Adicción a cannabis: bases neurobiológicas y consecuencias médicas

La adicción a los preparados de cannabis sativa es un problema relevante en nuestra sociedad, con especial importancia durante la adolescencia. Su fácil disponibilidad y los episodios adversos asociados a su abuso y/o dependencia han incrementado la demanda de tratamiento derivada por su consumo. En los últimos 20 años se ha podido avanzar mucho sobre la farmacología del cannabis y de sus principios activos, moléculas grasas que actúan a través de un sistema de señalización endógeno denominado sistema endocannabinoide implicado en el desarrollo y la plasticidad cerebrales. Su estimulación crónica puede inducir no sólo dependencia y adicción, sino también derivar en consecuencias neurobiológicas que tienen repercusión clínica. Así, por un lado se puede encontrar el incremento de trastornos mentales tanto primarios como inducidos (trastornos del estado de ánimo, trastornos de ansiedad y trastornos psicóticos) y por el otro, alteraciones en los procesos cognitivos (memoria, atención, toma de decisiones, asunción de riesgos, control de impulsos). Estas consecuencias son más graves si el consumo se realiza en la adolescencia. Algunos de estos efectos son permanentes y el conocimiento de los mismos necesario para una correcta atención sanitaria.Addiction to products derived from the plant cannabis sativa has become a relevant problem in western societies. Its prevalence in both teenagers and young adults has grown in the last decade. The problem is aggravated by the availability of plant derivatives with a high THC content. Today, the number of cannabis users requesting medical treatment is growing, as well as the incidence and variety of the adverse effects associated with its chronic consumption. On the other hand, the last 20 years' research have revealed the hidden pharmacology of the active principles of cannabis. Cannabinoids, the psychoactive chemicals of the plant, exert their pharmacological actions through their interaction with an endogenous signaling system, the endocannabinoid system. This system is involved in brain development, plasticity and repair, and its chronic stimulation can induce not only dependence/addiction, but also result in adverse clinical effects. The negative side of cannabis use has greatest impact in the adolescent period. The main adverse effects of chronic cannabis use include the increase in the incidence of mental disorders (mainly psychosis), as well as alterations in cognitive processes including memory, attention, decision-making, risk behaviors as well as impulsivity. Some of these effects are permanent and information and research on their nature is greatly needed in order to achieve a correct public health approach to cannabis use

Evaluación de la adquisición de competencias en sistema cardiovascular en Medicina: autopercepción, asistencia a clase y rendimiento académico.

The acquisition of competencies is essential in clinically relevant areas such as cardiovascular pathology. This study aims to assess the acquisition of the main competencies regarding the cardiovascular system by medical students, as well as their self-perception, and the relation with regular lecture attendance and academic performance. In order to achieve this aim, data were remotely obtained from 142 students in the fourth, fifth and sixth year of Medicine Degree at University of Málaga using an author-made questionnaire (0-15 points) with multiple-choice questions based on clinical situations and a self-evaluation survey about competencies. Analyzing the results, the competencies that were considered as acquired by the largest and the lowest number of students were, respectively, the handling of cardiovascular risk factors (100%) and cardiopulmonary auscultation (38.3%), respectively. Better results were obtained by students who regularly attended lectures (11.28±1.84 vs 9.54±2.45; p<0.01). In addition, it was demonstrated that self-perception (odds ratio [OR]=1.26; 95% confidence interval [95%CI]=1.07-1.50), lecture attendance (OR=3.55; 95%CI=1.64-7.70) and better academic performance (OR=2.6; 95%CI=1.46-4.63) were predictors of high scores in the questionnaire (≥11 points). In conclusion, lecture attendance seems to be fundamental in learning. In addition, self-perception could be used as a tool to guide teaching. On the other hand, it is detected an insufficient development of eminently practical competencies as well as the importance of interrelating knowledge, since a better general academic performance during degree is also reflected in the speciality studied in this research.  La adquisición de competencias resulta fundamental en ámbitos tan relevantes clínicamente como la patología cardiovascular. Este estudio pretende valorar la adquisición por parte de estudiantes de Medicina de las principales competencias respecto al sistema cardiovascular, así como su autopercepción y la relación con la asistencia presencial y el rendimiento académico. Para lograr este objetivo, se analizaron los datos obtenidos mediante la cumplimentación telemática por parte de 142 estudiantes de cuarto, quinto y sexto curso del Grado en Medicina de la Universidad de Málaga de un cuestionario de elaboración propia (0-15 puntos) con preguntas de elección múltiple basadas en situaciones clínicas y una autoevaluación sobre competencias. Analizando los resultados, las competencias consideradas como adquiridas por un mayor y menor número de estudiantes fueron, respectivamente, el manejo de los factores de riesgo cardiovascular (100%) y la auscultación cardiopulmonar (38,3%). Se obtuvieron mejores resultados en estudiantes que asistieron a clase (11,28±1,84 vs 9,54±2,45; p<0,01). Además, se demostró que la autopercepción de un correcto aprendizaje (odds ratio [OR]=1,26, intervalo de confianza al 95% [IC95%]=1,07-1,50), la asistencia a clase (OR=3,55; IC95%=1,64-7,7) y la nota media del expediente (OR=2,6; IC95%=1,46-4,63) son variables predictoras de calificaciones altas en el cuestionario (≥11 puntos). Esto nos permite inferir que la asistencia a clase se antoja fundamental en el aprendizaje. Además, la autopercepción podría utilizarse como herramienta para guiar la docencia. Por otro lado, se sugiere un insuficiente desarrollo de las competencias eminentemente prácticas, así como la importancia de interrelacionar conocimientos, pues un mejor rendimiento académico general durante el grado se refleja también en la especialidad estudiada en este trabaj

