Reinforcing the Evidence of Mitochondrial Dysfunction in Long COVID Patients Using a Multiplatform Mass Spectrometry-Based Metabolomics Approach.

Despite the recent and increasing knowledge surrounding COVID-19 infection, the underlying mechanisms of the persistence of symptoms for a long time after the acute infection are still not completely understood. Here, a multiplatform mass spectrometry-based approach was used for metabolomic and lipidomic profiling of human plasma samples from Long COVID patients (n = 40) to reveal mitochondrial dysfunction when compared with individuals fully recovered from acute mild COVID-19 (n = 40). Untargeted metabolomic analysis using CE-ESI(+/-)-TOF-MS and GC-Q-MS was performed. Additionally, a lipidomic analysis using LC-ESI(+/-)-QTOF-MS based on an in-house library revealed 447 lipid species identified with a high confidence annotation level. The integration of complementary analytical platforms has allowed a comprehensive metabolic and lipidomic characterization of plasma alterations in Long COVID disease that found 46 relevant metabolites which allowed to discriminate between Long COVID and fully recovered patients. We report specific metabolites altered in Long COVID, mainly related to a decrease in the amino acid metabolism and ceramide plasma levels and an increase in the tricarboxylic acid (TCA) cycle, reinforcing the evidence of an impaired mitochondrial function. The most relevant alterations shown in this study will help to better understand the insights of Long COVID syndrome by providing a deeper knowledge of the metabolomic basis of the pathology.

Effect of Operational Variables on Supercritical Foaming of Caffeic Acid-Loaded Poly(lactic acid)/Poly(butylene adipate-co-terephthalate) Blends for the Development of Sustainable Materials.

Expanded polystyrene will account for 5.3% of total global plastic production in 2021 and is widely used for food packaging due to its excellent moisture resistance and thermal insulation. However, some of these packages are often used only once before being discarded, generating large amounts of environmentally harmful plastic waste. A very attractive alternative to the conventional methods used for polymer processing is the use of supercritical carbon dioxide (scCO2) since it has mass-transfer properties adapted to the foam morphology, generating different path lengths for the diffusion of active compounds within its structure and can dissolve a wide range of organic molecules under supercritical conditions. The objective of this research was to evaluate the effect of operational variables on the process of caffeic acid (CA) impregnation and subsequent foaming of polylactic acid (PLA) as well as two PLA/poly(butylene-co-terephthalate-adipate) (PBAT) blends using scCO2. The results showed an increase in the degree of crystallinity of the CA-impregnated samples due to the nucleation effect of the active compound. On the other hand, SEM micrographs of both films and foams showed significant differences due to the presence of PBAT and its low miscibility with PLA. Finally, the results obtained in this work contribute to the knowledge of the important parameters to consider for the implementation of the impregnation and foaming process of PLA and PLA/PBAT blends with potential use in food packaging.

Inflammasome-Related Genetic Polymorphisms as Severity Biomarkers of COVID-19.

The most critical forms of coronavirus disease 2019 (COVID-19) are associated with excessive activation of the inflammasome. Despite the COVID-19 impact on public health, we still do not fully understand the mechanisms by which the inflammatory response influences disease prognosis. Accordingly, we aimed to elucidate the role of polymorphisms in the key genes of the formation and signaling of the inflammasome as biomarkers of COVID-19 severity. For this purpose, a large and well-defined cohort of 377 COVID-19 patients with mild (n = 72), moderate (n = 84), severe (n = 100), and critical (n = 121) infections were included. A total of 24 polymorphisms located in inflammasome-related genes (NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, IL18, NFKB1, ATG16L1, and MIF) were genotyped in all of the patients and in the 192 healthy controls (HCs) (who were without COVID-19 at the time of and before the study) by RT-qPCR. Our results showed that patients with mild, moderate, severe, and critical COVID-19 presented similar allelic and genotypic distribution in all the variants studied. No statistically significant differences in the haplotypic distribution of NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, and ATG16L1 were observed between COVID-19 patients, who were stratified by disease severity. Each stratified group of patients presented a similar genetic distribution to the HCs. In conclusion, our results suggest that the inflammasome polymorphisms studied are not associated with the worsening of COVID-19.

