Dysautonomia and small fiber neuropathy in post-COVID condition and Chronic Fatigue Syndrome.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID condition can present similarities such as fatigue, brain fog, autonomic and neuropathic symptoms. METHODS: The study included 87 patients with post-COVID condition, 50 patients with ME/CFS, and 50 healthy controls (HC). The hemodynamic autonomic function was evaluated using the deep breathing technique, Valsalva maneuver, and Tilt test. The presence of autonomic and sensory small fiber neuropathy (SFN) was assessed with the Sudoscan and with heat and cold evoked potentials, respectively. Finally, a complete neuropsychological evaluation was performed. The objective of this study was to analyze and compare the autonomic and neuropathic symptoms in post-COVID condition with ME/CFS, and HC, as well as, analyze the relationship of these symptoms with cognition and fatigue. RESULTS: Statistically significant differences were found between groups in heart rate using the Kruskal-Wallis test (H), with ME/CFS group presenting the highest (H = 18.3; p ≤ .001). The Postural Orthostatic Tachycardia Syndrome (POTS), and pathological values in palms on the Sudoscan were found in 31% and 34% of ME/CFS, and 13.8% and 19.5% of post-COVID patients, respectively. Concerning evoked potentials, statistically significant differences were found in response latency to heat stimuli between groups (H = 23.6; p ≤ .01). Latency was highest in ME/CFS, and lowest in HC. Regarding cognition, lower parasympathetic activation was associated with worse cognitive performance. CONCLUSIONS: Both syndromes were characterized by inappropriate tachycardia at rest, with a high percentage of patients with POTS. The prolonged latencies for heat stimuli suggested damage to unmyelinated fibers. The higher proportion of patients with pathological results for upper extremities on the Sudoscan suggested a non-length-dependent SFN.

Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder?

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor? OBJECTIVE: To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition. METHODS: The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated. RESULTS: Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue. CONCLUSIONS: The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19.

Effects of sugammadex on incidence of postoperative residual neuromuscular blockade: a randomized, controlled study.

BACKGROUND: This study aimed to investigate whether reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade and facilitated operating room discharge readiness. METHODS: Adult patients undergoing abdominal surgery received rocuronium, followed by randomized allocation to sugammadex (2 or 4 mg kg(-1)) or usual care (neostigmine/glycopyrrolate, dosing per usual care practice) for reversal of neuromuscular blockade. Timing of reversal agent administration was based on the providers' clinical judgement. Primary endpoint was the presence of residual neuromuscular blockade at PACU admission, defined as a train-of-four (TOF) ratio <0.9, using TOF-Watch® SX. Key secondary endpoint was time between reversal agent administration and operating room discharge-readiness; analysed with analysis of covariance. RESULTS: Of 154 patients randomized, 150 had a TOF value measured at PACU entry. Zero out of 74 sugammadex patients and 33 out of 76 (43.4%) usual care patients had TOF-Watch SX-assessed residual neuromuscular blockade at PACU admission (odds ratio 0.0, 95% CI [0-0.06], P<0.0001). Of these 33 usual care patients, 2 also had clinical evidence of partial paralysis. Time between reversal agent administration and operating room discharge-readiness was shorter for sugammadex vs usual care (14.7 vs. 18.6 min respectively; P=0.02). CONCLUSIONS: After abdominal surgery, sugammadex reversal eliminated residual neuromuscular blockade in the PACU, and shortened the time from start of study medication administration to the time the patient was ready for discharge from the operating room. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov:NCT01479764.

UD Interference Test: creation and validation of a new instrument of resistance to interference. Normalisation and standardisation for Spanish population.

INTRODUCTION: The UD Interference Test measures processing speed and attention, and is based on the concept of interference of the Stroop Color and Word Test. The main purpose of the study is to provide an alternative version of the Stroop Color and Word Test that overcomes some of the limitations of previous versions in assessing individuals with daltonism or age-related reading difficulties, and to obtain normative and standardised data for the Spanish population. METHODS: This study is part of the Normacog project. We evaluated 905 individuals (age range, 18-93 years) to analyse the test's reliability and concurrent and construct validity. We evaluated the effect of age, sex, and level of education on UD Interference Test performance and calculated percentiles and age- and education-adjusted scaled scores. RESULTS: The test has good reliability (α = 0.875) and concurrent (r = 0.443-0.725; P < .001) and construct validity (r = 0.472-0.737; P < .001). We observed age and educational level to have a significant effect on UD Interference Test scores, explaining 12% to 40% of variance. Sex only had a significant effect on the resistance to interference index. CONCLUSIONS: We present an alternative version of the Stroop Color and Word Test with some advantages over previous versions. We provide standardised and normalised data for the Spanish population to correct the test according to the subject's age and level of education.

Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases.

BACKGROUND AND OBJECTIVE: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. MATERIAL AND METHODS: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. RESULTS: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. CONCLUSION: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity.

[Adolescent radiculopathy associated with extradural intraspinal tumor]. / Radiculopatía asociada a tumor intrarraquídeo extradural en adolescente.

INTRODUCTION: Expansive intra-spinal processes usually have an insidious course that makes their early diagnosis difficult. Intra-spinal tumors are classified according to their location in the spinal canal: extradural and intradural, and these are classified as extramedullary and intramedullary. At the beginning, they can cause non-specific pain conditions and, sometimes, root-type pain. The patient may have symptoms such as: loss of strength, loss of balance, loss of sensation, sphincter disorders. Intra-spinal neoplasms, when diagnosed, have an indication for surgical treatment. MATERIAL AND METHODS: The clinical case of a 14-year-old male adolescent is described, pain in the lumbar region for four years, of insidious onset, intermittent, progressive, exacerbated six months ago, with radiation to the lower extremities, which is accompanied by progressive paresthesia and paresis predominantly in the lower right limb. RESULTS: Bilateral L4 and L5 laminotomy is performed, exploration and resection of the tumor and release of nerve roots. Tumor with characteristics similar to adipose tissue is obtained, where a wide vascular network is observed inside, with an approximate size of 14 × 10 × 4 mm, ovoid in shape, flattened with a smooth and shiny surface. CONCLUSION: Spinal tumors are relatively rare tumors, however, of these tumors, the extradural intraspinal location accounts for half of the cases. In our patient, the diagnosis of lipoma of the filum terminale was integrated, which corresponds to less than 1% of all tumors of the spine.

INTRODUCCIÓN: Los procesos expansivos intrarraquídeos suelen tener una evolución insidiosa que dificultan su diagnóstico precoz. Los tumores intrarraquídeos son clasificados de acuerdo con su localización en el conducto raquídeo: extradural e intradural, y éstos se clasifican en extramedular e intramedular. Al comienzo, pueden provocar cuadros de dolor poco específicos y, a veces, dolores de tipo radicular. El paciente podrá tener síntomas como: pérdida de fuerza, pérdida de equilibrio, pérdida de sensibilidad y disturbios esfinterianos. Las neoplasias intrarraquídeas, cuando son diagnosticadas, tienen indicación de tratamiento quirúrgico. MATERIAL Y MÉTODOS: Se describe el caso clínico de adolescente masculino de 14 años, dolor en región lumbar desde hace cuatro años, de inicio insidioso, intermitente, progresivo, que se exacerba hace seis meses, con irradiación a extremidades inferiores, que se acompaña de parestesias y paresias progresivas de predominio en extremidad inferior derecha. RESULTADOS: Se realiza laminotomía L4 y L5 bilateral, exploración y resección de tumoración y liberación de raíces nerviosas. Se obtiene tumor de características similares a tejido adiposo en donde se observa amplia red vascular en su interior, con tamaño aproximado de 14 × 10 × 4 mm de forma ovoide, aplanada con superficie lisa y brillante. CONCLUSIÓN: Los tumores raquimedulares son tumores relativamente raros; sin embargo, de estos tumores, la localización intrarraquídea extradural corresponde a la mitad de los casos. En nuestro paciente, se integró el diagnóstico de lipoma del filum terminale, el cual corresponde a menos de 1% de todos los tumores de la columna vertebral.

[Brief visuospatial memory test-revised (BVMT-R): normalization and standardization for Spanish population]. / Test breve de memoria visuoespacial-revisado: normalización y estandarización de la prueba en población española.

INTRODUCTION: The brief visuospatial memory test-revised (BVMT-R) assesses visuospatial learning and memory in adults. It has equivalent forms that allow reassessing patients. AIM: To obtain normative and standardized data for the BVMT-R taking into account the sociodemographic characteristics of the Spanish population. SUBJECTS AND METHODS: The present study is part of the Normacog Project. Nine hundred three participants (18 to 93 years old) were assessed using the BVMT-R (form 1). The effect of age, level of education and gender was analyzed on the BVMT-R, and percentiles and scalar scores adjusted by age and level of education were created. RESULTS: A significant effect of age and educational level on the analyzed variables was observed (trial 1; total recall; trial 4; discrimination index), explaining from 12% to 40% of the variance. The older and less educated participants obtained lower performance in all the analyzed variables of the BVMT-R. Gender had not a significant effect in the analyzed variables. CONCLUSION: The study provides standardized and normalized data for the BVMT-R taking into account the Spanish sociodemographic characteristics. The results confirm the in?uence of age and level of education in the performance of the test, so normative data are provided to correct the BVMT-R taking into account these characteristics.

