Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert / Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease

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Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease. / Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert.

BACKGROUND AND OBJECTIVES: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. MATERIAL AND METHODS: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. RECOMMENDATIONS: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. CONCLUSION: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.

Effect of a chronotype-adjusted diet on weight loss effectiveness: A randomized clinical trial.

BACKGROUND & AIMS: The alteration of normal biological rhythms, also known as chronodisruption, may be associated with obesity development. For instance, those subject with preference for vespertinity seem to be prone to develop obesity. However, the current hypocaloric dietary treatment of obesity does not take into account these aspects. Therefore, the objective of this trial was to evaluate whether a diet adjusted to patient's chronotype is more effective that the current dietary recommendations. METHODS: 209 subjects take part on a 3 month randomized, double-blind trial. 104 subjects followed a typical hypocaloric dietary treatment and the other 105 subjects undergone a diet with a daily caloric distribution adjusted to their chronotype. There were no sex or age differences between groups. RESULTS: Baseline characteristics were similar in both groups. Dropout rate was also similar in both interventions (p = 0.683). Although both groups improved their anthropometrical parameters, the chronotype-adjusted diet group achieved a statistically significant greater reduction in percentage of total body weight loss (%TWL), BMI and waist circumference than the control group (p < 0.010 in all contrasts). The effect on clinical parameters was less pronounced. CONCLUSIONS: This randomized trial has demonstrated for the first time that in overweight/obese subjects, a chronotype-adjusted diet is more effective than the traditional hypocaloric dietary treatment, at least regarding the anthropometrical parameters. Further research will confirm if this intervention is also more effective in the long term. TRIAL REGISTRATION: NCT-ID: #NCT03755674, (available at: http://www.clinicaltrials.gov).

Musicoterapia en la enfermedad de Alzheimer: efectos cognitivos, psicológicos y conductuales / Music therapy and Alzheimer's disease: Cognitive, psychological, and behavioural effects

Introducción: La musicoterapia forma parte de los programas de envejecimiento activo que se ofrecen a las personas mayores. Su utilidad en el campo de las demencias empieza a ser valorada por la comunidad científica, ya que se han reportado efectos positivos a nivel físico, cognitivo y psicológico. Son necesarios más estudios que perfilen el alcance de tales cambios en la enfermedad de Alzheimer. Objetivos: Conocer el perfil de mejoría clínica que experimentan los pacientes con enfermedad de Alzheimer con la aplicación de una intervención de musicoterapia. Pacientes y métodos: Se aplicó un tratamiento con musicoterapia durante 6 semanas a 42 pacientes con enfermedad de Alzheimer en estadio leve-moderado. Se estudiaron los cambios en las puntuaciones de Mini-examen del estado mental, Inventario de síntomas neuropsiquiátricos, Escala hospitalaria de ansiedad y depresión, e índice de Barthel. Se estudió si estos cambios se influían por el grado de severidad de la demencia. Resultados: Se observó una mejoría significativa de memoria, orientación, depresión y ansiedad (escala HAD) en pacientes leves y moderados; de ansiedad (escala NPI) en pacientes leves; de los delirios, alucinaciones, agitación, irritabilidad y trastornos del lenguaje en el grupo con demencia moderada. El efecto sobre las medidas cognitivas es ya apreciable a las 4 sesiones de musicoterapia. Conclusiones: En la muestra estudiada, la musicoterapia mejoró algunas alteraciones cognitivas, psicológicas y conductuales de los pacientes con enfermedad de Alzheimer. Sería interesante complementar la musicoterapia con intervenciones de danzaterapia a fin de mejorar los aspectos motores y funcionales (AU)