Foaming of 3D-Printed PLA/CaCO3 Composites by Supercritical CO2 Process for Sustainable Food Contact Materials.

In the last decade, among the emerging technologies in the area of bioplastics, additive manufacturing (AM), commonly referred to as 3D printing, stands out. This technology has gained great interest in the development of new products, mainly due to its capability to easily produce customized and low-cost plastic products. This work aims to evaluate the effect of supercritical foaming of 3D-printed parts based on a commercial PLA matrix loaded with calcium carbonate, for single-use sustainable food contact materials. 3D-printed PLA/CaCO3 parts were obtained by 3D printing with a 20% and 80% infill, and two infill patterns, rectilinear and triangular, were set for each of the infill percentages selected. Supercritical fluid foaming of PLA/CaCO3 composite printed parts was performed using a pressure of 25 MPa, a temperature of 130 °C for 23 min, with a fast depressurization rate (1 s). Closed-cell foams were achieved and the presence of CaCO3 did not influence the surface of the foams or the cell walls, and no agglomerations were observed. Foam samples with 80% infill showed subtle temperature fluctuations, and thermogravimetric analysis showed that samples were thermally stable up to ~300 °C, while the maximum degradation temperature was around 365 °C. Finally, tensile test analysis showed that for lower infill contents, the foams showed lower mechanical performance, while the 80% infill and triangular pattern produced foams with good mechanical performance. These results emphasize the interest in using the supercritical CO2 process to easily produce foams from 3D-printed parts. These materials represent a sustainable alternative for replacing non-biodegradable materials such as Expanded Polystyrene, and they are a promising option for use in many industrial applications, such as contact materials.

Long-term depressive symptom trajectories and related baseline characteristics in primary care patients: Analysis of the PsicAP clinical trial.

BACKGROUND: There is heterogeneity in the long-term trajectories of depressive symptoms among patients. To date, there has been little effort to inform the long-term trajectory of symptom change and the factors associated with different trajectories. Such knowledge is key to treatment decision-making in primary care, where depression is a common reason for consultation. We aimed to identify distinct long-term trajectories of depressive symptoms and explore pre-treatment characteristics associated with them. METHODS: A total of 483 patients from the PsicAP clinical trial were included. Growth mixture modeling was used to identify long-term distinct trajectories of depressive symptoms, and multinomial logistic regression models to explore associations between pre-treatment characteristics and trajectories. RESULTS: Four trajectories were identified that best explained the observed response patterns: "recovery" (64.18%), "late recovery" (10.15%), "relapse" (13.67%), and "chronicity" (12%). There was a higher likelihood of following the recovery trajectory for patients who had received psychological treatment in addition to the treatment as usual. Chronicity was associated with higher depressive severity, comorbidity (generalized anxiety, panic, and somatic symptoms), taking antidepressants, higher emotional suppression, lower levels on life quality, and being older. Relapse was associated with higher depressive severity, somatic symptoms, and having basic education, and late recovery was associated with higher depressive severity, generalized anxiety symptoms, greater disability, and rumination. CONCLUSIONS: There were different trajectories of depressive course and related prognostic factors among the patients. However, further research is needed before these findings can significantly influence care decisions.

rhIL-7-hyFc and hIL-2/TCB2c combination promotes an immune-stimulatory tumor microenvironment that improves antitumor efficacy of checkpoint inhibitors.

