The influence of CYP enzymes and ABCB1 on treatment outcomes in schizophrenia: association of CYP1A2 activity with adverse effects

Aim: Genetic variants on metabolic and transport enzymes are good candidates to explain inter-individual differences in response to antipsychotics. The aim of this study is to evaluate and compare the influence of the CYP2D6, CYPC19, CYP1A2 and ABCB1 variants on plasma levels, treatment response and side effects of antipsychotics. Methods: Twenty polymorphisms in selected genes were genotyped in 318 patients diagnosed with schizophrenia, schizoaffective or delusional disorder treated with antipsychotics (clozapine, olanzapine, paliperidone, risperidone, aripiprazole and quetiapine). Plasma drug levels were determined after 6 weeks of treatment. The Positive and Negative Symptoms Scale (PANSS) and UKU scale of side effects were recorded at baseline and after 12 weeks of treatment. The effect of gene variants on plasma drug levels, treatment response and adverse effects were examined by multinomial regression. Results:CYP1A2 was found to be associated with psychic side effects (P = 0.02), with variants predicting higher enzyme activity associated with lower adverse effects, and was the strongest predictor for this adverse effect of all the studied factors. Functional variants in CYP genes were associated with plasma level differences, with higher activity variants associated with lower plasma levels. No association with improvement of the condition, as measured by the PANSS score, was found in this study. Conclusion: The results suggest that increased CYP1A2 activity protects against psychic side effects. Few studies have evaluated the impact of genetic factors on treatment response or side effects, and only in relation to a selection of adverse reactions. These results are a step towards better understanding of the factors behind the different aspects of clinical outcomes, such as various adverse effects

A pharmacogenetic intervention for the improvement of the safety profile of antipsychotic treatments

Antipsychotic drugs fail to achieve adequate response in 30-50% of treated patients and about 50% of them develop severe and lasting side effects. Treatment failure results in poorer prognosis with devastating repercussions for the patients, carers and broader society. Our study evaluated the clinical benefits of a pharmacogenetic intervention for the personalisation of antipsychotic treatment. Pharmacogenetic information in key CYP polymorphisms was used to adjust clinical doses in a group of patients who started or switched treatment with antipsychotic drugs (PharmG+, N = 123), and their results were compared with those of a group of patients treated following existing clinical guides (PharmG−, N = 167). There was no evidence of significant differences in side effects between the two arms. Although patients who had their antipsychotic dose adjusted according to CYPs polymorphisms (PharmG+) had a bigger reduction in side effects than those treated as usual (PharmG−), the difference was not statistically significant (p > 0.05 for all comparisons). However, PharmG+ patients treated with CYP2D6 substrates that were carriers of CYP2D6 UMs or PMs variants showed a significantly higher improvement in global, psychic and other UKU side effects than PharmG− patients (p = 0.02, p = 0.05 and p = 0.01, respectively). PharmG+ clozapine treated patients with CYP1A2 or CYP2C19 UM and PMs variants also showed higher reductions in UKU scores than PharmG− clozapine patients in general. However, those differences were not statistically significant. Pharmacogenetic interventions may improve the safety of antipsychotic treatments by reducing associated side effects. This intervention may be particularly useful when considering treatment with antipsychotics with one major metabolic pathway, and therefore more susceptible to be affected by functional variants of CYP enzymes

Nivel de conocimiento sobre carcinoma basocelular en estudiantes de Estomatología

