Epigenetic and sex differences in opioid use disorder in chronic pain: A real-world study linked with OPRM1 DNA methylation

Opioid use disorder (OUD) is a multifaceted condition influenced by sex, genetic and environmental factors that could be linked with epigenetic changes. Understanding how these factors interact is crucial to understand and address the development and progression of this disorder. Our aim was to elucidate different potential epigenetic and genetic mechanisms between women and men that correlate with OUD under real-world pain unit conditions. Associations between analgesic response and the DNA methylation level of the opioid mu receptor (OPRM1) gene (CpG sites 1–5 selected in the promoter region) were evaluated in 345 long opioid-treated chronic non cancer pain: cases with OUD (n = 67) and controls (without OUD, n = 278). Cases showed younger ages, low employment status and quality of life, but higher morphine equivalent daily dose and psychotropic use, compared to the controls. The patients with OUD showed a significant decrease in OPRM1 DNA methylation, which correlated with clinical outcomes like pain relief, depression and different adverse events. Significant differences were found at the five CpG sites studied for men, and exclusively in women for CpG site 3, in relation to OUD diagnosis. These findings support the importance of epigenetics and sex as biological variables to be considered toward efficient OUD understanding and therapy developmen

Sex-Differences in Pain and Opioid Use Disorder Management: A Cross-Sectional Real-World Study

Background: It is essential to focus attention on sex-specific factors which are clinically relevant in pain management, especially with regards to opioid use disorder (OUD) risk. The aim of this study was to explore potential sex-differences in chronic non-cancer pain (CNCP) outpatients. (2) Methods: An observational cross-sectional study was conducted under CNCP outpatients with long-term prescribed opioids (n = 806), wherein 137 patients had an OUD diagnosis (cases, 64% females) and 669 did not (controls, 66% females). Socio-demographic, clinical, and pharmacological outcomes were analyzed. (3) Results: Female controls presented an older age and less intensive pain therapy but higher psychotropic prescriptions and emergency department visits compared to male controls. Meanwhile, cases demonstrated a younger age, higher work disability, double morphine equivalent daily dose, and benzodiazepine use compared with controls. Here, female cases showed an 8% greater substance use disorder (OR 2.04 [1.11-3.76]) and 24% lower tramadol use, while male cases presented a 22% higher fentanyl use (OR 2.97 [1.52-5.81]) and reported the highest number of adverse drug reactions (24%, OR 2.40 [1.12-5.16]) compared with controls. (4) Conclusions: An OUD individual risk profile was evidenced with sex-differences to take into consideration to design equal prevention programs

Erectile dysfunction in cardiovascular patients: A prospective study of the eNOS gene T-786C, G894T, and INTRON variable number of the tandem repeat functional interaction

