Evaluating the QileX-RhE skin corrosion test for chemical subcategorization in accordance with OECD TG 431.

Skin corrosion testing is integral to evaluating the potential harm posed by chemicals, impacting regulatory decisions on safety, transportation, and labeling. Traditional animal testing methods are giving way to in vitro alternatives, such as reconstructed human epidermis (RhE) models, aligning with evolving ethical standards. This study evaluates the QileX-RhE test system's performance for chemical subcategorization within the OECD TG 431 framework. Results demonstrate its ability to differentiate subcategories, accurately predicting 83% of UN GHS Category 1A and 73% of UN GHS Category 1B/1C chemicals with 100% sensitivity in corrosive prediction. Additionally, this study provides a comprehensive assessment of the test method's performance by employing nuanced parameters such as positive predictive value (PPV), negative predictive value (NPV), post-test odds and likelihood rations, offering valuable insights into the applicability and effectiveness of the QileX-RhE test method.

Localization and symbiotic status of probiotics in the coral holobiont.

Corals establish symbiotic relationships with microorganisms, especially endosymbiotic photosynthetic algae. Although other microbes have been commonly detected in coral tissues, their identity and beneficial functions for their host are unclear. Here, we confirm the beneficial outcomes of the inoculation of bacteria selected as probiotics and use fluorescence in situ hybridization (FISH) to define their localization in the coral Pocillopora damicornis. Our results show the first evidence of the inherent presence of Halomonas sp. and Cobetia sp. in native coral tissues, even before their inoculation. Furthermore, the relative enrichment of these coral tissue-associated bacteria through their inoculation in corals correlates with health improvements, such as increases in photosynthetic potential, and productivity. Our study suggests the symbiotic status of Halomonas sp. and Cobetia sp. in corals by indicating their localization within coral gastrodermis and epidermis and correlating their increased relative abundance through active inoculation with beneficial outcomes for the holobiont. This knowledge is crucial to facilitate the screening and application of probiotics that may not be transient members of the coral microbiome. IMPORTANCE: Despite the promising results indicating the beneficial outcomes associated with the application of probiotics in corals and some scarce knowledge regarding the identity of bacterial cells found within the coral tissue, the correlation between these two aspects is still missing. This gap limits our understanding of the actual diversity of coral-associated bacteria and whether these symbionts are beneficial. Some researchers, for example, have been suggesting that probiotic screening should only focus on the very few known tissue-associated bacteria, such as Endozoicomonas sp., assuming that the currently tested probiotics are not tissue-associated. Here, we provide specific FISH probes for Halomonas sp. and Cobetia sp., expand our knowledge of the identity of coral-associated bacteria and confirm the probiotic status of the tested probiotics. The presence of these beneficial microorganisms for corals (BMCs) inside host tissues and gastric cavities also supports the notion that direct interactions with the host may underpin their probiotic role. This is a new breakthrough; these results argue against the possibility that the positive effects of BMCs are due to factors that are not related to a direct symbiotic interaction, for example, that the host simply feeds on inoculated bacteria or that the bacteria change the water quality.

An effective method for culturing functional human corneal endothelial cells using a xenogeneic free culture medium.

Endothelial dysfunction is a leading cause of corneal blindness in developed countries and the only available treatment is the endothelial transplantation. However, the limited availability of suitable donors remains a significant challenge, driving the exploration of alternative regenerative therapies. Advanced Therapy Medicinal Products show promise but must adhere to strict regulations that prohibit the use of animal-derived substances. This study investigates a novel culture methodology using Plasma Rich in Growth Factors (PRGF) as the only source of growth factors for primary cultures of human corneal endothelial cells (CECs). CECs were obtained from discarded corneas or endothelial rings and cultured in two different media: one supplemented with xenogeneic factors and other xenogeneic-free, using PRGF. Comprehensive characterization through immunofluorescence, morphological analyses, trans-endothelial electrical resistance measurements, RNA-seq, and qPCR was conducted on the two groups. Results demonstrate that CECs cultured in the xenogeneic-free medium exhibit comparable gene expression, morphology, and functionality to those cultured in the xenogeneic medium. Notably, PRGF-expanded CECs share 46.9% of the gene expression profile with native endothelium and express all studied endothelial markers. In conclusion, PRGF provides an effective source of xenogeneic-free growth factors for the culture of CECs from discarded corneal tissue. Further studies will be necessary to demonstrate the applicability of these cultures to cell therapies that make clinical translation possible.