BACKGROUND: Recombinant human interleukin (rhIL)-7-hyFc (efineptakin alfa; NT-I7) is a potent T-cell amplifier, with two IL-7 molecules fused to IgD/IgG4 elements. rhIL-7-hyFc promotes extensive infiltration of CD8+ T cells into the tumor, concurrently increasing the numbers of intratumoral PD-1+CD8+ T cells. The hIL-2/TCB2 complex (SLC-3010) inhibits tumor growth by preferential activation of CD122 (IL-2Rß)high CD8+ T cells and natural killer cells, over regulatory T cells (Tregs). We investigated the underlying mechanisms of rhIL-7-hyFc and hIL-2/TCB2c antitumor activity and the potential synergistic efficacy, specifically focusing on tumor-specific CD8+ cells within the tumor and the tumor-draining lymph nodes (tdLN). METHODS: MC38 and CT26 tumor-bearing mice were administered with 10 mg/kg rhIL-7-hyFc intramuscularly and 0.9 mg/kg hIL-2/TCB2c intravenously. Anti-PD-1 monoclonal antibody was administered intraperitoneally three times at 3-day intervals at a dose of 5 mg/kg. Tumor volume was measured to assess efficacy. To compare the composition of immune cells between each monotherapy and the combination therapy, we analyzed tumors and tdLNs by flow cytometry. RESULTS: Our data demonstrate that the combination of rhIL-7-hyFc and hIL-2/TCB2c increases efficacy and generates an immune-stimulatory tumor microenvironment (TME). The TME is characterized by an increased infiltration of tumor-specific CD8+ T cells, and a decreased frequency of CD39highTIM-3+ Treg cells. Most importantly, rhIL-7-hyFc increases infiltration of a CD62L+Ly108+ early progenitor population of exhausted CD8+ T cells (TPEX), which may retain long-term proliferation capacity and replenish functional effector CD8+ T cells. hIL-2/TCB2c induces differentiation of CD62L+Ly108+ TPEX rapidly into CD101+ terminally differentiated subsets (terminally exhausted T cell (TEX term)). Our study also demonstrates that rhIL-7-hyFc significantly enhances the proliferation rate of TPEX in the tdLNs, positively correlating with their abundance within the tumor. Moreover, rhIL-7-hyFc and hIL-2/TCB2c can overcome the limited therapeutic effectiveness of PD-1 blockade, culminating in the complete regression of tumors. CONCLUSIONS: rhIL-7-hyFc can expand and maintain the progenitor pool of exhausted CD8+ T cells, whereas hIL-2/TCB2c promotes their differentiation into TEX term. Together, this induces an immune-stimulatory TME that improves the efficacy of checkpoint blockade.

Short physical performance battery is not associated with falls and injurious falls in older persons: longitudinal data of the SCOPE project.

INTRODUCTION: Falls and fall-related injuries in older persons are a major public health problem. Our objective was to study the predictive value of the Short Physical Performance Battery (SPPB) in the cohort of the SCOPE project on falls, injurious falls, and possible difference of prediction between indoors and outdoors falls. METHODS: For this sub-study of the SCOPE project participants reporting no falls at baseline, and survey data on falls at the 12-month and 24-month follow-up were included. Participant´s characteristics were assessed during the baseline interview and medical examinations. Falls as well as injurious falls and fall circumstances were obtained self-reported. SPPB and its association with fallers vs. no fallers at 12 and at 24 months were studied with logistic regression models. RESULTS: The 1198 participants had a median age of 79 years (77-82), and a median SPPB of 10 (8-11), with a 52.5% of female. A total of 227 and 277 falls (12- and 24- month visits, respectively) were reported. In the crude model, the SPPB sum scores (p < 0.001) as well as most single item scores were significant different between fallers and non-fallers over time. However, the association was attenuated in models adjusted for age, sex, marital status, number of medications, quality of life, handgrip strength, and muscle mass [e.g., 12 months; OR 0.94 (0.87-1.02)]. While SPPB fails to differentiate between injurious and non-injurious falls (p = 0.48), a lower SPPB score was associated with falls at home (p < 0.01) after 24 months. CONCLUSION: SBPP was not able to significantly predict the risk of falling as well as experiencing an injurious fall. TRIAL REGISTRATION: This study was registered prospectively on 25th February 2016 at clinicaltrials.gov (NCT02691546).

Retinal vessel volume reference database derived from volume-rendered optical coherence tomography angiography.

Optical coherence tomography angiography (OCTA) enables three-dimensional reconstruction of the functional blood vessels in the retina. Therefore, it enables the quantification of 3D retinal vessel parameters such as surface area and vessel volume. In spite of the widespread use of OCTA, no representative volume-rendered vessel volume (VV) data are published to date. In this study, OCTA 3 × 3 mm macular cubes were processed with volume-rendering techniques to measure VV in 203 eyes from 107 healthy volunteers. Generalized linear models (GLM) were constructed to assess the impact of age, gender, visual acuity (VA), spherical equivalent (SE), and axial length (AL) on VV. Overall mean VV was 0.23 ± 0.05mm3. Age and axial length showed a negative correlation with VV. However, GLM model analysis found that AL exerted the most pronounced influence on VV. No statistically significant associations were identified between gender or between left and right eyes. This is the first study to assess 3D OCTA VV and its naturally occurring variations in a large series of healthy subjects. It offers novel insights into the characterization of normal retinal vascular anatomy in healthy individuals, contributing to a valuable reference for future research in this field.