Embryology of the abnormally high origin of a coronary artery (High Take-Off) in a mouse model.

High take-off (HTO) is a rare congenital coronary artery anomaly associated with sudden cardiac death. The coronary ostium is located in the ascending aorta above the sinotubular junction. The morphogenetic defect leading to HTO is currently unknown. Our group has shown occurrence of HTO in different strains of laboratory mice, including C57Bl/6 strain with 58% incidence of HTO and Balb/c strain with null incidence. Our aim is to investigate the aetiology of HTO, using C57BL/6 and Balb/c mice strains as experimental models. The process of coronariogenesis was examined in E13.5 and E14.5 mouse embryos of C57Bl/6 (n=27) and Balb/c (n=23) strains. We used histochemistry and immunohistochemistry with specific markers for the vascular plexuses involved in the formation of coronary arteries (PROX1 and ERG 1/2/3). In the mouse embryo, coronary ostia develop at approximately stage E14.5. The location of the ostia is determined by the confluence of two vascular plexuses. The transient lymphatic subepicardial aortic plexus migrates from the pharyngeal region, invading the subepicardial space of the intrapericardial thoracic arteries at around E13.5. The primary or ventricular plexus, which constitutes the future coronary vascular network, forms in situ, reaching the embryonic cardiac outflow tract at around E14. Eighteen of the 27 (66.7%) C57Bl/6 embryos showed an exacerbated subepicardial aortic plexus compared to the 23 Balb/c embryos, in which the subepicardial aortic plexus exhibited a normal size. These results suggest that the embryonic origin of HTO could be due to a defect in the growth of the subepicardial aortic plexus, resulting in an exacerbated vessel network. This overgrowth seems to alter the invasion and connection of the primary plexus to the aortic root for the establishment of the ostia and coronary trunks. From a biomedical viewpoint, it would be of great interest to investigate the molecular mechanisms underlying the overgrowth of the aortic plexus.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech; PI-0530-2019 (Consejería de Salud y Familias, Junta de Andalucía); UMA20-FEDERJA-041 (Junta de Andalucía y Fondos FEDER); PROYEXCEL_01009 (PAIDI, Junta de Andalucía); PRE2018-083176 (Ministerio de Ciencia, Innovación y Universidades), CONT-FIMABIS-0610/2023 (Junta de Andalucía)

Experimental evidence of the genetic hypothesis on the etiology of bicuspid aortic valve aortopathy in the hamster model.

