Age and sex differences in pharmaceutical contamination in a keystone scavenger.

Pharmaceutical contaminants have a recognized negative impact on wildlife health. However, there are still many knowledge gaps on the factors influencing exposure and metabolic processing of compound mixtures as a function of season and individual characteristics such as age and sex. We evaluated age and sex differences in a set of seventeen compounds, including eleven antibiotics, five NSAIDs and caffeine, evaluated by HPLC-MS-TOF analysis in griffon vultures (Gyps fulvus) from central Spain. Pharmaceutical cocktails (up to 10 compounds simultaneously) were found in all individuals. Lincomycin was detected in all individuals, and fluoroquinolones were found at high frequencies, while NSAIDs were at low frequencies and concentrations, including flumixin meglumine, which can be lethal to vultures. A higher total number of compounds and sum of concentrations, as well as prevalence and concentration of several of the pharmaceuticals tested was found in females than in males for both nestlings and adults. This is the first study to present evidence of sex differences in the pharmacokinetics of dietary drug contaminants in a vulture species. Chronic exposure to "medications" in entire populations can potentially have sub-lethal health effects that affect fitness differently according to age and sex, with demographic implications for population viability. Specifically, if females have higher mortality after fledging due to high pharmaceutical contamination, this should be considered when modelling the population dynamic of this species for conservation purposes.

Experiencias de madres al cuidado del niño con cáncer: una mirada desde la enfermería transcultural / Experiences of mothers taking care to your child with cancer: a look from transcultural nursing

La enfermería transcultural permite valorar el cuidado desde la perspectiva de las familias afectadas durante el proceso de la enfermedad oncológica. Objetivo principal: El propósito del estudio fue comprender las experiencias de las madres al cuidado de su hijo con cáncer desde la mirada de la enfermería transcultural. Metodología: Estudio cualitativo de diseño exploratorio. Se aplicaron entrevistas semiestructuradas a madres de niños y adolescentes con cáncer en un centro de salud de Valparaíso, previa aprobación del proyecto por parte del Comité de Bioética de la Universidad de Valparaíso. Se realizó análisis de contenido temático de Bardin. Resultados: Surgieron cuatro temas: (1) Valor del cuidado, (2) Prácticas de cuidado y creencias en salud, (3) Creencias religiosas y (4) Redes de apoyo. Conclusión principal: Las experiencias de las madres permitieron valorar la importancia de incorporar los factores socioculturales propuestos por Leininger, para la planificación de los cuidados, con el fin de apoyar a las familias durante el padecimiento de la enfermedad de su hijo.(AU)

Transcultural nursing allows us to assess care from the perspective of the families affected during the oncological disease process. Main objective: The purpose of the study was to understand the experiences of mothers caring for their child with cancer from the perspective of transcultural nursing. Methodology: Qualitative study with an exploratory design. Semi-structured interviews were applied to mothers of children and adolescents with cancer in a health center in Valparaíso, following project approval by the Bioethics Committee of the University of Valparaíso. Thematic content analysis, following Bardin's approach, was carried out. Results: Four themes emerged: (1) Value of care, (2) Care practices and health beliefs, (3) Religious beliefs and (4) Support networks. Main conclusion: The mothers' experiences highlighted the importance of incorporating the sociocultural factors proposed by Leininger into care planning in order to support families during their child's illness.(AU)

Peroxisome proliferator activated receptor-γ agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus.

OBJECTIVES: Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases. We hypothesised that PGZ could improve vascular dysfunction and cardiometabolic parameters in SLE. METHODS: Eighty SLE subjects with mild to severe disease activity were randomised to a sequence of PGZ followed by placebo for 3 months, or vice versa, in a double-blind, cross-over design with a 2-month wash-out period. Primary endpoints were parameters of endothelial function and arterial inflammation, measured by multimodal assessments. Additional outcome measures of disease activity, neutrophil dysregulation, metabolic disturbances and gene expression studies were performed. RESULTS: Seventy-two subjects completed the study. PGZ was associated with a significant reduction in Cardio-Ankle Vascular Index (a measure of arterial stiffness) compared with placebo. Various metabolic parameters improved with PGZ, including insulin resistance and lipoprotein profiles. Circulating neutrophil extracellular trap levels also significantly decreased with PGZ compared with placebo. Most adverse events experienced while on PGZ were mild and resolved with reduction in PGZ dose. CONCLUSION: PGZ was well tolerated and induced significant improvement in vascular stiffness and cardiometabolic parameters in SLE. The results suggest that PGZ should be further explored as a modulator of cardiovascular disease risk in SLE. TRIAL REGISTRATION NUMBER: NCT02338999.

Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus.

Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In lupus animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled clinical trial of tofacitinib in SLE subjects (ClinicalTrials.gov NCT02535689). In this study, 30 subjects are randomized to tofacitinib (5 mg twice daily) or placebo in 2:1 block. The primary outcome of this study is safety and tolerability of tofacitinib. The secondary outcomes include clinical response and mechanistic studies. The tofacitinib is found to be safe in SLE meeting study's primary endpoint. We also show that tofacitinib improves cardiometabolic and immunologic parameters associated with the premature atherosclerosis in SLE. Tofacitinib improves high-density lipoprotein cholesterol levels (p = 0.0006, CI 95%: 4.12, 13.32) and particle number (p = 0.0008, CI 95%: 1.58, 5.33); lecithin: cholesterol acyltransferase concentration (p = 0.024, CI 95%: 1.1, -26.5), cholesterol efflux capacity (p = 0.08, CI 95%: -0.01, 0.24), improvements in arterial stiffness and endothelium-dependent vasorelaxation and decrease in type I IFN gene signature, low-density granulocytes and circulating NETs. Some of these improvements are more robust in subjects with STAT4 risk allele.

[Sarcopenia index in hospitalized patients with chronic obstructive pulmonary disease exacerbation]. / Índice de sarcopenia en pacientes hospitalizados por agudización de la enfermedad pulmonar obstructiva crónica.

Sarcopenia (loss of muscle mass and function) implies a worse prognosis. However, its diagnosis is complex and is not made in routine clinical care. A biomarker has been proposed as a surrogate estimator of skeletal muscle mass, the so-called sarcopenia index ([serum creatinine/cystatine C] x100) which is associated with prognostic features in various diseases including patients with stable chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate the potential clinical and prognostic information of this biomarker in COPD exacerbation. This is a one-year prospective study of consecutive patients admitted for COPD exacerbation. A total of 89 patients, 70 men (79%) and 19 women (21%) were included. Those with lower values of the sarcopenia index had a higher level of dyspnoea and a longer hospitalization. In the correlation analysis, the index had statistically significant values with FEV1 (r = 0.23), PaCO2 (r = -0.30), bicarbonate (r = -0.31), dyspnoea (r = -0.25) and length of admission (r = -0.30). In patients admitted for COPD exacerbation, the sarcopenia index was related to prognostic characteristics, so that lower values were associated with longer duration of hospital admission, more dyspnoea and greater functional impairment. As this is an index associated with muscle mass, its determination may identify patients who could be the subject of a differentiated therapeutic plan.

La presencia de sarcopenia (pérdida de masa y función muscular) implica peor pronóstico. Sin embargo, su diagnóstico es complejo y no se realiza en la atención clínica habitual. Se ha propuesto un biomarcador como estimador subrogado de la masa muscular esquelética, el denominado índice de sarcopenia ([creatinina sérica/cistatina C] x100) que se asocia a características pronósticas en diversas enfermedades incluyendo pacientes con enfermedad pulmonar obstructiva crónica (EPOC) estable. El objetivo de nuestro estudio ha sido evaluar de forma prospectiva la potencial información clínica y pronóstica de este biomarcador en agudización de la EPOC. Se trata de un estudio prospectivo, durante un año, de los pacientes consecutivos que ingresan por agudización de su EPOC. Se incluyeron 89 pacientes, 70 varones (79%) y 19 mujeres (21%). Aquellos con valores disminuidos del índice de sarcopenia tenían más disnea y requerían una internación más prolongada. En el análisis de correlación se obtuvo valores con significación estadística del índice con FEV1 (r = 0.23), PaCO2 (r = -0.30) y bicarbonato (r = -0.31), y con la disnea (r = -0.25) y la duración del ingreso (r =- 0.30). En los ingresados por agudización de la EPOC el índice de sarcopenia se relacionó con características pronósticas, de modo que los valores inferiores se asociaron a mayor duración de la internación, más disnea y mayor afectación funcional. Al tratarse de un índice asociado a la masa muscular, su determinación podría identificar a pacientes a incluir en un plan terapéutico diferenciado.