Introduction: Music therapy is one of the types of active ageing programmes which are offered to elderly people. The usefulness of this programme in the field of dementia is beginning to be recognised by the scientific community, since studies have reported physical, cognitive, and psychological benefits. Further studies detailing the changes resulting from the use of music therapy with Alzheimer patients are needed. Objectives: Determine the clinical improvement profile of Alzheimer patients who have undergone music therapy. Patients and methods: Forty-two patients with mild to moderate Alzheimer disease underwent music therapy for 6 weeks. The changes in results on the Mini-mental State Examination, Neuropsychiatric Inventory, Hospital Anxiety and Depression Scale and Barthel Index scores were studied. We also analysed whether or not these changes were influenced by the degree of dementia severity. Results: Significant improvement was observed in memory, orientation, depression and anxiety (HAD scale) in both mild and moderate cases; in anxiety (NPI scale) in mild cases; and in delirium, hallucinations, agitation, irritability, and language disorders in the group with moderate Alzheimer disease. The effect on cognitive measures was appreciable after only 4 music therapy sessions. Conclusions: In the sample studied, music therapy improved some cognitive, psychological, and behavioural alterations in patients with Alzheimer disease. Combining music therapy with dance therapy to improve motor and functional impairment would be an interesting line of research (AU)

Music therapy and Alzheimer's disease: Cognitive, psychological, and behavioural effects. / Musicoterapia en la enfermedad de Alzheimer: efectos cognitivos, psicológicos y conductuales.

INTRODUCTION: Music therapy is one of the types of active ageing programmes which are offered to elderly people. The usefulness of this programme in the field of dementia is beginning to be recognised by the scientific community, since studies have reported physical, cognitive, and psychological benefits. Further studies detailing the changes resulting from the use of music therapy with Alzheimer patients are needed. OBJECTIVES: Determine the clinical improvement profile of Alzheimer patients who have undergone music therapy. PATIENTS AND METHODS: Forty-two patients with mild to moderate Alzheimer disease underwent music therapy for 6 weeks. The changes in results on the Mini-mental State Examination, Neuropsychiatric Inventory, Hospital Anxiety and Depression Scale and Barthel Index scores were studied. We also analysed whether or not these changes were influenced by the degree of dementia severity. RESULTS: Significant improvement was observed in memory, orientation, depression and anxiety (HAD scale) in both mild and moderate cases; in anxiety (NPI scale) in mild cases; and in delirium, hallucinations, agitation, irritability, and language disorders in the group with moderate Alzheimer disease. The effect on cognitive measures was appreciable after only 4 music therapy sessions. CONCLUSIONS: In the sample studied, music therapy improved some cognitive, psychological, and behavioural alterations in patients with Alzheimer disease. Combining music therapy with dance therapy to improve motor and functional impairment would be an interesting line of research.

[How far reaches earliness of optical coherence tomography in cognitive impairment]. / Hasta donde llega la precocidad de la tomografia de coherencia optica en el deterioro cognitivo?

INTRODUCTION: Alzheimer's disease (AD) is the leading cause of dementia in the world today. Increasingly greater efforts are being made to be able to detect cognitive impairment in earlier stages, and diagnostic entities such as mild cognitive impairment (MCI) and subjective memory complaints (SMC) are appearing. The number of biomarkers studied with the aim of reaching this goal continues to rise, and include optical coherence tomography. SUBJECTS AND METHODS: The study conducted employed optical coherence tomography to measure the macular thickness and the retinal nerve fibre layer in patients diagnosed with AD (n = 36), in patients with MCI (n = 33), in individuals with SMC (n = 24) and in control subjects (n = 45). RESULTS: Statistically significant differences have been found in terms of the macular thickness among all the groups studied (SMC: 261.8 ± 25.88 µm; MCI: 259.19 ± 22.582 µm; mild AD: 258.53 ± 14.804 µm; moderate AD: 249.32 ± 18.467 µm) and control subjects (271.96 ± 15.57 µm). The same occurs as regards the retinal nerve fibre layer and the difference is statistically significant compared with the control group (94.51 ± 9.203 µm) of all the groups (SMC: 90.44 ± 9.059 µm; MCI: 89.4 ± 10.421 µm; mild AD: 87.12 ± 10.279 µm; moderate AD: 82.25 ± 10.636 µm). CONCLUSION: Optical coherence tomography could be a future biomarker and support tool to facilitate the early diagnosis of cognitive impairment and AD.

