Nano-Regulation of Gene Expression in Chlamydomonas reinhardtii: Harnessing AuNPs for Remotely Switchable Lipid Biosynthesis via Antisense Oligonucleotides.

Antisense oligonucleotide (ASO)-mediated gene silencing has broad applications, spanning from biomedicine to agriculture, involving molecular biology, synthetic biology, and genetic manipulation. This research harnessed nanotechnology to augment ASO-mediated gene silencing, introducing a remotely switchable gene expression system for precise temporal control. We targeted lipid biosynthesis and accumulation enhancement in the photosynthetic eukaryote Chlamydomonas reinhardtii. Gold nanoparticles (AuNPs) transported double-stranded DNA (dsDNA), forming dsDNA-AuNP complexes. These complexes comprised 3'-thiolated sense strands attached to AuNPs and fluorescent antisense oligonucleotides. To avoid harmful laser effects on cells, we adopted a light-emitting diode (LED). Confocal microscopy confirmed dsDNA-AuNP internalization in C. reinhardtii. LED-triggered antisense release led to an 83% decrease in Citrate Synthase 2 (CIS 2) expression. Thiolated sense strand attachment postillumination inhibited antisense reannealing, enhancing gene silencing. This led to significant lipid body accumulation in cells, verified through fluorometric and fluorescence microscopy. This union of nanotechnology and ASO-mediated silencing provides gene regulation opportunities across sectors like biomedicine and agriculture. The system's remote switching capability underscores its potential in synthetic biology and genetic engineering. Our findings substantiate the utility of this approach for enhancing lipid biosynthesis in C. reinhardtii but also underscores its broader applicability to other organisms, fostering the development of novel solutions for pressing global challenges in energy, agriculture, and healthcare.

Baseline Characteristics of Fabry Disease "Amenable" Migalastat Patients in Argentinian Cohort.

Fabry disease (FD) is a multisystem lysosomal storage disorder induced by genetic variants in the alpha-galactosidase A (αGalA) gene. Some FD patients have GLA variants with a reduction in overall αGalA enzymatic activity due to mutated proteins with reduced stability, caused by protein misfolding and premature degradation, but the αGalA catalytic activity remains conserved ("amenable" genetic variants). To correct this misfolding and to prevent premature degradation, migalastat, a small iminosugar molecule was developed. We report the clinical characteristics of FD "amenable" cohort patients from Argentina, prior to starting treatment with migalastat. Seventeen Fabry adult patients were recruited from 13 Argentinian Centers; 8 males (47.1%) and 9 females (52.9%) were included. All genotypes included were missense-type "amenables" mutations. Some classic FD typical early manifestations were more frequent in patients with "classic" versus "late-onset" FD phenotype (pain, p=0.002; cornea verticillata, p=0.019). There was a statistically significant difference in estimated glomerular filtration rate in the "classic" versus "late-onset" phenotype (p=0.026) but no difference between genders (p=0.695). Left ventricular mass was similar between genders (p=0.145) and phenotypes (p=0.303). Cardiovascular risk factors were present among "late-onset" females (obesity 50% and smoke 25%). In patients who started "de novo" migalastat, the main indications were (i) heart disease, (ii) kidney damage, and (iii) pain, while in "switched from prior enzyme replacement therapy" patients, the most frequent indication was "patient decision;" this coincides with publications by other authors.

Characterization of Partial Discharges in Dielectric Oils Using High-Resolution CMOS Image Sensor and Convolutional Neural Networks.

In this work, an exhaustive analysis of the partial discharges that originate in the bubbles present in dielectric mineral oils is carried out. To achieve this, a low-cost, high-resolution CMOS image sensor is used. Partial discharge measurements using that image sensor are validated by a standard electrical detection system that uses a discharge capacitor. In order to accurately identify the images corresponding to partial discharges, a convolutional neural network is trained using a large set of images captured by the image sensor. An image classification model is also developed using deep learning with a convolutional network based on a TensorFlow and Keras model. The classification results of the experiments show that the accuracy achieved by our model is around 95% on the validation set and 82% on the test set. As a result of this work, a non-destructive diagnosis method has been developed that is based on the use of an image sensor and the design of a convolutional neural network. This approach allows us to obtain information about the state of mineral oils before breakdown occurs, providing a valuable tool for the evaluation and maintenance of these dielectric oils.

CAR-T Cell Therapy: From the Shop to Cancer Therapy.

