequency ratios of the pairs $^{42}$Ca$^+$-$^{40}$Ca$^+$, $^{44}$Ca$^+$-$^{40}$Ca$^+$ and $^{48}$Ca$^+$-$^{40}$Ca$^+$ in a 7-tesla Penning trap. A single laser-cooled ($T\approx 1$~mK) ion serves, together with photon-counting and/or photon-imaging units, as a radiofrequency detector covering a broad-band frequency spectrum, in the present case from kHz to a few MHz. Such detectors ($^{40,42,44,48}$Ca$^{\scriptsize{+}}$) allow measuring extremely small forces, with measured normalized sensitivities down to $7.4(3.5)$ yN$/\sqrt{\text{Hz}}$ and $24.9(9.9)$ yN$/\sqrt{\text{Hz}}$ in the MHz and kHz regime, respectively. The direct determination of the ions' amplitudes makes a cyclotron-frequency measurement process more robust against inhomogeneities of the magnetic field and/or deviations of the electric quadrupole field due to mechanical imperfections of the trap.Comment: 6 pages, 3 figure

Impaired Mesopic Visual Acuity in Eyes with Early Age-Related Macular Degeneration

Purpose.: To determine photopic and mesopic distance high-contrast visual acuity (HC-VA) and low-contrast visual acuity (LC-VA) in eyes with early age-related macular degeneration (AMD). Methods.: Measurements were made in 22 subjects with early AMD and 28 healthy control subjects. Inclusion criteria included a photopic HC-VA of 20/25 or better. Distance VA was measured using HC (96%) and LC (10%) Bailey-Lovie logMAR letter charts under photopic (85 cd/m2) and mesopic (0.1–0.2 cd/m2) luminance conditions. Results.: Mean mesopic distance HC-VA and LC-VA were significantly worse (0.1 logMAR and 0.28 logMAR, respectively) in the early AMD group than in the control group. Under mesopic conditions, the mean difference between LC-VA and HC-VA was significantly greater in the early AMD (0.45 logMAR) than the control group (0.27 logMAR). Mean differences between mesopic versus photopic HC-VA and mesopic versus photopic LC-VA were significantly greater in the early AMD than the control group (0.13 and 0.32 logMAR of difference between the means, respectively). Sensitivity and specificity were significantly greater for mesopic LC-VA than for mesopic HC-VA (Receiver Operating Characteristics, area under the curve [AUC], 0.94 ± 0.030 and 0.76 ± 0.067, respectively). AUC values for photopic HC-VA and LC-VA were below 0.70. Conclusions.: Visual acuity testing under low luminance conditions emerged as an optimal quantitative measure of retinal function in early AMD

Urinary cyclophilin A as marker of tubular cell death and kidney injury

Background: Despite the term acute kidney injury (AKI), clinical biomarkers for AKI re-flect function rather than injury and independent markers of injury are needed. Tubular cell death, including necroptotic cell death, is a key feature of AKI. Cyclophilin A (CypA) is an intracellular protein that has been reported to be released during necroptosis. We have now explored CypA as a potential marker for kidney injury in cultured tubular cells and in clinical settings of ischemia-reperfusion injury (IRI), characterized by limitations of current diagnostic criteria for AKI. Meth-ods: CypA was analyzed in cultured human and murine proximal tubular epithelial cells exposed to chemical hypoxia, hypoxia/reoxygenation (H/R) or other cell death (apoptosis, necroptosis, fer-roptosis) inducers. Urinary levels of CypA (uCypA) were analyzed in patients after nephron sparing surgery (NSS) in which the contralateral kidney is not disturbed and kidney grafts with initial function. Results: Intracellular CypA remained unchanged while supernatant CypA increased in parallel to cell death induction. uCypA levels were higher in NSS patients with renal artery clamping (that is, with NSS-IRI) than in no clamping (NSS-no IRI), and in kidney transplantation (KT) recipients (KT-IRI) even in the presence of preserved or improving kidney function, while this was not the case for urinary Neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, higher uCypA levels in NSS patients were associated with longer surgery duration and the incidence of AKI increased from 10% when using serum creatinine (sCr) or urinary output criteria to 36% when using high uCypA levels in NNS clamping patients. Conclusions: CypA is released by kidney tubular cells during different forms of cell death, and uCypA increased during IRI-induced clinical kidney injury independently from kidney function parameters. Thus, uCypA is a potential bi-omarker of kidney injury, which is independent from decreased kidney functionResearch by the authors was funded by FIS/ FEDER funds (PI17/00257, PI18/01386, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM. Salary support: ISCIII Miguel Servet to A.B.S., MICIN Ramon y Cajal to M.D.S.-N., REDinREN RD016/0009 to M.F.-B.,SENEFRO to D.M.-S. and Consejería de Educación, Juventud y Deporte (Comunidad de Madrid/FSE) to A.M.L.-