TITLE: Hasta donde llega la precocidad de la tomografia de coherencia optica en el deterioro cognitivo?Introduccion. La enfermedad de Alzheimer (EA) es la primera causa de demencia mundial. Cada vez son mas los esfuerzos para lograr una deteccion temprana del deterioro cognitivo y surgen en el panorama cientifico entidades diagnosticas como el deterioro cognitivo leve (DCL) y las quejas subjetivas de memoria (QSM). Debido a ello, aparecen numerosos biomarcadores estudiados para conseguir dicho objetivo, entre ellos la tomografia de coherencia optica. Sujetos y metodos. Se ha realizado un estudio que utiliza la tomografia de coherencia optica para medir el grosor macular y la capa de fibras nerviosas de la retina en pacientes diagnosticados de EA (n = 36), pacientes con DCL (n = 33), en individuos con QSM (n = 24) y en sujetos control (n = 45). Resultados. Se han encontrado diferencias estadisticamente significativas en cuanto al grosor macular entre todos los grupos estudiados (QSM: 261,8 ± 25,88 µm; DCL: 259,19 ± 22,582 µm; EA leve: 258,53 ± 14,804 µm; EA moderada: 249,32 ± 18,467 µm) y sujetos control (271,96 ± 15,57 µm). Respecto a la capa de fibras nerviosas de la retina, ocurre de igual manera, y la diferencia es estadisticamente significativa frente al grupo control (94,51 ± 9,203 µm) de todos los grupos (QSM: 90,44 ± 9,059 µm; DCL: 89,4 ± 10,421 µm; EA leve: 87,12 ± 10,279 µm; EA moderada: 82,25 ± 10,636 µm). Conclusion. La tomografia de coherencia optica podria situarse como un futuro biomarcador y una herramienta de apoyo para facilitar el diagnostico precoz del deterioro cognitivo y de la EA.

Addressing the bias problem in the assessment of the quality of life of patients with dementia: determinants of the accuracy and precision of the proxy ratings.

OBJECTIVES: We aimed to examine the discrepancy between patients and caregivers' ratings of quality of life in terms of accuracy and precision, and identify factors associated with it, in order to facilitate the use of this scale as dementia progresses. DESIGN: Cross-sectional analytic study. SETTING: Day care centres. PARTICIPANTS: Community-living patients with Alzheimer's disease in early or moderate stage and their principal caregivers. MEASUREMENTS: PARTICIPANTS rated patients' quality of life using DEMQOL. The discrepancy was assessed using the individual difference score and the residuals for each domain of DEMQOL. The scores on Mini-Mental State Examination, Geriatric Depression Scale, Neuropsychiatric Inventory, Clinical Insight Rating Scale, Cumulative Illness Rating Scale, Health Utilities Index Mark 3 and Zarit Burden Interview were considered as possible predictors of the discrepancy. RESULTS: A total of 276 subjects participated in the study (138 patients with Alzheimer's disease and their caregivers). Discrepancy measured by individual difference score was lower than that measured by the residuals. Burden and mood-related symptoms explained the positive differences and residuals, while pain, self-perceived depression and cognition determined the negative ones. CONCLUSIONS: Differences exist between patients and caregivers' perceptions about subjective states. The evaluations of each informant seem to be influenced by their own emotional state and the inner experience of the effects of the disease. Caregivers' ratings on DEMQOL could be useful to monitor the efficacy of any treatment whenever burden is low and patients have no great physical or emotional suffering.

Impact of alternative technique to ageing using oak chips in alcoholic or in malolactic fermentation on volatile and sensory composition of red wines.