Cancer is a worldwide health problem. Nevertheless, new technologies in the immunotherapy field have emerged. Chimeric antigen receptor (CAR) technology is a novel biological form to treat cancer; CAR-T cell genetic engineering has positively revolutionized cancer immunotherapy. In this paper, we review the latest developments in CAR-T in cancer treatment. We present the structure of the different generations and variants of CAR-T cells including TRUCK (T cells redirected for universal cytokine killing. We explain the approaches of the CAR-T cells manufactured ex vivo and in vivo. Moreover, we describe the limitations and areas of opportunity for this immunotherapy and the current challenges of treating hematological and solid cancer using CAR-T technology as well as its constraints and engineering approaches. We summarize other immune cells that have been using CAR technology, such as natural killer (NK), macrophages (M), and dendritic cells (DC). We conclude that CAR-T cells have the potential to treat not only cancer but other chronic diseases.

Effective Electrical Properties and Fault Diagnosis of Insulating Oil Using the 2D Cell Method and NSGA-II Genetic Algorithm.

In this paper, an experimental analysis of the quality of electrical insulating oils is performed using a combination of dielectric loss and capacitance measurement tests. The transformer oil corresponds to a fresh oil sample. The paper follows the ASTM D 924-15 standard (standard test method for dissipation factor and relative permittivity of electrical insulating liquids). Effective electrical parameters, including the tan δ of the oil, were obtained in this non-destructive test. Subsequently, a numerical method is proposed to accurately determine the effective electrical resistivity, σ, and effective electrical permittivity, ε, of an insulating mineral oil from the data obtained in the experimental analysis. These two parameters are not obtained in the ASTM standard. We used the cell method and the multi-objective non-dominated sorting in genetic algorithm II (NSGA-II) for this purpose. In this paper, a new numerical tool to accurately obtain the effective electrical parameters of transformer insulating oils is therefore provided for fault detection and diagnosis. The results show improved accuracy compared to the existing analytical equations. In addition, as the experimental data are collected in a high-voltage domain, wireless sensors are used to measure, transmit, and monitor the electrical and thermal quantities.

Utilización medicinal de cannabis en pacientes oncológicos de San Carlos de Bariloche: Estudio basado en una encuesta / Medicinal use of cannabis in cancer patients in San Carlos de Bariloche: a survey-based study

RESUMEN INTRODUCCIÓN El uso medicinal del cannabis en pacientes oncológicos se ha popularizado en los últimos años. Para poder brindar asesoramiento que redunde en un uso más eficaz y seguro, es necesario conocer la experiencia y expectativas de los usuarios. El objetivo fue conocer los motivos y la experiencia del uso medicinal de cannabis en adultos con enfermedades oncológicas en San Carlos de Bariloche (Río Negro). MÉTODOS Se realizó un estudio basado en una encuesta en línea autoadministrada sobre uso de cannabis, tiempo y motivo de uso, grado de satisfacción, asesoramiento profesional, vía de administración y efectos adversos. RESULTADOS Participaron 201 pacientes. Un 19% utilizaba cannabis, y el 31% lo había utilizado antes. La principal forma de uso fue el aceite. Los principales motivos fueron tratar el dolor, dormir mejor y sentirse mejor. Las experiencias fueron satisfactorias o muy satisfactorias para más del 50%, y las más favorables fueron para tratar el dolor, mejorar el ánimo, tolerar la quimioterapia y dormir mejor. Entre las razones para dejar de usarlo se mencionó falta de utilidad, efectos adversos, dudas sobre dosis, tiempo de uso y calidad del producto adquirido. Menos del 50% de los pacientes habían recibido asesoramiento profesional sobre uso de cannabis. DISCUSIÓN El 50% de los participantes utilizó cannabis. Este relevamiento ofrece un diagnóstico útil para promover políticas que reflejen las necesidades frente al uso de cannabis.