Introduction: basal cell carcinoma is the most diagnosed skin cancer, which requires an adequate knowledge of its diagnosis, characteristics and treatment by the stomatologist given the incidence of patients with this pathology.Objective: to determine the level of knowledge of the Stomatology students of the Faculty of Medical Sciences of Manzanillo about basal cell carcinoma.Method: a descriptive, cross-sectional study was carried out in Stomatology students from the Faculty of Medical Sciences of Manzanillo, from April to May 2021. The universe consisted of 80 students belonging to the fourth and fifth year of Stomatology. A survey was made in Google Forms, where the variables referring to the level of knowledge of the students about basal cell carcinoma were studied. The level of knowledge was evaluated as good, regular and bad and for information processing a database was created in SPSS and Cronbach's alpha coefficient and Fisher's exact test were determined.Results: fifth-year Stomatology students predominated (82,5 %), a predominance of the level of regular knowledge in terms of epidemiology, anatomical location and treatment of basal cell carcinoma (48,75 %, 52,5 % and 56,25 % respectively) was observed and a good level of knowledge about the etiology of basal cell carcinoma (53,75 %) and 63,75 % of the students reported the need for a study on basal cell carcinoma.Conclusions: the level of knowledge it was Regular in most of the variables evaluated about the knowledge of basal cell carcinoma.Introducción: el carcinoma basocelular es el cáncer de piel más diagnosticado, lo que hace necesario un adecuado conocimiento sobre su diagnóstico, características y tratamiento por parte del estomatólogo dada la incidencia de pacientes con esta patología. Objetivo: determinar el nivel de conocimiento de los estudiantes de Estomatología de la Facultad de Ciencias Médicas de Manzanillo sobre carcinoma basocelular. Método: se realizó un estudio descriptivo, transversal, en estudiantes de Estomatología de la Facultad de Ciencias Médicas de Manzanillo, en el período de abril a mayo del 2021. El universo estuvo conformado por 80 estudiantes pertenecientes al cuarto y quinto año de Estomatología. Se confeccionó una encuesta en Google Forms, donde se estudiaron las variables referentes al nivel de conocimiento de los estudiantes sobre carcinoma basocelular. El nivel de conocimiento fue evaluado en bueno, regular y malo y para el procesamiento de la información se confeccionó una base de datos en SPSS y se determinó el coeficiente de alfa de Cronbach y test exacto de Fisher.Resultados: predominaron los estudiantes de quinto año de Estomatología (82,5 %), se observó un predominio del nivel de conocimiento regular en cuanto a epidemiología, localización anatómica y tratamiento del carcinoma basocelular (48,75 %, 52,5 % y 56,25 % respectivamente) y un nivel de conocimiento bueno sobre etiología del carcinoma basocelular (53,75 %) y el 63,75 % de los estudiantes refirió necesidad de estudio sobre carcinoma basocelular.Conclusiones: el nivel de conocimiento fue regular en la mayoría de las variables evaluadas sobre conocimiento del carcinoma basocelular

Nivel de conocimiento sobre carcinoma basocelular en estudiantes de Estomatología

Introduction: basal cell carcinoma is the most diagnosed skin cancer, which requires an adequate knowledge of its diagnosis, characteristics and treatment by the stomatologist given the incidence of patients with this pathology.Objective: to determine the level of knowledge of the Stomatology students of the Faculty of Medical Sciences of Manzanillo about basal cell carcinoma.Method: a descriptive, cross-sectional study was carried out in Stomatology students from the Faculty of Medical Sciences of Manzanillo, from April to May 2021. The universe consisted of 80 students belonging to the fourth and fifth year of Stomatology. A survey was made in Google Forms, where the variables referring to the level of knowledge of the students about basal cell carcinoma were studied. The level of knowledge was evaluated as good, regular and bad and for information processing a database was created in SPSS and Cronbach's alpha coefficient and Fisher's exact test were determined.Results: fifth-year Stomatology students predominated (82,5 %), a predominance of the level of regular knowledge in terms of epidemiology, anatomical location and treatment of basal cell carcinoma (48,75 %, 52,5 % and 56,25 % respectively) was observed and a good level of knowledge about the etiology of basal cell carcinoma (53,75 %) and 63,75 % of the students reported the need for a study on basal cell carcinoma.Conclusions: the level of knowledge it was Regular in most of the variables evaluated about the knowledge of basal cell carcinoma.Introducción: el carcinoma basocelular es el cáncer de piel más diagnosticado, lo que hace necesario un adecuado conocimiento sobre su diagnóstico, características y tratamiento por parte del estomatólogo dada la incidencia de pacientes con esta patología. Objetivo: determinar el nivel de conocimiento de los estudiantes de Estomatología de la Facultad de Ciencias Médicas de Manzanillo sobre carcinoma basocelular. Método: se realizó un estudio descriptivo, transversal, en estudiantes de Estomatología de la Facultad de Ciencias Médicas de Manzanillo, en el período de abril a mayo del 2021. El universo estuvo conformado por 80 estudiantes pertenecientes al cuarto y quinto año de Estomatología. Se confeccionó una encuesta en Google Forms, donde se estudiaron las variables referentes al nivel de conocimiento de los estudiantes sobre carcinoma basocelular. El nivel de conocimiento fue evaluado en bueno, regular y malo y para el procesamiento de la información se confeccionó una base de datos en SPSS y se determinó el coeficiente de alfa de Cronbach y test exacto de Fisher.Resultados: predominaron los estudiantes de quinto año de Estomatología (82,5 %), se observó un predominio del nivel de conocimiento regular en cuanto a epidemiología, localización anatómica y tratamiento del carcinoma basocelular (48,75 %, 52,5 % y 56,25 % respectivamente) y un nivel de conocimiento bueno sobre etiología del carcinoma basocelular (53,75 %) y el 63,75 % de los estudiantes refirió necesidad de estudio sobre carcinoma basocelular.Conclusiones: el nivel de conocimiento fue regular en la mayoría de las variables evaluadas sobre conocimiento del carcinoma basocelular