This paper reports on a complete study of the effect of wood, in the form of oak chips, on the volatile composition and sensory characteristics of Moravia Agria wines added at different stages of the fermentation process. Aroma compounds were analyzed by gas chromatography-mass spectrometry (GC-MS). Sensory profile was evaluated by experienced wine-testers. Oak chips were added to wines in two dose rates at different stages of the winemaking process: during alcoholic fermentation (AF), during malolactic fermentation (MLF) and in young, red Moravia Agria wine. Wines fermented with oak chips during AF showed higher concentrations of the ethyl esters of straight-chain fatty acids, ethyl, hexyl, isoamyl acetates and superior alcohols than the control wines. The higher concentrations of benzene compound, oak lactones and furanic compounds were found in wines in contact with oak chips during MLF. The use of oak chips gives rise to a different sensorial profile of wines depending of the point of addition. Higher intensities of woody, coconut, vanilla and sweet spices descriptors were obtained when a large dose rate of chips was employed.

Validación de la versión española de la escala QoL-AD en pacientes con enfermedad de Alzheimer, cuidadores y profesionales sanitarios / Validation of the Spanish version of the QoL-AD Scale in alzheimer disease patients, their carers, and health professionals

Background: Quality of life (QOL) is becoming increasingly important to measure the effect of interventions on the life of patients with Alzheimer's disease (AD), particularly on the most meaningful issues. However, most of the instruments used to measure QOL have not been validated in the Spanish population. The aim of this study was to determine the psychometric properties of a Spanish version of QoL Scale in patients with AD, carers and health professionals. Material and methods: On hundred and two patients, their carers and 25 health professionals were recruited from day centres. Patients’ QOL was rated by patients, carers and health professionals. The Health Utilities Index, Clinical Insight Rating Scale and Mini Mental State Examination were also administered. Results: The internal and external reliability of QoL-AD were excellent. Criterion validity was indicated by a significant correlation of QoL-AD scores with HUI-3 and QoL-AD global item scores (p<.05). Lack of insight and cognitive impairment did not have an effect on these properties. QoL-AD scores were not significantly different between groups made according sociodemographic characteristics and cognitive impairment (p>.05). The exploratory factor analysis result revealed a three factor solution, which accounted for 61.3% of variance: health factor, functional status factor, and social relationship-environment factor. Conclusions: QoL-AD Scale has proved to be a valid and reliable instrument to measure QoL of Spanish AD patients with mild-to-moderate cognitive impairment and a wide range of anosognosia (AU)

Introducción: La calidad de vida (CV) está adquiriendo cada vez más relevancia como medida para evaluar los resultados de las distintas intervenciones terapéuticas sobre los pacientes con enfermedad de Alzheimer (EA), dado que contempla aspectos que son especialmente valiosos en su vida diaria. Sin embargo, son escasos los instrumentos para medir la CV que han sido validados en población española. El objetivo de este estudio es explorar las propiedades psicométricas de la escala QoL-AD en pacientes, cuidadores y profesionales sanitarios. Pacientes y métodos: Se seleccionó a 102 pacientes con EA en fase leve-moderada, sus cuidadores y 25 profesionales sanitarios. La CV de los pacientes fue valorada por pacientes, cuidadores y profesionales mediante la escala QoL-AD. Además, se administraron MMSE, escala de valoración de insight clínico (CIR) e índice de utilidades de salud (HUI-3). Resultados: La fiabilidad interna y externa de la escala QoL-AD fueron excelentes. La escala presenta validez de criterio dado que sus puntuaciones correlacionaron con las de HUI-3 y la medida global de CV (p<0,05). La falta de insight y el deterioro cognitivo no tuvieron un efecto sobre estas propiedades. Las puntuaciones en la escala QoL-AD no difirieron entre grupos establecidos según MMSE y factores sociodemográficos (p>0,05). En el análisis factorial se obtuvo una solución de tres factores que explica el 61,3% de la varianza: factor salud, factor estado funcional y factor relaciones sociales-ambiente. Conclusiones: La escala QoL-AD es un instrumento válido y fiable para medir la CV en la pacientes españoles con AD que presenten deterioro cognitivo leve-moderado, sea cual fuese su grado de insight (AU)

[Validation of the Spanish version of the QoL-AD Scale in alzheimer disease patients, their carers, and health professionals]. / Validación de la versión española de la escala QoL-AD en pacientes con enfermedad de Alzheimer, cuidadores y profesionales sanitarios.