TITLE: Test breve de memoria visuoespacial-revisado: normalización y estandarización de la prueba en población española.Introducción. El test breve de memoria visuoespacial-revisado (BVMT-R) evalúa el aprendizaje y la memoria visuoespacial en población adulta. Este test cuenta con versiones paralelas que permiten su readministración. Objetivo. Obtener datos normativos y estandarizados para el BVMT-R adecuados a las características sociodemográficas de la población española. Sujetos y métodos. El estudio se enmarca dentro del proyecto Normacog. Se evaluó a 903 participantes (rango de edad: 18-93 años) con el BVMT-R (versión 1). Se analizaron el efecto de la edad, el nivel educativo y el sexo sobre el BVMT-R, y se crearon los percentiles y las puntuaciones escalares ajustadas por edad y nivel educativo. Resultados. Se observó un efecto significativo de la edad y el nivel educativo sobre todas las variables analizadas (ensayo 1, recuerdo total, ensayo 4 e índice de discriminación), que explica entre el 12 y el 40% de la varianza. Los participantes más mayores y con menor nivel educativo obtuvieron un menor rendimiento en el BVMT-R. El sexo no presentó un efecto significativo en las variables analizadas. Conclusión. Este estudio aporta baremos estandarizados y normalizados para el BVMT-R, teniendo en cuenta las características sociodemográficas de la población española. Los resultados confirman la influencia de la edad y la educación en el rendimiento del test, por lo que aportamos datos que permiten corregir el BVMT-R teniendo en cuenta dichas características.

Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases.

BACKGROUND AND OBJECTIVE: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. MATERIAL AND METHODS: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. RESULTS: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. CONCLUSION: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity.

[Hopkins Verbal Learning Test-revised: normalization and standardization for Spanish population]. / Test de aprendizaje verbal de Hopkins revisado: normalización y estandarización de la prueba en población española.

INTRODUCTION: The Hopkins Verbal Learning Test-revised (HVLT-R) was originally created with the objective of providing a short verbal memory and learning test with six alternative forms that allow the re-administration. AIM: To obtain normative and standardized data for the HVLT-R taking into account the sociodemographic characteristics of the current Spanish population. SUBJECTS AND METHODS: The study is part of the Normacog Project. Seven hundred participants (18 to 90 years old) were assessed. The effect of age, level of education and gender on the performance of HVLT-R were analyzed, and percentiles and scalar scores adjusted by age and level of education were created. RESULTS: A significant effect of age and educational level on the analyzed variables of the test was observed, explaining from 15% to 29% of the variance (trial 1, total recall, trial 4, discrimination index). As expected, the older and less educated obtained lower performance in all the analyzed variables of the HVLT-R. However, sex only had a significant effect on the variables trial 1, total recall and discrimination index. CONCLUSION: This study provides standardized and normalized data for the HVLT-R for the Spanish population, offering current norms to clinicians and researchers. The results confirm the influence of age and level of education on all the indicators of the test, so normative data are provided to correct the HVLT-R taking into account these characteristics.

TITLE: Test de aprendizaje verbal de Hopkins revisado: normalización y estandarización de la prueba en población española.Introducción. El test de aprendizaje verbal de Hopkins revisado (HVLT-R) se creó originalmente con el objetivo de proporcionar un test de aprendizaje y memoria verbal corto y con seis versiones paralelas que permitieran su readministración. Objetivo. Obtener datos normativos y estandarizados para el HVLT-R adaptado a las características sociodemográficas de la población española actual. Sujetos y métodos. El estudio se enmarca dentro del proyecto Normacog, para el cual se evaluó a 700 participantes (rango de edad: 18-90 años). Se analizó el efecto de la edad, el nivel educativo y el sexo sobre el rendimiento del HVLT-R, y se crearon los percentiles y las puntuaciones escalares ajustadas por edad y nivel educativo. Resultados. Se observó un efecto significativo de la edad y el nivel educativo sobre las variables analizadas del test, que explicaba entre el 15 y el 29% de la varianza (ensayo 1, recuerdo total, ensayo 4, índice de discriminación). Como era de esperar, a mayor edad y menor nivel educativo, el rendimiento en el HVLT-R fue menor en todas las variables analizadas. Sin embargo, el sexo presentó un efecto significativo únicamente en las variables ensayo 1, recuerdo total e índice de discriminación. Conclusión. Este estudio presenta baremos estandarizados y normalizados para el HVLT-R para población española, y ofrece normas actuales para los clínicos e investigadores. Los resultados confirman la influencia de la edad y la educación en todos los indicadores del test, por lo que se aportan datos que permiten corregir el HVLT-R teniendo en cuenta dichas características.

