Assessing the impact of imidacloprid, glyphosate, and their mixtures on multiple biomarkers in Corbicula largillierti.

Pesticide mixtures are frequently utilized in agriculture, yet their cumulative effects on aquatic organisms remain poorly understood. Aquatic animals can be effective bioindicators and invasive bivalves, owing to their widespread distribution, provide an opportunity to assess these impacts. Glyphosate and imidacloprid, among the most prevalent pesticides globally, are frequently detected in freshwater systems in South America. This study aims to understand the cumulative effects of pesticide mixtures on aquatic organisms, using invasive Corbicula largillierti clams from a natural stream in northwestern Argentina. We conducted 48-hour exposure experiments using two concentrations of imidacloprid (20 and 200 µg L-1 a.i), two concentrations of glyphosate (0.3 and 3 mg L-1 a.i), and two combinations of these pesticides (both at low and high concentrations, respectively), simulating the direct contamination of both pesticides based on their agronomic recipe and observed values in Argentine aquatic environments. Clam metabolism was assessed through the examination of multiple oxidative stress parameters and measuring oxygen consumption rate as a proxy for standard metabolic rate (SMR). Our findings revealed that imidacloprid has a more pronounced effect compared to glyphosate. Imidacloprid significantly decreased clam SMR and cellular levels of reduced glutathione (GSH). However, when both pesticides were present, also cellular glycogen and thiobarbituric acid-reactive substances (TBARS) were affected. Proteins and glutathione S-Transferase (GST) activity were unaffected by either pesticide or their mixture at the assayed concentrations, highlighting the need to test several stress parameters to detect toxicological impacts. Our results indicated additive effects of imidacloprid and glyphosate across all measured parameters. The combination of multiple physiological and cytological biomarkers in invasive bivalves offers significant potential to enhance biomonitoring sensitivity and obtain insights into the origins and cellular mechanisms of chemical impacts. These studies can improve pollution regulatory policies and pesticide management.

Impact of pharmaceutical validation on prescribing errors in a neonatal intensive care unit. Randomised and controlled study.

Purpose: To compare the frequency of electronic prescription errors when the prescription was validated by the clinical pharmacist vs. when it was not. Methods: This prospective randomised controlled study was conducted in three phases. A randomised phase, in which patients were divided into control and intervention groups, and a pre- and post-intervention phase were consecutively performed to analyse the impact of pharmaceutical validation of prescriptions in a neonatal intensive care unit (NICU). This study was performed at a highly complex NICU at a tertiary hospital. All patients born during the study period who were admitted to the NICU, with a stay lasting ≥24 h, and received active pharmacological treatment were included in the study. Pharmaceutical validation was performed according to the paediatric pharmaceutical care model. A high level of validation was selected for this study. In the intervention group, discrepancies found during the review process were communicated to the medical team responsible for the patients and resolved on the same day. Results: In total, 240 patients were included in this study. Sixty-two patients were allocated to the pre-intervention (n = 38) or post-intervention (n = 24) groups, and 178 patients were randomly sorted into two groups, control (n = 82 newborns) and intervention (n = 96 newborns). During the randomisation phase, the number of prescription errors detected was significantly lower in the intervention group than that in the control group (129 vs. 270; p < 0.001). Similarly, prescription errors reaching the patient were significantly reduced from 40% (n = 108) in the control group to 1.6% (n = 2) in the intervention group. In the pre- and post-intervention periods, the prescription lines containing prescription errors decreased from 3.4% to 1.5% (p = 0.005). Conclusions: This study showed that the pharmaceutical validation process decreased both the number of errors in the electronic prescribing tools and the number of prescription errors reaching the patient.

What is bad news in fertility care? A qualitative analysis of staff and patients' accounts of bad and challenging news in fertility care.

