Oncolytic adenovirus coding for shedding-resistant MICA enhances immune responses against tumors.

Cancer immunotherapies strive to overcome tumor-induced immune suppression and activate antitumor immune responses. Although cytotoxic T lymphocytes (CTLs) play a pivotal role in this process, natural killer (NK) cells have also demonstrated remarkable tumor-killing abilities, given their ability to discriminate tumor cells from normal cells and mediate specific antitumoral cytotoxicity. NK cells activation depends on a balance between activation and inhibition signals from several ligands/receptors. Among them, MICA/NKG2D axis is a master regulator of NK activation. MHC class I chain-related polypeptide A (MICA) expression is upregulated by many tumor cell lines and primary tumors and serves as a ligand for the activating NK group 2D (NKG2D) receptor on NK cells and subpopulations of T cells. However, cancer cells can cleave MICA, making it soluble and de-targeting tumor cells from NK cells, leading to tumor immune escape.In this study, we present ICOVIR15KK-MICAMut, an oncolytic adenovirus (OAdv) armed with a transgene encoding a non-cleavable MICA to promote NK-mediated cell-killing capacity and activate the immune response against cancer cells. We first demonstrated the correct MICA overexpression from infected cells. Moreover, our MICA-expressing OAdv promotes higher NK activation and killing capacity than the non-armed virus in vitro. In addition, the armed virus also demonstrated significant antitumor activity in immunodeficient mice in the presence of human PBMCs, indicating the activation of human NK cells. Finally, OAdv-MICA overexpression in immunocompetent tumor-bearing mice elicits tumor-specific immune response resulting in a greater tumor growth control.In summary, this study highlights the significance of NK cells in cancer immunotherapy and presents an innovative approach using a modified oncolytic virus to enhance NK cell activation and antitumor immune response. These findings suggest promising potential for future research and clinical applications.

Relación entre grosor coroideo y densidad vascular en población joven sana / Relationship between choroidal thickness and vascular density in young healthy population

Antecedentes y objetivo El objetivo es analizar la densidad vascular (DV) coroidea en individuos sanos y compararla con el grosor coroideo (GC). Materiales y métodos Estudio transversal incluyendo individuos entre 18 y 35 años, caucásicos y con longitud axial (LA) 21-26 mm. Se estudió la coroides con tomografía de coherencia óptica-angiografía (OCTA) Triton DRI (Topcon) y se obtuvo un cubo macular de 6x6 mm. El software dio los valores de GC automáticamente. Los valores de DV se obtuvieron mediante codificación en números de los colores de los mapas de DV. Resultados Se analizaron 102 ojos (51 pacientes). La edad media fue 27,32 ± 3,94 años, la presión intraocular media fue 18,07 ± 2,38 mmHg, y la LA media fue 23,71 ± 0,66 mm. El GC fue mayor en el eje vertical y menor al acercarse a los lados nasal y temporal. El mayor GC se encontró en la mácula superior. La mayor DV coroidea fue en la fóvea y en la región yuxtapapilar. La menor DV coroidea se halló en la mácula superior e inferior. Se encontraron correlaciones moderadas inversas entre GC y DV coroidea en las regiones yuxtapapilar e inferior. Conclusiones La coroides tiene un patrón de grosor diferente del de la retina. Los vasos coroideos representan un porcentaje muy alto de la coroides en las regiones peripapilar y fóvea. Por el contrario, la mácula superior e inferior muestra valores bajos de DV (AU)

Background and purpose The purpose is to analyze choroidal vascular density (VD) in healthy individuals and to compare it with choroidal thickness (CT). Materials and methods Cross-sectional study enrolling healthy individuals between 18 and 35 years old of Caucasian race and with an axial length (AL) 21–26 mm. Choroid was imaged with swept-source optical coherence tomography angiography (OCTA) Triton DRI (Topcon) and a macular cube of 6 mm × 6 mm was obtained. CT values were automatically given by the software. VD values were obtained through codifying colors of the VD map into numbers. Results One hundred and two (51 patients) were analyzed. Mean age was 27.32 ± 3.94 years old, mean intraocular pressure was 18.07 ± 2.38 mmHg, and mean AL was 23.71 ± 0.66 mm. CT was higher in the vertical axis and lower when approaching nasal and temporal sides. The highest CT was in superior macula. The highest choroidal VD were in the fovea and in the juxtapapillary region. The lowest choroidal VD were found in superior and inferior macular areas. Moderate inverse correlations between CT and choroidal VD were found in the juxtapapillary and inferior regions. Conclusions The choroid has a thickness pattern that differs from retina. Choroidal vessels represent a very high percentage of choroid in the peripapillary region and in the fovea. On the contrary, superior and inferior macula reveals low values of VD (AU)