An IROA Workflow for correction and normalization of ion suppression in mass spectrometry-based metabolomic profiling data.

Ion suppression is a major problem in mass spectrometry (MS)-based metabolomics; it can dramatically decrease measurement accuracy, precision, and signal-to-noise sensitivity. Here we report a new method, the IROA TruQuant Workflow, that uses a stable isotope-labeled internal standard (IROA-IS) plus novel companion algorithms to 1) measure and correct for ion suppression, and 2) perform Dual MSTUS normalization of MS metabolomic data. We have evaluated the method across ion chromatography (IC), hydrophilic interaction liquid chromatography (HILIC), and reverse phase liquid chromatography (RPLC)-MS systems in both positive and negative ionization modes, with clean and unclean ion sources, and across different biological matrices. Across the broad range of conditions tested, all detected metabolites exhibited ion suppression ranging from 1% to 90+% and coefficient of variations ranging from 1% to 20%, but the Workflow and companion algorithms were highly effective at nulling out that suppression and error. Overall, the Workflow corrects ion suppression across diverse analytical conditions and produces robust normalization of non-targeted metabolomic data.

Versican accumulation drives Nos2 induction and aortic disease in Marfan syndrome via Akt activation.

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition associated with Marfan syndrome (MFS), a disease caused by fibrillin-1 gene mutations. While various conditions causing TAAD exhibit aortic accumulation of the proteoglycans versican (Vcan) and aggrecan (Acan), it is unclear whether these ECM proteins are involved in aortic disease. Here, we find that Vcan, but not Acan, accumulated in Fbn1C1041G/+ aortas, a mouse model of MFS. Vcan haploinsufficiency protected MFS mice against aortic dilation, and its silencing reverted aortic disease by reducing Nos2 protein expression. Our results suggest that Acan is not an essential contributor to MFS aortopathy. We further demonstrate that Vcan triggers Akt activation and that pharmacological Akt pathway inhibition rapidly regresses aortic dilation and Nos2 expression in MFS mice. Analysis of aortic tissue from MFS human patients revealed accumulation of VCAN and elevated pAKT-S473 staining. Together, these findings reveal that Vcan plays a causative role in MFS aortic disease in vivo by inducing Nos2 via Akt activation and identify Akt signaling pathway components as candidate therapeutic targets.

Normothermic Machine Perfusion Systems: Where Do We Go From Here?

Normothermic machine perfusion (NMP) aims to preserve organs ex vivo by simulating physiological conditions such as body temperature. Recent advancements in NMP system design have prompted the development of clinically effective devices for liver, heart, lung, and kidney transplantation that preserve organs for several hours/up to 1 d. In preclinical studies, adjustments to circuit structure, perfusate composition, and automatic supervision have extended perfusion times up to 1 wk of preservation. Emerging NMP platforms for ex vivo preservation of the pancreas, intestine, uterus, ovary, and vascularized composite allografts represent exciting prospects. Thus, NMP may become a valuable tool in transplantation and provide significant advantages to biomedical research. This review recaps recent NMP research, including discussions of devices in clinical trials, innovative preclinical systems for extended preservation, and platforms developed for other organs. We will also discuss NMP strategies using a global approach while focusing on technical specifications and preservation times.

Biodegradable nanocomposite poly(lactic acid) foams containing carvacrol-based cocrystal prepared by supercritical CO2 processing for controlled release in active food packaging.

Compounds derived from essential oils have been used in active packaging, but their volatility and degradability negatively affect stability and leads to high release rates. The present study aimed to develop PLA bionanocomposite foams loaded with carvacrol cocrystal by supercritical CO2 and its release into a food simulant for control release in food packaging. For this purpose, 4,4'-bipyridine was used as coformer and carvacrol as active agent. Cocrystallized closed cell foams were obtained using supercritical CO2 and were characterized in terms of their physicochemical and mechanical properties, and release kinetics to a D1 simulant were evaluated as well as the antioxidant ability. A better overall mechanical behavior due to the nanoclay promoting a higher interfacial adhesion with the polymeric matrix was revealed. A higher incorporation of carvacrol was observed in samples with higher C30B content. The incorporated cocrystals showed a decrease of one order of magnitude in the estimated effective diffusion coefficient of carvacrol and showed antioxidant activity. These results suggest that the nanocomposite foam containing carvacrol-based cocrystals could be used in active packaging systems with controlled release characteristics, especially with highly volatile compounds, and can be proposed for other fields such as biomedical applications.