STUDY QUESTION: What do fertility staff and patients think is bad news in fertility care? SUMMARY ANSWER: Staff and patients agree bad news is any news that makes patients less likely to achieve parenthood spontaneously or access and do successful treatment, but their appraisals of how bad the news is are differently influenced by specific news features and the context of its delivery. WHAT IS KNOWN ALREADY: Bad news is common in fertility care, but staff feel unprepared to share it and four in 10 patients react to it with unanticipated emotional or physical reactions. Research has paid much attention to how bad news should be shared, but considerably less to what news is perceived as bad, despite the fact this may dictate elements of its delivery. STUDY DESIGN, SIZE, DURATION: Two cross-sectional, online, mixed-method surveys (active 7 January-16 July 2022) were distributed to fertility staff and patients across the UK and Europe. PARTICIPANTS/MATERIALS, SETTING, METHODS: Staff inclusion criteria were being a healthcare professional working in fertility care and having experience of sharing bad news at least once a month. Patients' inclusion criteria were being adults and having had a conversation in which staff shared or explained bad news concerning their fertility care within the last 2 months. Surveys were created in English using Qualtrics, reviewed by patients and healthcare professionals, and distributed via social media, Prolific, fertility organizations, and scientific societies. Patients were asked, regarding the last time bad news were shared with them, 'What was the bad news?' and 'What other news would you consider bad news in fertility care?'. Staff were asked to 'List the three most challenging topics of bad news you share with your patients'. Staff and patient data were separately thematically analysed to produce basic codes, organized into sub-themes and themes. Themes emerging from patients' and staff data were compared and synthesized into meta themes. MAIN RESULTS AND THE ROLE OF CHANCE: Three hundred thirty-four staff accessed the survey, 286 consented, and 217 completed (65% completion rate). Three hundred forty-four patients accessed the survey, 304 consented, and 222 completed (64% completion rate). Eighty-five percent of participants were women, 62% resided in Europe, and 59% were in private care. Average staff age was 45.2 (SD = 12.0), 44% were embryologists or lab technicians, 40% were clinicians (doctors, consultants, or physicians), and 8% nurses or midwifes. Average patient age was 32.2 (SD = 6.4) and 54% had children. Staff answers originated 100 codes, 19 sub-themes and six themes. Patients' answers produced 196 codes, 34 sub-themes, and 7 themes. Staff and patient themes were integrated into three meta-themes reflecting main topics of bad news. These were Diagnosis and negative treatment events and outcomes, Inability to do (more) treatment, and Care and patient factors disrupting communication. Staff and patients agreed that some news features (uncertain, disruptive, definitive) made news more challenging but disagreed in relation to other features (e.g. unexpected/expected). Patient factors made bad news more challenging to staff (e.g. difficult emotions) and care factors made bad news more challenging to patients (e.g. disorganized care). LIMITATIONS, REASONS FOR CAUTION: Participants were self-selected, and most were women from private European clinics. Questions differed for staff and patients, focused on subjective perceptions of news, and did not measure news impact. WIDER IMPLICATIONS OF THE FINDINGS: The badness of fertility news is not only a product of the extent to which the news compromises parenthood goals but also of its features (timing, nature, number) and the context in which the news is delivered. Guidance on sharing bad news in fertility care needs to go beyond easing the process for patients to also consider staff experiences. Guidance may need to be tailored to news features and context. STUDY FUNDING/COMPETING INTEREST(S): Cardiff University funded the research. S.G., J.B., O'.H., and A.D. report funding from the Higher Education Funding Council for Wales and the European Society for Human Reproduction and Embryology (ESHRE) to develop fertiShare: a sharing bad news eLearning course for fertility care. fertiShare will be distributed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Licence (CC BY-NC-SA 4.0). No other conflicts are reported in relation to this work. TRIAL REGISTRATION NUMBER: N/A.

MGRN1 depletion promotes intercellular adhesion in melanoma by upregulation of E-cadherin and inhibition of CDC42.

Mahogunin Ring Finger 1 is an E3-ubiquitin ligase encoded by the color gene MGRN1. Our previous in vitro and in vivo studies demonstrated that Mgrn1 deletion in mouse melanoma cells induced cell differentiation and adhesion, and decreased cell motility and invasion on collagen I, and lung colonization in an in vivo model. Here, we investigated the role of MGRN1 on human melanoma cell morphology, adhesion and expression of genes/proteins involved in an EMT-like transition. We demonstrated that wild-type BRAF human melanoma cells adopted a clustering-like morphology on collagen I, with permanent MGRN1 abrogation resulting in bigger cell clusters. Enhanced intercellular adhesion was mostly mediated by induction of E-cadherin and higher co-localization with ß-catenin. Transcriptional upregulation of E-cadherin likely occurred through downregulation of the ZEB1 repressor. Finally, pulldown assays showed reduced activation of CDC42 in the absence of MGRN1, which was reverted after E-cadherin silencing. Overall, these findings highlight a new MGRN1-dependent pathway regulating melanoma cell shape, motility, and invasion potential.

