TET enzymes and 5hmC epigenetic mark: new key players in carcinogenesis and progression in gynecological cancers.

DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine (5mC). In general, DNA methylation in cancer is associated with the repression of the expression of tumor suppressor genes (TSG) and the demethylation with the overexpression of oncogenes. DNA methylation was considered a stable modification for a long time, but in 2009, it was reported that DNA methylation is a dynamic modification. The Ten-Eleven-Translocations (TET) enzymes include TET1, TET2, and TET3 and participate in DNA demethylation through the oxidation of 5mC to 5-hydroxymethylcytosine (5hmC). The 5hmC oxidates to 5-formylcytosine (5fC) and 5-carboxylcitosine (5caC), which are replaced by unmodified cytosines via Thymine-DNA Glycosylase (TDG). Several studies have shown that the expression of TET proteins and 5hmC levels are deregulated in gynecological cancers, such as cervical (CC), endometrial (EC), and ovarian (OC) cancers. In addition, the molecular mechanisms involved in this deregulation have been reported, as well as their potential role as biomarkers in these types of cancers. This review shows the state-of-art TET enzymes and the 5hmC epigenetic mark in CC, EC, and OC.

[Translated article] Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Esofagitis eosinofílica de tórpida evolución / Eosinophilic esophagitis with torpid evolution

Introducción: La esofagitis eosinofílica es una enfermedad inmunomediada, crónica y progresiva, combinando disfunción esofágica e infiltrado eosinofílico exclusivo del esófago. Tanto su diagnóstico como su respuesta a los tratamientos requieren de evaluación histológica mediante endoscopias repetidas. Caso clínico. Varón de 11 años con disfagia para sólidos de años de evolución con empeoramiento en los últimos meses; angustia ante las ingestas con estancamiento ponderal; vómitos en impactaciones alimentarias; pirosis postprandial. Antecedentes patológicos: broncoespasmos de repetición y sensibilización a Alternaria. Exploración física: signos de hipotrofia pondero-estatural (somatometría: alrededor de –2 desviaciones estándares; Carrascosa 2017). Pruebas complementarias: analítica general sin alteraciones significativas incluyendo inmunoglobulinas E específicas alimentarias; prick test sensibilización a neumoalérgenos; gastroscopia mucosa esofágica edematosa, estrías longitudinales y exudados blanquecinos, mucosa gástrica signos de gastritis, mucosa duodenal normal; histología con un máximo 35 eosinófilos por campos de gran aumento y gastritis crónica leve-moderada con infección por Helicobacter pylori. Tratamiento y evolución: inducción a la remisión con inhibidores bomba de protones a dosis altas con buena respuesta clínica y macroscópica (parcial histológica), reduciendo a dosis de mantenimiento; ante recaída macroscópica (no histológica) se cambia a dieta exenta de leche y gluten sin respuesta; segundo intento de remisión con inhibidores sin éxito; finalmente se pautan corticoides deglutidos con buena respuesta tanto macroscópica como histológica; pendiente control con dosis de mantenimiento, asintomático. Comentarios. Como se aprecia en nuestro caso, esta enfermedad conlleva un difícil manejo ante la afectación parcheada de la mucosa y la discordancia clínico-histológica, lo que complica la interpretación de sus resultados.(AU)

