Homofobia en España : análisis de variables mediadoras en las actitudes hacia la homosexualidad

Treball Final de Màster Universitari en Psicologia General Sanitària. Codi: SBF018. Curs: 2015/2016La elaboración de esta investigación se justifica tanto en la actualización como en la aportación de nueva información dentro del ámbito de las actitudes hacia las orientaciones sexuales no heterosexuales. Así, se pretende estudiar en población española la influencia de las variables sexo, edad, creencias religiosas, orientación sexual y relación con personas LGB en las actitudes hacia la homosexualidad, bisexualidad y homoparentalidad. Los resultados obtenidos a partir de las encuestas realizadas (n=505) muestran que las mujeres, las personas ateas o agnósticas y aquellas que tienen amigos LGB parecen mostrar actitudes más favorables hacia este colectivo. Los resultados no parecen encontrar que las variables edad y el hecho de tener familiares LGB influyan en las actitudes hacia la homosexualidad. Por último, el presente estudio evidencia que aquellas personas con actitudes más igualitarias respecto al género suelen ser a su vez menos homófobas.The development of this research is justified in order to update and provide new information about the attitudes toward non-heterosexual orientations. Thus, it is intended to study, in Spanish population, the influence of sex, age, religious beliefs, sexual orientation and relationship with LGB people in the attitudes toward homosexuality, bisexuality and homoparentality. The results obtained from the surveys (n=505) show that women, agnostics and atheists and those who have LGB friends seem to show more favorable attitudes towards this group. The results do not seem to find an influence in attitudes towards homosexuality in the variables ‘age’ and ‘having an LGB family member’. Finally, this study shows that those with more egalitarian gender attitudes often are less homophobic

Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias

Cerebellar atrophy; Exome sequencing; Movement disordersAtrofia del cerebelo; Secuenciación del exoma; Trastornos del movimientoAtròfia del cerebel; Seqüenciació de l'exoma; Trastorns del movimentOur clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype.This work was supported by the Instituto de Salud Carlos III (ISCIII)—Subdirección General de Evaluación y Fomento de la Investigación within the framework of the National R + D+I Plan co-funded with European Regional Development Funds (ERDF) [Grants PI18/00147 and PI21/00103 to CE]; the Fundació La Marató TV3 [Grants 20143130 and 20143131 to BPD and CE]; and by the Generalitat Valenciana [Grant PROMETEO/2018/135 to CE]. Part of the equipment employed in this work was funded by Generalitat Valenciana and co-financed with ERDF (OP ERDF of Comunitat Valenciana 2014–2020). PS had an FPU-PhD fellowship funded by the Spanish Ministry of Education, Culture and Sport [FPU15/00964]. IH has a PFIS-PhD fellowship [FI19/00072]. ASM has a contract funded by the Spanish Foundation Per Amor a l’Art (FPAA)

NR4A2 Mutations Can Cause Intellectual Disability and Language Impairment With Persistent Dystonia-Parkinsonism

Dystonia; Parkinson's disease/Parkinsonism; Genetic linkageMalaltia de Parkinson/Parkinsonisme; Vinculació genètica; DistoniaEnfermedad de Parkinson/Parkinsonismo; Enlace genético; DistoníaThis work was supported by the Health Institute Carlos III—General Subdirectorate for Research Evaluation and Promotion (PI16/01575, PI18/01898, PI18/00147, PI19/01576), the Spanish Ministry of Economy and Competitiveness (SAF2007-60700), the Ministry of Economy, Innovation, Science and Business of the Government of Andalucía (CVI-02526, CTS-7685), the Ministry of Health and Social Welfare of the Government of Andalucía (PI-0459-2018, PE-0210-2018, PE-0186-2019) and by the Valencian Government (PROMETEO/2018/135), within the framework of the National Research and Development Plan co-funded with European Regional Development Funds. Part of the equipment employed in this study was funded by the Valencian Government and co-financed with European Regional Development Funds (OP ERDF of Valencian Community 2014-2020). I. Hinarejos has a PFIS-PhD fellowship (FI19/00072), S. Jesús has a contract “Acción B Clínicos-Investigadores” (Action B Clinicians-Researchers) contract (B-0007-2019) funded by the Ministry of Health and Family of the Government of Andalucía, and D. Macías-García has a Río Hortega contract (CM18/00142) funded by the Health Institute Carlos III