[EN] Background: Cardiovascular disease induces erectile dysfunction modulated by endothelial nitric oxide synthase enzyme and an impaired ejection fraction that restricts penis vascular congestion. However, the mechanisms regulating endothelial dysfunction are not understood. Objectives: Exploring the functional impact of endothelial nitric oxide synthase genetic polymorphisms on erectile dysfunction and drug therapy optimization in high-risk cardiovascular disease patients. Materials and methods: Patients with erectile dysfunction symptoms and candidates for andrology therapy were included (n = 112). Clinical data and endothelial nitric oxide synthase rs1799983 (G894T) and rs2070744 (T-786C), genotyped by fluorescence polarization assays, were registered. The 27-bp variable number of the tandem repeat polymorphism in intron 4 (intron4b/a) was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Association analyses were run with the R-3.2.0 software. Results: A significant association between endothelial nitric oxide synthase 786-TT (p = 0.005) and the aa/ac of intron 4 variable number of the tandem repeat (p = 0.02) with higher erectile dysfunction susceptibility was observed in cardiovascular disease patients (60 +/- 9 years, 66% severe erectile dysfunction, 56% ejection fraction). After 3-months of phosphodiesterase type 5 inhibitors, erectile dysfunction (International Index of Erectile Function, 50 +/- 16 scores, the International Index of Erectile Function-Erectile Function 21 +/- 10 scores, p < 0.001) and sexual quality of life (modified Sexual Life Quality Questionnaire 55 +/- 23 scores, p < 0.001) had significantly improved. The cardiovascular ejection fraction was influenced positively with better sexual quality of life (0.1941), and also in the endothelial nitric oxide synthase G894-T allele (p = 0.076) carriers, which could merit future analyses. Erectile dysfunction was present as the primary clinical manifestation in 62% of cases, with cardiovascular disease occurring concurrently. Only former smokers and obese subjects debuted prior to cardiovascular disease than to erectile dysfunction. Conclusions: Our study provides comprehensive insights into the functional interaction linking endothelial nitric oxide synthase gene polymorphisms, erectile function, and ejection fraction in high-risk cardiovascular disease patients. Future therapeutic strategies could target endothelial nitric oxide synthase activity by including lifestyle changes and epigenetic modulations.Segura, A.; Muriel, J.; Miró Martínez, P.; Agulló, L.; Arrarte, V.; Carracedo-Garnateo, P.; Zandonai, T.... (2024). Erectile dysfunction in cardiovascular patients: A prospective study of the eNOS gene T-786C, G894T, and INTRON variable number of the tandem repeat functional interaction. Andrology. https://doi.org/https://doi.org/10.1111/andr.1367

Viabilidad de una plataforma de e-commerce para la producción ecológica en la Comunidad Valenciana

El sector agrario valenciano, sustentado por empresas familiares con pequeñas producciones y una enorme diversidad de cultivos, representa un gran potencial para la explotación agroecológica. Sin embargo, el acceso a los mercados para los pequeños productores es complicado. En este escenario, se ha considerado la posibilidad de desarrollar una plataforma de venta online para productores ecológicos, que estaría gestionada por el organismo certificador del territorio (CAE-CV). El objetivo es determinar si los actores del mercado, productores y consumidores de productos ecológicos, estarían dispuestos a utilizar este tipo de comercio y establecer cuáles son las características más importantes que debe tener la herramienta. Se realizó una encuesta a consumidores y una entrevista a productores antes del desarrollo de la herramienta (2019). Con los resultados obtenidos se realizó una versión demo de la web, considerando los parámetros aportados por los actores y, finalmente, se evaluó la aceptación de la misma (2020). En los resultados, se observa una aceptación alta, tanto por parte de los consumidores como de los productores, y sobre todo un incremento importante de la intención de compra online por parte de los consumidores entre los períodos considerados, lo que muestra el creciente desarrollo de este tipo de canal

Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study

Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the CYP2D6 phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients (n = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by CYP2D6, μ-opioid receptor (OPRM1), and catechol-O-methyl transferase (COMT) genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity (76 vs. 59 mm, p < 0.01) by improving pain relief (28 vs. 48 mm, p < 0.05), increased quality of life (43 vs. 56 mm p < 0.001), and lowered the incidence of clinically relevant adverse events (3 [1-5] vs. 1 [0-2], p < 0.01) and 42% opioid dose (35 [22-61] vs. 60 [40-80] mg/day, p < 0.05) as opposed to usual prescribing arm. The final health utility score was significantly higher (0.71 [0.58-0.82] vs. 0.51 [0.13-0.67] controls, p < 0.05) by improving sleepiness and depression comorbidity, with a significant reduction of 30-34% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation

Monstres creats pels homes : estudi sobre la traducció i la cultura dels vampirs, homes llop i bruixes