Introduction: Eosinophilic esophagitis is an immunemediated, chronic and progressive disease, combining esophageal dysfunction and eosinophilic infiltrate exclusive to the esophagus. Both its diagnosis and its response to treatments require histological evaluation through repeated endoscopies. Case report. 11-year-old male with dysphagia for solids of years of evolution with worsening in recent months; anxiety before eating with weight stagnation; vomiting in food impactions; postprandial heartburn. Pathological history: repeated bronchospasms and sensitization to Alternaria. Physical examination: signs of weight-height hypotrophy (somatometry: around –2 standard deviations; Carrascosa 2017). Complementary tests: general blood test without significant alterations including food-specific immunoglobulins E; prick test sensitization to pneumoallergens; gastroscopy edematous esophageal mucosa, longitudinal furrows and whitish exudates, gastric mucosa signs of gastritis, normal duodenal mucosa; histology with a maximum of 35 eosinophils per high-power fields and mild-moderate chronic gastritis with Helicobacter pylori infection. Treatment and evolution: induction of remission with high-dose proton pump inhibitors with good clinical and macroscopic response (partial histological), reducing to maintenance doses; In the event of a macroscopic (non-histological) relapse, a diet free of milk and gluten is started without response; second attempt at remission with inhibitors without success; finally, swallowed corticosteroids are prescribed with good macroscopic and histological response; pending control with maintenance dose, asymptomatic. Discussion. Like our case shows, this disease has a difficult management due to patchy involvement of the mucosa and clinical-histological discordance, which complicates the interpretation of its results.(AU)

Classification of light Yorkshire pigs at different production stages using ordinary least squares and machine learning methods.

Pig homogeneity and growth are major concerns for the pig industry today. Variability in pigs' size has a strong impact on profitability as uniformity plays a key role in the overall economic value of pigs produced. This research focused on statistical methods to identify pigs at risk of growth retardation at different stages of production. Data from 125 083 Yorkshire pigs at weaning (18-28 d), 59 533 pigs at the end of the nursery period (70-82 d) and 48 862 pigs at slaughter (155-170 d) were analyzed under three different cut-points (lowest 10, 20 and 30%) to characterize light animals. Records were randomly split into 2:1 training:testing sets, and each training data set was analyzed through an ordinary least squares approach and four machine learning algorithms (decision tree, random forest, and two alternative boosting approaches). A wide range of weighting functions were applied to give increased relevance to lighter pigs. Each resulting classification norm was used to classify light pigs in the testing data set. Both sensitivity and specificity were retained to construct the receiver operating characteristic curve, and the statistical performance of each analytical approach was evaluated by the area under the curve (AUC). In all production stages and cut-points, the random forest machine learning algorithm provided the highest AUC, closely followed by boosting procedures. For weaning BW (WW), factors related to birth BW and litter size accounted for more than 75% of the important prediction factors for light pigs. BW at the end of the nursery period and slaughter BW analyses revealed a similar pattern where WW and BW at the end of the nursery period accounted for more than 40 and 50% of statistical importance among the prediction factors, respectively. Machine learning algorithms are useful tools to easily evaluate the risk factors affecting the efficiency and homogeneity in swine. Since the BW at birth and weaning are key factors, sow nutrition and feeding management during gestation and lactation, along with piglet management during lactation, are identified as important influences on pig weight variability.

Multiphase diets may improve feed efficiency in fattening crossbreed Holstein bulls: a retrospective simulation of the economic and environmental impact.

