ACK1 and BRK non-receptor tyrosine kinase deficiencies are associated with familial systemic lupus and involved in efferocytosis.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease, the pathophysiology and genetic basis of which are incompletely understood. Using a forward genetic screen in multiplex families with systemic lupus erythematosus (SLE) we identified an association between SLE and compound heterozygous deleterious variants in the non-receptor tyrosine kinases (NRTKs) ACK1 and BRK. Experimental blockade of ACK1 or BRK increased circulating autoantibodies in vivo in mice and exacerbated glomerular IgG deposits in an SLE mouse model. Mechanistically, non-receptor tyrosine kinases (NRTKs) regulate activation, migration, and proliferation of immune cells. We found that the patients' ACK1 and BRK variants impair efferocytosis, the MERTK-mediated anti-inflammatory response to apoptotic cells, in human induced Pluripotent Stem Cell (hiPSC)-derived macrophages, which may contribute to SLE pathogenesis. Overall, our data suggest that ACK1 and BRK deficiencies are associated with human SLE and impair efferocytosis in macrophages.

Alginate Improves the Chondrogenic Capacity of 3D PCL Scaffolds In Vitro: A Histological Approach.

Polycaprolactone (PCL) scaffolds have demonstrated an effectiveness in articular cartilage regeneration due to their biomechanical properties. On the other hand, alginate hydrogels generate a 3D environment with great chondrogenic potential. Our aim is to generate a mixed PCL/alginate scaffold that combines the chondrogenic properties of the two biomaterials. Porous PCL scaffolds were manufactured using a modified salt-leaching method and embedded in a culture medium or alginate in the presence or absence of chondrocytes. The chondrogenic capacity was studied in vitro. Type II collagen and aggrecan were measured by immunofluorescence, cell morphology by F-actin fluorescence staining and gene expression of COL1A1, COL2A1, ACAN, COL10A1, VEGF, RUNX1 and SOX6 by reverse transcription polymerase chain reaction (RT-PCR). The biocompatibility of the scaffolds was determined in vivo using athymic nude mice and assessed by histopathological and morphometric analysis. Alginate improved the chondrogenic potential of PCL in vitro by increasing the expression of type II collagen and aggrecan, as well as other markers related to chondrogenesis. All scaffolds showed good biocompatibility in the in vivo model. The presence of cells in the scaffolds induced an increase in vascularization of the PCL/alginate scaffolds. The results presented here reinforce the benefits of the combined use of PCL and alginate for the regeneration of articular cartilage.

Mesenchymal Stem Cells Cultured in a 3D Microgel Environment Containing Platelet-Rich Plasma Significantly Modify Their Chondrogenesis-Related miRNA Expression.

The aim of this work is to study the effect of platelet factors on the differentiation of mesenchymal stem cells (MSCs) to hyaline cartilage chondrocytes in a three-dimensional environment. MSCs were cultured in a microgel environment with a chondrogenic medium. The microgel consisted of microspheres that combine gelatin and platelet-rich plasma (PRP). The gelatin/PRP microdroplets were produced by emulsion. The gelatin containing the microdroplets was enzymatically gelled, retaining PRP and, just before seeding the cells, platelets were activated by adding calcium chloride so that platelet growth factors were released into the culture media but not before. Platelet activation was analyzed before activation to rule out the possibility that the gelatin cross-linking process itself activated the platelets. The gene expression of characteristic chondrogenic markers and miRNA expression were analyzed in cells cultured in a differentiation medium and significant differences were found between gelation/PRP microgels and those containing only pure gelatin. In summary, the gelatin microspheres effectively encapsulated platelets that secreted and released factors that significantly contributed to cellular chondrogenic differentiation. At the same time, the microgel constituted a 3D medium that provided the cells with adherent surfaces and the possibility of three-dimensional cell-cell contact.

Perception of patient safety culture among nursing students: A cross-sectional study.