BACKGROUND: Quality of life (QOL) is becoming increasingly important to measure the effect of interventions on the life of patients with Alzheimer's disease (AD), particularly on the most meaningful issues. However, most of the instruments used to measure QOL have not been validated in the Spanish population. The aim of this study was to determine the psychometric properties of a Spanish version of QoL Scale in patients with AD, carers and health professionals. MATERIAL AND METHODS: On hundred and two patients, their carers and 25 health professionals were recruited from day centres. Patients' QOL was rated by patients, carers and health professionals. The Health Utilities Index, Clinical Insight Rating Scale and Mini Mental State Examination were also administered. RESULTS: The internal and external reliability of QoL-AD were excellent. Criterion validity was indicated by a significant correlation of QoL-AD scores with HUI-3 and QoL-AD global item scores (p<.05). Lack of insight and cognitive impairment did not have an effect on these properties. QoL-AD scores were not significantly different between groups made according sociodemographic characteristics and cognitive impairment (p>.05). The exploratory factor analysis result revealed a three factor solution, which accounted for 61.3% of variance: health factor, functional status factor, and social relationship-environment factor. CONCLUSIONS: QoL-AD Scale has proved to be a valid and reliable instrument to measure QoL of Spanish AD patients with mild-to-moderate cognitive impairment and a wide range of anosognosia.

[Gene therapy for Parkinson's disease]. / Terapia génica en la enfermedad de Parkinson.

Parkinson's disease is a chronic and progressive disorder whose treatment does not prevent middle term appearance of invalidating motor and psychic complications. Gene therapy techniques which are increasingly applied in the field of neurodegenerative diseases are added to the possibility of treatment of this disease. Among the existing modalities, the in vivo strategies that use potent viral vectors are those which have obtained the best results in the different existing models of the disease. This article aims to review the information regarding the use of these latter techniques, the therapeutic trials that have been conducted and the advantages and disadvantages that the use of the different vectors have.

Terapia génica en la enfermedad de Parkinson / Gene therapy for Parkinson's disease

La enfermedad de Parkinson es un trastorno crónico y progresivo cuyo tratamiento no impide a medio plazo la aparición de complicaciones motoras y psíquicas invalidantes. Las técnicas de terapia génica de aplicación cada vez mayor en el campo de las enfermedades neurodegenerativas se suman a las posibilidades de tratamiento de esta patología. Entre las modalidades existentes, las estrategias in vivo que emplean potentes vectores virales son las que mejores resultados han obtenido en los distintos modelos existentes de la enfermedad. Este artículo pretende revisar la información referente al empleo de estas últimas técnicas, los ensayos terapéuticos que se han llevado a cabo y las ventajas e inconvenientes que tiene la utilización de los diferentes vectores

Parkinson's disease is a chronic and progressive disorder whose treatment does not prevent middle term appearance of invalidating motor and psychic complications. Gene therapy techniques which are increasingly applied in the field of neurodegenerative diseases are added to the possibility of treatment of this disease. Among the existing modalities, the in vivo strategies that use potent viral vectors are those which have obtained the best results in the different existing models of the disease. This article aims to review the information regarding the use of these latter techniques, the therapeutic trials that have been conducted and the advantages and disadvantages that the use of the different vectors have

Changes in the neuronal activity in the pedunculopontine nucleus in chronic MPTP-treated primates: an in situ hybridization study of cytochrome oxidase subunit I, choline acetyl transferase and substance P mRNA expression.

The pedunculopontine nucleus is a mesencephalic nucleus that has widespread and reciprocal connections with the basal ganglia. It has been implicated in the physiopathology of akinesia, rigidity, gait failure and sleep disorders associated with Parkinson's disease. In this study, in situ hybridization was used to examine the changes in neuronal metabolic activity (measuring cytochrome oxidase subunit I) and in the level of acetylcholine and Substance P synthesis in the pedunculopontine nucleus of monkeys chronically treated with MPTP. Significant reductions were observed in cytochrome oxidase subunit I (p = 0.001), choline acetyl transferase (p = 0.003) and substance P (p = 0.006) mRNA expression in parkinsonian animals compared with controls, indicating that pedunculopontine cholinergic neurons activity decreases with parkinsonism.