Beef industry needs alternative feeding strategies to enhance both economic and environmental sustainability. Among these strategies, adjusting the diet dynamically according to the change of nutritional requirements (multiphase diet) has demonstrated its economic and environmental benefits in pig production systems. Therefore, this retrospective study aims to assess, through simulation, the theoretical economic and environmental benefits of introducing a multiphase diet for crossbreed bulls feeding (one or more diet changes). For this, individual data of BW, BW gain, and daily intake were recorded from 342 bulls during the last fattening period (112 days). These data were used to estimate individual trajectory of energy and protein requirements, which were subsequently divided by individual intake to calculate the required dietary energy and protein concentrations. The area between two functions (i.e., ƒ1: constant protein concentration in the original diet during fattening and ƒ2: estimated protein concentration requirements) was minimised to identify the optimal moments to adjust the dietary concentration of energy and protein. The results indicated that both energy and protein intake exceeded requirements on average (+16% and +28% respectively, P < 0.001), justifying the adoption of a multiphase diet. Modelling the individual trajectories of required metabolisable protein (MP, g/kg DM) during the fattening period resulted in exponential decay model in relation to BW [32120 × exp(-0.026 × BW) + 59.9], while the dietary net energy concentration followed a slightly quadratic model [2.26-0.0026 × BW + 0.000003 × BW2]. Minimisation of the area between curves showed two optimal moments to adjust the diet: at 312 kg and 385 kg of BW, indicating three diet phases: (a) <312 kg, (b) 312-385 kg, and (c) 385-600 kg. For the second and third phases, the dietary energy and protein concentration should be 70 g MP/kg DM and 1.70 Mcal/kg DM and 61 g MP/kg DM and 1.65 Mcal/kg DM, respectively. These diet adjustments might improve economic profitability by 29 €/animal, reduce estimated nitrogen excretions by 16% (P < 0.001), and maintain similar weight gain (P > 0.16) compared to the commercial diet. However, the decrease in dietary energy concentration led to increased fibre concentration, which in turn increased the estimated CH4 emissions of animals with the multiphase diet (+44%, P < 0.001). Hence, multiphase diet could theoretically reduce feeding cost and nitrogen excretion from fattening cattle. Further in vivo studies should confirm these results and find optimal nutritional strategies to improve economic profitability and environmental impact.

Parálisis de sueño durante la siesta como síntoma inicial de narcolepsia / Sleep paralysis during naptime as initial symptom of narcolepsy

Introducción: La narcolepsia es una enfermedad de etiología desconocida, de prevalencia muy baja (el 0,02-0,16% en adultos, aunque debe ser mayor, dado el infradiagnóstico), caracterizada por la presencia de somnolencia diurna excesiva, alucinaciones hipnagógicas y/o hipnopómpicas, parálisis de sueño y/o cataplejía (si está presente, se habla de narcolepsia de tipo 1 y, si no, de narcolepsia de tipo 2), cuya media de retraso diagnóstico se sitúa entre los 10 y los 15 años. Caso clínico: Varón de 16 años que consulta tras visitar a distintos especialistas por presentar parálisis de sueño durante las siestas, que le producen miedo y ocasional caída de objetos de las manos (diagnosticadas como posibles mioclonías). En la anamnesis nos sorprendió la presencia de parálisis de sueño inmediatamente tras el inicio de las siestas y, en la anamnesis dirigida, esos movimientos bruscos provocados por emociones eran compatibles con cataplejías, por lo que realizamos un estudio polisomnográfico nocturno y un test de latencias múltiples del sueño. Con la evolución aparecieron alucinaciones hipnopómpicas y sueño fragmentado nocturno, así como ocasional somnolencia diurna (se completó así la tétrada sintomatológica típica de la narcolepsia con cataplejía de tipo 1). Conclusión: Es importante el conocimiento de esta enfermedad, plantearla como diagnóstico diferencial en pacientes con episodios de somnolencia incoercible, realizar la derivación a consultas especializadas en trastornos de sueño y una buena anamnesis dirigida, e indicar las pruebas complementarias necesarias para el diagnóstico de esta enfermedad infradiagnosticada para su correcto manejo, tan determinante para la mejora de la calidad de vida de estos pacientes.(AU)

Introduction: Narcolepsy is a disease of unknown etiology, with a very low prevalence (0.02-0.16% in adults, although it must be higher, given the underdiagnosis), characterized by the presence of excessive daytime sleepiness, hypnagogic and/or hypnopompic hallucinations, sleep paralysis and/or cataplexy (if present, we speak of type 1 narcolepsy and, if not, type 2 narcolepsy), whose average diagnostic delay is between 10 and 15 years. Case report: A 16-year-old male who consulted after visiting different specialists for presenting sleep paralysis during naps, which cause him fear and occasional objects falling from his hands (diagnosed as possible myoclonus). In the anamnesis we were surprised by the presence of sleep paralysis immediately after the start of the naps and, in the directed anamnesis, these sudden movements caused by emotions were compatible with cataplexies, so we performed a nocturnal polysomnographic study and a multiple sleep latency test. With evolution came hypnopompic hallucinations and fragmented nocturnal sleep, as well as occasional daytime sleepiness (thus completing the typical symptomatic tetrad of type 1 narcolepsy with cataplexy). Conclusion: Knowledge of this disease is important, considering it as a differential diagnosis in patients with episodes of intractable sleepiness, send these patients to expert doctors in sleep disorders and doing a good anamnesis, performing the necessary complementary tests for the diagnosis of this underdiagnosed disease for its correct management, which is decisive for improving the quality of life of these patients.(AU)