Bicuspid aortopathy occurs in approximately 50% of patients with bicuspid aortic valve (BAV), the most prevalent congenital cardiac malformation. Although different molecular players and etiological factors (genetic and hemodynamic) have been suggested to be involved in aortopathy predisposition and progression, clear etiophysiopathological mechanisms of disease are still missing. The isogenic (genetically uniform) hamster (T) strain shows 40% incidence of BAV, but aortic dilatations have not been detected in this model. We have performed comparative anatomical, histological and molecular analyses of the ascending aorta of animals with tricuspid aortic valve (TAV) and BAV from the T strain (TTAV and TBAV, respectively) and with TAV from a control strain (HTAV). Aortic diameter, smooth muscle apoptosis, elastic waviness, and Tgf-β and Fbn-2 expression were significantly increased in T strain animals, regardless of the valve morphology. Strain and aortic valve morphology did not affect Mmp-9 expression, whereas Mmp-2 transcripts were reduced in BAV animals. eNOS protein amount decreased in both TBAV and TTAV compared to HTAV animals. Thus, histomorphological and molecular alterations of the ascending aorta appear in a genetically uniform spontaneous hamster model irrespective of the aortic valve morphology. This is a direct experimental evidence supporting the genetic association between BAV and aortic dilatation. This model may represent a population of patients with predisposition to BAV aortopathy, in which increased expression of Tgf-β and Fbn-2 alters elastic lamellae structure and induces cell apoptosis mediated by eNOS. Patients either with TAV or BAV with the same genetic defect may show the same risk to develop bicuspid aortopathy.This work was supported by Consejería de Salud y Familias, Junta de Andalucía (PI-0530-2019), Consejería de Economía y Conocimiento, Junta de Andalucía (UMA20-FEDERJA-041), Ministerio de Ciencia e Innovación (grants CGL2017-85090- P and PT20/00101, fellowship PRE2018-083176 to MS-N), and FEDER funds.S

Antipsychotic Medication Influences the Discriminative Value of Acylethanolamides as Biomarkers of Substance Use Disorder.

Plasma acylethanolamides (NAEs), including the endocannabinoid anandamide (AEA), have been proposed as circulating biomarkers of substance use disorders. However, the concentration of these lipid transmitters might be influenced by the use of drugs prescribed for either the treatment of addiction or the associated psychiatric co-morbidities such as psychosis. As an example, neuroleptics, used for attenuation of psychotic symptoms and sedation, might theoretically interfere with the monoamine-mediated production of NAEs, obstructing the interpretation of plasma NAEs as clinical biomarkers. To solve the lack of information on the impact of neuroleptics on the concentration of NAEs, we evaluated the concentrations of NAEs in a control group and compared them to those present in (a) substance use disorders (SUD) patients that are not prescribed with neuroleptics, and (b) SUD patients (both alcohol use disorder and cocaine use disorder patients) using neuroleptics. The results demonstrate that SUD patients exhibited greater concentrations of NAEs than the control population, affecting all species with the exception of stearoylethanolamide (SEA) and palmitoleoylethanolamide (POEA). Neuroleptic treatment enhanced the concentrations of NAEs, especially those of AEA, linoleoylethanolamide (LEA), and oleoylethanolamide (OEA). This effect of neuroleptic treatment was observed independently of the drug addiction that motivated the demand for treatment (either alcohol or cocaine). This study remarks the need to control the current use of psychotropic medication as a potential confounding variable when considering the use of NAEs as biomarkers in SUDPartial funding for open access charge: Universidad de Málag

Postural orthostatic tachycardia syndrome and other related dysautonomic disorders after SARS-CoV-2 infection and after COVID-19 messenger RNA vaccination

The COVID-19 pandemic has caused a challenge for our society due to the post-acute sequelae of the disease. Persistent symptoms and long-term multiorgan complications, known as post-acute COVID-19 syndrome, can occur beyond 4 weeks from the onset of the COVID-19 infection. Postural orthostatic tachycardia syndrome (POTS) is considered a variety of dysautonomia, which is characterized by chronic symptoms that occur with standing and a sustained increase in heart rate, without orthostatic hypotension. POTS can lead to debilitating symptoms, significant disability, and impaired quality of life. In this narrative review, the etiopathogenic basis, epidemiology, clinical manifestations, diagnosis, treatment, prognosis, and socioeconomic impact of POTS, as well as other related dysautonomic disorders, after COVID-19 infection and SARS-CoV-2 postvaccination, were discussed. After a search conducted in March 2023, a total of 89 relevant articles were selected from the PubMed, Google Scholar, and Web of Science databases. The review highlights the importance of recognizing and managing POTS after COVID-19 infection and vaccination, and the approach to autonomic disorders should be known by all specialists in different medical areas. The diagnosis of POTS requires a comprehensive clinical assessment, including a detailed medical history, physical examination, orthostatic vital signs, and autonomic function tests. The treatment of POTS after COVID-19 infection or vaccination is mainly focused on lifestyle modifications, such as increased fluid and salt intake, exercise, and graduated compression stockings. Pharmacotherapy, such as beta-blockers, fludrocortisone, midodrine, and ivabradine, may also be used in selected cases. Further research is needed to understand the underlying mechanisms, risk factors, and optimal treatment strategies for this complication