Nivel de conocimiento sobre carcinoma basocelular en estudiantes de Estomatología

Introduction: basal cell carcinoma is the most diagnosed skin cancer, which requires an adequate knowledge of its diagnosis, characteristics and treatment by the stomatologist given the incidence of patients with this pathology.Objective: to determine the level of knowledge of the Stomatology students of the Faculty of Medical Sciences of Manzanillo about basal cell carcinoma.Method: a descriptive, cross-sectional study was carried out in Stomatology students from the Faculty of Medical Sciences of Manzanillo, from April to May 2021. The universe consisted of 80 students belonging to the fourth and fifth year of Stomatology. A survey was made in Google Forms, where the variables referring to the level of knowledge of the students about basal cell carcinoma were studied. The level of knowledge was evaluated as good, regular and bad and for information processing a database was created in SPSS and Cronbach's alpha coefficient and Fisher's exact test were determined.Results: fifth-year Stomatology students predominated (82,5 %), a predominance of the level of regular knowledge in terms of epidemiology, anatomical location and treatment of basal cell carcinoma (48,75 %, 52,5 % and 56,25 % respectively) was observed and a good level of knowledge about the etiology of basal cell carcinoma (53,75 %) and 63,75 % of the students reported the need for a study on basal cell carcinoma.Conclusions: the level of knowledge it was Regular in most of the variables evaluated about the knowledge of basal cell carcinoma.Introducción: el carcinoma basocelular es el cáncer de piel más diagnosticado, lo que hace necesario un adecuado conocimiento sobre su diagnóstico, características y tratamiento por parte del estomatólogo dada la incidencia de pacientes con esta patología. Objetivo: determinar el nivel de conocimiento de los estudiantes de Estomatología de la Facultad de Ciencias Médicas de Manzanillo sobre carcinoma basocelular. Método: se realizó un estudio descriptivo, transversal, en estudiantes de Estomatología de la Facultad de Ciencias Médicas de Manzanillo, en el período de abril a mayo del 2021. El universo estuvo conformado por 80 estudiantes pertenecientes al cuarto y quinto año de Estomatología. Se confeccionó una encuesta en Google Forms, donde se estudiaron las variables referentes al nivel de conocimiento de los estudiantes sobre carcinoma basocelular. El nivel de conocimiento fue evaluado en bueno, regular y malo y para el procesamiento de la información se confeccionó una base de datos en SPSS y se determinó el coeficiente de alfa de Cronbach y test exacto de Fisher.Resultados: predominaron los estudiantes de quinto año de Estomatología (82,5 %), se observó un predominio del nivel de conocimiento regular en cuanto a epidemiología, localización anatómica y tratamiento del carcinoma basocelular (48,75 %, 52,5 % y 56,25 % respectivamente) y un nivel de conocimiento bueno sobre etiología del carcinoma basocelular (53,75 %) y el 63,75 % de los estudiantes refirió necesidad de estudio sobre carcinoma basocelular.Conclusiones: el nivel de conocimiento fue regular en la mayoría de las variables evaluadas sobre conocimiento del carcinoma basocelular

Caracterización y cuantificación automatizadas de menas metálicas mediante visión artificial: Proyecto CAMEVA