UD Interference Test: Creation and validation of a new instrument of resistance to interference. Normalization and standardization for Spanish population. / Test UD Interferencia: Creación y validación de un nuevo instrumento de resistencia a la interferencia. Normalización y estandarización en población española.

INTRODUCTION: The UD Interference Test measures processing speed and attention, and is based on the concept of interference of the Stroop Test. The main purpose of the study is to provide an alternative version of the Stroop Test that overcomes some of the limitations of previous versions in assessing individuals with daltonism or age-related reading difficulties, and to obtain normative and standardised data for the Spanish population. METHODS: This study is part of the Normacog project. We evaluated 905 individuals (age range, 18-93 years) to analyse the test's reliability and concurrent and construct validity. We evaluated the effect of age, sex, and level of education on UD Interference Test performance and calculated percentiles and age- and education-adjusted scaled scores. RESULTS: The test has good reliability (α = 0.875) and concurrent (r = 0.443-0.725; p < .001) and construct validity (r = 0.472-0.737; p < .001). We observed age and educational level to have a significant effect on UD Interference Test scores, explaining 12-40% of variance. Sex only had a significant effect on the resistance to interference index. CONCLUSIONS: We present an alternative version of the Stroop Color and Word Test with some advantages over previous versions. We provide standardised and normalised data for the Spanish population to correct the test according to the subject's age and level of education.

Model-based calculations of off-axis ratio of conic beams for a dedicated 6 MV radiosurgery unit.

PURPOSE: Because the small-radius photon beams shaped by cones in stereotactic radiosurgery (SRS) lack lateral electronic equilibrium and a detector's finite cross section, direct experimental measurement of dosimetric data for these beams can be subject to large uncertainties. As the dose calculation accuracy of a treatment planning system largely depends on how well the dosimetric data are measured during the machine's commissioning, there is a critical need for an independent method to validate measured results. Therefore, the authors studied the model-based calculation as an approach to validate measured off-axis ratios (OARs). METHODS: The authors previously used a two-component analytical model to calculate central axis dose and associated dosimetric data (e.g., scatter factors and tissue-maximum ratio) in a water phantom and found excellent agreement between the calculated and the measured central axis doses for small 6 MV SRS conic beams. The model was based on that of Nizin and Mooij ["An approximation of central-axis absorbed dose in narrow photon beams," Med. Phys. 24, 1775-1780 (1997)] but was extended to account for apparent attenuation, spectral differences between broad and narrow beams, and the need for stricter scatter dose calculations for clinical beams. In this study, the authors applied Clarkson integration to this model to calculate OARs for conic beams. OARs were calculated for selected cones with radii from 0.2 to 1.0 cm. To allow comparisons, the authors also directly measured OARs using stereotactic diode (SFD), microchamber, and film dosimetry techniques. The calculated results were machine-specific and independent of direct measurement data for these beams. RESULTS: For these conic beams, the calculated OARs were in excellent agreement with the data measured using an SFD. The discrepancies in radii and in 80%-20% penumbra were within 0.01 cm, respectively. Using SFD-measured OARs as the reference data, the authors found that the calculated OARs were more accurate than those measured with a microchamber or film dosimetry. CONCLUSIONS: The model produces sufficiently accurate conic beam dosimetric data that can be used to validate direct measurement results for such beams.

Radiculopatía asociada a tumor intrarraquídeo extradural en adolescente / Adolescent radiculopathy associated with extradural intraspinal tumor