IL-2 produced by HBV-specific T cells as a biomarker of viral control and predictor of response to PD-1 therapy across clinical phases of chronic hepatitis B.

BACKGROUND: There are no immunological biomarkers that predict control of chronic hepatitis B (CHB). The lack of immune biomarkers raises concerns for therapies targeting PD-1/PD-L1 because they have the potential for immune-related adverse events. Defining specific immune functions associated with control of HBV replication could identify patients likely to respond to anti-PD-1/PD-L1 therapies and achieve a durable functional cure. METHODS: We enrolled immunotolerant, HBeAg+ immune-active (IA+), HBeAg- immune-active (IA-), inactive carriers, and functionally cured patients to test ex vivo PD-1 blockade on HBV-specific T cell functionality. Peripheral blood mononuclear cells were stimulated with overlapping peptides covering HBV proteins +/-α-PD-1 blockade. Functional T cells were measured using a 2-color FluoroSpot assay for interferon-γ and IL-2. Ex vivo functional restoration was compared to the interferon response capacity assay, which predicts overall survival in cancer patients receiving checkpoint inhibitors. RESULTS: Ex vivo interferon-γ+ responses did not differ across clinical phases. IL-2+ responses were significantly higher in patients with better viral control and preferentially restored with PD-1 blockade. Inactive carrier patients displayed the greatest increase in IL-2 production, which was dominated by CD4 T cell and response to the HBcAg. The interferon response capacity assay significantly correlated with the degree of HBV-specific T cell restoration. CONCLUSIONS: IL-2 production was associated with better HBV control and superior to interferon-γ as a marker of T cell restoration following ex vivo PD-1 blockade. Our study suggests that responsiveness to ex vivo PD-1 blockade, or the interferon response capacity assay, may support stratification for α-PD-1 therapies.

Deep Learning-Based Predictive Model for Revascularization of Chronic Total Occlusions on Angiographic Imaging.

Revascularization of chronic total occlusions (CTO) is currently one of the most complex procedures in percutaneous coronary intervention (PCI), requiring the use of specific devices and a high level of experience to obtain good results. Once the clinical indication for extensive ischemia or angina uncontrolled with medical treatment has been established, the decision to perform coronary intervention is not simple, since this procedure has a higher rate of complications than non-PCI percutaneous intervention, higher ionizing radiation doses and a lower success rate. However, CTO revascularization has been shown to be helpful in symptomatic improvement of angina, reduction of ischemic burden, or improvement of ejection fraction. The aim of this work is to determine whether a model developed using deep learning techniques, and trained with angiography images, can better predict the likelihood of a successful revascularization procedure for a patient with a chronic total occlusion (CTO) lesion in their coronary artery (measured as procedure success and the duration of time during which X-ray imaging technology is used to perform a medical procedure) than the scales traditionally used. As a preliminary approach, patients with right coronary artery CTO will be included since they present standard angiographic projections that are performed in all patients and present less technical variability (duration, projection angle, image similarity) among them.The ultimate objective is to develop a predictive model to help the clinician in the decision to intervene and to analyze the performance in terms of predicting the success of the technique for the revascularization of chronic occlusions.Clinical Relevance- The development of a deep learning model based on the angiography images could potentially overcome the gold standard and help interventional cardiologists in the treatment decision for percutaneous coronary intervention, maximizing the success rate of coronary intervention.