El proyecto CAMEVA (Caracterización Automatizada de Menas metálicas mediante Visión Artificial) pretende desarrollar un sistema automatizado capaz de llevar a cabo la identificación y cuantificación de los minerales presentes en muestras de menas metálicas para facilitar su posible aprovechamiento industrial. El sistema integra un microscopio óptico de reflexión motorizado, una rueda de filtros monocromadores situada ante la fuente luminosa, una cámara B/N de investigación y un ordenador, en el que un programa de análisis digital de imagen asociado a un sistema experto especialmente desarrollado para esta aplicación controlarán el proceso. Se mide la reflectancia multiespectral y se ha optado por trabajar habitualmente sin polarizador, con el fin de reducir la variabilidad arbitraria de medidas ligada a la anisotropía de los minerales. Para la identificación se compararán las reflectancias medidas con las bases de datos de reflectancia espectral existentes (p. ej. IMA-COM). Las experiencias previas del equipo indican que es posible diferenciar las menas más comunes mediante el análisis de la imagen microscópica en color con cámara RGB y constriñendo las opciones de busca con información adicional, tal como la tipología del yacimiento y la asociación mineral real. El proyecto actual va más allá, y pretende identificar las menas a partir de imágenes multiespectrales, que incorporan valores espectrales entre 350 y 1000 nm (es decir, no sólo el espectro visible, sino el UV e IR cercanos), y recurriendo a un sistema experto construido específicamente para tener en cuenta los diversos tipos de información disponible (reflectancia espectral, origen de la muestra, asociaciones minerales, morfología, etc). La validación del método se efectúa mediante el análisis comparativo de muestras y patrones intercambiados entre laboratorios. El desarrollo previsto busca la automatización total del proceso (incluida la calibración) y la capacidad de auto-aprendizaje del sistema. Una vez terminado, el sistema será puesto a prueba en problemas industriales reales (mineralúrgicos o de protección ambiental), gracias a los contactos establecidos con entidades nacionales e internacionales del sector. En el futuro, cabe plantear la extensión del campo de aplicación del sistema a otros tipos de minerales, materiales o producto

Testing the efficacy of INtegral Cognitive REMediation (INCREM) in major depressive disorder : study protocol for a randomized clinical trial

Given the limitation of pharmacological treatments to treat cognitive symptoms in patients with Major Depressive Disorder (MDD), cognitive remediation programs has been proposed as a possible procognitive intervention but findings are not conclusive. This study investigates the efficacy of an INtegral Cognitive REMediation (INCREM) that includes a combination of a Functional Remediation (FR) strategy plus a Computerized Cognitive Training (CCT) in order to improve not only cognitive performance but also the psychosocial functioning and the quality of life. A single blind randomized controlled clinical trial in 81 patients with a diagnosis of MDD in clinical remission or in partial remission. Participants will be randomized to one of three conditions: INCREM (FR + CCT), Psychoeducation plus online games and Treatment As Usual (TAU). Intervention will consist in 12 group sessions, of approximately 110 min once a week. The primary outcome measure will be % of change in psychosocial functioning after treatment measured by the Functional Assessment Short Test (FAST); additionally, number of sick leaves and daily activities will also be recorded as pragmatic outcomes. To our knowledge, this is the first randomized controlled clinical trial using a combination of two different approaches (FR + CCT) to treat the present cognitive deficits and to promote their improvements into a better psychosocial functioning. Clinical Trials . Date registered 10th of August 2018 and last updated 24th August 2018

Testing the efficacy of INtegral Cognitive REMediation (INCREM) in major depressive disorder: study protocol for a randomized clinical trial

Background: Given the limitation of pharmacological treatments to treat cognitive symptoms in patients with Major Depressive Disorder (MDD), cognitive remediation programs has been proposed as a possible procognitive intervention but findings are not conclusive. This study investigates the efficacy of an INtegral Cognitive REMediation (INCREM) that includes a combination of a Functional Remediation (FR) strategy plus a Computerized Cognitive Training (CCT) in order to improve not only cognitive performance but also the psychosocial functioning and the quality of life. Methods: A single blind randomized controlled clinical trial in 81 patients with a diagnosis of MDD in clinical remission or in partial remission. Participants will be randomized to one of three conditions: INCREM (FR + CCT), Psychoeducation plus online games and Treatment As Usual (TAU). Intervention will consist in 12 group sessions, of approximately 110 min once a week. The primary outcome measure will be % of change in psychosocial functioning after treatment measured by the Functional Assessment Short Test (FAST); additionally, number of sick leaves and daily activities will also be recorded as pragmatic outcomes. Discussion: To our knowledge, this is the first randomized controlled clinical trial using a combination of two different approaches (FR + CCT) to treat the present cognitive deficits and to promote their improvements into a better psychosocial functioning. Trial registration: Clinical Trials NCT03624621 . Date registered 10th of August 2018 and last updated 24th August 2018