Resumen: Introducción: Los procesos expansivos intrarraquídeos suelen tener una evolución insidiosa que dificultan su diagnóstico precoz. Los tumores intrarraquídeos son clasificados de acuerdo con su localización en el conducto raquídeo: extradural e intradural, y éstos se clasifican en extramedular e intramedular. Al comienzo, pueden provocar cuadros de dolor poco específicos y, a veces, dolores de tipo radicular. El paciente podrá tener síntomas como: pérdida de fuerza, pérdida de equilibrio, pérdida de sensibilidad y disturbios esfinterianos. Las neoplasias intrarraquídeas, cuando son diagnosticadas, tienen indicación de tratamiento quirúrgico. Material y métodos: Se describe el caso clínico de adolescente masculino de 14 años, dolor en región lumbar desde hace cuatro años, de inicio insidioso, intermitente, progresivo, que se exacerba hace seis meses, con irradiación a extremidades inferiores, que se acompaña de parestesias y paresias progresivas de predominio en extremidad inferior derecha. Resultados: Se realiza laminotomía L4 y L5 bilateral, exploración y resección de tumoración y liberación de raíces nerviosas. Se obtiene tumor de características similares a tejido adiposo en donde se observa amplia red vascular en su interior, con tamaño aproximado de 14 × 10 × 4 mm de forma ovoide, aplanada con superficie lisa y brillante. Conclusión: Los tumores raquimedulares son tumores relativamente raros; sin embargo, de estos tumores, la localización intrarraquídea extradural corresponde a la mitad de los casos. En nuestro paciente, se integró el diagnóstico de lipoma del filum terminale, el cual corresponde a menos de 1% de todos los tumores de la columna vertebral.

Abstract: Introduction: Expansive intra-spinal processes usually have an insidious course that makes their early diagnosis difficult. Intra-spinal tumors are classified according to their location in the spinal canal: extradural and intradural, and these are classified as extramedullary and intramedullary. At the beginning, they can cause non-specific pain conditions and, sometimes, root-type pain. The patient may have symptoms such as: loss of strength, loss of balance, loss of sensation, sphincter disorders. Intra-spinal neoplasms, when diagnosed, have an indication for surgical treatment. Material and methods: The clinical case of a 14-year-old male adolescent is described, pain in the lumbar region for four years, of insidious onset, intermittent, progressive, exacerbated six months ago, with radiation to the lower extremities, which is accompanied by progressive paresthesia and paresis predominantly in the lower right limb. Results: Bilateral L4 and L5 laminotomy is performed, exploration and resection of the tumor and release of nerve roots. Tumor with characteristics similar to adipose tissue is obtained, where a wide vascular network is observed inside, with an approximate size of 14 × 10 × 4 mm, ovoid in shape, flattened with a smooth and shiny surface. Conclusion: Spinal tumors are relatively rare tumors, however, of these tumors, the extradural intraspinal location accounts for half of the cases. In our patient, the diagnosis of lipoma of the filum terminale was integrated, which corresponds to less than 1% of all tumors of the spine.

The IL-17A rs2275913 single nucleotide polymorphism is associated with protection to tuberculosis but related to higher disease severity in Argentina.

Mycobacterium tuberculosis (Mtb) causes nearly 10 millions of new tuberculosis disease cases annually. However, most individuals exposed to Mtb do not develop tuberculosis, suggesting the influence of a human genetic component. Here, we investigated the association of the rs2275913 SNP (G → A) from IL-17A and tuberculosis in Argentina by a case-control study. Furthermore, we evaluated in vitro the functional relevance of this SNP during the immune response of the host against Mtb and analyzed its impact on clinical parameters of the disease. We found an association between the AA genotype and tuberculosis resistance. Additionally, within the healthy donors population, AA cells stimulated with a Mtb lysate (Mtb-Ag) produced the highest amounts of IL-17A and IFN-γ, which further support the genetic evidence found. In contrast, within the tuberculosis patients population, AA Mtb-Ag stimulated cells showed the lowest immunological parameters and we evidenced an association between the AA genotype and clinical parameters of disease severity, such as severe radiological lesions and higher bacilli burden in sputum. Overall, our findings demonstrated that the AA genotype from the IL-17A rs2275913 SNP is positively associated with protection to active tuberculosis but related to higher disease severity in the Argentinean population.

Oxidative stress markers in plasma and urine of prepubertal patients with type 1 diabetes mellitus.

Markers of oxidative stress were studied in plasma and urine of prepubertal patients with type 1 diabetes mellitus (DM1) with less than 5 years of disease (n = 27). The results were compared to healthy, age- and sex-matched control children (n = 27). Oxidative stress parameters evaluated included advanced oxidation protein products (AOPP), total peroxyl radical-trapping antioxidant parameter (TRAP), and F2-isoprostanes (8-epi-prostaglandin-F2: 8-isoPGF2alpha). No statistically significant differences were found for any of the oxidative stress markers assessed between patients with DM1 and controls. In addition, weight, height, and routine metabolic tests, including creatininemia and cholesterol levels, were similar between the groups. The lack of significant differences between healthy controls and patients with DM1 suggests that treatment is able to counteract the increase in free radical production.