NR4A2 Mutations Can Cause Intellectual Disability and Language Impairment With Persistent Dystonia-Parkinsonism

TheNR4A2/NURR1gene (MIM*601828) has recently been associated with autosomal-dominantearly-onset dystonia-parkinsonism with intellectual disability.1NR4A2codifies for a nuclear tran-scription factor and is expressed mainly in the substantia nigra, ventral tegmental area, and limbicareas.2To date, 14 different alterations inNR4A2have been described associated with variousclinical phenotypes, mainly with neurodevelopment disorders (table e-1, links.lww.com/NXG/A371). We describe here an interesting case suffering a persistent dystonia-parkinsonism syndrome(DPS) with motor tics, which expands the clinical phenotype ofNR4A2-associated DPS

Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy

Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia. Novel variants were investigated by in silico or experimental approaches. Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD. The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. MAST1 is responsible for an ultrarare condition characterised by global developmental delay and cognitive decline; our index case added ataxia to the list of concomitant associated symptoms. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity. Finally, in a patient who suffers from mild ataxia with oculomotor apraxia, the de novo novel CLK2 c.1120T>C variant was found. The protein expression of the mutated protein was reduced, which may indicate instability that would affect its kinase activity

Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias

26 páginas, 4 figuras, 3 tablasOur clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype.This work was supported by the Instituto de Salud Carlos III (ISCIII)—Subdirección General de Evaluación y Fomento de la Investigación within the framework of the National R + D+I Plan co-funded with European Regional Development Funds (ERDF) [Grants PI18/00147 and PI21/00103 to CE]; the Fundació La Marató TV3 [Grants 20143130 and 20143131 to BPD and CE]; and by the Generalitat Valenciana [Grant PROMETEO/2018/135 to CE]. Part of the equipment employed in this work was funded by Generalitat Valenciana and co-financed with ERDF (OP ERDF of Comunitat Valenciana 2014–2020). PS had an FPU-PhD fellowship funded by the Spanish Ministry of Education, Culture and Sport [FPU15/00964]. IH has a PFIS-PhD fellowship [FI19/00072]. ASM has a contract funded by the Spanish Foundation Per Amor a l’Art (FPAA)Peer reviewe

The Mask of Sanity: La Psicopatía según Cleckley

Treball Final de Grau en Psicologia. Codi: PS1048. Curs acadèmic 2013-2014This paper focuses on analyzing and describing in detail the conceptualization of the construct of psychopathy according to one of the principal authors in this field, the psychiatrist Hervey Cleckley. Through his book, The Mask of Sanity, the most important aspects of his work will be analyzed, focusing on the description of the clinical cases as well as the characteristic criteria drawn from them. Moreover, the basic hypothesis about this disorder will be explained and it will be discussed some topics such as the relationship between psychopathy and variables like anxiety and crime, criminal liability and secondary psychopathy. The need to carry out a full review of the book is based on the multiple and diverse range of opinions on the author’s meaning and conclusions, that is, what psychopathy is for Cleckley. Thus, the results will show the existence of some level of anxiety (on the contrary to what the author states) in both primary and secondary psychopaths. Regarding to the crime it will be evaluated whether, based on the information from the book, psychopathy is necessarily understood with or without antisocial component, related this last term with criminal behavior.El presente trabajo tiene por objeto el análisis detallado de la conceptualización del constructo de psicopatía según uno de los principales referentes en este campo, el psiquiatra Hervey Cleckley. A raíz de su obra, The Mask of Sanity, se analizarán los aspectos más relevantes de su trabajo, centrándonos en la descripción de los casos clínicos, así como en la serie de criterios característicos que extrae de ellos. Además, se explicará su hipótesis básica sobre este trastorno y se abordarán temas tales como la relación entre la psicopatía y variables como la ansiedad y criminalidad, la responsabilidad penal y los llamados psicópatas secundarios. La necesidad de llevar a cabo una revisión completa del libro se basa en la cantidad y variedad de opiniones sobre el significado y las conclusiones del autor, esto es, sobre lo que Cleckley entiende por psicopatía. Así pues, en el apartado de los resultados, se abordará la cuestión de la necesidad de cierto nivel de ansiedad (al contrario de lo que el autor expone) tanto en los psicópatas primarios como en los secundarios. En relación con la criminalidad se evaluará si, basándose en los datos del libro, la psicopatía se entiende necesariamente con o sin el componente antisocial, relacionado éste con las conductas criminales