Beneficial effects of essential oils from the mediterranean diet on gut microbiota and their metabolites in ischemic heart disease and type-2 diabetes mellitus

[Abstract] Ischemic heart disease (IHD) and type-2 diabetes mellitus (T2DM) remain major health problems worldwide and commonly coexist in individuals. Gut microbial metabolites, such as trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), have been linked to cardiovascular and metabolic diseases. Previous studies have reported dysbiosis in the gut microbiota of these patients and the prebiotic effects of some components of the Mediterranean diet. Essential oil emulsions of savory (Satureja hortensis), parsley (Petroselinum crispum) and rosemary (Rosmarinus officinalis) were assessed as nutraceuticals and prebiotics in IHD and T2DM. Humanized mice harboring gut microbiota derived from that of patients with IHD and T2DM were supplemented with L-carnitine and orally treated with essential oil emulsions for 40 days. We assessed the effects on gut microbiota composition and abundance, microbial metabolites and plasma markers of cardiovascular disease, inflammation and oxidative stress. Our results showed that essential oil emulsions in mice supplemented with L-carnitine have prebiotic effects on beneficial commensal bacteria, mainly Lactobacillus genus. There was a decrease in plasma TMAO and an increase in fecal SCFAs levels in mice treated with parsley and rosemary essential oils. Thrombomodulin levels were increased in mice treated with savory and parsley essential oils. While mice treated with parsley and rosemary essential oils showed a decrease in plasma cytokines (INFɣ, TNFα, IL-12p70 and IL-22); savory essential oil was associated with increased levels of chemokines (CXCL1, CCL2 and CCL11). Finally, there was a decrease in protein carbonyls and pentosidine according to the essential oil emulsion. These results suggest that changes in the gut microbiota induced by essential oils of parsley, savory and rosemary as prebiotics could differentially regulate cardiovascular and metabolic factors, which highlights the potential of these nutraceuticals for reducing IHD risk in patients affected by T2DM.Junta de Andalucía; PI-0170-2018Instituto de Salud Carlos III; PT20/00101Junta de Andalucía; RH-0078-2021Instituto de Salud Carlos III; CPII19/00022Instituto de Salud Carlos III; FI20/0022

Associations of hypomagnesemia in patients seeking a first treatment of alcohol use disorder

Introduction: Hypomagnesemia (hypoMg) has not yet been extensively studied in alcohol use disorder (AUD) . We hypothesize that chronic, excessive alcohol consumption favors oxidative stress and pro-inflammatory alterations that may be exacerbated by hypoMg. The objective of this study was to analyze the prevalence and associations of hypoMg in AUD.Patients and Methods: Cross-sectional study in patients admitted for a first treatment of AUD in six tertiary centers between 2013 and 2020. Socio-demographic, alcohol use characteristics, and blood parameters were ascertained at admission.Results: 753 patients (71% men) were eligible; age at admission was 48 years [IQR, 41-56 years]. Prevalence of hypoMg was 11.2%, higher than that observed for hypocalcemia (9.3%), hyponatremia (5.6%), and hypokalemia (2.8%). HypoMg was associated with older age, longer duration of AUD, anemia, higher erythrocyte sedimen-tation rate, gamma-glutamyl transpeptidase, glucose levels, advanced liver fibrosis (FIB-4 >= 3.25) and estimated glomerular filtration rate (eGFR) < 60 mL/min. In multivariate analysis, advanced liver fibrosis (OR, 8.91; 95% CI, 3.3-23.9) and eGFR < 60 mL (OR, 5.2; 95% CI, 1.0-26.2) were the only factors associated with hypoMg.Conclusions: Mg deficiency in AUD is associated with liver damage and glomerular dysfunction suggesting that both comorbidities should be assessed in the course of serum hypoMg

Assessment of the acquisition of competencies incardiovascular system in Medicine: self-perception, lectureattendance and academic performance