AIM: To analyse the perception of patient safety culture among nursing students and to compare patient safety outcomes between the different year nursing groups. DESIGN: A cross-sectional descriptive study was conducted with nursing students (n = 266) between first and fourth years from one university in Spain. METHODS: The project was conducted during the 2020/21 academic year. The data were collected using a translated and adapted version of the "Hospital Survey on Patient Safety" developed by the Agency of Healthcare Quality (AHQR). RESULTS: Significant differences were found between the year of study of the nursing degree and whether or not specific training in patient safety culture had been received. The nursing students who had received specific training gave scores lower than anyone else in all questionnaire items, but only the indicators of "good practice" (p = 0.00) and "frequency of reported events" (p = 0.0012) showed significant differences. In some cases, fourth-year students had lower significant mean scores in their "perception of patient safety within unit/sector," "indicators of good practice" and "total score." PUBLIC CONTRIBUTION: Adverse events related to clinical practice continue to be a global problem. Improvements in patient safety require an increase in the patient safety culture of professionals and the promotion of development facilitators. Clinical practice and specific theoretical training foster greater awareness and demand related to patient safety, which is of interest when it comes to the development of new programmes that combine both methodologies and improve their effectiveness. Patient safety will continue to be a focus for all healthcare systems. The patient safety culture of future healthcare professionals should be developed at the university level in order to avoid unnecessary adverse events.

Patient journey of individuals tested for HCV in Spain: LiverTAI, a retrospective analysis of EHRs through natural language processing / Recorrido hospitalario de los pacientes testados para VHC en España: LiverTAI, un análisis retrospectivo de las HCE a través del procesamiento del lenguaje natural

Objectives: Limited screening and delays in diagnosis and linkage-to-care are barriers for hepatitis C virus (HCV) elimination. The LiverTAI study focused on patients tested for HCV using AI technologies to describe their demographic and clinical characteristics and pre-testing patient journeys, reflecting clinical practice in hospitals. Patients and methods: LiverTAI is a retrospective, secondary analysis of electronic health records (EHRs) from 6 tertiary Spanish hospitals, extracting unstructured clinical data using natural language processing (NLP) EHRead® technology. Adult subjects with an HCV testing procedure from January 2014 to December 2018 were grouped according to HCV seropositivity and viremia. Results: From 2,440,358 patients, 16,261 patients were tested for HCV (13,602 [83.6%] HCV seronegative; 2659 [16.4%] seropositive). Active HCV viremia appeared in 37.7% (n=1003) of patients, 18.6% (n=494) had negative viremia, and 43.7% (n=1162) unknown viremia. Patient journeys showed core departments (Gastroenterology, Internal Medicine, and Infectious Disease) and others including Emergency perform ample HCV testing in Spanish hospitals, whereas Medical Oncology lags. Patients were PCR-tested and genotyped significantly faster in core departments (p<.001). Conclusions: Our results highlight hospital departments responsible for HCV testing. However, further testing was sub-optimal during the study period. Therefore, we underscore the need for HCV screening and reflex testing to accelerate diagnosis and linkage-to-care.(AU)

Objetivos: El cribado limitado, los retrasos diagnósticos y la vinculación a la atención sanitaria son obstáculos para la eliminación del virus de la hepatitis C (VHC). El estudio LiverTAI se centró en analizar pacientes testeados para VHC mediante tecnologías de IA para describir sus características demográficas, clínicas y los recorridos de los pacientes antes del test, reflejando la práctica clínica en los hospitales. Pacientes y métodos: LiverTAI es un análisis retrospectivo y secundario de las historias clínicas electrónicas (HCE) de 6 hospitales españoles de tercer nivel, en el que se extraen datos clínicos no estructurados mediante la tecnología EHRead® de procesamiento del lenguaje natural (PLN). Los sujetos adultos con un test de VHC desde enero de 2014 hasta diciembre de 2018 se agruparon según la seropositividad y la viremia del VHC. Resultados: De 2.440.358 pacientes, 16.261 fueron testeados para VHC (13.602 [83,6%] seronegativos al VHC; 2.659 [16,4%] seropositivos). La viremia activa del VHC apareció en el 37,7% (n=1.003) de los pacientes, el 18,6% (n=494) mostró viremia negativa y el 43,7% (n=1.162), viremia desconocida. Los recorridos de los pacientes mostraron que los departamentos core (gastroenterología, medicina interna y enfermedades infecciosas) y otros, incluyendo urgencias, realizan numerosos test de VHC en los hospitales españoles, mientras que oncología médica se queda atrás. Los pacientes fueron sometidos a la prueba de la PCR y el genotipo significativamente más rápido en los departamentos core (p<0,001). Conclusiones: Nuestros resultados destacan los departamentos hospitalarios responsables de realizar test de VHC mediante pruebas serológicas. Sin embargo, las pruebas posteriores (PCR, genotipado) experimentaban retrasos durante el periodo de estudio. Por lo tanto, subrayamos la necesidad de realizar el cribado del VHC y de diagnóstico en un solo paso para acelerar el diagnóstico y la vinculación a la atención sanitaria.(AU)

Morphological Characterization of Human Lung Cancer Organoids Cultured in Type I Collagen Hydrogels: A Histological Approach.