Comparative analysis of signalling pathways in tissue protein metabolism in efficient and non-efficient beef cattle: acute response to an identical single meal size.

Protein turnover has been associated to residual feed intake (RFI) in beef cattle. However, this relationship may be confounded by feeding level and affected by the composition of the diet being fed. Our aim was to assess postmortem the protein metabolism signalling pathways in skeletal muscle and liver of 32 Charolais young bulls with extreme RFI phenotypes. Bulls were fed two contrasting diets during the whole fattening period but were subjected to a similar and single nutritional stimulus, induced by their respective concentrate, just prior to slaughter. The key targets were protein degradation (autophagy and ubiquitin) and synthesis signalling pathways through western-blot analysis, as well as hepatic transaminase activity. To ensure a precise assessment of all animals at the same postprandial time, they were provided with a test meal (2.5 kg of either a high-starch and high-protein concentrate or high-fibre and low-protein concentrate) 3 hours prior to slaughter, irrespective of their RFI grouping. Blood and tissues were sampled at the slaughterhouse (3 h and 3 h30 postprandially, respectively). In response to an identical single meal size, efficient RFI animals showed higher (P < 0.05) postprandial plasma ß-hydroxybutyrate concentrations and insulinemia (only with the high-starch concentrate) than non-efficient animals. Moreover, efficient RFI bulls had lower muscle (P = 0.04) and liver (P = 0.08) ubiquitin protein abundance (degradation pathway) and tended to have lower alanine transaminase activity in the liver (P = 0.06) compared to non-efficient bulls, regardless of diet. A positive correlation between protein degradation potential and amino acid catabolism was identified in this study (r = 0.52, P = 0.004), which was interpreted as being biologically linked to the RFI phenotype. Efficient RFI bulls also had a faster potential for protein synthesis in the muscle, as indicated by their greater ratio of phosphorylated to total form of ribosomal protein S6 kinase (P = 0.05), regardless of diet. Results on protein synthesis pathway in muscle and plasma metabolite concentrations suggested that efficient RFI cattle may have a faster nutrient absorption and insulin responsiveness after feeding than inefficient cattle. We did not find significant differences in hepatic protein synthesis pathways between the two RFI groups (P > 0.05). Our findings suggest that, in response to an identical single meal size, efficient RFI animals exhibited lower activation of tissue protein degradation pathways and faster muscle protein synthesis activation compared to their inefficient counterparts. This pattern was observed regardless of the composition of the tested meals.

Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study. / Condicionantes de acceso a nuevos medicamentos dermatológicos en España: resultados del proyecto EQUIDAD.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Isavuconazole-tacrolimus drug-drug interactions in HSCT patients.

OBJECTIVES: Because tacrolimus has a narrow therapeutic window and exhibits both intraindividual and interindividual variability, we attempted to establish the percentage of calcineurin inhibitor (CNI) dose reduction to prevent toxicity and ensure stem cell engraftment when using this immunosuppressant with the antifungal isavuconazole (ISA). By calculating the tacrolimus concentration/dose (C/D) ratio, we expected to demonstrate the magnitude of change in the C/D ratio from baseline after ISA administration. METHODS: We evaluated the interaction between ISA, a new triazole antifungal used in prophylaxis for invasive fungal infections, and the CNI class of immunosuppressive drugs, specifically tacrolimus, in 11 blood samples from HSCT recipients. RESULTS: The mean tacrolimus C/D ratio increased 1.44-fold from baseline 48 h after ISA administration (P = 0.001). CONCLUSIONS: Although further investigation is needed, the results of this study suggest that a reduction of 18% in tacrolimus may be recommended.