ABSTRACT INTRODUCTION The medicinal use of cannabis in cancer patients has become popular in recent years. In order to provide advice that results in a more effective and safe use, it is necessary to know the experience and expectations of users. The objective was to know the reasons and experience of the medicinal use of cannabis in adults with oncological diseases in San Carlos de Bariloche (Río Negro province). METHODS The study was based on a self-administered online survey on cannabis use, time and reason for use, degree of satisfaction, professional advice, route of administration and adverse effects. RESULTS A total of 201 patients participated, of which 19% used cannabis and 31% had previously used it. The main form of use was oil. The main reasons for use were to treat pain, sleep better and feel better. The experiences were satisfactory or very satisfactory for more than 50%, and the most favorable ones were to treat pain, improve mood, tolerate chemotherapy, and sleep better. Lack of usefulness, adverse effects, doubts about the dose, time of use and quality of the product purchased were mentioned among the reasons for the decision to stop using it. Less than 50% of the patients had received professional advice on the use of cannabis. DISCUSSION Half of the participants used cannabis. This survey provides a useful diagnosis to foster policies that reflect the needs regarding the use of cannabis.

Evaluation of food intake through residual analysis in 90 Basque school canteens / Evaluación de la ingesta de alimentos a través del análisis residual en 90 comedores escolares vascos

Objective: To measure the consumption of 25 food items (Comstock scale), to test whether school management type (public schools vs. private with subsidy schools) and food origin (on-site preparation vs. catering) affected food consumption and to quantify variability associated with territory, school and individual. Method: This cross-sectional study involved 14,717 schoolchildren of ages 2-16, recruited in 90 schools of the Basque Autonomous Community (Spain). Waste (non-consumed food) of 25 analysed food items was visually estimated by trained school monitors, via the Comstock categorical scale thus adapted: 1 = 0%; 2 = 25%; 3 = 50%, 4 = 75% and 5 = 100%. To analyse the data, mixed modelling was applied. Results: Vegetables, fish and fruits were the less-accepted food types. While school management did not affect food intake, on-site food preparation had better acceptance for legumes with vegetables, oily and lean fish, meat and pre-cooked meals. The largest source of variability in food intake not accounted for by school management and food preparation was the individual subject, while school and territory had moderate and almost no effects, respectively. Conclusions: Acceptance of the 25 evaluated foods is adequate, albeit can be improved. We believe that promoting on-site food preparation should improve the acceptance of legumes with vegetables, oily/lean fish, meat and pre-cooked meals. We recommend that future interventions oriented to improve intake should focus on individual subjects. (AU)

Objetivo: Medir el consumo de 25 alimentos (escala Comstock), comprobar si el tipo de gestión escolar (pública o concertada) y el origen de los alimentos (in situ o transportados) afecta al consumo, y cuantificar la variabilidad asociada con el territorio, la escuela y los individuos. Método: Estudio transversal con 14.717 escolares de 2-16 años reclutados en 90 escuelas del País Vasco. La estimación de residuos (alimento no consumido) de 25 grupos de alimentos la realizó visualmente personal escolar entrenado, mediante la escala categórica de Comstock así adaptada: 1 = 0%, 2 = 25%, 3 = 50%, 4 = 75% y 5 = 100%. Para analizar los datos se aplicó un modelo estadístico de efectos mixtos. Resultados: Verduras, pescado y frutas fueron los alimentos menos consumidos. Aunque el tipo de gestión escolar no afectó a la ingesta alimentaria, se determinó que la cocina in situ logró una mejor aceptación de legumbres con verduras, pescado azul y blanco, carne y precocinados. La mayor fuente adicional de variabilidad en la ingesta alimentaria fue el sujeto individual, mientras que la escuela y el territorio tuvieron efectos moderados y casi nulos, respectivamente. Conclusiones: La aceptación de los 25 alimentos evaluados es adecuada, aunque mejorable. Creemos que la promoción de cocinas in situ mejoraría la aceptación de legumbres con verduras, pescado azul y blanco, carne y platos precocinados. Recomendamos que las futuras intervenciones para mejorar la ingesta se dirijan al sujeto individual. (AU)

Evaluation of food intake through residual analysis in 90 Basque school canteens.

OBJECTIVE: To measure the consumption of 25 food items (Comstock scale), to test whether school management type (public schools vs. private with subsidy schools) and food origin (on-site preparation vs. catering) affected food consumption and to quantify variability associated with territory, school and individual. METHOD: This cross-sectional study involved 14,717 schoolchildren of ages 2-16, recruited in 90 schools of the Basque Autonomous Community (Spain). Waste (non-consumed food) of 25 analysed food items was visually estimated by trained school monitors, via the Comstock categorical scale thus adapted: 1=0%; 2=25%; 3=50%, 4=75% and 5=100%. To analyse the data, mixed modelling was applied. RESULTS: Vegetables, fish and fruits were the less-accepted food types. While school management did not affect food intake, on-site food preparation had better acceptance for legumes with vegetables, oily and lean fish, meat and pre-cooked meals. The largest source of variability in food intake not accounted for by school management and food preparation was the individual subject, while school and territory had moderate and almost no effects, respectively. CONCLUSIONS: Acceptance of the 25 evaluated foods is adequate, albeit can be improved. We believe that promoting on-site food preparation should improve the acceptance of legumes with vegetables, oily/lean fish, meat and pre-cooked meals. We recommend that future interventions oriented to improve intake should focus on individual subjects.