Validation of Visual Analogue Scale for loss of smell as a quick test in chronic rhinosinusitis with nasal polyps.

BACKGROUND AND OBJECTIVE: Diagnostic criteria of chronic rhinosinusitis with nasal polyps (CRSwNP) include, among others, olfactory dysfunction (OD). We hypothesize that patients suffering with CRSwNP are good at self-assessing their sense of smell through visual analogue scale (VAS) compared to smell tests. METHODS: A controlled cross-sectional study was planned. Adults diagnosed with severe CRSwNP waiting for endoscopic sinus surgery were included. A cohort of healthy controls was also studied. All participants performed Barcelona smell test (BAST-24), sinonasal outcomes test 22 (SNOT-22), and VAS for loss of smell. CRSwNP underwent blood test (eosinophils count, total serum IgE), CT scan (Lund-Mackay Score), and nasal endoscopy. RESULTS: 138 severe CRSwNP and 40 controls subjects were included. The BAST-24 identification score was strongly correlated with the VAS score in the CRSwNP group (rho=-0.79, p<0.001) but not in the control group (rho=-0.14; p=0.39), this difference between groups being statistically significant (p<0.001). A significant correlation of SNOT-22 item 21 (loss of smell) was also found with BAST-24 identification (rho=-0.65, p<0.001), this difference being statistically significant (Z=-2.43; p=0.015). In the ROC curve, the area under the curve (AUC) was 0.85 with 72.5% sensitivity and 93.1% specificity. CONCLUSION: This study demonstrates a potential role of the VAS score for the screening of OD in severe CRSwNP in daily clinical practice.

Butchering knives and hafting at the Late Middle Paleolithic open-air site of Nahal Mahanayeem Outlet (NMO), Israel.

Much of what is known about human behavior and subsistence strategies in the Levantine Middle Paleolithic comes from long sequences from caves and rock shelters. In this context, studies of stone tool function have traditionally focused on determining the use of Levallois points and triangular elements, either as projectiles or, more rarely, multipurpose knives. Little is known about such tool use and hafting in Middle Paleolithic open-air sites in the Levant through the systematic application of micro-wear analysis. Here we report the results of a low and high-power study performed on the lithic assemblage of the Late Middle Paleolithic open-air site of Nahal Mahanayeem Outlet (NMO, Israel). Most pointed items, including Levallois and non-Levallois points, were used as butchering knives, many of them while hafted; to a much lesser extent they were also used for hide, bone, and wood/plant processing activities. Blades and flakes were mostly handheld and used as butchering knives, with hide, bone, antler, and wood/plant-processing tasks being rare. Hafted artifacts include morphologies and activities for which hafting is not required, indicating that NMO inhabitants possessed varied hafting expertise. Wood/plant processing tools, some of which were hafted, attest that manufacture and maintenance tasks were planned well in advance of game procurement at the site. These results attest to early evidence of hafted butchering knives and hafted plant processing tools for a Late Middle Paleolithic open-air site in the Levant, and support previous interpretations of NMO as a short-term task-specific location focused on animal processing activities, mostly butchery.