Relationship between choroidal thickness and vascular density in young healthy population.

BACKGROUND AND PURPOSE: The purpose is to analyze choroidal vascular density (VD) in healthy individuals and to compare it with choroidal thickness (CT). MATERIALS AND METHODS: Cross-sectional study enrolling healthy individuals between 18 and 35 years old of Caucasian race and with an axial length (AL) 21-26 mm. Choroid was imaged with swept-source optical coherence tomography angiography (OCTA) Triton DRI (Topcon) and a macular cube of 6 × 6 mm was obtained. CT values were automatically given by the software. VD values were obtained through codifying colors of the VD map into numbers. RESULTS: 102 (51 patients) were analyzed. Mean age was 27.32 ±â€¯3.94 years old, mean intraocular pressure was 18.07 ±â€¯2.38 mmHg, and mean AL was 23.71 ±â€¯0.66 mm. CT was higher in the vertical axis and lower when approaching nasal and temporal sides. The highest CT was in superior macula. The highest choroidal VD were in the fovea and in the juxtapapillary region. The lowest choroidal VD were found in superior and inferior macular areas. Moderate inverse correlations between CT and choroidal VD were found in the juxtapapillary and inferior regions. CONCLUSIONS: The choroid has a thickness pattern that differs from retina. Choroidal vessels represent a very high percentage of choroid in the peripapillary region and in the fovea. On the contrary, superior and inferior macula reveals low values of VD.

Diagnostic Approach to Acute Liver Failure in Children: A Position Paper by the SIGENP Liver Disease Working Group.

Acute liver failure (ALF) is a clinical condition characterized by the abrupt onset of coagulopathy and biochemical evidence of hepatocellular injury, leading to rapid deterioration of liver cell function. In children, ALF has been characterized by raised transaminases, coagulopathy, and no known evidence of pre-existing chronic liver disease; unlike in adults, the presence of hepatic encephalopathy is not required to establish the diagnosis. Although rare, ALF has a high mortality rate without liver transplantation (LT). Etiology of ALF varies with age and geographical location, although it may remain indeterminate in a significant proportion of cases. However, identifying its etiology is crucial to undertake disease-specific management and evaluate indication to LT. In this position statement, the Liver Disease Working Group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) reviewed the most relevant studies on pediatric ALF to provide recommendations on etiology, clinical features and diagnostic work-up of neonates, infants and children presenting with ALF. Recommendations on medical management and transplant candidacy will be discussed in a following consensus conference.

Enhanced removal of the endocrine disruptor compound Bisphenol A by adsorption onto green-carbon materials. Effect of real effluents on the adsorption process.

