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INTRODUCTION Advances in the treatment of myasthenia gravis (MG) have improved quality of life and prognosis for the majority of patients. However, 10%-20% of patients present refractory MG, with frequent relapses and significant functional limitations. PATIENTS AND METHODS Patients with refractory MG were selected from a cohort of patients diagnosed with MG between January 2008 and June 2019. Refractory MG was defined as lack of response to treatment with prednisone and at least 2 immunosuppressants, inability to withdraw treatment without relapse in the last 12 months, or intolerance to treatment with severe adverse reactions. RESULTS We identified 84 patients with MG, 11 of whom (13%) met criteria for refractory MG. Mean (standard deviation) age was 47 (18) years; 64% of patients with refractory MG had early-onset generalised myasthenia (as compared to 22% in the group of patients with MG; P

Resumen Introduccion La miastenia gravis ocular (MGo) es la forma de presentacion de la enfermedad mas frecuente. Un porcentaje variable de estos pacientes desarrollan una forma generalizada (MGg), siendo los factores de riesgo de conversion y el efecto protector del tratamiento inmunosupresor objeto de controversia en el momento actual. Pacientes y metodos Disenamos un estudio monocentrico retrospectivo, con el objetivo de describir las caracteristicas demograficas, clinicas y de laboratorio de una cohorte espanola de MGo, a partir de una serie de MG registrada en el Hospital Universitario de Albacete desde enero del 2008 hasta febrero de 2020. Resultados Seleccionamos 62 pacientes con MGo de una cohorte de 91 sujetos con MG (68,1%). La mediana de edad al diagnostico fue de 68 (RIQ 52-75,3), con predominio de MGo de inicio muy tardio (n = 34, 54,8%) y de varones (n = 38, 61,3%). La diplopia binocular fue el sintoma inicial mas frecuente (51,7%). La tasa de conversion a MGg fue del 50% (n = 31), con una mediana de tiempo de seis meses (RIQ 2-12,8). Encontramos asociacion significativa entre ser mujer (OR: 5,46, IC 95% 1,16-25-74, p = 0,03) y tener AcAchR (OR: 8,86, IC 95% 1,15-68,41, p = 0,04), con el riesgo de desarrollar una MGg. Conclusiones La tasa de conversion de MGo en nuestra serie es relativamente elevada. La generalizacion tiene lugar principalmente durante los primeros dos anos de evolucion y esta asociada al sexo femenino y, sobre todo, a la presencia de AcAchR.

La asociación de meningioangiomatosis (MA) con displasia cortical focal (DCF) ha sido escasamente publicada. Presentamos el caso de una adolescente de 15 años con antecedentes de epilepsia farmacorresistente de 10 años de evolución, sin historia de neurofibromatosis. La imagen de resonancia magnética mostró un aumento de volumen del hipocampo y de la región parahipocampal derecha. La lesión fue interpretada como posible tumor. Se realizó en este caso una lobectomía temporal derecha guiada por electrocorticografía (ECoG) intraoperatoria. El estudio histológico evidenció una DCF tipo IIIc (MA predominantemente vascular asociada a DCF). La paciente se encuentra libre de crisis (escala de Engel IA) luego de 4 años de evolución postquirúrgica. Ante la sospecha de MA, se recomienda realizar estudios de ECoG intraoperatoria por la posible asociación con DCF en la neocorteza perilesional lo que pudiera incrementar su incidencia y el conocimiento sobre estas dos lesiones. El estudio histológico proporciona el diagnóstico definitivo.