Use of direct oral anticoagulants and low molecular weight heparin in venous thromboembolism associated with cancer: real-world evidence in Argentina.

BACKGROUND: Venous thromboembolism (VTE) and major bleeding (MB) are common in cancer patients. Reduced-doses of antithrombotics as secondary prophylaxis have limited data. This work aims to describe and to compare treatments and outcomes for cancer-associated VTE. RESEARCH DESIGN AND METHODS: Retrospective study. Adults with cancer-associated VTE were included. After 3-6 months of full-doses of anticoagulants, three strategies were considered: A) lowering the doses; B) maintaining full-doses; C) stopping treatment. The strategy and medication used were shown in a descriptive analysis and the rate of bleeding and VTE-recurrence between those in a comparative analysis. RESULTS: A total of 420 patients were included, 56.2% received DOACs, 43.8% enoxaparin. Strategy was defined in 257 patients: A (50.2%), B (46.3%), and C (3.5%). Forty-one (9.8%) had VTE-recurrence and 15 (3.6%) had MB or clinically relevant non-major bleeding (CRNMB).According to strategy, recurrent-VTE was 8.5% (A), 4.2% (B), and 11.1 (C) (p = 0.22), MB or CRNMB was 0.8% (A), 1.7% (B), and 0% (C) (p = 0.64). CONCLUSIONS: DOACs and strategy A were the most frequently used agent and strategy, respectively. There were no differences between medications or strategies used. The results must be interpreted with caution, and it is a retrospective single-center study, probably with information and selection bias.

Role of HDAC6-STAT3 in immunomodulatory pathways in Colorectal cancer cells.

Colorectal cancer (CRC) is one of the most common malignant neoplasms and the second leading cause of death from tumors worldwide. Therefore, there is a great need to study new therapeutical strategies, such as effective immunotherapies against these malignancies. Unfortunately, many CRC patients do not respond to current standard immunotherapies, making it necessary to search for adjuvant treatments. Histone deacetylase 6 (HDAC6) is involved in several processes, including immune response and tumor progression. Specifically, it has been observed that HDAC6 is required to activate the Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor involved in immunogenicity, by activating different genes in these pathways, such as PD-L1. Over-expression of immunosuppressive pathways in cancer cells deregulates T-cell activation. Therefore, we focused on the pharmacological inhibition of HDAC6 in CRC cells because of its potential as an adjuvant to avoid immunotolerance in immunotherapy. We investigated whether HDAC6 inhibitors (HDAC6is), such as Nexturastat A (NextA), affected STAT3 activation in CRC cells. First, we found that NextA is less cytotoxic than the non-selective HDACis panobinostat. Then, NextA modified STAT3 and decreased the mRNA and protein expression levels of PD-L1. Importantly, transcriptomic analysis showed that NextA treatment affected the expression of critical genes involved in immunomodulatory pathways in CRC malignancies. These results suggest that treatments with NextA reduce the functionality of STAT3 in CRC cells, impacting the expression of immunomodulatory genes involved in the inflammatory and immune responses. Therefore, targeting HDAC6 may represent an interesting adjuvant strategy in combination with immunotherapy.

Mortality rates for Parkinson's disease are increasing in Spain. An age-period-cohort and joinpoint analysis of mortality rates from 1981 to 2020.

BACKGROUND: Mortality in Parkinson's disease is increasing worldwide, but Spanish data need further study. OBJECTIVE: To analyse the mortality trends of Parkinson's disease in Spain between 1981 and 2020. METHODS: This observational retrospective study assessed the Parkinson's disease mortality data from 1981 to 2020 collected from the National Statistics Institute of Spain. Age-standardised mortality rates were analysed by age and sex groups, detecting significant mortality trends through a joinpoint analysis. Age-period-cohort effect and potential years of life lost analyses were conducted. The European standard population of 2013 was considered for the analyses. RESULTS: A total of 88 034 deaths were assessed. The overall age-standardised mortality rate rose throughout the period from 3.67 to 8.57 per 100 000 inhabitants. Mortality rates in men were higher than in women, 11.63 versus 6.57 deaths per 100 000 inhabitants. The sex ratio showed an increase in premature mortality in men during 2020. The overall joinpoint analysis recorded a rise in mortality, primarily since the 20th century, mainly in male and older groups, that matched with a period effect. The age effect was detected, confirming higher mortality at an older age. The analysis of potential years of life lost detected a growth in this rate, changing from 0.66 in 1981 to 1.06 in 2020. CONCLUSIONS: Mortality data for Parkinson's disease in Spain rose significantly in forty years. Mortality rate was higher in the male and age group above 75 years of age. The sex ratio showed premature mortality in men in 2020, which will need further study.