Curcumin Sensitizes 4T1 Murine Breast Cancer Cells to Cisplatin Through PAR4 Secretion.

BACKGROUND/AIM: Prostate apoptosis response 4 (PAR4), a tumour-suppressor protein, selectively induces apoptosis of cancer cells without affecting normal cells. Its soluble form is induced by secretagogues (e.g., chloroquine), and it induces apoptosis by interacting with the receptor of glucose-regulated protein 78, which is overexpressed in cancer cells. In this study, curcumin was analyzed as an inducer of PAR4 expression in 4T1 murine breast cancer cell. and its ability to induce PAR4 secretion in Balb/c mice. In addition, the cisplatin sensitizing effect of soluble PAR4 was analyzed. MATERIAL AND METHODS: The 4T1 cell line was treated in vitro using different concentrations of curcumin; cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and PAR4 expression by western blotting. The expression of soluble PAR4 in the serum of mice treated with intraperitoneal curcumin was analyzed using the dot-blot method. Moreover, MTT assay was used to analyze the effects of serum from curcumin-treated mice on cell viability. Tumor size was analyzed in mice treated with curcumin alone and in combination with cisplatin. RESULTS: Curcumin showed a dose- and time-dependent effects on cell viability on 4T1 cells, as well as increasing PAR4 expression. Compared with the control group (phosphate-buffered saline), mice treated with curcumin showed an increase in plasma PAR4. In the Balb/C tumor model, mice treated with curcumin and cisplatin showed greater tumor shrinkage than the control group. CONCLUSION: These results indicate that curcumin induces expression of soluble PAR4 and sensitizes tumor cells to cisplatin.

Characterization of Dielectric Oil with a Low-Cost CMOS Imaging Sensor and a New Electric Permittivity Matrix Using the 3D Cell Method.

In this paper, a new method for characterizing the dielectric breakdown voltage of dielectric oils is presented, based on the IEC 60156 international standard. In this standard, the effective value of the dielectric breakdown voltage is obtained, but information is not provided on the distribution of Kelvin forces an instant before the dynamic behavior of the arc begins or the state of the gases that are produced an instant after the moment of appearance of the electric arc in the oil. In this paper, the behavior of the oil before and after the appearance of the electric arc is characterized by combining a low-cost CMOS imaging sensor and a new matrix of electrical permittivity associated with the dielectric oil, using the 3D cell method. In this way, we also predict the electric field before and after the electric rupture. The error compared to the finite element method is less than 0.36%. In addition, a new method is proposed to measure the kinematic viscosity of dielectric oils. Using a low-cost imaging sensor, the distribution of bubbles is measured, together with their diameters and their rates of ascent after the electric arc occurs. This method is verified using ASTM standards and data provided by the oil manufacturer. The results of these tests can be used to prevent incipient failures and evaluate preventive maintenance processes such as transformer oil replacement or recovery.

The Inflammatory Process Modulates the Expression and Localization of WT1 in Podocytes Leading to Kidney Damage.

BACKGROUND/AIM: Wilms' tumor 1 (WT1) is involved in the development of the urogenital system and is expressed in podocytes throughout life. Inflammation of renal glomeruli causes renal damage-induced nephrotic syndrome and steroid-resistant nephrotic syndrome have mutations in the WT1 gene. The aim of this work was to determine if the inflammatory process modulates the expression and localization of WT1 in podocytes that cause kidney damage using lipopolysaccharide (LPS)-treated mice as a sepsis model. MATERIALS AND METHODS: In investigation of renal damage, proteinuria and histology were analyzed. WT1 modulation was analyzed by indirect immunofluorescence, immunohistochemistry and western blot assays, and proinflammatory cytokines were analyzed by quantitative polymerase chain reaction assay. RESULTS: WT1 expression decreased most at 24 and 36 h after the induction of inflammation and phosphorylated WT1 was mainly localized in the cytoplasm, reduced nephrin mRNA expression and increased mRNA expression of tumor necrosis factor α and interleukin 1ß. CONCLUSION: These results indicate that the immune system plays an important role in the modulation of WT1, leading to kidney damage.