Aislamiento de microorganismos productores de carbapenemasas en orina: significación clínica y descripción del tratamiento antibiótico

Introducción: la resistencia antibiótica es un problema de gran magnitud, siendo los microorganismos productores de carbapenemasas el paradigma de la multirresistencia. El tracto urinario es el sitio más común de infección, presentando la decisión de tratar su aislamiento una dificultad añadida por el perfil del paciente en el que se presenta. Material y métodos: estudio descriptivo transversal unicéntrico y retrospectivo que incluyó 106 pacientes con aislamiento en urocultivo de un microorganismo productor de carbapenemasas. Se recogieron las variables descriptoras de la población, del tipo de infección, del microorganismo y del tratamiento antibiótico pautado, que fue calificado mediante una escala de calificación simplificada basada en el denominado “Medication Appropiateness Index”. Resultados: de los 175 cultivos revisados se seleccionaron 106 según los criterios de inclusión, con una proporción de 62.3% de varones, una edad media de 70.6 años, mayoritariamente procedentes de domicilio y con un índice de Charlson de 4.9 puntos. El aislamiento tuvo origen nosocomial hasta en un 32.45%, observándose predominantemente K. pneumoniae (65.1%) y cepas productoras de OXA-48. Se administró tratamiento en 72 episodios, de los cuales 60 fueron monoterapia, siendo los carbapenémicos los fármacos más utilizados. Del total de la muestra murieron 9 pacientes, siendo la infección urinaria la causa únicamente en 3. No se encontraron diferencias estadísticamente significativas entre los pacientes que recibieron un tratamiento antibiótico calificado como inadecuado versus adecuado, a excepción de la edad, siendo significativamente más jóvenes (p=0.019) aquellos pacientes que recibieron una calificación adecuada. Globalmente sólo el 33% de los casos obtuvo una calificación adecuada en el tratamiento. No se objetivaron desde esta comparación diferencias entre las características de la infección ni en la elección de monoterapia versus biterapia. Al desglosar los criterios de la escala diseñada no hubo diferencias entre los pacientes que fallecieron y los que no. Conclusiones: siendo una población comparable a las presentes en otros estudios, al tratarse exclusivamente de infecciones del tracto urinario, es posible que, pese a una calificación global del tratamiento desfavorable, esto no influyese tanto en la evolución de los pacientes como en otras infecciones de mayor gravedad.Background: antibiotic resistance is a major problem, being carbapenem-resistant microorganisms the paradigm of multiresistance. Urinary tract is the most frequent site of infection, being the decision of treating its isolation an added difficulty due to the patient’s profile. Methods: descriptive transversal unicentric and retrospective study involving 106 patients with carbapenem-resistant microorganism in an urine culture. Epidemiological, clinical, microbiological characteristics and antibiotic treatment descriptive variables were gathered, and a rating scale was used to score the treatment based on the “Medication Appropiateness Index”. Results: considering the inclusion terms, 106 of the total 175 cultures reviewed were taken, with a male percentage of 62.3% with an average age of 70.6 years old, mainly from home and 4.9 points in Charlson's index. The isolation of the microorganism was nosocomial origin up to 32.45%, 65.1% corresponded to K. pneumoniae and producing strains of OXA-48. It was applied treatment in 72 patients, 60 of which were monotherapy, being carbapenems the widest drug used. From the total sample, 9 patients died, only 3 of them caused by urinary infection. No statistically significant differences were found among the patients who received antibiotic treatment classified as inadequate versus adequate, except for age, being the considerably younger (p=0.019) those who received an adequated qualification. Globally, only 33% got an adequate qualification in the treatment. From this comparative, no differences were found among the infection characteristics nor were they on the election of monotherapy versus bi-therapy. When looking at the scale design criteria there were no differences among the patients who died and those who did not. Conclusions: being a comparable population with other studies and dealing exclusively with tract urinary infections, it could be that despite an overall unfavorable treatment, this did not influence both the evolution of the patients and other more severe infections

Diagnóstico genético de neuropatías periféricas hereditarias e investigación de la patogenicidad de una mutación mediante el empleo de un organismo modelo