Obesity is a global health issue, in which modifications in gut microbiota composition have a key role. Different therapeutic strategies are being developed in combination with diet and exercise, including the use of plant extracts, such as those obtained from Morus alba L. leaves. Recent studies have revealed their anti-inflammatory and antioxidant properties. The aim of the present work was to evaluate whether the beneficial effects of M. alba L. leaf extract in high-fat diet-induced obesity in mice is correlated with its impact on gut microbiota. The extract reduced body weight gain and attenuated lipid accumulation, as well as increased glucose sensitivity. These effects were associated with an amelioration of the obesity-associated inflammatory status, most probably due to the described antioxidant properties of the extract. Moreover, M. alba L. leaf extract mitigated gut dysbiosis, which was evidenced by the restoration of the Firmicutes/Bacteroidota ratio and the decrease in plasma lipopolysaccharide (LPS) levels. Specifically, the extract administration reduced Alistipes and increased Faecalibaculum abundance, these effects being correlated with the beneficial effects exerted by the extract on the obesity-associated inflammation. In conclusion, anti-obesogenic effects of M. alba L. leaf extract may be mediated through the amelioration of gut dysbiosis., Junta de Andalucia CTS 164, Instituto de Salud Carlos III PI19.01058, Spanish Government AGL2015-67995-C3-3-R, perational Programme of the Region of Murcia (CCI) 2007ES161PO001 14-20/20, European Commission, Instituto de Salud Carlos III, i-pFIS, Instituto de Salud Carlos III; Programa de Doctorado Biomedicina, pFIS, Instituto de Salud Carlos III; Programa de Doctorado Nutricion

The SARS-CoV-2 infection has increased the number of patients entering Intensive Care Unit (ICU) facilities and antibiotic treatments. Concurrently, the multi-drug resistant bacteria (MDRB) colonization index has risen. Considering that most of these bacteria are derived from gut microbiota, the study of its composition is essential. Additionally, SARS-CoV-2 infection may promote gut dysbiosis, suggesting an effect on microbiota composition. This pilot study aims to determine bacteria biomarkers to predict MDRB colonization risk in SARS-CoV-2 patients in ICUs. Seventeen adult patients with an ICU stay >48 h and who tested positive for SARS-CoV-2 infection were enrolled in this study. Patients were assigned to two groups according to routine MDRB colonization surveillance: non-colonized and colonized. Stool samples were collected when entering ICUs, and microbiota composition was determined through Next Generation Sequencing techniques. Gut microbiota from colonized patients presented significantly lower bacterial diversity compared with non-colonized patients (p < 0.05). Microbiota in colonized subjects showed higher abundance of Anaerococcus, Dialister and Peptoniphilus, while higher levels of Enterococcus, Ochrobactrum and Staphylococcus were found in non-colonized ones. Moreover, LEfSe analysis suggests an initial detection of Dialister propionicifaciens as a biomarker of MDRB colonization risk. This pilot study shows that gut microbiota profile can become a predictor biomarker for MDRB colonization in SARS-CoV-2 patients., Junta de Andalucía (CTS 164; CV20-77708), Instituto de Salud Carlos III (PI19/01058; PI20/01447, Fundación Andaluza de Farmacia Hospitalaria” (3095/2020).

Lactobacillus probiotics contained in dietary supplements or functional foods are wellknown for their beneficial properties exerted on host health and diverse pathological situations. Their capacity to improve inflammatory bowel disease (IBD) and regulate the immune system is especially remarkable. Although bacteria–host interactions have been thought to occur directly, the key role that extracellular vesicles (EVs) derived from probiotics play on this point is being unveiled. EVs are lipid bilayer-enclosed particles that carry a wide range of cargo compounds and act in different signalling pathways. Notably, these EVs have been recently proposed as a safe alternative to the utilisation of live bacteria since they can avoid the possible risks that probiotics may entail in vulnerable cases such as immunocompromised patients. Therefore, this review aims to give an updated overview of the existing knowledge about EVs from different Lactobacillus strains, their mechanisms and effects in host health and different pathological conditions. All of the information collected suggests that EVs could be considered as potential tools for the development of future novel therapeutic approaches., Junta de Andalucia CTS 164 PY20_01157, Instituto de Salud Carlos III European Commission PI19/01058 European Commission

Los estudios sobre exportaciones a nivel de firmas abundan en Colombia, pero son escasos los estudios sobre el mercado importador y las firmas que importan. Este trabajo busca cerrar esa brecha describiendo el mercado importador, la dinámica importadora de las firmas y el papel que jugaron en ese mercado en el periodo 1995-2019. Para hacerlo, el estudio usa la información disponible en la declaración de importación (DIAN Formulario 500) que los importadores deben hacer para poder nacionalizar la mercancía. El estudio encuentra que el mercado de importaciones presenta gran heterogeneidad, pocos agentes responden por un alto porcentaje del valor importado; muchos importadores compran bienes por bajos montos; las firmas tienen unas altas tasas de entrada y de salida; un pequeño número de firmas importaron todos los años; y los productos que no se importan tienen más medidas no arancelarias que aquellos que se importan.