A Single Dose of Ibuprofen Impacts IL-10 Response to 164-km Road Cycling in the Heat.

Purpose: The purpose was to determine the effect of a single-dose prophylactic ibuprofen use before a 164-km road cycling event in high ambient temperature on the circulating cytokine and leukocyte responses. Methods: Twenty-three men (53 ± 8 y, 172.0 ± 22.0 cm, 85.1 ± 12.8 kg, 19.6 ± 4.4% body fat) completed a 164-km self-paced recreational road cycling event in a hot, humid, sunny environment (WBGT = 29.0 ± 2.9°C) after consuming 600 mg of ibuprofen (n = 13) or a placebo (n = 10). Blood samples were obtained one to two hours before (PRE) and immediately after (POST) the event, and analyzed for concentrations of circulating cytokines interleukins (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, GM-CSF, IFN-γ, and TNF-α and leukocytes (total leukocytes, granulocytes, monocytes, and lymphocytes). Results: Event completion time was 400.2 ± 74.8 min. Concentrations of all cytokines (except IL-1ß, IL-2, IL-5, IL-12, GM-CSF, and IFN-γ) and of all leukocyte subsets increased from PRE to POST. Ibuprofen ingestion attenuated the increase in IL-10 (86% increase with Ibuprofen; 270% increase with placebo). Conclusions: Consuming 600 mg of Ibuprofen prior to a 164-km road cycling event in a hot-humid environment attenuates exercise-induced increases in the concentration of the anti-inflammatory cytokine IL-10, but does not alter the effect of the exercise event on concentrations of other circulating cytokines or leukocyte subset concentrations.

Anthropometric characteristics according to the role performed by World Tour road cyclists for their team.

Certain anthropometric characteristics are required for athletes to successfully perform in elite endurance sports. The present study aims to analyse the anthropometric characteristics of professional cyclists according to their specialty. Anthropometric measurements were conducted of the body composition of 76 male professional road cyclists in line with International Society for Advancement of Kinanthropometry protocol. Fat mass did not differ (p > 0.05) between climbers, all-rounders and flat specialists, although the following anthropometric variables did differ according to the role played within the team (p < 0.05): Body mass (climbers: 63.8 ± 3.6, all-rounders: 68.8 ± 5.3, flat specialists: 74.5 ± 5.6 kg) skeletal body mass (climbers: 29.7 ± 1.6, all-rounders: 31.4 ± 1.9, flat specialists: 33.5 ± 2.4 kg); body surface area (climbers: 1.78 ± 0.07, all-rounders: 1.89 ± 0.10, flat specialists: 1.96 ± 0.1 m2); frontal area (climbers: 0.33 ± 0.01, all-rounders: 0.35 ± 0.02, flat specialists: 0.36 ± 0.02 m2). Anthropometric characteristics differ between world-class cyclists depending on their specialty. These differences could influence performance in relation to different types of road cycling competitions. The present study identified characteristics that could be used by coaches to evaluate their athletes in the context of elite or professional road cycling.HighlightsNormative reference values of a large sample of professional cyclists of the highest category are presented.Anthropometric characteristics differ between world-class cyclists depending on their specialty.Body mass, BMI, height and skeletal muscle mass are determining factors to determine the role of the cyclist.

Tasa de egreso hospitalario por episodio depresivo recurrente en los años 2018-2021 en Chile / Hospital discharge rate due to recurrent depressive episode in the years 2018-2021 in Chile