Androgen deprivation therapy in localized prostate cancer. Current status and future trends.

INTRODUCTION: Prostate cancer (PCa) has been recognized as an androgen-sensitive disease since the investigations from Huggins and Hodges in 1941. Thanks to these findings, they received the Nobel Prize in 1966. This was the beginning of the development of androgen deprivation therapy (ADT) as treatment for patients with PCa. OBJECTIVE: To summarize the current indications of ADT in localized PCa. EVIDENCE ACQUISITION: We conducted a comprehensive English and Spanish language literature research, focused on the main indications for ADT in localized PCa. EVIDENCE SYNTHESIS: Nowadays, the indications for ADT as monotherapy in localized PCa have been limited to specific situations, to patients unwilling or unable to receive any form of local treatment if they have a PSA-DT < 12 months, and either a PSA > 50 ng/mL, a poorly differentiated tumor, or troublesome local disease-related symptoms. ADT can be used in combination with local treatment in different scenarios. Although neoadjuvant treatment with ADT prior to surgery with curative intent has no clear oncological impact, as a future sight, PCa is a heterogeneous disease, and there could be a group of patients with high-risk localized disease that could benefit. CONCLUSIONS: We need to optimize the treatment with ADT in localized PCa, selecting the patients accordingly to their disease characteristics. Given that the therapeutic armamentarium evolves day by day, there is a need for the development of new clinical trials, as well as a molecular studies of patients to identify those who might benefit from an early multimodal treatment.

Terapia de privación de andrógenos en el cáncer de próstata localizado. Situación actual y tendencias futuras / Androgen deprivation therapy in localized prostate cancer. Current status and future trends

Introducción El cáncer de próstata (CaP) se ha reconocido como una enfermedad sensible a los andrógenos desde las investigaciones de Huggins y Hodges en 1941, quienes, gracias a estos hallazgos, recibieron el Premio Nobel en 1966. Aquí se originó el desarrollo de la terapia de privación de andrógenos (TPA) como tratamiento para los pacientes con CaP. Objetivo Resumir las indicaciones actuales de la TPA en el CaP localizado. Adquisición de la evidencia Hemos realizado una investigación bibliográfica exhaustiva en inglés y español, centrada en las principales indicaciones de la TPA en el CaP localizado. Síntesis de la evidencia En la actualidad, las indicaciones de la TPA como monoterapia en el CaP localizado se han limitado a situaciones específicas, a pacientes que no desean o no pueden recibir ninguna forma de tratamiento local y que tienen un PSA-DT<12 meses y un PSA>50 ng/mL, un tumor poco diferenciado o síntomas locales molestos relacionados con la enfermedad. La TPA puede utilizarse en combinación con tratamiento local en diferentes escenarios. Aunque el tratamiento neoadyuvante con TPA antes de la cirugía con intención curativa no tiene un impacto oncológico claro, el CaP es una enfermedad heterogénea y en el futuro podría haber un grupo de pacientes con enfermedad localizada de alto riesgo que se beneficiaran de este tratamiento. Conclusiones Necesitamos optimizar el tratamiento con TPA en el CaP localizado, seleccionando a los pacientes en función de las características de su enfermedad. Dado que el arsenal terapéutico evoluciona día a día, es necesario el desarrollo de nuevos ensayos clínicos, así como el estudio molecular en los pacientes, para identificar a aquellos que podrían beneficiarse de un tratamiento multimodal temprano (AU)