Marcadores genéticos y séricos relacionados con una rápida progresión clínica de la arteriosclerosis coronaria / Serum and genetic markers related to rapid clinical progression of coronary artery disease

Introducción y objetivos: La progresión de la enfermedad coronaria una vez se hace evidente a la clínica tiene una gran variabilidad interindividual. El objetivo es determinar marcadores séricos y genéticos en pacientes con rápida progresión clínica (RPC) de la enfermedad coronaria frente a pacientes con estabilidad clínica mantenida (ECM). Métodos: Estudio retrospectivo de casos (RPC) y controles (ECM) (1:2). Se consideró RPC a los pacientes que precisaron al menos 2 revascularizaciones por progresión de la ateroesclerosis en los 10 años posteriores a una primera angioplastia y ECM a aquellos sin eventos durante el mismo periodo tras la primera angioplastia. Una vez seleccionados, se determinaron los valores séricos, la expresión de ácido ribonucleico mensajero (ARNm) y polimorfismos genéticos de interleucina 6, proteína C reactiva y factor de necrosis tumoral alfa (TNFα) como marcadores de inflamación y proproteína convertasa subtilisina/kexina tipo 9 (PCSK9), receptor de lipoproteínas de baja densidad, proteína 2 de unión a elementos reguladores de esteroles y apolipoproteína B como marcadores aterogénicos. Resultados: Se incluyó a 180 pacientes (58 en RPC y 122 en ECM). Las características basales demográficas, del perfil de riesgo clásico y de la extensión de la enfermedad coronaria fueron comparables. El grupo de RPC presentó valores séricos más altos de interleucina 6 y PCSK9 y mayor expresión de ARNm de TNF. Los alelos de Interleucina-6 rs180075C, de TNF rs3093664 non-G y de PCSK9 rs2483205 T confieren riesgo de RPC (p<0,05 en todos los casos). Un 51,7% de los pacientes del grupo RPC presentaron los tres alelos de riesgo frente al 18% de los pacientes del grupo en ECM (p<0,001). Conclusiones: Se propone la existencia de marcadores genotípicos y fenotípicos asociados con la RPC de enfermedad coronaria y que podrían servir para individualizar la intensidad y el tipo de tratamiento.(AU)

Introduction and objectives: Patients with clinically evident coronary artery disease differ in their rate of progression, which impacts prognosis. We aimed to characterize serum and genetic markers in patients with rapid clinical progression (RCP) of coronary artery disease vs those with long standing stable (LSS) disease. Methods: Retrospective study of cases (RCP) and controls (LSS) (1:2). Patients requiring ≥ 2 revascularizations due to atherosclerotic progression in the 10 years after a first angioplasty were considered to be RCP and those without events during the same period after the first angioplasty were considered to have LSS disease. After patient selection, we analyzed serum values, mRNA expression and genetic polymorphisms of inflammatory markers, including interleukin-6, C-reactive protein, and tumor necrosis factor (TNF)-a, and atherogenic markers consisted of proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein receptor, sterol regulatory element binding transcription factor 2, and apolipoprotein-B. Results: The study included 180 patients (58 RCP and 122 LSS). Demographic characteristics, classic risk factors and the extent of coronary disease were similar in the 2 groups. Patients with RCP showed higher serum levels of interleukin-6 and PCSK9 and higher TNF mRNA expression. Interleukin-6 rs180075C, TNF rs3093664 non-G and PCSK9 rs2483205 T alleles conferred a risk of RCP (P<.05 in all cases). Among patients with RCP, 51.7% had all 3 risk alleles vs 18% of those with LSS (P<.001). Conclusions: We suggest the existence of specific phenotypic and genotypic markers associated with RCP of coronary artery disease that could help to individualize the type and intensity of treatment.(AU)

Value of estimating pulse wave velocity compared to SCORE in cardiovascular risk stratification in community pharmacies / Valor de la estimación de la velocidad de onda de pulso en comparación con SCORE en la estratificación del riesgo cardiovascular en farmacias comunitarias