Introducción: La depresión es un trastorno del ánimo frecuente, cuya recurrencia altera su manejo y pronóstico. El objetivo del trabajo es describir la tasa de egreso hospitalario (TEH) por episodio depresivo recurrente (EDR) entre 2018-2021 en Chile, según sexo, edad y gravedad. Materiales y métodos: Estudio observacional y transversal que considera los egresos hospitalarios por EDR en el período 2018-2021 en Chile (N=1551). Se utilizaron las bases de datos del Departamento de Estadísticas e Información de Salud y el Instituto Nacional de Estadística. Las variables estudiadas fueron sexo, grupo etario y gravedad. No requirió aprobación de comité de ética. Resultados: Se observó la menor TEH en 2020 con 1,91 egresos por cada 100.000 habitantes. Las mujeres sobresalieron durante todo el período con una TEH de 3,68 egresos por cada 100.000 habitantes. Destacó el grupo de 15 a 19 años con la mayor TEH en ambos sexos con 5,3 egresos por cada 100.000 habitantes. Respecto a gravedad, las hospitalizaciones se concentraron en pacientes de diagnóstico no especificado. Discusión: La pandemia de COVID 19 podría explicar la disminución de la TEH en 2020, al reducirse el diagnóstico y hospitalización por EDR; presumiblemente debido al fenómeno de reconversión de camas. La TEH es mayor en el sexo femenino, lo cual es concordante con la literatura. El predominio del grupo de 15 a 19 años discrepa de la evidencia, la cual indica que suele concentrarse en individuos de 25 a 64 años. Conclusión: Las TEH por EDR se concentraron en mujeres jóvenes. Es relevante conocer la epidemiología local para focalizar los recursos en la detección oportuna de factores de riesgo, para evitar episodios graves y disminuir su recurrencia.

Introduction: Depression is a common mood disorder, whose recurrence alters its management and prognosis. The aim of the paper is to describe the hospital discharge rate (HED) for recurrent depressive episode (RDE) between 2018-2021 in Chile, according to sex, age and severity. Materials and methods: Observational and cross-sectional study considering hospital discharges due to DRE in the period 2018-2021 in Chile (N=1551). The databases of the Department of Health Statistics and Information and the National Institute of Statistics were used. The variables studied were sex, age group and severity. Ethics committee approval was not required. Results: The lowest HTE was observed in 2020 with 1.91 discharges per 100,000 inhabitants. Females stood out during the entire period with an HTE of 3.68 discharges per 100,000 population. The 15-19 years age group stood out with the highest HTE in both sexes with 5.3 admissions per 100,000 inhabitants. In terms of severity, hospitalizations were concentrated in patients with unspecified diagnosis. Discussion: The COVID 19 pandemic could explain the decrease in HTE in 2020, with a reduction in diagnosis and hospitalization for RDE, presumably due to the bed conversion phenomenon. HTE is higher in the female sex, which is consistent with the literature. The predominance of the 15 to 19 years age group disagrees with the evidence, which indicates that it tends to be concentrated in individuals aged 25 to 64 years. Conclusion: HTE due to DRE was concentrated in young women. It is important to know the local epidemiology in order to focus resources on the timely detection of risk factors to avoid serious episodes and reduce their recurrence.

Evaluación de la interacción de capecitabina con inhibidores de la bomba de protones en pacientes con cáncer de colon metastásico / Evaluation of the interaction of capecitabin with proton pump inhibitors in patients with metastatic colon cáncer

Objetivo: Evaluar el impacto clínico que la interacción de capecitabina con inhibidores de la bomba de protones (IBP) puede tener sobre la efectividad del tratamiento de mantenimiento en pacientes con cáncer de colon metastásico (CCm). Material y métodos: Estudio retrospectivo, observacional descriptivo que incluyó a todos los pacientes con CCm tratados con capecitabina sola o en combinación entre enero 2013-diciembre 2016. Los pacientes fueron divididos en dos grupos según si fueron o no tratados con IBP concomitantemente con capecitabina. Se evaluaron variables demográficas, farmacológicas y clínicas, siendo la supervivencia libre de progresión (SLP) la variable elegida para evaluar el impacto clínico de la interacción. Resultados: Se incluyeron 150 pacientes. De ellos, el 57,33% varones, media de edad 70,10±12,06 años; el 55,33% tuvieron un ECOG 1 y el 58,67% utilizaron IBP. Un 39,33% fueron tratados con capecitabina en monoterapia, 31,33% CapeOx, y 20% capecitabina+bevacizumab y 9,33% CapeOx+bevacizumab. El 53,33% tuvo un tratamiento basado en capecitabina en primera línea, la frecuencia de variaciones de tratamiento fue de 42,0% reducción de dosis, 38,0% retraso, y 12% interrupción tratamiento. El 78,0% presentó alguna toxicidad, destacando 34,67% diarrea y 30,0% (síndrome mano-pie). La SLP media fue de 6,69 vs 6,0 meses (HR=0,97; IC95% 0,68-1,39; p=0,87) en favor de los pacientes que no utilizaron IBP, aunque la relación fue no significativa. Conclusiones: En la población estudiada, los pacientes con CCm que recibieron tratamiento de mantenimiento basado en capecitabina y que utilizaron IBP simultáneamente, presentaron una tendencia no significativa a la disminución de la SLP. (AU)