Symptoms in patients with asthma infected by SARS-CoV-2.

INTRODUCTION: Organ tropism of SARS-CoV-2 to the respiratory tract could potentially aggravate asthma. The susceptibility of patients with asthma to develop an exacerbation when they are infected with SARS-CoV-2 is unknown. We aimed to investigate the symptoms presented in patients with asthma who became infected with SARS-CoV-2. METHODS AND RESULTS: All patients over 14 years of age who tested positive for SARS-CoV-2 (by RT-PCR) were included (n = 2995). In patients with asthma (n = 77, 2.6%; 44 females), symptoms, therapy and phenotype were recorded. Seventeen (22%) patients had mild asthma, 55 (71%) moderate and five severe (6%). Twenty-six patients with asthma (34%) were asymptomatic, 34 (44%) developed symptoms but did not require hospital admission, and 17 (22%) were hospitalised. One patient was admitted because of asthma exacerbation without pneumonia or other symptoms. Ten patients (13%) had wheezes (six with pneumonia). Comparison of wheezing between patients with non-T2 asthma and the rest of the patients was statistically significant, (p < 0.001). CONCLUSIONS: SARS-CoV-2 infection is not a significant cause of asthma exacerbation, although some patients may present wheezing, especially in cases of pneumonia. The severity of asthma does not seem to be associated with symptoms of the disease.

Índice de sarcopenia en pacientes hospitalizados por agudización de la enfermedad pulmonar obstructiva crónica / Sarcopenia index in hospitalized patients with chronic obstructive pulmonary disease exacerbation

Resumen La presencia de sarcopenia (pérdida de masa y función muscular) implica peor pronóstico. Sin embargo, su diagnóstico es complejo y no se realiza en la atención clínica habitual. Se ha propuesto un biomarcador como estimador subrogado de la masa muscular esquelética, el denominado índice de sarcopenia ([creatinina sérica/cistatina C] x100) que se asocia a características pronósticas en diversas enfermedades incluyendo pacientes con enfermedad pulmonar obstructiva crónica (EPOC) estable. El objetivo de nuestro estudio ha sido evaluar de forma prospectiva la potencial información clínica y pronóstica de este biomarcador en agudización de la EPOC. Se trata de un estudio prospectivo, durante un año, de los pacientes consecutivos que ingresan por agudización de su EPOC. Se incluyeron 89 pacientes, 70 varones (79%) y 19 mujeres (21%). Aquellos con valores disminuidos del índice de sarcopenia tenían más disnea y requerían una internación más prolongada. En el análisis de correlación se obtuvo valores con significación estadística del índice con FEV1 (r = 0.23), PaCO (r = -0.30) y bicarbonato (r = -0.31), y con la disnea (r = -0.25) y la duración del ingreso (r =0.30). En los ingresados por agudización de la EPOC el índice de sarcopenia se relacionó con características pronósticas, de modo que los valores inferiores se asociaron a mayor duración de la internación, más disnea y mayor afectación funcional. Al tratarse de un índice asociado a la masa muscular, su determinación podría identificar a pacientes a incluir en un plan terapéutico diferenciado.

Abstract Sarcopenia (loss of muscle mass and function) implies a worse prognosis. However, its diagnosis is complex and is not made in routine clinical care. A biomarker has been proposed as a surrogate estimator of skeletal muscle mass, the so-called sarcopenia index ([serum creatinine/cystatine C] x100) which is associated with prognostic features in various diseases including patients with stable chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate the potential clinical and prognostic information of this biomarker in COPD exacerbation. This is a one-year prospective study of consecutive patients admitted for COPD exacerbation. A total of 89 patients, 70 men (79%) and 19 women (21%) were included. Those with lower values of the sarcopenia index had a higher level of dyspnoea and a longer hospitalization. In the correlation analysis, the index had statistically significant values with FEV1 (r = 0.23), PaCO (r = -0.30), bicarbonate (r = -0.31), dyspnoea (r = -0.25) and length of admission (r = -0.30). In patients admitted for COPD exacerbation, the sarcopenia index was related to prognostic characteristics, so that lower values were associated with longer duration of hospital admission, more dyspnoea and greater functional impairment. As this is an index associated with muscle mass, its determination may identify patients who could be the subject of a differentiated therapeutic plan.