Coping with intimate partner violence and the COVID-19 lockdown: The perspectives of service professionals in Spain

Socioeconomic crisis and humanitarian disasters can cause increased stress for women who experience inter-partner violence (IPV). This study analyzed the impact of the COVID-19 lockdown on this important issue, their related health and social services and working conditions from the perspectives of professionals in different sectors. Forty-three semi-structured interviews were carried out with 47 professionals (44 women and 3 men) from 40 different entities (September 2020-April 2021). This content analysis suggests that the pandemic and its associated prevention measures have had a negative impact on women exposed to IPV and their children, which affected their social wellbeing. Professionals described burnout, difficult and slow administrative processes, and problems with coordination and access to information. These negative impacts were mitigated, in part, by the work of professionals, but this suggests that a series of key strategies are needed to improve the response capacity of the service sector to IPV in situations of crisis. These improvements are related to the availability of human and material resources; an efficient coordination network between the professionals from different sectors; existence of informal support networks in the community; protocols/procedures and prior training for better implementation; and greater flexibility and accessibility of basic services that benefit women who experience IPV.This study was financed through the project “Gender violence and social and health responses during the COVID-19 crisis” by the Fondo Supera Covid-19 CRUE-Santander for the period 2020-2021 (Ref. FSCovid19-03). It was also co-supported by the CIBER of Epidemiology and Public Health of Spain for its aid to the Gender-based Violence and Youth Research Program.S

Molecular pathways driving omeprazole nephrotoxicity

Omeprazole, a proton pump inhibitor used to treat peptic ulcer and gastroesophageal reflux disease, has been associated to chronic kidney disease and acute interstitial nephritis. However, whether omeprazole is toxic to renal cells is unknown. Omeprazole has a lethal effect over some cancer cells, and cell death is a key process in kidney disease. Thus, we evaluated the potential lethal effect of omeprazole over tubular cells. Omeprazole induced dose-dependent cell death in human and murine proximal tubular cell lines and in human primary proximal tubular cell cultures. Increased cell death was observed at the high concentrations used in cancer cell studies and also at lower concentrations similar to those in peptic ulcer patient serum. Cell death induced by omeprazole had features of necrosis such as annexin V/7-AAD staining, LDH release, vacuolization and irregular chromatin condensation. Weak activation of caspase-3 was observed but inhibitors of caspases (zVAD), necroptosis (Necrostatin-1) or ferroptosis (Ferrostatin-1) did not prevent omeprazole-induced death. However, omeprazole promoted a strong oxidative stress response affecting mitochondria and lysosomes and the antioxidant N-acetyl-cysteine reduced oxidative stress and cell death. By contrast, iron overload increased cell death. An adaptive increase in the antiapoptotic protein BclxL failed to protect cells. In mice, parenteral omeprazole increased tubular cell death and the expression of NGAL and HO-1, markers of renal injury and oxidative stress, respectively. In conclusion, omeprazole nephrotoxicity may be related to induction of oxidative stress and renal tubular cell deathSupported by FIS CP12/03262, CP14/00133, PI16/02057, PI16/ 01900, PI18/01366, PI19/00588, PI19/00815, DTS18/00032, ERAPerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009 FEDER funds, Sociedad Española de Nefrología, Fundacion Renal Iñigo Álvarez de Toledo (FRIAT), ISCIII Miguel Servet (ABS, MDS-N), ISCIII Sara Borrell (JMM-M), Comunidad de Madrid CIFRA2 B2017/BMD-3686 (MF-B and DM-S

Measurement with 2m resolution using a Raman-assisted BOTDA sensor featuring 75km dynamic range

We have used distributed Raman amplification to extend the measurement distance of a Brillouin Optical Time-Domain Analysis (BOTDA) sensor. We successfully demonstrate a dynamic range of 75 km with 2 meter spatial resolution