Objective: To evaluate the clinical impact that the interaction of capecitabine with proton pump inhibitors (PPIs) may have on the effectiveness of maintenance treatment in patients with metastatic colon cancer (mCC). Material and methods: Retrospective, observational, descriptive study that included all patients with CCm treated with capecitabine alone or in combination between January 2013-December 2016. The patients were divided into two groups according to whether or not they were treated with PPIs concomitantly with capecitabine. Demographic, pharmacological and clinical variables were evaluated, with progression free survival (PFS) being the variable chosen to evaluate the clinical impact of interaction. Results:150 patients were included. Of them, 57.33% were men, mean age 70.10±12.06 years; 55.33% had an ECOG 1 and 58.67% used it in PPIs. 39.33% were treated with capecitabine in monotherapy, 31.33% CapeOx, and 20% capecitabine+bevacizumab and 9.33% CapeOx+bevacizumab. 53.33% had a first-line capecitabine-based treatment, the frequency of treatment variations was 42.0% dose reduction, 38.0% delay, and 12% treatment interruption. 78.0% presented any toxicity, (highlighting 34.67% diarrhea and 30.0% hand-foot syndrome). The mean PFS was 6.69 vs 6.0 months (HR=0.97; 95% CI 0.68-1.39; p=0.87) in favor of patients who did not use IBP, although the relationship was not significant. Conclusions: In the population studied, patients with mCC who received maintenance treatment based on capecitabine and who used PPIs simultaneously, showed a non-significant trend towards a decrease in PFS. (AU)

Prediction of nitrogen excretion from data on dairy cows fed a wide range of diets compiled in an intercontinental database: A meta-analysis.

Manure nitrogen (N) from cattle contributes to nitrous oxide and ammonia emissions and nitrate leaching. Measurement of manure N outputs on dairy farms is laborious, expensive, and impractical at large scales; therefore, models are needed to predict N excreted in urine and feces. Building robust prediction models requires extensive data from animals under different management systems worldwide. Thus, the study objectives were (1) to collate an international database of N excretion in feces and urine based on individual lactating dairy cow data from different continents; (2) to determine the suitability of key variables for predicting fecal, urinary, and total manure N excretion; and (3) to develop robust and reliable N excretion prediction models based on individual data from lactating dairy cows consuming various diets. A raw data set was created based on 5,483 individual cow observations, with 5,420 fecal N excretion and 3,621 urine N excretion measurements collected from 162 in vivo experiments conducted by 22 research institutes mostly located in Europe (n = 14) and North America (n = 5). A sequential approach was taken in developing models with increasing complexity by incrementally adding variables that had a significant individual effect on fecal, urinary, or total manure N excretion. Nitrogen excretion was predicted by fitting linear mixed models including experiment as a random effect. Simple models requiring dry matter intake (DMI) or N intake performed better for predicting fecal N excretion than simple models using diet nutrient composition or milk performance parameters. Simple models based on N intake performed better for urinary and total manure N excretion than those based on DMI, but simple models using milk urea N (MUN) and N intake performed even better for urinary N excretion. The full model predicting fecal N excretion had similar performance to simple models based on DMI but included several independent variables (DMI, diet crude protein content, diet neutral detergent fiber content, milk protein), depending on the location, and had root mean square prediction errors as a fraction of the observed mean values of 19.1% for intercontinental, 19.8% for European, and 17.7% for North American data sets. Complex total manure N excretion models based on N intake and MUN led to prediction errors of about 13.0% to 14.0%, which were comparable to models based on N intake alone. Intercepts and slopes of variables in optimal prediction equations developed on intercontinental, European, and North American bases differed from each other, and therefore region-specific models are preferred to predict N excretion. In conclusion, region-specific models that include information on DMI or N intake and MUN are required for good prediction of fecal, urinary, and total manure N excretion. In absence of intake data, region-specific complex equations using easily and routinely measured variables to predict fecal, urinary, or total manure N excretion may be used, but these equations have lower performance than equations based on intake.