[Montreal Cognitive Assessment Test: normalization and standardization for Spanish population]. / Test de evaluacion cognitiva de Montreal: normalizacion y estandarizacion de la prueba en poblacion española.

INTRODUCTION: The Montreal Cognitive Assessment (MoCA) is a brief screening test that assesses the general cognitive state. It has become very popular and useful as an alternative resource for the traditional Mini-Mental State Examination. AIM: To normalize and to standardize the MoCA taking into account the sociodemographic characteristics of the Spanish population (INE data, 2012). SUBJECTS AND METHODS: The present study is part of the Normacog Project. Seven hundred participants were recruited (older than 18 years old). The effect of age, level of education and sex was analyzed on the performance of MoCA and percentiles and scalar score for nine ranges of age and scalar score adjusted by the level of education. RESULTS: Results showed a significant effect of age, level of education and sex on the cognitive performance of MoCA. However, sex was only significant in two domains (attention and delayed recall). Age, education and sex explained from 1.0% to 32.3% of the variance of the performance. The older participants with lower level of formal education obtained the worse performance shown in MoCA. Percentiles and scalar score for each range of age, and scalar score adjusted by the level of education were obtained. CONCLUSION: The normative data of the MoCA is provided taking into account the Spanish sociodemographic characteristics for adults in Spain and the cut-off to distinguish between normal cognitive performance and mild cognitive impairment according to different range of ages have been proposed.

TITLE: Test de evaluacion cognitiva de Montreal: normalizacion y estandarizacion de la prueba en poblacion española.Introduccion. La evaluacion cognitiva de Montreal (MoCA) es un test de cribado breve que evalua el estado cognitivo general, y resulta un recurso alternativo, muy util, al tradicional test minimental. Objetivo. Normalizar y estandarizar el test MoCA, teniendo en cuenta las caracteristicas sociodemograficas de la poblacion española (datos INE, 2012). Sujetos y metodos. El estudio se enmarca dentro del proyecto Normacog, en el que se evaluo a 700 participantes (18-86 años). Se analizaron el efecto de la edad, el nivel educativo y el sexo sobre el rendimiento del test MoCA, y se crearon los percentiles, las puntuaciones escalares para nueve rangos de edad y la puntuacion escalar normalizada ajustada por edad y nivel educativo. Resultados. Los resultados mostraron un efecto significativo de la edad, el nivel educativo y el sexo sobre el rendimiento cognitivo en el test MoCA. Sin embargo, el sexo solo presento un efecto significativo sobre dos dominios cognitivos: atencion y recuerdo diferido. La edad, la educacion y el sexo explicaron entre el 1% y el 32,3% de la varianza en las variables analizadas del test. Los participantes mas mayores con menor nivel de educacion formal obtuvieron peor rendimiento cognitivo. Se obtuvieron los percentiles y las puntuaciones escalares para cada rango de edad y la puntuacion escalar normalizada individual. Conclusion. Se presentan los datos normativos del test MoCA adecuados a las caracteristicas sociodemograficas de la sociedad española y los puntos de corte propuestos para discriminar entre rendimiento cognitivo normal y deterioro cognitivo leve segun los diferentes rangos de edad.

Influence of postnatal-development on I(f) occurrence and properties in neonatal rat ventricular myocytes.