Análisis e implementación de un modelo asistencial basado en la integración de un farmacéutico de hospital en un Servicio de Hematología y Hemoterapia / Analysis and implementation of a healthcare model based on the integration of a hospital pharmacist in a Hematology and Hemotherapy Service

Objetivo: Analizar el impacto sanitario y económico, así como evaluar la actividad clínica y asistencial, que supone la integración de un farmacéutico de hospital en un Servicio de Hematología y Hemoterapia. Material y métodos: Se trata de un estudio observacional prospectivo, unicéntrico, realizado en un hospital de tercer nivel desde enero de 2014 hasta febrero de 2019, diseñado para definir las funciones y las actividades clínicas a realizar por un farmacéutico de hospital integrado en un Servicio de Hematología de un hospital de tercer nivel y medir los resultados que se obtienen mediante la adopción de este nuevo modelo asistencial integrado Hematología-Farmacia, basado en la multidisciplinariedad. Resultados: El farmacéutico se integró totalmente en la actividad clínica diaria del equipo multidisciplinar perteneciente al Servicio de Hematología y Hemoterapia, siendo un facilitador del trabajo diario de los profesionales del Servicio de Hematología y un mediador de las necesidades de ambos servicios implicados (Hematología y Farmacia). Esta integración permitió garantizar la seguridad en la administración de tratamientos hematológicos en 9.125 pacientes hematológicos, reducir los errores de medicación en un 95%, detectar y notificar 45 reacciones adversas a medicamentos, diseñar medidas de eficiencia y seguimiento de las mismas en patologías de elevado impacto económico como mieloma múltiple, leucemia linfática crónica, leucemia mieloide crónica y hemofilia, consiguiendo un ahorro de 1.500.000 euros, entre otros resultados. Conclusiones: La integración de un farmacéutico de hospital en un Servicio de Hematología constituye una medida de innovación y eficiencia, mejora la calidad asistencial, garantiza la seguridad, favorece la sostenibilidad del sistema sanitario y facilita la incorporación de innovación. (AU)

Objective: To analyze the health and economic impact and to evaluate the clinical and care activity of the integration of a hospital pharmacist in a Hematology and Hemotherapy Service. Material and methods: This is a prospective, single-centre, observational study conducted in a tertiary hospital from January 2014 to February 2019, designed to define the functions and clinical activities to be performed by a hospital pharmacist integrated into a Hematology and Hemotherapy Service of a tertiary hospital and to measure the results obtained by adopting this new integrated Hematology-Pharmacy care model, based on multidisciplinarity. Results: The pharmacist was fully integrated into the daily clinical activity of the multidisciplinary team belonging to the Hematology and Hemotherapy Service, being a facilitator of the daily work of the professionals of the Hematology Service and a mediator of the needs of both services involved (Hematology and Pharmacy). This integration made it possible to guarantee safety in the administration of hematological treatments in 9,125 hematological patients, to reduce medication errors by 95%, to detect and notify 45 adverse drug reactions, to design efficiency measures and follow-up of these in pathologies with a high economic impact such as multiple myeloma, chronic lymphatic leukemia, chronic myeloid leukemia and hemophilia, achieving savings of 1,500,000 euros, among other results. Conclusions: The integration of a hospital pharmacist in a Hematology and Hemotherapy Service constitutes a measure of innovation and efficiency, improves the quality of care, guarantees safety, favours the sustainability of the health system and facilitates the incorporation of innovation. (AU)

Cardiac function unchanged following reanimation with normothermic regional perfusion in donation after circulatory death.

Objectives: To determine whether hearts reanimated with normothermic regional perfusion (NRP) have clinically detectable changes in function using echocardiography comparing the prearrest and post-NRP imaging. As heart transplantation from donation after circulatory death (DCD) continues to increase, preliminary results suggest outcomes comparable with donation after brain death. It is unknown whether the obligatory period of warm ischemia experienced during DCD withdrawal process causes immediate changes in cardiac allograft function following in situ reanimation. Methods: We retrospectively reviewed and compared predonation with postreanimation echocardiographic findings in all DCD donors at our institution from January to October 2021. All DCD donor organs were reanimated with in situ thoracoabdominal NRP after circulatory death. Echocardiographic assessment included (1) 2-dimensional and speckle-tracking measures of chamber size and function; (2) ejection fraction; (3) fractional area change; and (4) global longitudinal strain. Results: Altogether, 4 DCD heart donations were performed during the study period. Basic demographics and withdrawal ischemic time periods are reported. There were no changes in left ventricular ejection fraction and right ventricular fractional area change when comparing the predonation and the postreanimation echocardiogram. There was a minimal, nonstatistically significant decrease in left ventricular global longitudinal strain and right ventricular free-wall systolic strain in 3 of the 4 donors following reanimation. Conclusions: DCD cardiac allografts reanimated with NRP demonstrated no change in echocardiographic parameters used for a standard predonation donor heart evaluation. Findings suggest cardiac function of DCD allografts reanimated with thoracoabdominal NRP is not adversely impacted by limited period of warm ischemia following circulatory arrest.