Detection of SARS-CoV-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patients.

COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (viremia) was performed with samples collected at 48-72 h of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19. Viremia was detected in 50-60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with viremia were older (p = 0.006), had poorer baseline oxygenation (PaO2/FiO2; p < 0.001), more severe lymphopenia (p < 0.001) and higher LDH (p < 0.001), IL-6 (p = 0.021), C-reactive protein (CRP; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined "relevant viremia" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35% specificity. Relevant viremia predicted death during hospitalization (OR 9.2 [3.8-22.6] for Roche, OR 10.3 [3.6-29.3] for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant viremia (HR = 9.87 [4.13-23.57] for TFS viremia and HR = 7.09 [3.3-14.82] for Roche viremia) as the best markers to predict mortality. Viremia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 patients. Viremia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 and better predictive accuracy.

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study.

BACKGROUND: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. OBJECTIVE: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. METHODS: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. RESULTS: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. CONCLUSIONS: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.

Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19 patients.

SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID-19. We investigated whether the specific immune responses in the peripheral blood of 276 patients were associated with the severity and progression of COVID-19. At admission, dramatic lymphopenia of T, B, and NK cells is associated with severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56- CD16+ NK-cells increased. Regarding humoral immunity, levels of IgM, IgA, and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless of their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes, and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID-19 patients, associating severity with an imbalanced humoral response, and identifying new targets for therapeutic intervention.

[Usefulness of laser Holmium Lumenis Pulse 120 H® in the treatment of renal lithiasis through RIRS: Preliminary experience.] / Utilidad del láser Holmium Lumenis Pulse 120 H® en el tratamiento de las litiasis renales mediante RIRS: experiencia preliminar.

INTRODUCTION: The Holmium laser is the most used energy source in flexible ureterrenoscopy (URSf). The Lumenis Pulse 120H® laser has a higher system energy, a higher energy per pulse and a higher repetition frequency in relation to other types of lasers, which offers advantages in the treatment of lithiasis. OBJECTIVE: To analyze the results that we have obtained with the use of the Lumenis Pulse120H® laser in patients treated by intrarenal retrograde surgery (RIRS). As secondary objectives there are: the study of the demographic variables of the patients, the characteristics of the stones and the complications associated with the procedure. MATERIAL AND METHODS: An observational, retrospective study of the first 26 patients treated by RIRS and Lumenis Pulse 120H® laser has been performed in our Service between August 2018 and February 2019. The size of the lithiasis was measured on the simple radiography and the CT, in addition, the volume of the lithiasis was calculated. For the realization of RIRS, 8.5Fr digital flexible ureterorenoscope (Olympus®) and the Holmium Lumenis 120H® laser with 200 micron laser fibers from Lumenis® were used. Statistical analysis was performed with the SPSSv21 system. RESULTS: A total of 26 patients with renal lithiasis have been analyzed. The median age was 55.15 years (40.67-67.05). 57.7% of the patients had prior surgical treatment of lithiasis. Thirteen patients presented the litiasis in the renal pelvis, ten in the Upper Calicial Group (GCS), fifteen in the Middle Calicial Group (GCM) and eighteen in the Lower Calicial Group (GCI). The median of the lithiasic volume was 1826.41 mm3. Our overall success rate was 80.8% (100% success in lithiasis less than 2 cm and 85.7% in lithiasis between 2-3 cm). Five patients presented complications, of which 4 were ClavienII and 1 Clavien IIIb. No significant results were found between the lithiasic size and the presence of complications (p = 0.128). CONCLUSIONS: The use of the Lumenis Pulse 120H®laser is an useful tool for the treatment of kidney stones by RIRS, due to his efficiency in the fragmentation and dusting, taking into account that very large lithiasic masses require, in a high percentage of cases, more than one treatment session.