The malignity of lung cancer is conditioned by the tumor microenvironment (TME), in which cancer-associated fibroblasts (CAFs) are relevant. In this work, we generated organoids by combining A549 cells with CAFs and normal fibroblasts (NF) isolated from adenocarcinoma tumors. We optimized the conditions for their manufacture in a short time. We evaluated the morphology of organoids using confocal microscopy analysis of F-actin, vimentin and pankeratin. We determined the ultrastructure of the cells in the organoids via transmission electron microscopy and the expression of CDH1, CDH2 and VIM via RT-PCR. The addition of stromal cells induces the self-organization of the organoids, which acquired a bowl morphology, as well as their growth and the generation of cell processes. They also influenced the expression of genes related to epithelial mesenchymal transition (EMT). CAFs potentiated these changes. All cells acquired a characteristic secretory phenotype, with cohesive cells appearing inside the organoids. In the periphery, many cells acquired a migratory phenotype, especially in organoids that incorporated CAFs. The deposit of abundant extracellular matrix could also be observed. The results presented here reinforce the role of CAFs in the progression of lung tumors and could lay the foundation for a useful in vitro pharmacological model.

Patient journey of individuals tested for HCV in Spain: LiverTAI, a retrospective analysis of EHRs through natural language processing.

OBJECTIVES: Limited screening and delays in diagnosis and linkage-to-care are barriers for hepatitis C virus (HCV) elimination. The LiverTAI study focused on patients tested for HCV using AI technologies to describe their demographic and clinical characteristics and pre-testing patient journeys, reflecting clinical practice in hospitals. PATIENTS AND METHODS: LiverTAI is a retrospective, secondary analysis of electronic health records (EHRs) from 6 tertiary Spanish hospitals, extracting unstructured clinical data using natural language processing (NLP) EHRead® technology. Adult subjects with an HCV testing procedure from January 2014 to December 2018 were grouped according to HCV seropositivity and viremia. RESULTS: From 2,440,358 patients, 16,261 patients were tested for HCV (13,602 [83.6%] HCV seronegative; 2659 [16.4%] seropositive). Active HCV viremia appeared in 37.7% (n=1003) of patients, 18.6% (n=494) had negative viremia, and 43.7% (n=1162) unknown viremia. Patient journeys showed core departments (Gastroenterology, Internal Medicine, and Infectious Disease) and others including Emergency perform ample HCV testing in Spanish hospitals, whereas Medical Oncology lags. Patients were PCR-tested and genotyped significantly faster in core departments (p<.001). CONCLUSIONS: Our results highlight hospital departments responsible for HCV testing. However, further testing was sub-optimal during the study period. Therefore, we underscore the need for HCV screening and reflex testing to accelerate diagnosis and linkage-to-care.

Human Dental Pulp Stem Cells Differentiate into Cementoid-Like-Secreting Cells on Decellularized Teeth Scaffolds.

Periodontitis is a common inflammatory disease that in some cases can cause tooth loss. Cementum is a mineralized tissue that forms part of the insertion periodontium and serves to fix the teeth to the alveolar bone. In addition, it acts as a reservoir of different growth and differentiation factors, which regulate the biology of the teeth. Cementogenesis is a complex process that is still under investigation and involves different factors, including dentin sialophosphoprotein (DSPP). In this work we studied the role of surface microtopography in the differentiation of human dental pulp stem cells (hDPSCs) into cementoid-like secreting cells. We cultured hDPSCs on decellularized dental scaffolds on either dentin or cementum surfaces. Cell morphology was evaluated by light and electron microscopy. We also evaluated the DSPP expression by immunohistochemistry. The hDPSCs that was cultured on surfaces with accessible dentinal tubules acquired an odontoblastic phenotype and emitted characteristic processes within the dentinal tubules. These cells synthesized the matrix components of a characteristic reticular connective tissue, with fine collagen fibers and DSPP deposits. The hDPSCs that was cultured on cementum surfaces generated a well-organized tissue consisting of layers of secretory cells and dense fibrous connective tissue with thick bundles of collagen fibers perpendicular to the scaffold surface. Intra- and intercellular deposits of DSPP were also observed. The results presented here reinforce the potential for hDPSCs to differentiate in vitro into cells that secrete a cementoid-like matrix in response to the physical stimuli related to the microtopography of contact surfaces. We also highlight the role of DSPP as a component of the newly formed matrix.