Sinonasal mucosal melanomas: defining profiles for better survival outcomes.

BACKGROUND: Sinonasal mucosal melanoma is an aggressive malignancy with a 5-year survival rate ranging from 20% to 39%. Despite the evolving surgical and radiotherapy techniques, and introduction of immune-checkpoint inhibitor therapy, overall survival rates remain poor. METHODOLOGY: A retrospective cohort study was conducted at the Hospital Clinic de Barcelona and the Hospital de la Santa Creu i Sant Pau between 1984 and 2020; primary outcome measures were 3 and 5-year melanoma-specific survival (MSS). Kaplan-Meier survival analysis and Cox proportional hazards model were performed to identify predictors of survival. RESULTS: Fifty patients were included, the mean age was 70.4, MSS at 3 and 5 years was 51.2%, and 29.5%, respectively. The median follow-up was 39.6 months during which 46% presented locoregional recurrence and 36%, metastasis. The univariate and multivariate analyses found as survival predictors the N category, the treatment received, the surgical margins and the mitotic index. CONCLUSIONS: We found an overall 5-year MSS of 29.5%. Those patients with intention-to-cure (stages III and IVa) treated by surgery that were N0 at diagnosis, with < 10 mitoses per HPF showed a 5-year MSS rate of 74.1%. More studies will be needed to adequately define the patients' profiles that will benefit from a better survival outcome.

The 8-Odorant Barcelona Olfactory Test (BOT-8): Validation of a New Test in the Spanish Population During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVE: Most smell tests are difficult to implement in daily clinical practice owing to their long duration. The aim of the present study was to develop and validate a short, easy-to-perform, and reusable smell test to be implemented during the COVID-19 pandemic. METHODS: The study population comprised 120 healthy adults and 195 patients with self-reported olfactory dysfunction (OD). The 8-Odorant Barcelona Olfactory Test (BOT-8) was used for detection, memory/recognition, and forced-choice identification. In addition, a rose threshold test was performed, and a visual analog scale was applied. The Smell Diskettes Olfaction Test (SDOT) was used for correlation in healthy volunteers, and the University of Pennsylvania Smell Identification Test (UPSIT) was used for patients with OD to establish cut-offs for anosmia and hyposmia. In order to take account of the COVID-19 pandemic, disposable cotton swabs with odorants were compared with the original test. RESULTS: In healthy persons, the mean (SD) BOT-8 score was 100% for detection, 94.5% (1.07) for memory/recognition, and 89.6% (0.86) for identification. In patients with OD, the equivalent values were 86% (32.8), 73.2% (37.9), and 77.1% (34.2), respectively. BOT-8 demonstrated good test-retest reliability, with agreement of 96.7% and a quadratic k of 0.84 (P<.001). A strong correlation was observed between BOT-8 and SDOT (r=0.67, P<.001) and UPSIT (r=0.86, P<.001). Agreement was excellent for disposable cotton swabs, with a k of 0.79 compared with the original test. The cut-off point for anosmia was ≤3 (area under the curve, 0.83; sensitivity, 0.673; specificity, 0.993). CONCLUSION: BOT-8 offers an efficient and fast method for assessment of smell threshold, detection, memory, and identification in daily clinical practice. Disposable cotton swabs with odorants proved to be useful and safe during the COVID-19 pandemic.

SELNET clinical practice guidelines for bone sarcoma.

Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context.