Wildlife poisoning: a novel scoring system and review of analytical methods for anticoagulant rodenticide determination.

Anticoagulant rodenticides (ARs) are commonly used to control rodent populations and frequently involved in wildlife and domestic animal poisoning. These poisoning cases (especially for ARs) are a challenge for forensic toxicologists, and adequate post-mortem examination and toxicological analyses become essential for a proper diagnosis. Publications describing different analytical methods for AR analysis in biological samples are growing, and a clear compilation of the overall picture is needed to standardize methodologies in future research. This review aims to compile and compare the analytical procedures applied for AR determination in the literature. Using this information, a scoring system was developed for those techniques using liver and blood as matrices, and the techniques were ranked considering different criteria (i.e. sample amount required, recoveries, limits of quantification (LOQs), number of ARs analysed, points of the calibration curve and multi-class methods). This review shows an overview of the main methods used for AR analysis in forensic toxicology and will help to elucidate future directions to improve multi-residue techniques to detect the ARs involved in wildlife lethal poisoning.

Diferencia de género en la autoría de artículos en Archivos de Bronconeumología / Gender Differences in the Authorship of Articles in Archivos de Bronconeumología

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Temporal Persistence of Bromadiolone in Decomposing Bodies of Common Kestrel (Falco tinnunculus).

Bromadiolone is a second generation anticoagulant rodenticide (SGAR) used to control pest rodents worldwide. SGARs are frequently involved in secondary poisoning in rodent predators due to their persistence and toxicity. This study aims to evaluate the persistence of bromadiolone in liver at different stages of carcass decomposition in experimentally-dosed common kestrels (Falco tinnunculus) to understand the possibility of detecting bromadiolone in cases of wildlife poisoning and the potential risk of tertiary poisoning. Twelve individuals were divided into the bromadiolone-dose group (dosed with 55 mg/kg b.w) and the control group. Hepatic bromadiolone concentrations found in each stage of decomposition were: 3000, 2891, 4804, 4245, 8848, and 756 ng/g dry weight at 1-2 h (fresh carcass), 24 h (moderate decomposition), 72 h, 96 h (advanced decomposition), seven days (very advanced decomposition), and 15 days (initial skeletal reduction) after death, respectively. Liver bromadiolone concentrations in carcasses remained relatively stable over the first four days and raised on day 7 of decomposition under the specific conditions of this experiment, presenting a risk of causing tertiary poisoning. However, at the initial skeletal reduction stage, liver bromadiolone concentration declined, which should be considered to interpret toxicological analyses and for proper diagnosis. This experimental study provides for the first time some light to better understand the degradation of SGARs in carcasses in the wild.

Mercury Exposure in Birds Linked to Marine Ecosystems in the Western Mediterranean.

Mercury (Hg), particularly as methylmercury (MeHg), is a nonessential, persistent, and bioaccumulative toxic element with high biomagnification capacity and is considered a threat to marine environments. We evaluated total Hg concentrations in liver, kidney, and brain in 62 individuals of 9 bird species linked to marine ecosystems from western Mediterranean admitted in a Wildlife Rehabilitation Center (WRC) (Alicante, Spain, 2005-2020). Age- and sex-related differences in Hg levels, as well as the cause of admission to the WRC, were also evaluated in certain species. The species studied were: northern gannet (Morus bassanus), European shag (Phalacrocorax aristotelis), great cormorant (Phalacrocorax carbo), osprey (Pandion haliaetus), Balearic shearwater (Puffinus mauretanicus), yellow-legged gull (Larus michahellis), razorbill (Alca torda), common tern (Sterna hirundo), and black-headed gull (Chroicocephalus ridibundus). Concentrations in feathers of 27 individuals, and concentrations in internal tissues in 7 other individuals of 7 different species were also reported but not statistically evaluated due to the limited number of samples. Results suggest that individuals were chronically exposed to Hg through diet. The differences in Hg concentrations among species may be explained by their diet habits. Mercury concentrations strongly correlated between tissues (r = 0.78-0.94, p < 0.001, n = 61-62). Some individuals of certain species (i.e., European shag, northern gannet, and great cormorant) showed Hg concentrations close to or above those described in the literature as causing reproductive alterations in other avian species. Consequently, certain individuals inhabiting western Mediterranean could be at risk of suffering long-term, Hg-related effects. Some of the species evaluated are listed within different categories of threat according to the International Union for Conservation of Nature (IUCN) and are endangered at a national level, so this study will provide valuable information for assessors and authorities in charge of the management of the environment and pollution.