In Vitro Effect of Δ9-Tetrahydrocannabinol and Cannabidiol on Cancer-Associated Fibroblasts Isolated from Lung Cancer.

There is evidence that demonstrates the effect of cannabinoid agonists inhibiting relevant aspects in lung cancer, such as proliferation or epithelial-to-mesenchymal transition (EMT). Most of these studies are based on evidence observed in in vitro models developed on cancer cell lines. These studies do not consider the complexity of the tumor microenvironment (TME). One of the main components of the TME is cancer-associated fibroblasts (CAFs), cells that are relevant in the control of proliferation and metastasis in lung cancer. In this work, we evaluated the direct effects of two cannabinoid agonists, tetrahydrocannabinol (THC) and cannabidiol (CBD), used alone or in combination, on CAFs and non-tumor normal fibroblasts (NFs) isolated from adenocarcinoma or from healthy lung tissue from the same patients. We observed that these compounds decrease cell density in vitro and inhibit the increase in the relative expression of type 1 collagen (COL1A1) and fibroblast-specific protein 1 (FSP1) induced by transforming growth factor beta (TGFß). On the other hand, we studied whether THC and CBD could modulate the interactions between CAFs or NFs and cancer cells. We conditioned the culture medium with stromal cells treated or not with THC and/or CBD and cultured A549 cells with them. We found that culture media conditioned with CAFs or NFs increased cell density, induced morphological changes consistent with EMT, inhibited cadherin-1 (CDH1) gene expression, and induced an increase in the relative expression of cadherin-2 (CDH2) and vimentin (VIM) genes in A549 cells. These changes were inhibited or decreased by THC and CBD administered alone or in combination. In another series of experiments, we conditioned culture media with A549 cells treated or not with THC and/or CBD, in the presence or absence of TGFß. We observed that culture media conditioned with A549 in the presence of TGFß induced an increase in the expression of COL1A1 and VIM, both in CAFs and in non-tumor NFs. Both THC and CBD ameliorated these effects. In summary, the results presented here reinforce the usefulness of cannabinoid agonists for the treatment of some relevant aspects of lung cancer pathology, and demonstrate in a novel way their possible effects on CAFs as a result of their relationship with cancer cells. Likewise, the results reinforce the usefulness of the combined use of THC and CBD, which has important advantages in relation to the possibility of using lower doses, thus minimizing the psychoactive effects of THC.

Neumonía secundaria por Bordetella hinzii enpaciente con infección por SARS-CoV-2 / Secondary Bordetella hinzii pneumonia in a patient with SARS-CoV-2 infection

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Impact of Social Determinants of Health on Women's Satisfaction with Their Sexual Life and Its Relationship with the Use of Psychotropic Drugs: A Cross-Sectional Study.

Sexual satisfaction (SS) is defined as an affective response arising from one's subjective evaluation of the positive and negative dimensions associated with one's sexual relationship. It is an important indicator of health. In women, SS has an important personal component consisting of the physical experiences of pleasure and the positive feelings and emotions that they experience in their affective-sexual relationships. The socioeconomic position is determined by income, educational level, and work, and it conditions women's sexual health. We aimed to assess whether social determinants of health (income, education, work, and gender) are associated with women's sexual satisfaction and to identify whether the impact of social determinants on sexual satisfaction differs with psychotropic consumption. We conducted a cross-sectional study designed to assess the association between variables related to the social determinants of health (work, education, income, and gender) and sexual satisfaction in women of reproductive age in La Rioja (Spain). The women in this study ranged in age from 17 to 52 years, with a mean age of 33.4 (Standar Deviation 8.6). Most were Spanish (82.9%), had undertaken non-compulsory specialized education (84%), and worked (72.7%). Regarding their relationships, 87% maintained monogamous relationships, 84.5% had stable relationships, and 65.7% lived with their partners. In total, 12.3% of the women were taking psychotropic drugs prescribed for the treatment of anxiety and/or depression. We observed that SS is significantly lower among women who have only undertaken compulsory education (Student-t = −4.745; p < 0.01), in those who have unstable affective-sexual relationships (Student-t = −2.553; p < 0.01), and in those who take psychotropic drugs (Student-t = −4.180, p < 0.01). We conclude that the social determinants of health such as education, not continuing to study beyond compulsory education, gender, and taking psychoactive drugs have a significant impact on women's degree of satisfaction with their sexual life.