Changes in body composition and cardiometabolic risk factors in relation to the reduction in body mass index in adolescents with obesity / Cambios en la composición corporal y factores de riesgo cardiometabólico en relación con la reducción del índice de masa corporal en adolescentes con obesidad

Introduction: there are controversial data in relation to the reduction in body mass index standard deviation score (BMI-SDS) needed to improve adiposity in the pediatric population with obesity. The aim of this work was to determine the minimum variation in BMI-SDS required to improve the values of adiposity markers and cardiometabolic risk factors in growing adolescents with obesity. Methods: a longitudinal study consisting of clinical evaluation (waist circumference, waist-to-height ratio, fat mass index, and blood pressure) and blood testing (insulin resistance and lipid profile) was conducted in 350 adolescents with obesity (152 boys and 198 girls) aged 10.2-14.3 years who went through a combined intervention (12 months). Results: a decrease in SDS-BMI ≤ 0.5 was not associated with any significant improvement in the clinical features and blood testing recorded. A decrease in BMI-SDS > 0.5, and especially if > 1.0, was linked to a significant improvement in adiposity markers. A decrease in BMI-SDS > 0.5 was associated with a significant improvement in insulin resistance, and a decrease in BMI-SDS > 1.0 was associated with a significant decrease in the percentage of patients who showed high values of systolic blood pressure, HOMA-IR, and lipid profile Conclusions: improvement in body composition, insulin resistance, and lipid profile can be observed with reductions in BMI-SDS ≥ 0.5 in obese adolescents, while extended benefits are obtained by losing at least 1.0 BMI-SDS (AU)

Introducción: los datos en relación con la reducción del índice de masa corporal (IMC-SDS) necesario para mejorar la adiposidad en la población pediátrica con obesidad son controvertidos. El objetivo de este trabajo es determinar la variación mínima del IMC-SDS necesaria para mejorar los valores de los marcadores de adiposidad y los factores de riesgo cardiometabólico en adolescentes obesos. Métodos: estudio longitudinal clínico (perímetro de cintura, índice cintura-estatura e índice de masa grasa y presión arterial) y analítico (HOMA-R y perfil lipídico) realizado en 350 adolescentes con obesidad (152 niños y 198 niñas) de entre 10,2 y 14,3 años de edad que completaron una intervención combinada (12 meses). Resultados: una disminución en el índice de masa corporal (SDS-BMI) ≤ 0,5 no se asoció con ninguna mejora significativa de las características clínicas y analíticas registradas. Una disminución del IMC-SDS > 0,5, y especialmente si > 1,0, se relacionó con una mejora significativa de los marcadores clínicos de adiposidad. Una disminución del IMC-SDS > 0,5 se asoció con una mejora significativa de la resistencia a la insulina y una disminución del BMI-SDS > 1,0 se asoció con una disminución significativa del porcentaje de pacientes que mostraban valores altos de presión arterial sistólica, HOMA-IR y perfil lipídico Conclusiones: con una reducción del IMC-SDS ≥ 0,5 se observa una mejoría tanto en la composición corporal como en los factores de riesgo cardiovascular en los adolescentes obesos; no obstante, estos beneficios son mayores si la reducción del IMC-SDS es superior a 1.0 (AU)

Thoracoabdominal Normothermic Perfusion in Donation After Circulatory Death.

Donation after circulatory death is emerging as an alternative pathway to donation after brain death to expand the cardiac organ donor pool. We describe the surgical technique and circuit configuration for in-situ organ reperfusion with thoracoabdominal normothermic regional perfusion using portable venoarterial extracorporeal membrane oxygenation.

[Hyperlipoproteinaemia(a) and stroke. A case report of a family with early-onset severe atherosclerotic disease]. / Hiperlipoproteinemia(a) e ictus. A propósito de una familia con enfermedad ateroesclerótica grave precoz.

TITLE: Hiperlipoproteinemia(a) e ictus. A propósito de una familia con enfermedad ateroesclerótica grave precoz.