OBJECTIVE: I(f) is a hyperpolarization-activated current, which plays a key role in determining the spontaneous rate of cardiac pacemaker cells. We have previously shown that I(f) is also expressed in left ventricular myocytes isolated from spontaneously hypertensive rats; in these cells, its occurrence and density is linearly related with the severity of myocardial hypertrophy. Since hypertrophy induces a re-expression of genes encoding fetal proteins, we investigated changes in I(f) properties during post-natal development. METHODS: Fresh ventricular myocytes were enzymatically isolated from the heart of 1-2- to 28-day-old Wistar rats. The whole-cell configuration of the patch-clamp technique was employed to record the action potential and I(f). RESULTS: Membrane capacitance, an index of cell size, progressively increased from 13 +/- 1 pF at 1-2 days to 66 +/- 4 pF at 28 days of age (p < 0.01). At 1-2 days, a cesium-sensitive hyperpolarization-activated inward current (I(f)) was recorded in the majority of tested cells (n = 51). The midpoint of the activation curve (V1/2) was -78 +/- 2 mV (n = 32), and specific current conductance of fully activated I(f) (gf.max) was 60 +/- 11 pS/pF. Reversal potential (Vrev) measured by tail-current analysis was -24 +/- 3 mV (n = 8). Reduction of extracellular Na+ from 140 to 35 mM or extracellular K+ from 25 to 5.4 mM caused a shift of -12 +/- 1 mV (n = 3) or -11 +/- 2 mV (n = 5) of Vrev, respectively. Occurrence of I(f) decreased with aging, being present in 64%, 48% and 32% of cells at 10, 15 and 28 days, respectively. When present, I(f) density was significantly smaller than at 1-2 days (p < 0.05), reaching a value of 8 +/- 2 pS/pF at 28 days. However, V1/2 did not change in the older rats, being -80 +/- 2, -83 +/- 4 and -85 +/- 3 mV at 10, 15 and 28 days, respectively. Vrev at 10 and 15 days was -27 and -28 mV, respectively, thus suggesting that channel selectivity did not change. CONCLUSIONS: The pacemaker current, I(f), is expressed in ventricular myocytes from neonatal rats and progressively disappears; when present, it shows electrophysiological properties similar to I(f) re-expressed in hypertrophied adult rat ventricular myocytes. Thus, it is likely that the occurrence of I(f) in ventricular myocytes of hypertrophied and failing hearts is due to the re-expression of a fetal gene.

Modulation of the pacemaker current If by beta-adrenoceptor subtypes in ventricular myocytes isolated from hypertensive and normotensive rats.

OBJECTIVE: Both beta 1- and beta 2-adrenoceptors (beta 1-AR and beta 2-AR) are functionally present in human and rat ventricular myocytes. The two receptor subtypes are differently regulated during the development of myocardial hypertrophy and failure. I(f) is expressed in human and rat ventricular myocytes. In hypertrophied myocytes isolated from old spontaneously hypertensive rats (SHR) the density is much larger than in age-matched normotensive Wistar Kyoto (WKY). Due to the possible relevance of I(f) as an arrhythmogenic mechanism in the rat and human ventricle, we studied and compared the effects of beta 1-AR and beta 2-AR stimulation on I(f) in both hypertrophied and normal left ventricular myocytes of 18-month old SHR and WKY. METHODS: The whole-cell configuration of the patch-clamp technique was employed. Noradrenaline (NA, 1 microM) was used to stimulate beta 1-AR and isoprenaline (ISO, 1 microM) in the presence of the beta 1-AR antagonist CGP 20712A (0.1 microM) to stimulate beta 2-AR. RESULTS: In SHR, NA increased I(f) by causing a 10.8 +/- 0.9 mV (n = 10) positive shift in the voltage of maximal activation (V1/2); this effect was completely reversed by CGP 20712A. beta 2-AR stimulation was effective in seven out of 13 cells tested, where it caused a small positive shift in V1/2 (4.0 +/- 1.7 mV). Cyclopentyladenosine (CPA), a selective A1-receptor agonist, reversed the effect of NA; the antiadrenergic action of CPA was abolished in cells pre-incubated with pertussis toxin (PTX) to block inhibitory G proteins (Gi). In PTX-treated cells the shift in V1/2 caused by both beta 2-AR (9.6 +/- 1.7 mV, n = 6, p < 0.05) and beta 1-AR (17.6 +/- 1.9 mV, n =7, p < 0.05) was significantly greater than in control cells. Both beta-AR subtypes modulated I(f) activation also in WKY: beta 1-AR shifted V1/2 by 16.0 +/- 1.4 mV (n = 15) and beta 2-AR by 4.2 +/- 1.1 mV (n = 7). However, in PTX-treated WKY cells only the beta 2-AR effect was potentiated (shift in V1/2: 11.4 +/- 1.4 mV, n = 9, p < 0.01), while the beta 1-AR response was unchanged (18.9 +/- 4.2 mV, n = 5, n.s.). CONCLUSIONS: I(f) expressed in SHR hypertrophied ventricular myocytes is modulated by catecholamines mainly through the stimulation of the beta 1-AR subtype. The beta 1-AR response is, however, significantly lower than that observed in myocytes from normotensive rats, probably as a consequence of the presence of an increased inhibitory activity of Gi proteins. This post-receptorial control may be seen as a mechanism to limit the arrhythmogenicity of beta-AR stimulation in myocardial hypertrophy and failure.

Long-term treatment of spontaneously hypertensive rats with losartan and electrophysiological remodeling of cardiac myocytes.