Objectives Arterial stiffness is considered to be an intermediate marker with independent prognostic value. The objective of this study is to assess whether the estimation of arterial stiffness can improve CV risk stratification compared to SCORE in patients at community pharmacies. Methods Observational prospective epidemiological study in which consecutive individuals entering a participating Community Pharmacy are offered a voluntary measurement of blood pressure and estimation of pulse wave velocity by oscillometry (AGEDIO, IEM®) to stratify their CV risk according to SCORE compared to the use of arterial stiffness. Results After nine months of recruitment, data from 923 patients (570 women, 353 men) were collected. 16/122 (13.1%) patients under 40 years and 72/364 (19.8%) over 65 years of age presented pathological stiffness and could be classified as high-risk, even though being out of the age-range of SCORE. Of the 437 (47.3%) patients who were susceptible to calculating SCORE, 42/437 patients (9.6%) presented pathological arterial stiffness. Cholesterol values were available in 281 patients (64.3%). Among them, according to SCORE, only 6 (2.1%) fell into the high-risk category. Conclusions More than half of the subjects who randomly enter a community pharmacy had ages that make it impossible to calculate the CV risk by SCORE. Among them, arterial damage was detected in 18.1%. Of the other half, 9.6% presented arterial damage and, therefore, high CV risk, when SCORE only detected it in 2.1%. Therefore, estimating arterial stiffness in community pharmacies markedly improves detection of high CV risk compared to SCORE (AU)

Objetivos La rigidez arterial es un marcador intermedio con valor pronóstico independiente. Nuestro objetivo es valorar si la estimación de la rigidez arterial puede mejorar la estratificación del riesgo cardiovascular (CV) en comparación con SCORE. Métodos Estudio epidemiológico observacional prospectivo en el que se ofrece a pacientes consecutivos que entran en una farmacia participante la medición voluntaria de la presión arterial y de la velocidad de onda de pulso estimada por oscilometría (AGEDIO, IEM®) para estratificar su riesgo CV según SCORE o según la presencia de rigidez arterial. Resultados Tras 9 meses de reclutamiento, presentamos datos de 923 pacientes (570 mujeres, 353 hombres). Dieciséis/122 (13,1%) pacientes <40años y 72/364 (19,8%) >65años presentaron rigidez arterial patológica y fueron clasificados de alto riesgo, aun hallándose fuera del rango de edad de SCORE. De los 437 (47,3%) pacientes evaluables por SCORE, 42/437 pacientes (9,6%) mostraron rigidez elevada. Los valores de colesterol estaban disponibles en 281 de estos pacientes (64,3%). Entre ellos, según SCORE, solo 6 (2,1%) eran de la categoría de alto riesgo. Conclusiones Más de la mitad de sujetos que entran aleatoriamente en una farmacia comunitaria tenían edades situadas fuera de los rangos de SCORE, imposibilitando el cálculo del riesgo CV con SCORE. En este grupo se constató daño arterial en el 18,1%. En la otra mitad, el 9,6% presentaron daño vascular y, consecuentemente, riesgo elevado, mientras que SCORE solo detectó riesgo elevado en el 2,1%. Por tanto, la estimación de la rigidez arterial en farmacias comunitarias mejora claramente la detección de riesgo CV elevado en comparación con SCORE (AU)

Suicidio más allá del diagnóstico: un enfoque centrado en la persona y su circunstancia / Suicide Beyond Diagnosis: A Person and Their Circumstances-Centered Approach

Existe una pluralidad de enfoques sobre el suicidio. En la literatura científica y en el ámbito sanitario es hegemónico el modelo biomédico. En este trabajo se presen-ta un modelo alternativo, existencial-contextual, de estudio, comprensión, prevención y posvención del suicidio en el ámbito sanitario. El trabajo se divide en dos partes. La primera expone los tres elementos esenciales del modelo existencial-contextual: la no-ción de persona, el concepto de problemas de la vida y la práctica de la relación de cui-dado y acompañamiento. La segunda desarrolla algunas de las diferencias asistenciales más importantes entre el modelo biomédico y el existencial-contextual del suicidio. Se concluye en la necesidad de superar el paradigma suicidológico biomédico tradicional y construir un espacio amplio transdisciplinar de reflexión suicidológica crítica a la altura de nuestro tiempo. Este cambio de paradigma requiere pasar de una lógica que prioriza lo patológico-biológico-farmacológico a otra socio-psico-política del suicidio que integre las aportaciones del modelo biomédico sin reducirse a ellas. (AU)

There is a plurality of understanding approaches to suicide. In the scientific literature and the healthcare field, the biomedical model is hegemonic. This paper pre-sents an alternative existential-contextual model for the study, understanding, preven-tion and postvention of suicide in the healthcare field. The academic paper is divided into two parts. The first part sets out the three essential elements of the existential-contex-tual model: the notion of personhood, the concept of life problems and the practice of caring and supportive relationships. The second one develops some of the most impor-tant differences in care between the biomedical and the existential-contextual models of suicide. It concludes with the need to overcome the traditional biomedical suicidological paradigm and to build a broad transdisciplinary space for critical suicidological reflection that is up to date with our times. This paradigm shift requires moving from a logic that prioritizes the pathological-biological-pharmacological to a socio-psycho-political logic of suicide that integrates the contributions of the biomedical model without being reduced to them. (AU)

Nitrogen Utilization in Goats Consuming Buffelgrass Hay and Molasses-Based Blocks with Incremental Urea Levels.