The high exposure to the endocrine disrupting compounds (EDC) in water represents a relevant issue for the health of living beings. The xenoestrogen Bisphenol A (BPA), a suspected EDC, is an industrial additive broadly used for manufacturing polycarbonate and epoxy resins. Due to its harmful effect in humans and the aquatic environment, an efficient method to remove BPA from wastewater is urgently required. The present work aims to study the adsorption of BPA from aqueous solutions onto carbonaceous materials, e.g., a synthesized carbon xerogel (RFX), a chemical-activated carbon from Kraft lignin (KLP) and a commercial activated carbon (F400) for comparative purposes. Batch kinetic and adsorption tests of BPA in ultrapure water were accomplished, finding higher adsorption capacities of BPA onto both F400 activated carbon (qsat = 407 mg g-1) and the biochar KLP (qsat = 220 mg g-1), versus to that obtained for the xerogel (qsat = 78 mg g-1). Furthermore, kinetic experiments revealed faster kinetic adsorption for RFX and KLP materials, achieving the equilibrium time within 24 h, attributed to their more-opened porous structure. Pseudo-first order, pseudo-second order, Elovich, intra-particle diffusion and film diffusion models were used to fit the experimental data. Thus, the BPA adsorption isotherms were analysed by Langmuir, Freundlich, Sips, Redlich-Peterson and Dual-site Langmuir (DLS) isotherm models.In addition, the influence of different aqueous matrices, such as a hospital wastewater, a wastewater treatment plant (WWTP) effluent and a river water, on BPA removal efficiency has been explored. These adsorption tests revealed a clear competitive effect between the target compound (BPA) and the natural organic matter content (NOM) present in the matrices for the active sites, resulting in a high decreasing of BPA adsorption removal.

New insights from modelling and estimation of mass transfer parameters in fixed-bed adsorption of Bisphenol A onto carbon materials.

The removal of Bisphenol A, 2,2-bis (4-hydroxyphenyl) propane (BPA) in fixed-bed columns was investigated by breakthrough adsorption tests at different operation conditions and further prediction by a mathematical model to describe the adsorption-diffusion process onto two synthesized carbon porous materials. In this study, a xerogel (RFX) prepared by an optimized conventional sol-gel method and a lignin-based activated carbon (KLP) obtained via chemical activation were used in batch and fixed-bed adsorption experiments. The materials were fully characterized and their adsorptive properties were compared to those obtained with a commercial activated carbon (F400). RFX and KLP materials reached the equilibrium adsorption in only 24 h, whereas F400 activated carbon required 48 h. In addition, F400 and KLP adsorbents showed higher equilibrium adsorption capacity values (qe = 0.40 and 0.22 kg/kg, for F400 and KLP, respectively) than that obtained for the xerogel (qe = 0.08 kg/kg). Both synthesized carbon-adsorbents were studied in fixed-bed adsorption tests, exploring the effect of the operation conditions, e.g., initial BPA concentration (0.005-0.04 kg/m3), weight of adsorbent (0.01-0.05 g) and volumetric flow rate (0.2 to 1.0 mL/min), on the adsorption performance of the column. All the tested adsorption columns reached the equilibrium in a very short time, due to the efficient dimensionless of the bed. Additionally, the regeneration of the exhausted adsorbent was studied, achieving the total reuse of the solids after three consecutive cycles using methanol as regeneration agent. Finally, a mathematical model based on mass conservation equations was proposed, allowing to efficiently fit the experimental BPA breakthrough curves and estimate the external and adsorbed-phase mass transfer coefficients with a high accuracy.

La escisión de la glándula de Bartholin como causa de distorsión anatómica y dolor vulvar / Excision of Bartholin gland as a cause of anatomy distortion and vulvar pain

Introducción: Los quistes y abscesos de Bartholin pueden producirse en cerca del 2% de las consultas ginecológicas por año. Se han propuesto diferentes tipos de tratamientos (punción, marsupialización, esclerosis, escisión de la glándula, etc.), con porcentajes diferentes de recurrencia y complicaciones. Presentamos 5 casos en los que tras practicar escisión completa de la glándula por enfermedad benigna, aparecen como complicación tardía el dolor vulvar y la distorsión anatómica. Objetivo: Analizar los casos, así como su repercusión en la calidad de vida posterior. Resultados: Ante la enfermedad benigna de la glándula de Bartholin (quística abscesificada o no) debemos mantener la glándula para que siga ejerciendo su función y valorar la funcionalidad posterior, utilizando para este fin los test de calidad de vida en ese seguimiento que incluya la sexualidad. Por último, debemos mejorar nuestras prácticas asistenciales y, en caso de una evolución tórpida, no permitir la cronificación del estímulo doloroso