[ES] La enfermedad de Charcot-Marie-Tooth (CMT) y neuropatías relacionadas comprenden un grupo de trastornos neurológicos con una amplia variabilidad clínica y genética. Las técnicas basadas en Next Generation Sequencing (NGS) han mejorado el diagnóstico genético, pero, a veces, el gran número de variantes identificadas dificulta determinar cuál de éstas es la causante de la enfermedad. En la mayoría de casos, se identifican variantes que deben ser investigadas mediante ensayos funcionales, empleando organismos modelo, con el fin de determinar su patogenicidad. En el presente Trabajo Final de Grado se ha realizado el análisis de datos procedentes de un panel de genes dirigido al diagnóstico de la enfermedad de CMT, atrofia espinal distal (AED), esclerosis lateral amiotrófica (ELA), y atrofia muscular espinal (AME). Con esta herramienta diagnóstica se han evaluado 44 pacientes, que cursan con alguna de estas enfermedades. En este conjunto, se han detectado variantes genéticas poco frecuentes en 33 genes. El rendimiento diagnóstico obtenido en el presente trabajo se encuentra en un 29,5%, pudiendo ampliarse hasta un 66% con posteriores investigaciones. La variante NM_004990; c.1808T>C; (P.F603S) detectada en el gen MARS, en el paciente SGT/742, ha sido investigada en profundidad. Debido al reducido número de casos descritos que asocian variantes genéticas en MARS a la enfermedad CMT, así como por la naturaleza de la mutación detectada, se decidieron abordar ensayos funcionales que pudieran confirmar la posible implicación de la misma en el fenotipo del paciente. Para ello, se ha investigado el efecto de la mutación trabajando con el gen ortólogo de MARS en el nematodo Caenorhabditis elegans: mars-1. En este trabajo se han conseguido cepas de gusanos transgénicas estables, sin embargo, no se ha observado un fenotipo anómalo asociado al gen portador de la mutación, en comparación con el gen mars-1 salvaje. Posteriores experimentos nos permitirán ajustar el diseño experimental y, en consecuencia, ser capaces de generar un modelo de la enfermedad en C. elegans.[EN] Charcot-Marie-Tooth disease (CMT) and related neuropathies comprise a group of heterogeneous hereditary neuropathies with wide genetic variability. The techniques based on Next Generation Sequencing (NGS) have improved the genetic diagnosis, although sometimes the large number of changes identified makes it difficult to determine the cause of the disease. In most cases, the identified variants must be investigated through functional assays using model organisms to determine their pathogenicity. In the present bachelor’s thesis, it has been analyzed the data from a panel of genes comprising 119 genes involved in CMT disease, distal spinal atrophy (AED), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (AME). With this diagnostic tool 44 patientsshowing any of these neuropathies have been studied. In this group, there have been detected lowfrequency genetic variants in 33 genes. The diagnostic performance obtained in this bachelor’s thesis is 29,5%, and can be expanded to 66% with further investigations. The genetic variant NM_004990; C.1808> C; (P.F603S) detected in the MARS gene in the patient SGT/742 has been investigated in depth. Due to the small number of cases described that associate genetic variants in MARS with CMT disease, as well as the nature of the detected mutation, it was decided to address functional assays that could confirm the possible implication of the mutation in the phenotype of the patient. It has been investigated the effect of the mutation working with the orthologous gene of MARS in the nematode Caenorhabditis elegans: mars-1. In this work, stable transgenic worm strains have been obtained; however, an abnormal phenotype associated with the mutation has not been observed, as compared to the wild mars- 1 gene. Further experiments will allow us to adjust the experimental design and, consequently, to be able to generate a model of the disease in C. elegans.Hinarejos Martínez, MI. (2017). Diagnóstico genético de neuropatías periféricas hereditarias e investigación de la patogenicidad de una mutación mediante el empleo de un organismo modelo. http://hdl.handle.net/10251/86540TFG

Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA)

The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are related to extrapyramidal features (dystonia, parkinsonism and choreoathetosis), and neuropsychiatric abnormalities. Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17. Nonetheless, many patients remain without a conclusive genetic diagnosis, which shows that there must be additional as yet undiscovered NBIA genes. In line with this, isolated cases of known monogenic disorders, and also, new genetic diseases, which present with abnormal brain iron phenotypes compatible with NBIA, have been described. Several pathways are involved in NBIA syndromes: iron and lipid metabolism, mitochondrial dynamics, and autophagy. However, many neurodegenerative conditions share features such as mitochondrial dysfunction and oxidative stress, given the bioenergetics requirements of neurons. This review aims to describe the existing link between the classical ten NBIA forms by examining their connection with mitochondrial impairment as well as oxidative stress and neuroinflammation