Endocarditis por Kingella kingae en un paciente adulto / Kingella kingae endocarditis in an adult pacient

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BMP-2 Enhances Osteogenic Differentiation of Human Adipose-Derived and Dental Pulp Stem Cells in 2D and 3D In Vitro Models.

Bone tissue provides support and protection to different organs and tissues. Aging and different diseases can cause a decrease in the rate of bone regeneration or incomplete healing; thus, tissue-engineered substitutes can be an acceptable alternative to traditional therapies. In the present work, we have developed an in vitro osteogenic differentiation model based on mesenchymal stem cells (MSCs), to first analyse the influence of the culture media and the origin of the cells on the efficiency of this process and secondly to extrapolate it to a 3D environment to evaluate its possible application in bone regeneration therapies. Two osteogenic culture media were used (one commercial from Stemcell Technologies and a second supplemented with dexamethasone, ascorbic acid, glycerol-2-phosphate, and BMP-2), with human cells of a mesenchymal phenotype from two different origins: adipose tissue (hADSCs) and dental pulp (hDPSCs). The expression of osteogenic markers in 2D cultures was evaluated in several culture periods by means of the immunofluorescence technique and real-time gene expression analysis, taking as reference MG-63 cells of osteogenic origin. The same strategy was extrapolated to a 3D environment of polylactic acid (PLA), with a 3% alginate hydrogel. The expression of osteogenic markers was detected in both hADSCs and hDPSCs, cultured in either 2D or 3D environments. However, the osteogenic differentiation of MSCs was obtained based on the culture medium and the cell origin used, since higher osteogenic marker levels were found when hADSCs were cultured with medium supplemented with BMP-2. Furthermore, the 3D culture used was suitable for cell survival and osteogenic induction.

Neuropsychological screening with TOWI: Performance in 6- to 12-year-old children.

Videogames represent an exciting development in neuropsychological assessment of cognitive function. Here, we used TOWI, a series of games based on standardized tests, to evaluate the cognitive performance of a large sample of school-age children. We compared the metrics produced by TOWI with the performance metrics reported for the standardized tests that inspired each of these tasks. We found ascending values together with age for scores reflecting correct answers and descending values together with age for scores reflecting completion times, mistakes or missed entries. Sensitivity to developmental changes, similarities with standardized tests of task metrics contribute to the validity of TOWI as a screening tool.

Ertapenem neurotoxicity in liver transplantation.

Carbapenems are antibiotics of the cephalosporin family with a good penetrance into the central nervous system. Neurotoxicity is a rare adverse effect, most often associated with imipenem (0.4-10 %) and unusual with ertapenem. It usually presents as seizures, although encephalopathy or hallucinations may develop. However, a recent large study (n = 544) found neurotoxicity associated to the use of ertapenem with an incidence of 4.6 %. There were associated factors such as advanced age or renal dysfunction (ertapenem has a renal metabolism level of 80 %).

Etiquetado nutricional de alimentos procesados (semáforo nutri-cional) y su relación con factores socioeconómicos, culturales, demográficos y publicitarios, según padres de niños entre 5-11 años de dos colegios de Quito / Nutritional labeling of processed foods (nutritional stoplight) and its relationship with socioeconomic, cultural, demographic and advertising factors, according to parents of children between 5-11 years of age from two schools in Quito