La adquisición de competencias resulta fundamental en ámbitos tan relevantes clínicamente como la patología cardiovascular. Este estudio pretende valorar la adquisición por parte de estudiantes de Medicina de las principales competencias respecto al sistema cardiovascular, así como su autopercepción y la relación con la asistencia presencial y el rendimiento implantación telemática por parte de 142 estudiantes de cuarto, quinto y sexto curso delGrado en Medicina de la Universidad de Málaga de un cuestionario de elaboración propia (0-15puntos) con preguntas de elección múltiple basadas en situaciones clínicas y una autoevaluaciónsobre competencias. Analizando los resultados, las competencias consideradas como adquiridaspor un mayor y menor número de estudiantes fueron, respectivamente, el manejo de los factoresde riesgo cardiovascular (100%) y la auscultación cardiopulmonar (38,3%). Se obtuvieron mejoresresultados en estudiantes que asistieron a clase (11,28±1,84 vs 9,54±2,45; p<0,01). Además, sedemostró que la autopercepción de un correcto aprendizaje (odds ratio [OR]=1,26, intervalo deconfianza al 95% [IC95%]=1,07-1,50), la asistencia a clase (OR=3,55; IC95%=1,64-7,7) y la notamedia del expediente (OR=2,6; IC95%=1,46-4,63) son variables predictoras de calificaciones altasen el cuestionario (≥11 puntos). Esto nos permite inferir que la asistencia a clase se antojafundamental en el aprendizaje. Además, la autopercepción podría utilizarse como herramientapara guiar la docencia. Por otro lado, se sugiere un insuficiente desarrollo de las competenciaseminentemente prácticas, así como la importancia de interrelacionar conocimientos, pues un mejorrendimiento académico general durante el grado se refleja también en la especialidad estudiada eneste trabajoThe acquisition of competencies is essential in clinically relevant areas such ascardiovascular pathology. This study aims to assess the acquisition of the main competenciesregarding the cardiovascular system by medical students, as well as their self-perception, and therelation with regular lecture attendance and academic performance. In order to achieve this aim,data were remotely obtained from 142 students in the fourth, fifth and sixth year of MedicineDegree at University of Málaga using an author-made questionnaire (0-15 points) with multiple-choice questions based on clinical situations and a self-evaluation survey about competencies.Analyzing the results, the competencies that were considered as acquired by the largest and the lowest number of students were, respectively, the handling of cardiovascular risk factors (100%)and cardiopulmonary auscultation (38.3%), respectively. Better results were obtained by studentswho regularly attended lectures (11.28±1.84 vs 9.54±2.45; p<0.01). In addition, it wasdemonstrated that self-perception (odds ratio [OR]=1.26; 95% confidence interval [95%CI]=1.07-1.50), lecture attendance (OR=3.55; 95%CI=1.64-7.70) and better academic performance (OR=2.6;95%CI=1.46-4.63) were predictors of high scores in the questionnaire (≥11 points). In conclusion,lecture attendance seems to be fundamental in learning. In addition, self-perception could be usedas a tool to guide teaching. On the other hand, it is detected an insufficient development ofeminently practical competencies as well as the importance of interrelating knowledge, since abetter general academic performance during degree is also reflected in the speciality studied inthis researc

Repeated Restraint Stress and Binge Alcohol during Adolescence Induce Long-Term Effects on Anxiety-like Behavior and the Expression of the Endocannabinoid System in Male Rats.

(1) Background: Negative experiences during adolescence increase the vulnerability to develop mental disorders later in life. A better understanding of the mechanisms underlying these long-term alterations could help to identify better therapeutic interventions. (2) Methods: Adolescent male Wistar rats were used to explore the effects of repeated stress and alcohol exposure on anxiety-like behaviors, plasma corticosterone levels and the gene expression of the endocannabinoid system (ECS) and other relevant signaling systems (glutamatergic, corticotropin-releasing hormone (CRH) and neuropeptide Y (NPY)) in the amygdala and the medial prefrontal cortex (mPFC). (3) Results: Overall, both stress and alcohol induced anxiety-like behaviors, but only the alcohol-exposed rats displayed increased plasma levels of corticosterone. In the amygdala, there was a general deficit in the gene expression of the ECS and increases in the mRNA levels of certain subunits of glutamate receptors. Interestingly, there were significant interaction effects between stress and alcohol on the expression of the NMDA receptor subunits. In addition, increased mRNA levels of the CRH receptor were observed in alcohol-exposed rats. In the mPFC, alcohol exposure was associated with an increase in the gene expression of the ECS. By contrast, the combination of stress and alcohol produced opposite effects. (4) Conclusions: In summary, early stress and alcohol exposure induced long-term anxiety-like behavior in male rats but different mechanisms are involved in these maladaptive changes in the brain