INTRODUCCIÓN: El láser de Holmium es la fuente de energía más utilizada en la ureterrenoscopia flexible (URSf). El láser Lumenis Pulse 120H® tiene una mayor energía del sistema, una mayor energía por pulso y una frecuencia de repetición más elevada en relación a otros tipos de láser, lo que ofrece ventajas en el tratamiento de las litiasis. OBJETIVO: Analizar los resultados que hemos obtenido con la utilización del láser Lumenis Pulse120H® en pacientes tratados mediante RIRS. Como objetivos secundarios se encuentra el estudio de las variables demográficas de los pacientes, de las características del cálculo y de las complicaciones asociadas al procedimiento.MATERIAL Y MÉTODOS: Se ha realizado un estudio observacional, retrospectivo, de los primeros 26 pacientes tratados mediante RIRS y láser Lumenis Pulse 120H® en nuestro Servicio entre agosto 2018 y febrero 2019. El tamaño de la litiasis fue medido en la radiografía simple y el TC (tomografía computarizada) y, aparte, se calculó el volumen de la litiasis. El análisis estadístico se realizó con el sistema SPSSv21. RESULTADOS: Se han analizado un total de 26 pacientes con litiasis renales. Un 57,7% de los pacientes tenían tratamiento quirúrgico previo de litiasis. Presentaban litiasis en la pelvis renal 13 pacientes, en Grupo Calicial Superior (GCS) 10, en Grupo Calicial Medio (GCM) 15 y en Grupo Calicial Inferior (GCI) 18. La mediana del volumen litiásico fue de 1.826,41 mm3. Nuestra tasa global de éxito fue del 80,8% (100% éxito en litiasis menores de 2 cm y 85,7% en litiasis entre 2-3cm). Cinco pacientes presentaron complicaciones, de ellos 4 fueron Clavien II y 1 Clavien IIIb. No se hallaron resultados significativos al relacionar el tamaño litiásico con las complicaciones (p=0,128). CONCLUSIONES: La utilización del láser Lumenis Pulse120H® es una herramienta útil y segura para el tratamiento de los cálculos renales mediante RIRS, debido a la eficacia en la fragmentación y pulverización de los mismos, teniendo en cuenta que las masas litiásicas muy grandes requieren, en un alto porcentaje de casos, más de una sesión de tratamiento.

Utilidad del láser Holmium Lumenis Pulse 120 H® en el tratamiento de las litiasis renales mediante RIRS: experiencia preliminar / Usefulness of laser Holmium Lumenis Pulse 120 H® in the treatment of renal lithiasis through RIRS: Preliminary experience

INTRODUCCIÓN: El láser de Holmium es la fuente de energía más utilizada en la ureterrenoscopia flexible (URSf). El láser Lumenis Pulse 120H® tiene una mayor energía del sistema, una mayor energía por pulso y una frecuencia de repetición más elevada en relación a otros tipos de láser, lo que ofrece ventajas en el tratamiento de las litiasis. OBJETIVO: Analizar los resultados que hemos obtenido con la utilización del láser Lumenis Pulse120H® en pacientes tratados mediante RIRS. Como objetivos secundarios se encuentra el estudio de las variables demográficas de los pacientes, de las características del cálculo y de las complicaciones asociadas al orocedimiento. MATERIAL Y MÉTODOS: Se ha realizado un estudio observacional, retrospectivo, de los primeros 26 pacientes tratados mediante RIRS y láser Lumenis Pulse 120H® en nuestro Servicio entre agosto 2018 y febrero 2019. El tamaño de la litiasis fue medido en la radiografía simple y el TC (tomografía computarizada) y, aparte, se calculó el volumen de la litiasis. El análisis estadístico se realizó con el sistema SPSSv21. RESULTADOS: Se han analizado un total de 26 pacientes con litiasis renales. Un 57,7% de los pacientes tenían tratamiento quirúrgico previo de litiasis. Presentaban litiasis en la pelvis renal 13 pacientes, en Grupo Calicial Superior (GCS) 10, en Grupo Calicial Medio (GCM) 15 y en Grupo Calicial Inferior (GCI) 18. La mediana del volumen litiásico fue de 1.826,41 mm3. Nuestra tasa global de éxito fue del 80,8% (100% éxito en litiasis menores de 2 cm y 85,7% en litiasis entre 2-3cm). Cinco pacientes presentaron complicaciones, de ellos 4 fueron Clavien II y 1 Clavien IIIb. No se hallaron resultados significativos al relacionar el tamaño litiásico con las complicaciones (p = 0,128). CONCLUSIONES: La utilización del láser Lumenis Pulse120H® es una herramienta útil y segura para el tratamiento de los cálculos renales mediante RIRS, debido a la eficacia en la fragmentación y pulverización de los mismos, teniendo en cuenta que las masas litiásicas muy grandes requieren, en un alto porcentaje de casos, más de una sesión de tratamiento