Aquest treball s'ha centrat en l'estudi antropològic i traductològic de personatges folklòrics i ficticis. Primer s'ha realitzat un estudi sobre la influència de la ficció i la realitat sobre aquests personatges, el paper de la traducció i de la censura, i els arquetips literaris. S'ha recercat l'origen i l'evolució tant en la ficció com en la realitat, fent èmfasis en la discriminació de certs grups de persones, com les dones, el col·lectiu LGBT, les persones grans o els practicants de religions no cristianes. S'ha buscat una explicació científica i social a la creença en els vampirs, els homes llop i les bruixes i s'han estudiat els prejudicis relacionats amb aquests éssers, junt amb la influència que hi ha tingut la literatura i el cinema. Seguidament, s'han traduït entrades enciclopèdiques relacionades amb els personatges per acabar de desenvolupar la part teòrica, s'han comentat les dificultats i s'han corregit els errors dels textos originals.Este trabajo se ha centrado en el estudio antropológico y traductológico de personajes folklóricos y ficticios. Primero se ha realizado un estudio sobre la influencia de la ficción y la realidad de estos personajes, el rol de la traducción y de la censura, y los arquetipos literarios. Se ha investigado el origen i la evolución tanto en la ficción como en la realidad, haciendo énfasis en la discriminación de ciertos grupos de personas, como las mujeres, el colectivo LGBT, la gente mayor o los practicantes de religiones no cristianas. Se ha buscado una explicación científica y social a la creencia en los vampiros, los hombres lobo y las brujas, y se han estudiado los prejuicios relacionados con estos seres, junto con la influencia que ha tenido la literatura y el cinema. Seguidamente, se han traducido entradas enciclopédicas relacionadas con los personajes para acabar de desarrollar la parte teórica, se han comentado las dificultades y se han corregido los errores de los textos originales.This project has focused on the anthropological and translational study of folk and fictional characters. First, a study has been carried out on the influence of fiction and reality on these characters, the role of translation and censorship, and literary archetypes. The origin and evolution have been investigated both in fiction and in real life, emphasizing on the discrimination of certain groups of people, such as women, the LGBT community, the elderly, or practitioners of non-Christian religions. I looked for a scientific and social explanation for the belief in vampires, werewolves and witches, and the prejudices related to these beings have been studied, along with the influence that literature and cinema have had. Afterwards, encyclopedic entries related to the characters have been translated to finish developing the theoretical part, difficulties have been commented on and errors in the original texts have been corrected

Familial Mediterranean fever in the pediatric population

Familial Mediterranean fever; Amyloid A; ColchicineFebre mediterrània familiar; Amiloide A; ColchicinaFiebre mediterránea familiar; Amiloide A; ColchicinaFamilial Mediterranean fever (FMF) is the most frequent autoinflammatory disorder characterized by short, repeated, and self-limiting crises of fever and serositis. The disease was described as autosomal recessive hereditary transmission secondary to variants of the MEFV (MEditerranean FeVer) gene, even though a variable proportion of patients only present a heterozygous variant. FMF is very common in certain ethnic groups (Turkish, Armenian, Arab, and Jewish), even though it has been described throughout the Mediterranean and elsewhere in the world. The clinical manifestations are variable, with secondary amyloidosis being the most serious complication of the disorder. Treatment and prophylaxis are mainly based on the administration of colchicine, which prevents the crises and avoids complications in most cases. This study reviews the course of seven pediatric patients diagnosed with FMF during the period 2010-2018 at a district hospital. Most of the patients were of Caucasian origin, with onset at an early age in the form of fever as the main symptom, and some patients moreover presented less frequent manifestations (pericardial effusion, sensorineural hearing loss). Two cases presented plasmatic amyloid A protein elevation that subsided with the treatment. All the patients initially received colchicine, and one of them required prescription of anakinra, which was replaced by canakinumab due to a serious adverse reaction. There were no cases of consanguinity, and all the patients were of Mediterranean origin. The subjects showed a favorable course over the years, which was attributed to the early diagnosis and treatment provided

Confinamiento por Covid-19: ¿cómo ha impactado en el consumo de vino y en las actividades de enoturismo?