Introduction: Bartholin cysts and abscesses may occur in about 2% of gynaecological cases per year. Different types of treatment (puncture, marsupialisation, sclerosis, excision of the gland, etc.) have been proposed, with different percentages of recurrence and complications. A series of 5 cases are presented, in which, after practicing complete excision of the gland due to benign disease, vulvar pain and anatomic distortion appeared as late complications. Objective: To analyse the results based on the technique used, including the importance of late complications (pain and anatomical distortion), as well as their impact on the quality of later life. Results: Given the benign disease of the Bartholin gland (abscess or cyst), the gland must be maintained so that it can continue fulfilling its role. Its future functioning can be assessed during follow-up by using a quality of life test that includes sexuality. Finally, care practices in these patients must be improved, especially in the case of a slow progress, not allowing the development of chronic pain stimulus

Discharge properties of morphologically identified vestibular neurons recorded during horizontal eye movements in the goldfish.

Computational capability and connectivity are key elements for understanding how central vestibular neurons contribute to gaze-stabilizing eye movements during self-motion. In the well-characterized and segmentally distributed hindbrain oculomotor network of goldfish, we determined afferent and efferent connections along with discharge patterns of descending octaval nucleus (DO) neurons during different eye motions. Based on activity correlated with horizontal eye and head movements, DO neurons were categorized into two complementary groups that either increased discharge during both contraversive (type II) eye (e) and ipsiversive (type I) head (h) movements (eIIhI) or vice versa (eIhII). Matching time courses of slow-phase eye velocity and corresponding firing rates during prolonged visual and head rotation suggested direct causality in generating extraocular motor commands. The axons of the dominant eIIhI subgroup projected either ipsi- or contralaterally and terminated in the abducens nucleus, Area II, and Area I with additional recurrent collaterals of ipsilaterally projecting neurons within the parent nucleus. Distinct feedforward commissural pathways between bilateral DO neurons likely contribute to the generation of eye velocity signals in eIhII cells. The shared contribution of DO and Area II neurons to eye velocity storage likely represents an ancestral condition in goldfish that is clearly at variance with the task separation between mammalian medial vestibular and prepositus hypoglossi neurons. This difference in signal processing between fish and mammals might correlate with a larger repertoire of visuo-vestibular-driven eye movements in the latter species that potentially required a shift in sensitivity and connectivity within the hindbrain-cerebello-oculomotor network. NEW & NOTEWORTHY We describe the structure and function of neurons within the goldfish descending octaval nucleus. Our findings indicate that eye and head velocity signals are processed by vestibular and Area II velocity storage integrator circuitries whereas the velocity-to-position Area I neural integrator generates eye position solely. This ancestral condition differs from that of mammals, in which vestibular neurons generally lack eye position signals that are processed and stored within the nucleus prepositus hypoglossi.

Complicación durante una traqueostomía: ligadura de la arteria carótida interna / Complication during tracheostomy: Internal carotid artery ligation

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Radiofrecuencia pulsada para el tratamiento de la neuralgia occipital: análisis de predictores y resultados / Occipital nerve pulsed radiofrequency treatment: analysis predictors and outcomes

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A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion.

The Rift Valley fever virus (RVFV) is transmitted by infected mosquitoes, causing severe disease in humans and livestock across Africa. We determined the x-ray structure of the RVFV class II fusion protein Gc in its postfusion form and in complex with a glycerophospholipid (GPL) bound in a conserved cavity next to the fusion loop. Site-directed mutagenesis and molecular dynamics simulations further revealed a built-in motif allowing en bloc insertion of the fusion loop into membranes, making few nonpolar side-chain interactions with the aliphatic moiety and multiple polar interactions with lipid head groups upon membrane restructuring. The GPL head-group recognition pocket is conserved in the fusion proteins of other arthropod-borne viruses, such as Zika and chikungunya viruses, which have recently caused major epidemics worldwide.