Asma y EPOC en pacientes hospitalizados por COVID-19 / Asthma and COPD in Hospitalized COVID-19 Patients

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Platelet-to-Lymphocyte Ratio and Survival in Malignant Pleural Effusion.

BACKGROUND: Efforts have been made to search for parameters that facilitate the prediction of the 3-month survival for clinical decisions in patients with malignant pleural effusion (MPE). We sought to evaluate whether the platelet-to-lymphocyte ratio (PLR) may be a useful marker of 3-month survival in a series of consecutive patients with MPE. METHODS: A total of 81 patients with MPE were included, 46 (57%) of whom were female. Twenty-six patients (32%) died during the first 3 months according to thoracentesis data. RESULTS: The area under the receiver operating characteristics curve was 0.73 for PLR. Using a cutoff point of 158, patients with higher PLR values experienced higher mortality at 3 months (p = 0.001). CONCLUSIONS: PLR was able to successfully differentiate patients with different survival at 3 months. Outcomes of the PLR (a fast and inexpensive test) could be included among the prognostic factors able to guide the personalized management of MPE.

Asthma prevalence in patients with SARS-CoV-2 infection detected by RT-PCR not requiring hospitalization.

INTRODUCTION: The prevalence of asthma in patients hospitalized with SARS-CoV-2 has been studied and varies widely in the different series. However, the prevalence in SARS-infected patients not requiring hospitalization is not known. The objective of this study was to analyze the presence of asthma in a consecutive series of patients who tested positive in the RT-PCR assay for SARS-CoV-2 and did not require hospital admission. METHODS AND RESULTS: A total of 218 patients (58% of those who tested positive) did not require hospitalization; they had a median age of 45 years (IQR 34-57) and 57% were female. Six patients (2.8%) had a previous diagnosis of asthma. Only one patient developed a mild aggravation of asthma symptoms associated with SARS-CoV-2 infection. CONCLUSIONS: Few patients with asthma were infected by SARS-CoV-2, and this infection was not a significant cause of asthma exacerbation.

Dust and bullets: Stable isotopes and GPS tracking disentangle lead sources for a large avian scavenger.

Lead intoxication is an important threat to human health and a large number of wildlife species. Animals are exposed to several sources of lead highlighting hunting ammunition and lead that is bioavailable in topsoil. Disentangling the role of each in lead exposure is an important conservation issue, particularly for species potentially affected by lead poisoning, such as vultures. The identification of lead sources in vultures and other species has been classically addressed by means of stable-isotope comparisons, but the extremely varied isotope signatures found in ammunition hinders this identification when it overlaps with topsoil signatures. In addition, assumptions related to the exposure of individual vultures to lead sources have been made without knowledge of the actual feeding grounds exploited by the birds. Here, we combine lead concentration analysis in blood, novel stable isotope approaches to assign the origin of the lead and GPS tracking data to investigate the main foraging grounds of two Iberian griffon vulture populations (N = 58) whose foraging ranges differ in terms of topsoil lead concentration and intensity of big game hunting activity. We found that the lead signature in vultures was closer to topsoil than to ammunition, but this similarity decreased significantly in the area with higher big game hunting activity. In addition, attending to the individual home ranges of the tracked birds, models accounting for the intensity of hunting activity better explained the higher blood lead concentration in vultures than topsoil exposure. In spite of that, our finding also show that lead exposure from topsoil is more important than previously thought.