La declaración de pandemia mundial por la COVID-19 ha tenido efectos muy negativos en multitud de sectores económicos. El sector de la hostelería y el turismo no ha sido ajeno a esta situación. El consumo moderado de vino se ha considerado saludable, no tanto por los beneficios que reporta su ingesta, sino como factor de socialización. Las actividades de enoturismo tienen esta componente social, ya que conjugan el consumo de vino con una actividad lúdica, teniendo como consecuencia positiva la visita a bodegas, el conocimiento de una DO, el territorio, el paisaje... Sin embargo, la pandemia ha supuesto un cambio de guion en el hábito de consumo de vino y disfrute de actividades enoturísticas ya que estas acciones no se han podido realizar. En el presente trabajo se realizó una encuesta on line a 365 individuos para determinar el cambio de hábitos durante el confinamiento tanto de consumo como de las nuevas actividades enoturísticas propuestas, y si esto ha provocado una intención de consumo distinta para el futuro. El 76% ha realizado algunas de las posibles propuestas on line de enoturismo y a más del 80% les gustaría realizar enoturismo finalizado el confinamiento lo que muestra el creciente interés por dichas actividades

Vertical mass impact and features of Saharan dust intrusions derived from ground-based remote sensing in synergy with airborne in-situ measurements

A study of the vertical mass impact of Saharan dust intrusions is presented in this work. Simultaneous ground-based remote-sensing and airborne in-situ measurements performed during the AMISOC-TNF campaign over the Tenerife area (Canary Islands) in summertime from 01 July to 11 August 2013 were used for that purpose. A particular dusty (DD) case, associated to a progressively arriving dust intrusion lasting for two days on 31 July (weak incidence) and 01 August (strong incidence), is especially investigated. AERONET AOD and AEx values were ranging, respectively, from 0.2 to 1.4 and 0.35 to 0.05 along these two days. Vertical particle size distributions within fine and coarse modes (0.16e2.8 mm range) were obtained from aircraft aerosol spectrometer measurements. Extinction profiles and Lidar Ratio (LR) values were derived from MPLNET/Micro Pulse Lidar observations. MAXDOAS measurements were also used to retrieve the height-resolved aerosol extinction for evaluation purposes in comparison to Lidarderived profiles.This work is supported by the Spanish Ministerio de Economía y Competitividad (MINECO) under grants CGL2011-24891 and CGL2014-55230-R

Algunas reflexiones acerca del proceso de formación en investigación de estudiantes de grado y posgrado

En diversos proyectos dentro del programa de investigación dirigido por la Dra. María Teresa Sirvent en el marco de subsidios UBACYT, venimos trabajando desde hace más de diez años analizando diversas fuentes empíricas que nos han permitido construir categorías didácticas acerca de la formación de investigadores nóveles. Luego, sumamos las tareas del equipo de trabajo conformado por varios docentes de la UNER que nos permitieron enriquecer esas categorías en el marco de una carrera diferente con una propuesta de trabajo final de tesina para la obtención del título de grado. Las cuestiones de una Pedagogía y Didáctica de la investigación han sido y siguen siendo entonces parte de las preocupaciones compartidas por los dos equipos de investigación de UBA y UNER. En esta oportunidad, queremos compartir las reflexiones fruto de diálogos y debates con los compañeros de las cátedras y los tesistas a quienes acompañamos en diversos espacios de grado y posgrado. Una de las características principales del oficio científico es que los aprendizajes de este quehacer se constituyen tanto en el interior como en el exterior de una institución, o sea que es posible observar una cultura de formación de investigadores asociada a estas entidades, un modo de actuar que favorece u obstaculiza estos aprendizajes, y que revela la actitud de una comunidad respecto a la producción de conocimiento y a la formación para el oficio. Estos contextos de enseñanza tienen particularidades que consideramos necesario explicitar. Si bien es posible validar algunas categorías en los diversos espacios porque hay cuestiones comunes que hacen a la formación del investigador, hay aspectos propios del contexto que dan sentido a las interpretaciones que se presentan en este trabajo.Facultad de Humanidades y Ciencias de la Educació