Validación de escalas multiparamétricas de predicción de riesgo de muerte súbita en pacientes con síndrome de Brugada y estudio electrofisiológico / Validation of multiparametric approaches for the prediction of sudden cardiac death in patients with Brugada syndrome and electrophysiological study

Introducción y objetivos: Se han desarrollado puntuaciones multiparamétricas para una mejor estratificación del riesgo en el síndrome de Brugada (SBr). Nuestro objetivo es validar 3 abordajes multiparamétricos (las escalas Delise, Sieira y Shanghai BrS) en una cohorte de pacientes con síndrome de Brugada y estudio electrofisiológico (EEF). Métodos: Pacientes diagnosticados de SBr y con un EEF previo entre 1998-2019 en 23 hospitales. Se utilizaron análisis mediante estadístico C y modelos de regresión de riesgos proporcionales de Cox. Resultados: Se incluyó en total a 831 pacientes con una media de edad de 42,8±13,1 años; 623 (75%) eran varones; 386 (46,5%) tenían patrón electrocardiográfico (ECG) tipo 1; 677 (81,5%) estaban asintomáticos y 319 (38,4%) tenían un desfibrilador automático implantable. Durante un seguimiento de 10,2±4,7 años, 47 (5,7%) sufrieron un evento cardiovascular. En la cohorte total, un ECG tipo 1 y síncope fueron predictivos de eventos arrítmicos. Todas las puntuaciones de riesgo se asociaron significativamente con los eventos. Las capacidades discriminatorias de las 3 escalas fueron discretas (particularmente al aplicarlas a pacientes asintomáticos). La evaluación de las puntuaciones de Delise y Sieira con diferente número de extraestímulos (1 o 2 frente a 3) no mejoró sustancialmente el índice c de predicción de eventos. Conclusiones: En el SBr, los factores de riesgo clásicos como el ECG y el síncope previo predicen eventos arrítmicos. El número de extraestímulos necesarios para inducir arritmias ventriculares influye en las capacidades predictivas del EEF. Las escalas que combinan factores de riesgo clínico con EEF ayudan a identificar las poblaciones con más riesgo, aunque sus capacidades predictivas siguen siendo discretas tanto en población general con SBr como en pacientes asintomáticos (AU)

Introduction and objectives: Multiparametric scores have been designed for better risk stratification in Brugada syndrome (BrS). We aimed to validate 3 multiparametric approaches (the Delise score, Sieira score and the Shanghai BrS Score) in a cohort with Brugada syndrome and electrophysiological study (EPS). Methods: We included patients diagnosed with BrS and previous EPS between 1998 and 2019 in 23 hospitals. C-statistic analysis and Cox proportional hazard regression models were used. Results: A total of 831 patients were included (mean age, 42.8±13.1; 623 [75%] men; 386 [46.5%] had a type 1 electrocardiogram (ECG) pattern, 677 [81.5%] were asymptomatic, and 319 [38.4%] had an implantable cardioverter-defibrillator). During a follow-up of 10.2±4.7 years, 47 (5.7%) experienced a cardiovascular event. In the global cohort, a type 1 ECG and syncope were predictive of arrhythmic events. All risk scores were significantly associated with events. The discriminatory abilities of the 3 scores were modest (particularly when these scores were evaluated in asymptomatic patients). Evaluation of the Delise and Sieira scores with different numbers of extra stimuli (1 or 2 vs 3) did not substantially improve the event prediction c-index. Conclusions: In BrS, classic risk factors such as ECG pattern and previous syncope predict arrhythmic events. The predictive capabilities of the EPS are affected by the number of extra stimuli required to induce ventricular arrhythmias. Scores combining clinical risk factors with EPS help to identify the populations at highest risk, although their predictive abilities remain modest in the general BrS population and in asymptomatic patients (AU)

Clinical guide to perioperative management for videothoracoscopy lung resection (Section of Cardiac, Vascular and Thoracic Anesthesia, SEDAR; Spanish Society of Thoracic Surgery, SECT; Spanish Society of Physiotherapy).