Introducción: El etiquetado nutricional es una herramienta gráfica para notificar al consumidor sobre las propiedades nutricionales de un alimento lo que facilita su selección. El objetivo del presente estudio fue determinar la influencia del etiquetado nutricional y los factores socioeconómicos, culturales, demográficos, publicitarios en la selección de alimentos en un grupo de padres de niños entre 5-11 años en dos unidades educativas públicas y privadas de Quito. Métodos: Con diseño mixto, cuantitativo- transversal y cualitativa interpretativa se analizó una muestra de opiniones de 240 padres en las Unidades Educativas (UE) Nueva Aurora (Privada) y 235 padres en la UE Julio María Matovelle (Pública) de Quito. Se realizaron tres grupos focales, grabados y transcriptos de forma textual y se aplicó un cuestionario. El paquete esta-dístico usado fue SPSS v24.0. Resultados: Hubo mayor consumo de alimentos procesados en la UE Privada n=79/240 (32.9%). Selección por fácil preparación (39.2% UE Privada y 46.4% UE Pública). El 54.2 % y 57 % de los padres ven publicidad en la televisión. El conocimiento del etiquetado fue superior en la UE privada (94.9%; n=223). Asociación entre edad [OR: 2.3; IC 95%: 1.08-5.04] instrucción [OR: 3.95; IC 95%: 2.12-7.37], exposición a la publicidad [OR: 0.62; IC 95%: 0.36-1.05] y conocimientos (P<0.05). La actitud se asoció con el nivel de instrucción [OR: 2.57; IC 95%: 1.62-4.09] e ingresos (P<0.05). Análisis cualitativo: grado de conocimiento y publicidad elevados, con un impacto importante en la selección de los alimentos. Conclusiones: El conocimiento sobre el etiquetado nutricional fue elevado; pero no fue el principal factor para seleccionar alimentos. El tiempo de preparación y el sabor fueron más importantes que las especificaciones nutricionales

Introduction: Nutrition labeling is a graphic tool to notify consumers about the nutritional properties of a food, which facilitates their selection. The objective of this study was to determine the influence of nutri-tional labeling and socioeconomic, cultural, demographic, and advertising factors on food selection in a group of parents of children between 5-11 years old in two public and private educational units in Quito. Methods: With a mixed, quantitative-transversal and qualitative interpretative design, a sample of opin-ions of 240 parents in the Educational Units (EU) Nueva Aurora (Fiscal) and 235 parents in the EU Julio María Matovelle (Private) of Quito was analyzed. Three focus groups were carried out, recorded and transcribed textually, and a questionnaire was administered. The statistical package used was SPSS v24.0. Results: There was a higher consumption of processed foods in the private EU n = 79/240 (32.9%). Selection for easy preparation (39.2% Private EU and 46.4% Public EU). 54.2% and 57% of parents see advertising on television. Knowledge of labeling was higher in the private EU (94.9%; n = 223). Association between age [OR: 2.3; 95% CI: 1.08-5.04] instruction [OR: 3.95; 95% CI: 2.12-7.37], exposure to advertising [OR: 0.62; 95% CI: 0.36-1.05] and knowledge (P <0.05). Attitude was associated with educational level [OR: 2.57; 95% CI: 1.62-4.09] and admissions (P <0.05). Qualitative analysis: high degree of knowledge and publicity, with a significant impact on food selection. Conclusions: Knowledge about nutritional labeling was high, but it was not the main factor in selecting food. Prep time and flavor were more important than nutritional specifications.

Chondrogenic Potential of Human Dental Pulp Stem Cells Cultured as Microtissues.

Several tissue engineering stem cell-based procedures improve hyaline cartilage repair. In this work, the chondrogenic potential of dental pulp stem cell (DPSC) organoids or microtissues was studied. After several weeks of culture in proliferation or chondrogenic differentiation media, synthesis of aggrecan and type II and I collagen was immunodetected, and SOX9, ACAN, COL2A1, and COL1A1 gene expression was analysed by real-time RT-PCR. Whereas microtissues cultured in proliferation medium showed the synthesis of aggrecan and type II and I collagen at the 6th week of culture, samples cultured in chondrogenic differentiation medium showed an earlier and important increase in the synthesis of these macromolecules after 4 weeks. Gene expression analysis showed a significant increase of COL2A1 after 3 days of culture in chondrogenic differentiation medium, while COL1A1 was highly expressed after 14 days. Cell-cell proximity promotes the chondrogenic differentiation of DPSCs and important synthesis of hyaline chondral macromolecules.