Electrospray mass spectra of group 6 (Fischer) carbenes in the presence of electron-donor compounds.

Fischer carbene complexes 1-7 are not ionized under standard electrospray ionization (ESI) conditions. We report here that unsaturated chromium and tungsten (Fischer) carbene complexes can be ionized in an electrospray ion source in the presence of electron-donor compounds such as hydroquinone (HQ) or tetrathiafulvalene (TTF). The addition of these compounds, which seem to act as electron transfer agents, permits the recording and study of their ESI mass spectra in the negative mode of detection. Both chromium and tungsten(0) carbene complexes undergo in the first fragmentation stage a double simultaneous decarbonylation process.

Synthesis of ferrocene-substituted 2-azetidinones.

The photochemical reaction of alkoxychromium(0)carbene complexes and ferrocene mono- and disubstituted imines formed 2-azetidinones having one or two ferrocene moieties in good yields. Yields decrease when the carbene moiety bears an aminoferrocene moiety attached to the carbene carbon, while complex 9 having the ferrocene directly bonded to the carbene carbon was totally inert in these reactions. Access to beta-lactams with the ferrocene tethered to the C3 position through a methylene group was gained using the lithium enolate derived from ethyl 3-ferrocenylpropanoate. The reaction of this enolate produced two unexpected processes. Thus, 2-azetidinone 15 having an hydroxyl group at the C3 position was obtained together with the expected beta-lactam 14, by reaction of the lithium enolate of ethyl 3-ferrocenylpropenoate and imine 1. Additionally, unsaturated amide 17 was obtained by base-promoted Hoffmann-like breakage of the beta-lactam ring formed in the reaction of the same enolate and imine 2. Oxidation of the anion at the C3 of the 2-azetidinone ring on compound 14, as well as the sterically driven ring-breakage of the C3 anion derived from the nonisolated 2-azetidinone 18, should be responsible for this behavior.

Pd-catalyzed inter- and intramolecular carbene transfer from group 6 metal-carbene complexes.

The use of group 6 metal-carbene complexes in inter- and intramolecular carbene transfer reactions has been studied. Thus, pentacarbonyl[(aryl)(methoxy)carbene]chromium(0) and tungsten complexes, 10, efficiently dimerize at room temperature in the presence of diverse Pd(0) and Pd(II)/Et(3)N catalysts. The effect of additives (PPh(3), AsPh(3), or SbPh(3)) on the nature and the isomeric ratio of the reaction products is negligible. The nature of the reaction products is more catalyst-dependent for metal carbenes 12 bearing alkyl groups attached to the carbene carbon. In these cases, either carbene ligand dimerization or beta-hydrogen elimination reactions are observed, depending on the catalyst. The carbene ligand dimerization reaction can be used to prepare conjugated polyenes, including those having metal moieties at both ends of the polyene system, as well as enediyne derivatives. The intramolecular carbene ligand dimerization of chromium bis-carbene complexes 28 and 30 allows the preparation of mono- and bicyclic derivatives, with ring sizes from six to nine members. For bis-carbene derivatives the beta-hydrogen elimination reaction is inhibited, provided that both metal centers are tethered by an o-xylylene group. Other alkyl complexes 32 form new mononuclear carbene complexes 37 or decompose to complex reaction mixtures. The results obtained in these reactions may be explained by transmetalation from Cr(0) to Pd(0) and the intermediacy of Pd-carbene complexes. Aminocarbene-chromium(0) complexes 15, need harsher reaction conditions to transfer the carbene ligand, and this transfer occurs only in the presence of deactivated olefins. The corresponding insertion/hydrolysis products 48 resulted in these cases. A catalytic cycle involving transmetalation from a chromacyclobutane to a palladacyclobutane is proposed to explain these results.