The 8-Odorant Barcelona Olfactory Test(BOT-8): Validation of a New Test in the Spanish Population During the COVID-19 Pandemic

Background: Most smell tests are difficult to implement in daily clinical practice owing to their long duration. The aim of the present study was to develop and validate a short, easy-to-perform, and reusable smell test to be implemented during the COVID-19 pandemic. Methods: The study population comprised 120 healthy adults and 195 patients with self-reported olfactory dysfunction (OD). The 8-Odorant Barcelona Olfactory Test (BOT-8) was used for detection, memory/recognition, and forced-choice identification. In addition, a rose threshold test was performed, and a visual analog scale was applied. The Smell Diskettes Olfaction Test (SDOT) was used for correlation in healthy volunteers, and the University of Pennsylvania Smell Identification Test (UPSIT) was used for patients with OD to establish cut-offs for anosmia and hyposmia. In order to take account of the COVID-19 pandemic, disposable cotton swabs with odorants were compared with the original test. Results: In healthy persons, the mean (SD) BOT-8 score was 100% for detection, 94.5% (1.07) for memory/recognition, and 89.6% (0.86) for identification. In patients with OD, the equivalent values were 86% (32.8), 73.2% (37.9), and 77.1% (34.2), respectively. BOT-8 demonstrated good test-retest reliability, with agreement of 96.7% and a quadratic k of 0.84 (P<.001). A strong correlation was observed between BOT-8 and SDOT (r=0.67, P<.001) and UPSIT (r=0.86, P<.001). Agreement was excellent for disposable cotton swabs, with a k of 0.79 compared with the original test. The cut-off point for anosmia was ≤3 (area under the curve, 0.83; sensitivity, 0.673; specificity, 0.993). Conclusions: BOT-8 offers an efficient and fast method for assessment of smell threshold, detection, memory, and identification in daily clinical practice. Disposable cotton swabs with odorants proved to be useful and safe during the COVID-19 pandemic (AU)

Introducción: Las olfatometrías son difíciles de implementar en la práctica clínica diaria por su larga duración. El objetivo del presente estudio fue desarrollar y validar una prueba simple, fácil y reutilizable para ser utilizada durante la pandemia de COVID-19. Métodos: Se incluyeron 120 voluntarios sanos ≥18 años y 195 pacientes con disfunción olfatoria (DO) autoreportada. Se utilizó el Barcelona Olfactory Test (BOT-8) con 8 odorantes para la detección, memoria/reconocimiento e identificación. Además, se hizo una prueba de umbral de rosa (alcohol feniletílico) de 6 diluciones, escala visual analógica (EVA). Se compararon los resultados con una prueba validada Smell Diskettes Olfaction Test (SDOT), para definir puntos de corte de hiposmia y anosmia se comparó en pacientes con DO con UPSITTM. Considerando la pandemia de COVID-19, se compararon hisopos de algodón desechables con los odorantes respecto a la prueba original. Resultados: BOT-8 se tarda entre 3 y 7 minutos en realizar. En población sana, la media de detección fue del 100%, memoria 94,5% (DE=1,07) e identificación 89,6% (DE=0,86). En pacientes con DO fue de 86% (DE=32,8), 73,2% (DE=37,9) y 77,1% (DE=34,2), respectivamente. BOT-8 demostró buena fiabilidad test-retest con 96,7% de concordancia observada y una kappa cuadrática de 0,84 (p<0,001). Presentó una fuerte correlación con SDOT (r=0,673, p <0,001) en población sana y con UPSITTM en pacientes con DO (r=0,86, p<0,001). Los hisopos de algodón desechables mostraron una excelente concordancia (kappa de 0,79) en comparación con la prueba original. El punto de corte para anosmia fue ≤ 3 (AUC=0,83, Se= 0,673, Sp=0,993) y de hiposmia ≤ 6 (AUC=0,451, Se= 0,088, Sp= 0,814). Conclusiones: BOT-8 ofrece un método eficiente y rápido para ser utilizado en la práctica clínica diaria para evaluar el sentido del olfato mediante la detección, memoria, identificación y umbral (AU)