The introduction of video-assisted thoracoscopic (VATS) techniques has led to a new approach in thoracic surgery. VATS is performed by inserting a thoracoscope through a small incisions in the chest wall, thus maximizing the preservation of muscle and tissue. Because of its low rate of morbidity and mortality, VATS is currently the technique of choice in most thoracic procedures. Lung resection by VATS reduces prolonged air leaks, arrhythmia, pneumonia, postoperative pain and inflammatory markers. This reduction in postoperative complications shortens hospital length of stay, and is particularly beneficial in high-risk patients with low tolerance to thoracotomy. Compared with conventional thoracotomy, the oncological results of VATS surgery are similar or even superior to those of open surgery. This aim of this multidisciplinary position statement produced by the thoracic surgery working group of the Spanish Society of Anesthesiology and Reanimation (SEDAR), the Spanish Society of Thoracic Surgery (SECT), and the Spanish Association of Physiotherapy (AEF) is to standardize and disseminate a series of perioperative anaesthesia management guidelines for patients undergoing VATS lung resection surgery. Each recommendation is based on an in-depth review of the available literature by the authors. In this document, the care of patients undergoing VATS surgery is organized in sections, starting with the surgical approach, and followed by the three pillars of anaesthesia management: preoperative, intraoperative, and postoperative anaesthesia.

Real-life experience of hepatitis C treatment in a Spanish prison.

OBJECTIVE: Hepatitis C virus (HCV) infection is a major public health problem that causes multiple comorbidities. People in prisons who inject intravenous drugs are at increased risk of HCV infection, and HCV infection is 15-fold more prevalent among prisoners compared with the community. The objective of this study was to analyse the clinical and epidemiological characteristics of residents of a Spanish prison with HCV infection who received antiviral treatment. METHODS: An observational, descriptive and retrospective study was performed. All patients with HCV infection diagnosed or followed up in an Infectious Diseases attached to a penitentiary were included in this study. RESULTS: Of 81 patients analysed, sixty-nine (83.1%) patients were male. The mean age was 50.1 (SD8.8) years, and 70% of the inmates had a history of injection drug use. Coinfection with HIV was detected in 30%. In up to 25% of the sample, there were data on chronic liver disease in the degree of liver cirrhosis. The diagnosis of HCV infection had been made more than 15 years earlier in 28% of those studied. Decompensations from liver disease, hepatocellular carcinoma, or hospital admissions were exceptional. Most of the inmates with HCV accepted treatment, and approximately 94% of the patients who completed treatment achieved a sustained virological response without interactions or complications of interest. CONCLUSIONS: The availability of direct-acting antivirals and their exceptional side effects constitute an opportunity to reduce the burden of HCV infection in Spain, particularly in these high-risk populations.

First report of a hawfinch (Coccothraustes coccothraustes) parasitized by Harpirhynchus nidulans in the Iberian Peninsula.

Some avian Harpirhynchidae mites live under the skin and develop cutaneous cysts. Despite the obvious lesions that these parasites can produce, little is currently known about the behavioural disturbances that cyst-forming mites may cause in infected wild birds. We report an infection by Harpirhynchidae mites in a hawfinch (Coccothraustes coccothraustes) in southeast Spain. The bird was easily captured due to its inability to fly. During clinical examination it was found to have multiple severe traumatic injuries, possibly due to a blow or a fall, as result of which the bird was euthanized. At necropsy, the hawfinch was found to be in good body condition. Two yellowish and friable mite-filled cysts were detected in the subalar region of both wings. Mites were morphologically identified as Harpirhynchus nidulans, and histological analysis of the cystic lesions was also performed. This is the first time that the occurrence of a hawfinch infected by H. nidulans in the Iberian Peninsula has been reported.

Analysis of rainbow trout TCRαß/CD3 complex: An in-silico modeling approach.

In mammals, the T lymphocyte receptor (TCR) is a multiprotein complex formed by the proteins TCRα, TCRß, CD3ε, CD3γ, CD3δ, and CD3ζ. It is responsible for recognizing antigens processed and presented by antigen-presenting cells (APC). The TCR is located at the cytoplasmic membrane of the T lymphocyte but is functional assembled in the rough endoplasmic reticulum (RER). Most of the available information on TCR constituents in salmonids comes from numerous nucleotide sequences available in different databases. In this work, by in silico homology modeling, we generated the TCRαß/CD3 complex of rainbow trout (Oncorhynchus mykiss) and characterized the structure of the different proteins and their potential interactions. The results show that the main structural features described in mammalian TCR/CD3 are present in the model predicted for trout. Furthermore, we highlighted several aminoacidic interactions between TCRα, TCRß, CD3γδ, and CD3ε. In silico structural analyses suggest that trout TCRαß complex would fit similarly to that described for mammals. Herein, we explore the implications of the modeled trout complex and the leukocyte phenotypes, mainly associated with different regulation mechanisms of trout TCRαß/CD3 subunits gene expression or may be due to differences in the assembly process of the complex in the RER. However, further studies will be needed to study deeper the mechanisms involved.