OBJECTIVE: Cardiac hypertrophy due to pressure overload is associated with several cellular electrophysiological alterations such as prolongation of action potential duration (APD), decrease in transient outward current (Ito) and occurrence of the pacemaker current I(f). These alterations may play a role in sudden arrhythmic death, which is a major risk factor in myocardial hypertrophy and failure. Since angiotensin II is a key signal for myocyte hypertrophy, we tested if an 8-week treatment of old spontaneously hypertensive rats (SHR) with the antagonist of type-1 angiotensin II receptor (AT1), losartan (10 mg/kg/day), was able to influence the cellular electrophysiologic remodeling associated with cardiac hypertrophy. METHODS: Left ventricular myocytes were isolated from control (CTR) or losartan-treated (LOS) 18-month old SHR. Patch-clamped LVM were superfused with a normal Tyrode's solution (to measure action potential) or appropriately modified Tyrode's solution (to measure Ito and I(f)). RESULTS: Heart weight to body weight ratio (HW/BW) was significantly smaller in LOS (5.69 +/- 0.25 mg/g) than in CTR rats (6.67 +/- 0.37 mg/g; P < 0.05). Membrane capacitance, an index of cell size, was significantly reduced in LOS (342 +/- 12, n = 92) vs. CTR (422 +/- 14 pF, n = 96, P < 0.001). APD was significantly shorter in LOS than in CTR (at -60 mV: 197 +/- 23 vs. 277 +/- 19 ms, n = 28, P < 0.001); this effect was paralleled by a larger maximum Ito density in the LOS group (LOS: 15.1 +/- 1.4 pA/pF, CTR: 10.0 +/- 0.8 pA/pF) (n = 27, P < 0.02). I(f), elicited by hyperpolarizing steps (range: -60 to -130 mV), was consistently recorded in SHR cells; however, its maximal specific conductance was significantly lower in LOS than in CTR rats (28.6 +/- 3.6 vs. 54.2 +/- 8.0 pS/pF, n = 55, P < 0.001). Voltage of half-maximal activation (V1/2) of both Ito and I(f) was unchanged by the treatment. CONCLUSIONS: AT1 receptor blockade with losartan prevents the development of myocyte hypertrophy and associated electrophysiological alterations in old SHR.

Effect of 5-HT4 receptor stimulation on the pacemaker current I(f) in human isolated atrial myocytes.

OBJECTIVE: 5-HT4 receptors are present in human atrial cells and their stimulation has been implicated in the genesis of atrial arrhythmias including atrial fibrillation. An I(f)-like current has been recorded in human atrial myocytes, where it is modulated by beta-adrenergic stimulation. In the present study, we investigated the effect of serotonin (5-hydroxytryptamine, 5-HT) on I(f) electrophysiological properties, in order to get an insight into the possible contribution of I(f) to the arrhythmogenic action of 5-HT in human atria. METHODS: Human atrial myocytes were isolated by enzymatic digestion from samples of atrial appendage of patients undergoing coeffective cardiac surgery. Patch-clamped cells were superfused with a modified Tyrode's solution in order to amplify I(f) and reduce overlapping currents. RESULTS AND CONCLUSIONS: A time-dependent, cesium-sensitive increasing inward current, that we had previously described having the electrophysiological properties of the pacemaker current I(f), was elicited by negative steps (-60 to -130 mV) from a holding potential of -40 mV. Boltzmann fit of control activation curves gave a midpoint (V1/2) of -88.9 +/- 2.6 mV (n = 14). 5-HT (1 microM) consistently caused a positive shift of V1/2 of 11.0 +/- 2.0 mV (n = 8, p < 0.001) of the activation curve toward less negative potentials, thus increasing the amount of current activated by clamp steps near the physiological maximum diastolic potential of these cells. The effect was dose-dependent, the EC50 being 0.14 microM. Maximum current amplitude was not changed by 5-HT. 5-HT did not increase I(f) amplitude when the current was maximally activated by cAMP perfused into the cell. The selective 5-HT4 antagonists, DAU 6285 (10 microM) and GR 125487 (1 microM), completely prevented the effect of 5-HT on I(f). The shift of V1/2 caused by 1 microM 5-HT in the presence of DAU 6285 or GR 125487 was 0.3 +/- 1 mV (n = 6) and 1.0 +/- 0.6 mV (n = 5), respectively (p < 0.01 versus 5-HT alone). The effect of 5-HT4 receptor blockade was specific, since neither DAU 6285 nor GR 125487 prevented the effect of 1 microM isoprenaline on I(f). Thus, 5-HT4 stimulation increases I(f) in human atrial myocytes; this effect may contribute to the arrhythmogenic action of 5-HT in human atrium.