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.

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.

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.

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.

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.

Population-attributable risk of adverse childhood experiences for high suicide risk, psychiatric admissions, and recurrent depression, in depressed outpatients.

Background: Population-attributable risk (PAR) may help estimate the potential contribution of adverse childhood experiences (ACEs) to serious clinical presentations of depression, characterized by suicidality, previous psychiatric admissions, and episode recurrence. Objective: To determine the PAR of ACEs for serious clinical presentations of depression (high suicide risk, previous psychiatric admissions, and recurrent depression) in outpatients with ICD-10 clinical depression. Method: Systematic chart review of 1,013 adults who were assessed and/or treated in a mental health clinic in Santiago, Chile for a major depressive episode. Data were collected on demographics and clinical characteristics of depression. Exposure to ACEs was determined with the Brief Physical and Sexual Abuse Questionnaire, assessing seven types of ACEs. Multivariable logistic regression analysis was used to assess the association between exposure to ACEs and suicidality, previous psychiatric admissions, and recurrence. Predicted probabilities were used for calculations of PAR. Results: Of the 1,001 study participants with complete data, 53.3% had recurrent depression, 13.5% had high suicide risk, and 5.0% had previous psychiatric admissions. Exposure to at least one ACE was recorded for 69.0% of the sample. Exposure to at least one ACE and specific types of ACEs (i.e. childhood sexual abuse and traumatic separation from caregiver) were associated with serious clinical presentations of depression. A dose-response relationship was observed between cumulative exposure to ACEs and the most serious clinical presentations of depression. ACEs were attributed to a significant proportion of disease: 61.6% of previous psychiatric admissions, 45.0% of high suicide risk, and 14.5% of recurrent depression. Conclusions: A substantial proportion of serious clinical presentations of depression among outpatients are associated with ACEs. Early detection of depressive episodes associated with ACEs, and tailored treatment for these patients, may potentially reduce the incidence of serious complications in this population.

Introducción: El riesgo atribuible poblacional (RAP) puede ayudar a estimar la potencial contribución de las experiencias adversas infantiles (EAIs) a las presentaciones clínicas serias de la depresión, caracterizadas por riesgo suicida, hospitalizaciones psiquiátricas previas y recurrencia de episodios.Objetivo: Determinar el RAP de las EAIs para las presentaciones clínicas serias de la depresión (alto riesgo suicida, hospitalizaciones psiquiátricas previas y depresión recurrente) en pacientes deprimidos ambulatorios.Método: Revisión sistemática de fichas clínicas de 1.013 adultos que fueron evaluados y/o tratados en una clínica de salud mental en Santiago, Chile por un episodio depresivo mayor. Se recolectaron datos demográficos y sobre características clínicas de la depresión. La exposición a EAIs se determinó con el Brief Physical and Sexual Abuse Questionnaire, evaluándose siete tipos de EAIs. Se usó análisis de regresión logística multivariada para evaluar la asociación entre exposición a EAIs y riesgo suicida, hospitalizaciones psiquiátricas previas y recurrencia. Las probabilidades predichas fueron utilizadas para los cálculos de los RAP.Resultados: De 1.001 participantes del estudio con datos completos, 53,3% tuvieron una depresión recurrente, 13,5% tuvieron alto riesgo suicida, y 5,0% tuvieron hospitalizaciones psiquiátricas previas. La exposición a al menos un EAI se registró en 69,0% de la muestra. La exposición a al menos un EAI y tipos específicos de EAIs (i.e. abuso sexual infantil y la separación traumática del cuidador), se asociaron con presentaciones clínicas serias de la depresión. Se observó una relación dosis-respuesta entre la exposición cumulativa a EAIs y las presentaciones clínicas más serias de la depresión. Las EAIs se atribuyeron una proporción significativa de la enfermedad: 61,6% de las hospitalizaciones psiquiátricas previas, 45,0% del alto riesgo suicida, y 14,5% de depresión recurrente.Conclusiones: Una proporción sustancial de presentaciones clínicas serias de la depresión en pacientes deprimidos ambulatorios se asocian con EAIs. La detección temprana de los episodios depresivos asociados con EAIs y el tratamiento a la medida para estos pacientes podrían potencialmente reducir la incidencia de complicaciones serias en esta población.

The contribution of early adverse stress to complex and severe depression in depressed outpatients.

BACKGROUND: To assess whether linear effects or threshold effects best describe the association between early adverse stress (EAS) and complex and severe depression (i.e., depression with treatment resistance, psychotic symptoms, and/or suicidal ideation), and to examine the attributable risk of complex and severe depression associated with EAS. METHODS: A cross-sectional study was conducted using deidentified clinical data (on demographics, presence of complex and severe depression, and exposure to seven types of EAS) from 1,013 adults who were seen in an outpatient mental health clinic in Santiago, Chile, for a major depressive episode. Multivariate logistic regressions were fitted to estimate odds ratios (ORs), using a bootstrap approach to compute 95% bias-corrected confidence intervals (95% BC CIs). A detailed examination of the cumulative risk score and calculations of the attributable risk was conducted. RESULTS: Exposure to at least five EASs was reported by 3.6% of the sample. In the multivariate logistic regression models, there was a marked increase in the odds of having complex and severe depression associated with exposure to at least five EASs (OR = 4.24; 95% BC CI: 1.25 to 9.09), according to a threshold effect. The attributable risk of complex and severe depression associated with exposure to at least one EAS was 36.8% (95% BC CI: 17.7 to 55.9). CONCLUSIONS: High levels of EAS distinctively contribute to complex clinical presentations of depression in adulthood. Patients with complex clinical presentations of depression and history of EAS should need a differentiated treatment approach, particularly those having high levels of EAS.

Examining Neanderthal and carnivore occupations of Teixoneres Cave (Moià, Barcelona, Spain) using archaeostratigraphic and intra-site spatial analysis.

Teixoneres Cave (Moià, Barcelona, Spain) is a reference site for Middle Palaeolithic studies of the Iberian Peninsula. The cave preserves an extensive stratigraphic sequence made up of eight units, which is presented in depth in this work. The main goal of this study is to undertake an initial spatial examination of Unit III, formed during Marine Isotope Stage 3, with the aim of understanding spatial organization and past activities developed by Neanderthals and carnivores (bears, hyenas and smaller carnivores). The total sample analysed includes 38,244 archaeological items and 5888 limestone blocks. The application of GIS tools allows us to clearly distinguish three geologically-defined stratigraphic subunits. Unit III has been previously interpreted as a palimpsest resulting from alternating occupation of the cave by human groups and carnivores. The distribution study shows that faunal specimens, lithic artefacts, hearths and charcoal fragments are significantly concentrated at the entrance of the cave where, it is inferred, hominins carried out different activities, while carnivores preferred the sheltered zones in the inner areas of the cave. The results obtained reveal a spatial pattern characterized by fire use related zones, and show that the site was occupied by Neanderthals in a similar and consistent way throughout the ˃ 7000 years range covered by the analysed subunits. This spatial pattern is interpreted as resulting from repeated short-term human occupations.