Recent developments in radiotherapy for small-cell lung cancer: a review by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)

Small-cell lung cancer (SCLC) accounts for 13% of all lung tumours. The standard treatment in patients with limited-stage disease is radiotherapy combined with chemotherapy. In extensive SCLC, the importance of consolidation thoracic radiotherapy in patients with a good treatment response has become increasingly recognized. In both limited and extensive disease, prophylactic cranial irradiation is recommended in patients who respond to treatment. New therapeutic approaches such as immunotherapy are being increasingly incorporated into the treatment of SCLC, although more slowly than in non-small cell lung cancer (NSCLC). Diverse radiation dose and fractionation schemes, administered in varying combinations with these new drugs, are being investigated. In the present study we review and update the role of radiotherapy in the treatment of SCLC. We also discuss the main clinical trials currently underway in order to identify future trends (AU)

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Diagnóstico diferencial del dolor lumbar crónico con radiculopatía bilateral: meningioma intradural extramedular L1-L2 / Differencial diagnosis of chronic back pain with bilateral radiculopathy: spinal extramedullary meningioma L1-L2

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Recent developments in radiotherapy for small-cell lung cancer: a review by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

Small-cell lung cancer (SCLC) accounts for 13% of all lung tumours. The standard treatment in patients with limited-stage disease is radiotherapy combined with chemotherapy. In extensive SCLC, the importance of consolidation thoracic radiotherapy in patients with a good treatment response has become increasingly recognized. In both limited and extensive disease, prophylactic cranial irradiation is recommended in patients who respond to treatment. New therapeutic approaches such as immunotherapy are being increasingly incorporated into the treatment of SCLC, although more slowly than in non-small cell lung cancer (NSCLC). Diverse radiation dose and fractionation schemes, administered in varying combinations with these new drugs, are being investigated. In the present study we review and update the role of radiotherapy in the treatment of SCLC. We also discuss the main clinical trials currently underway in order to identify future trends.

Targeted therapy combined with radiotherapy in non-small-cell lung cancer: a review of the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)

In recent years, major advances in our understanding of the molecular biology of lung cancer, together with significant improvements in radiotherapy technologies, have revolutionized the treatment of non-small cell lung cancer (NSCLC). This has led to the development of new therapies that target molecular mutations specific to each tumor type, acting on the cell surface antigens or intracellular signaling pathways, or directly affecting cell survival. At the same time, ablative dose radiotherapy can be delivered safely in the context of metastatic disease. In this article, the GOECP/SEOR (Oncological Group for Study of Lung Cancer/Spanish Society of Radiation Oncology) reviews the role of new targeted therapies used in combination with radiotherapy in patients with locally advanced (stage III) NSCLC and in patients with advanced, metastatic (stage IV) NSCLC (AU)

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Diagnostic ability of Humphrey perimetry, Octopus perimetry, and optical coherence tomography for glaucomatous optic neuropathy.

PurposeTo evaluate and compare the diagnostic accuracy of the Humphrey Field Analyzer (HFA), Octopus perimetry, and Cirrus OCT for glaucomatous optic neuropathy.MethodsEighty-eight healthy individuals and 150 open-angle glaucoma patients were consecutive and prospectively selected. Eligibility criteria for the glaucoma group were intraocular pressure ≥21 mm Hg and glaucomatous optic nerve head morphology. All subjects underwent a reliable standard automated perimetry with the HFA and Octopus perimeter, and were imaged with the Cirrus OCT. Receiver-operating characteristic (ROC) curves were plotted for the threshold values and main indices of the HFA and Octopus, the peripapillary retinal nerve fiber layer thicknesses, and the optic nerve head parameters. Sensitivities at 85 and 95% fixed-specificities were also calculated. The best areas under the ROC curves (AUCs) were compared using the DeLong method.ResultsIn the glaucoma group, mean deviation (MD) was -5.42±4.6 dB for HFA and 3.90±3.6 dB for Octopus. The MD of the HFA (0.966; P<0.001), mean sensitivity of the Octopus (0.941; P<0.001), and average cup-to-disc (C/D) ratio measured by the Cirrus OCT (0.958; P<0.001) had the largest AUCs for each test studied. There were no significant differences among them. Sensitivities at 95% fixed-specificity were 82% for pattern standard deviation of the HFA, 81.3% for average C/D ratio of OCT, and 80% for the MD of the Octopus.ConclusionsHFA, Octopus, and Cirrus OCT demonstrated similar diagnostic accuracies for glaucomatous optic neuropathy. Visual field and OCT provide supplementary information and thus these tests are not interchangeable.