The use of goats for meat production faces challenges from environmental and nutritional factors. Urea is an affordable non-protein nitrogen source commonly utilized in ruminant nutrition. The objective of this study was to investigate nitrogen utilization in goats fed low-quality hay supplemented with molasses blocks containing urea. Twenty Anglo-Nubian doelings were individually housed in metabolic cages and provided with chopped Buffelgrass (Cenchrus ciliaris) hay ad libitum. Goats were randomly assigned to four urea levels (0, 2, 4, and 6%; n = 5 per treatment) in molasses blocks for a duration of 30 days. A negative nitrogen balance (-2.458 g/day) was observed in doelings consuming blocks without urea, compared with a positive balance (0.895 g/d) for those consuming the 6% urea blocks. Block nitrogen intake significantly increased with urea level, but urea supplementation did not affect dry matter (DM) or neutral detergent fiber (NDFom) intake or digestibility. A minimum crude protein (CP) requirement of 8% for maintenance in doelings consuming low-quality forage with a urea-based supplement was determined through regression analysis between CP intake (% of DM) and N balance (r2 = 0.479; p < 0.002). The value of 8% of CP obtained in this study is similar to several previous studies reported in the literature, but in this case, the increments in CP came exclusively from urea. In this study, increasing the urea content of molasses blocks up to 6% significantly increased nitrogen intake, retention, and balance in goats. These results contribute to a better understanding of nitrogen utilization in goats fed low-quality hay with urea supplementation.

Occupational practice in patients with hereditary transthyretin amyloidosis, a qualitative study.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is a rare genetic disease that negatively affects patients' quality of life through the involvement of various organs and tissues. Despite a large amount of research on medical and psychosocial interventions, the impact of occupational therapy (OT) on patients with ATTRv is not well understood. OBJECTIVE: The aim of this study was to develop an OT programme to improve the daily functioning and quality of life of patients with ATTRv. METHODS: Fourteen patients with ATTRv were interviewed. Together they developed short- and medium-term occupational goals. Patients received the OT intervention for six months. Outcomes were measured using scores for activities of daily living and psychological well-being. RESULTS: The study found that OT can have a positive impact as a complementary intervention to medical and other psychosocial treatments. Of the 14 patients, 12 maintained the same scores in activities of daily living. Two deteriorated and eight improved their psychological scores. CONCLUSION: This study highlights the need for further research in this area and the importance of OT in the management of patients with ATTRv. Early intervention is of paramount importance and further research is needed to evaluate the long-term effects of OT interventions in patients with ATTRv.

Quantitative Analysis of Acetyl-CoA, Malonyl-CoA, and Succinyl-CoA in Myocytes.

Several analytical challenges make it difficult to accurately measure coenzyme A (CoA) metaboforms, including insufficient stability and a lack of available metabolite standards. Consequently, our understanding of CoA biology and the modulation of human diseases may be nascent. CoA's serve as lipid precursors, energy intermediates, and mediators of post-translational modifications of proteins. Here, we present a liquid chromatography-mass spectrometry (LC-MS) approach to measure malonyl-CoA, acetyl-CoA, and succinyl-CoA in complex biological samples. Additionally, we evaluated workflows to increase sample stability. We used reference standards to optimize CoA assay sensitivity and test CoA metabolite stability as a function of the reconstitution solvent. We show that using glass instead of plastic sample vials decreases CoA signal loss and improves the sample stability. We identify additives that improve CoA stability and facilitate accurate analysis of CoA species across large sample sets. We apply our optimized workflow to biological samples of skeletal muscle cells cultured under hypoxic and normoxia conditions. Together, our workflow improves the detection and identification of CoA species through targeted analysis in complex biological samples.