β-Cyclodextrins as affordable antivirals to treat coronavirus infection

The SARS-CoV-2 pandemic made evident that there are only a few drugs against coronavirus. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety profile. Starting from a list of 116 drug candidates, we used molecular modelling tools to rank the 44 most promising inhibitors. Next, we tested their efficacy as antivirals against α and β coronaviruses, such as the HCoV-229E and SARS-CoV-2 variants. Four drugs, OSW-1, U18666A, hydroxypropyl-β-cyclodextrin (HβCD) and phytol, showed in vitro antiviral activity against HCoV-229E and SARS-CoV-2. The mechanism of action of these compounds was studied by transmission electron microscopy and by fusion assays measuring SARS-CoV-2 pseudoviral entry into target cells. Entry was inhibited by HβCD and U18666A, yet only HβCD inhibited SARS-CoV-2 replication in the pulmonary Calu-3 cells. Compared to the other cyclodextrins, β-cyclodextrins were the most potent inhibitors, which interfered with viral fusion via cholesterol depletion. β-cyclodextrins also prevented infection in a human nasal epithelium model ex vivo and had a prophylactic effect in the nasal epithelium of hamsters in vivo. All accumulated data point to β-cyclodextrins as promising broad-spectrum antivirals against different SARS-CoV-2 variants and distant alphacoronaviruses. Given the wide use of β-cyclodextrins for drug encapsulation and their high safety profile in humans, our results support their clinical testing as prophylactic antivirals

β-Cyclodextrins as affordable antivirals to treat coronavirus infection

The SARS-CoV-2 pandemic made evident that there are only a few drugs against coronavirus. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety profile. Starting from a list of 116 drug candidates, we used molecular modelling tools to rank the 44 most promising inhibitors. Next, we tested their efficacy as antivirals against α and β coronaviruses, such as the HCoV-229E and SARS-CoV-2 variants. Four drugs, OSW-1, U18666A, hydroxypropyl-β-cyclodextrin (HβCD) and phytol, showed in vitro antiviral activity against HCoV-229E and SARS-CoV-2. The mechanism of action of these compounds was studied by transmission electron microscopy and by fusion assays measuring SARS-CoV-2 pseudoviral entry into target cells. Entry was inhibited by HβCD and U18666A, yet only HβCD inhibited SARS-CoV-2 replication in the pulmonary Calu-3 cells. Compared to the other cyclodextrins, β-cyclodextrins were the most potent inhibitors, which interfered with viral fusion via cholesterol depletion. β-cyclodextrins also prevented infection in a human nasal epithelium model ex vivo and had a prophylactic effect in the nasal epithelium of hamsters in vivo. All accumulated data point to β-cyclodextrins as promising broad-spectrum antivirals against different SARS-CoV-2 variants and distant alphacoronaviruses. Given the wide use of β-cyclodextrins for drug encapsulation and their high safety profile in humans, our results support their clinical testing as prophylactic antivirals.This work has been funded by grant RTI2018-094445-B100 (MCIU/AEI/FEDER, UE) from the Ministry of Science and Innovation of Spain (C.R.), by Palex Medical S.A., Sika S.A.U. and 7 more companies, and by Ms. Raquel Casaus Alvarez, Mr. Miguel Pardo Gil, Mr. Jacques Noguès and a total of 2916 citizens through the Precipita crowdfunding platform of Fecyt (Fundación Española para la Ciencia y la Tecnología). NI-U is supported by the Spanish Ministry of Science and Innovation (grant PID2020-117145RB-I00), EU HORIZON-HLTH-2021-CORONA-01 (grant 101046118) and by institutional funding of Grifols, Pharma Mar, HIPRA, Amassence and Palobiofarma. This work used the computational resources of the Centro de Supercomputación de Galicia (CESGA) supported by the Partnership for Advanced Computing in Europe (PRACE) COVID-19 Fast Track Call for Proposals – Allocation Decision – Proposal COVID19-85.info:eu-repo/semantics/publishedVersio