Introduction Prostate cancer (PCa) has been recognized as an androgen-sensitive disease since the investigations from Huggins and Hodges in 1941. Thanks to these findings, they received the Nobel Prize in 1966. This was the beginning of the development of androgen deprivation therapy (ADT) as treatment for patients with PCa. Objective To summarize the current indications of ADT in localized PCa. Evidence acquisition We conducted a comprehensive English and Spanish language literature research, focused on the main indications for ADT in localized PCa. Evidence synthesis Nowadays, the indications for ADT as monotherapy in localized PCa have been limited to specific situations, to patients unwilling or unable to receive any form of local treatment if they have a PSA-DT<12 months, and either a PSA>50 ng/mL, a poorly differentiated tumor, or troublesome local disease-related symptoms. ADT can be used in combination with local treatment in different scenarios. Although neoadjuvant treatment with ADT prior to surgery with curative intent has no clear oncological impact, as a future sight, PCa is a heterogeneous disease, and there could be a group of patients with high-risk localized disease that could benefit. Conclusions We need to optimize the treatment with ADT in localized PCa, selecting the patients accordingly to their disease characteristics. Given that the therapeutic armamentarium evolves day by day, there is a need for the development of new clinical trials, as well as a molecular studies of patients to identify those who might benefit from an early multimodal treatment (AU)

Pneumonitis After Concurrent Chemoradiation and Immune Checkpoint Inhibition in Patients with Locally Advanced Non-small Cell Lung Cancer.

AIMS: Pneumonitis is a common and potentially deadly complication of combined chemoradiation and immune checkpoint inhibition (CRT-ICI) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). In this study we sought to identify the risk factors for pneumonitis with CRT-ICI therapy in LA-NSCLC cases and determine its impact on survival. MATERIALS AND METHODS: We conducted a retrospective chart review of 140 patients with LA-NSCLC who underwent curative-intent CRT-ICI with durvalumab between 2018 and 2021. Pneumonitis was diagnosed by a multidisciplinary team of clinical experts. We used multivariable cause-specific hazard models to identify risk factors associated with grade ≥2 pneumonitis. We constructed multivariable Cox proportional hazard models to investigate the impact of pneumonitis on all-cause mortality. RESULTS: The median age of the cohort was 67 years; most patients were current or former smokers (86%). The cumulative incidence of grade ≥2 pneumonitis was 23%. Among survivors, 25/28 patients had persistent parenchymal scarring. In multivariable analyses, the mean lung dose (hazard ratio 1.14 per Gy, 95% confidence interval 1.03-1.25) and interstitial lung disease (hazard ratio 3.8, 95% confidence interval 1.3-11.0) increased the risk for pneumonitis. In adjusted models, grade ≥2 pneumonitis (hazard ratio 2.5, 95% confidence interval 1.0-6.2, P = 0.049) and high-grade (≥3) pneumonitis (hazard ratio 8.3, 95% confidence interval 3.0-23.0, P < 0.001) were associated with higher all-cause mortality. CONCLUSIONS: Risk factors for pneumonitis in LA-NSCLC patients undergoing CRT-ICI include the mean radiation dose to the lung and pre-treatment interstitial lung disease. Although most cases are not fatal, pneumonitis in this setting is associated with markedly increased mortality.

[Sleep paralysis during naptime as initial symptom of narcolepsy]. / Parálisis de sueño durante la siesta como síntoma inicial de narcolepsia.

INTRODUCTION: Narcolepsy is a disease of unknown etiology, with a very low prevalence (0.02-0.16% in adults, although it must be higher, given the underdiagnosis), characterized by the presence of excessive daytime sleepiness, hypnagogic and/or hypnopompic hallucinations, sleep paralysis and/or cataplexy (if present, we speak of type 1 narcolepsy and, if not, type 2 narcolepsy), whose average diagnostic delay is between 10 and 15 years. CASE REPORT: A 16-year-old male who consulted after visiting different specialists for presenting sleep paralysis during naps, which cause him fear and occasional objects falling from his hands (diagnosed as possible myoclonus). In the anamnesis we were surprised by the presence of sleep paralysis immediately after the start of the naps and, in the directed anamnesis, these sudden movements caused by emotions were compatible with cataplexies, so we performed a nocturnal polysomnographic study and a multiple sleep latency test. With evolution came hypnopompic hallucinations and fragmented nocturnal sleep, as well as occasional daytime sleepiness (thus completing the typical symptomatic tetrad of type 1 narcolepsy with cataplexy). CONCLUSION: Knowledge of this disease is important, considering it as a differential diagnosis in patients with episodes of intractable sleepiness, send these patients to expert doctors in sleep disorders and doing a good anamnesis, performing the necessary complementary tests for the diagnosis of this underdiagnosed disease for its correct management, which is decisive for improving the quality of life of these patients.