INTRODUCTION: The Holmium laser is the most used energy source in flexible ureterrenoscopy (URSf). The Lumenis Pulse 120H® laser has a higher system energy, a higher energy per pulse and a higher repetition frequency in relation to other types of lasers, which offers advantages in the treatment of lithiasis. OBJECTIVE: To analyze the results that we have obtained with the use of the Lumenis Pulse120H® laser in patients treated by intrarenal retrograde surgery (RIRS). As secondary objectives there are: the study of the demographic variables of the patients, the characteristics of the stones and the complications associated with the procedure. MATERIAL AND METHODS: An observational, retrospective study of the first 26 patients treated by RIRS and Lumenis Pulse 120H® laser has been performed in our Service between August 2018 and February 2019. The size of the lithiasis was measured on the simple radiography and the CT, in addition, the volume of the lithiasis was calculated. For the realization of RIRS, 8.5 Fr digital flexible ureterorenoscope (Olympus®) and the Holmium Lumenis 120H® laser with 200 micron laser fibers from Lumenis® were used. Statistical analysis was performed with the SPSSv21 system. RESULTS: A total of 26 patients with renal lithiasis have been analyzed. The median age was 55.15 years (40.67-67.05). 57.7% of the patients had prior surgical treatment of lithiasis. Thirteen patients presented the litiasis in the renal pelvis, ten in the Upper Calicial Group (GCS), fifteen in the Middle Calicial Group (GCM) and eighteen in the Lower Calicial Group (GCI). The median of the lithiasic volume was 1826.41 mm3. Our overall success rate was 80.8% (100% success in lithiasis less than 2 cm and 85.7% in lithiasis between 2-3 cm). Five patients presented complications, of which 4 were Clavien II and 1 Clavien IIIb. No significant results were found between the lithiasic size and the presence of complications (p = 0.128). CONCLUSIONS: The use of the Lumenis Pulse 120H® laser is an useful tool for the treatment of kidney stones by RIRS, due to his efficiency in the fragmentation and dusting, taking into account that very large lithiasic masses require, in a high percentage of cases, more than one treatment session

A new role for circulating T follicular helper cells in humoral response to anti-PD-1 therapy.

BACKGROUND: Lung cancer is one of the most frequent malignancies in humans and is a major cause of death. A number of therapies aimed at reinforcing antitumor immune response, including antiprogrammed cell death protein 1 (anti-PD-1) antibodies, are successfully used to treat several neoplasias as non-small cell lung cancer (NSCLC). However, host immune mechanisms that participate in response to anti-PD-1 therapy are not completely understood. METHODS: We used a syngeneic immunocompetent mouse model of NSCLC to analyze host immune response to anti-PD-1 treatment in secondary lymphoid organs, peripheral blood and tumors, by flow cytometry, immunohistochemistry and quantitative real-time PCR (qRT-PCR). In addition, we also studied specific characteristics of selected immune subpopulations in ex vivo functional assays. RESULTS: We show that anti-PD-1 therapy induces a population of circulating T follicular helper cells (cTfh) with enhanced B activation capacity, which participates in tumor response to treatment. Anti-PD-1 increases the number of tertiary lymphoid structures (TLS), which correlates with impaired tumor growth. Of note, TLS support cTfh-associated local antibody production, which participates in host immune response against tumor. CONCLUSION: These findings unveil a novel mechanism of action for anti-PD-1 therapy and provide new targets for optimization of current therapies against lung cancer.

COVID-19 severity associates with pulmonary redistribution of CD1c+ DCs and inflammatory transitional and nonclassical monocytes.

SARS-CoV-2 is responsible for the development of coronavirus disease 2019 (COVID-19) in infected individuals, who can either exhibit mild symptoms or progress toward a life-threatening acute respiratory distress syndrome (ARDS). Exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. Here, we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood and lung of COVID-19 patients with different clinical severity in comparison with healthy individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Our results indicate that inflammatory transitional and nonclassical monocytes and CD1c+ conventional dendritic cells preferentially migrate from blood to lungs in patients with severe COVID-19. Thus, this study increases the knowledge of specific myeloid subsets involved in the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies for fighting SARS-CoV-2 infection.