TITLE: Parálisis de sueño durante la siesta como síntoma inicial de narcolepsia.Introducción. La narcolepsia es una enfermedad de etiología desconocida, de prevalencia muy baja (el 0,02-0,16% en adultos, aunque debe ser mayor, dado el infradiagnóstico), caracterizada por la presencia de somnolencia diurna excesiva, alucinaciones hipnagógicas y/o hipnopómpicas, parálisis de sueño y/o cataplejía (si está presente, se habla de narcolepsia de tipo 1 y, si no, de narcolepsia de tipo 2), cuya media de retraso diagnóstico se sitúa entre los 10 y los 15 años. Caso clínico. Varón de 16 años que consulta tras visitar a distintos especialistas por presentar parálisis de sueño durante las siestas, que le producen miedo y ocasional caída de objetos de las manos (diagnosticadas como posibles mioclonías). En la anamnesis nos sorprendió la presencia de parálisis de sueño inmediatamente tras el inicio de las siestas y, en la anamnesis dirigida, esos movimientos bruscos provocados por emociones eran compatibles con cataplejías, por lo que realizamos un estudio polisomnográfico nocturno y un test de latencias múltiples del sueño. Con la evolución aparecieron alucinaciones hipnopómpicas y sueño fragmentado nocturno, así como ocasional somnolencia diurna (se completó así la tétrada sintomatológica típica de la narcolepsia con cataplejía de tipo 1). Conclusión. Es importante el conocimiento de esta enfermedad, plantearla como diagnóstico diferencial en pacientes con episodios de somnolencia incoercible, realizar la derivación a consultas especializadas en trastornos de sueño y una buena anamnesis dirigida, e indicar las pruebas complementarias necesarias para el diagnóstico de esta enfermedad infradiagnosticada para su correcto manejo, tan determinante para la mejora de la calidad de vida de estos pacientes.

Farming Sparus aurata (Teleostei: Sparidae) in marsh ponds: trophic characterization and trace metal accumulation.

Considering the overexploitation of fishing on most of the world coasts, the ingestion of fish and shellfish will depend mostly on aquaculture production. Since intensive mariculture usually involves environmental impact, developing sustainable cultures is a priority. In this sense, salt marshes can provide ecosystem services and incorporate both conservation and extensive aquaculture activities. In the present study we compared gilthead seabream Sparus aurata Linnaeus, 1758 cultured in extensive and semi-intensive marsh ponds with wild conspecifics from surrounding coastal areas, using trophic characterization (diet analysis and stable isotopes) and trace metal accumulation. Stomach content analysis revealed different feeding habits among gilthead seabream from different origin. Although wild specimens had the most diverse diet, results of stable isotopes showed that extensive diet had the wider isotopic niche and revealed the highest similarities between wild and extensively cultured gilthead seabream. A similar trace element signature was also measured in wild and extensive culture, whereas the semi-intensive culture showed different concentrations for several elements. Cr, Fe and Mn showed the highest concentrations in semi-intensive cultured fish, while As and Zn showed the lowest values in this group. In any case, average values measured in both extensive and semi-intensive culture were, in general terms, below the hazardous limits provided by the standards recommended for trace metals by national and international regulations. Therefore, marsh ponds provide a suitable environment where the cultured fish, especially extensive, should be promoted.