Evolving data show a variable expression of clinical neurological manifestations in patients suffering with coronavirus disease 2019 (COVID-19) from early disease onset. The most frequent symptoms and signs are fatigue, dizziness, impaired consciousness, ageusia, anosmia, radicular pain, and headache, as well as others. Based on the high number of series of cases reported, there is evidence for the implication of the immune system in the pathological mechanism of COVID-19. Although the exact role of the immunological mechanism is not elucidated, two main mechanisms are suggested which implicate the direct effect of severe acute respiratory syndrome coronavirus 2 infection in the central nervous system and neuroinflammation. In the context of neurological manifestations associated with COVID-19, neuropsychiatric disorders show an exacerbation and are described by symptoms and signs such as depression, anxiety, mood alterations, psychosis, post-traumatic stress disorder, delirium, and cognitive impairment, which appear to be common in COVID-19 survivors. A worsened score on psychopathological measures is seen in those with a history of psychiatric comorbidities. We review the neuropsychiatric manifestations associated with COVID-19 and some critical aspects of the innate and adaptive immune system involved in mental health disorders occurring in COVID-19.

El artículo examina los efectos de la inversión pública y privada en infraestructura de transporte sobre la economía colombiana en el corto y largo plazo. En particular, analiza la evolución histórica de la infraestructura de transporte; revisa el marco institucional y las reformas realizadas en los últimos años, examina las características de la inversión destinada a la infraestructura de transporte y estima la contribución de la infraestructura al crecimiento económico. Además, caracteriza la evolución de la actividad portuaria y estima los efectos económicos de corto plazo de las inversiones en infraestructura realizadas en las regiones. Se encuentra que la inversión en infraestructura de transporte en Colombia ha sido históricamente baja, lo que ha limitado su crecimiento económico. Además, existe un sesgo de largo plazo que restringe la inversión pública en infraestructura de transporte, la cual exhibe un comportamiento procíclico. Por otro lado, subsisten fallas institucionales de planeación, regulación y de gobierno corporativo que dificultan el desarrollo del sector. En consecuencia, la contribución de la infraestructura de transporte al crecimiento económico ha disminuido y su rezago constituye una barrera, para el comercio externo e interno. Estos factores han llevado a que la infraestructura de transporte en Colombia se encuentre rezagada internacionalmente

Overweight and obesity are well-known independent risk factors for stroke in the general population although uncertain in the case of the elderly, according to the obesity paradox. Little is known about underlying mechanisms. Our study aims to assess whether there is a relationship between excess body weight (measured as waist circumference) and poor cerebral hemodynamics (measured by transcranial Doppler parameters: basal, mean flow velocity (MFV), and dynamic, cerebrovascular reserve (CvR) in the right middle cerebral artery (RMCA)). A possible underlying molecular mechanism was analyzed via plasma leptin, adiponectin, TNF-α, IL-6, VCAM, and CRP levels. One hundred sixty-five subjects were included. Bivariate and multivariate regression showed a linear correlation between waist circumference and hemodynamics in RMCA, with clear gender effects: MFV (global NS, men β − 0.26 p

Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of individuals worldwide. Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected. We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection. Patients were confirmed by microbiological/serological testing, or on chest CT semiology. Available data on co-morbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed. A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes. A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis. In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease. Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%). Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi). Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type. Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004). Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%). In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas. Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis. The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4–6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012–2.225; P = 0.043). Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality. We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition.

We aimed to evaluate the diagnostic value of orbital ultrasound in the etiologic diagnosis of central retinal artery occlusion (CRAO). For this purpose, patients with CRAO evaluated at our center between 2011 and 2021 were reviewed. Demographic variables, vascular risk factors and ultrasound findings were collected. An orbital duplex was performed in all cases and complemented with other diagnostic explorations. We attended 36 cases of CRAO. In all patients, orbital ultrasound confirmed the diagnosis of CRAO: in 75% emboli material (spot sign) was observed in CRA and in 25% flow alteration in CRA without visible embolus. The positive spot sign (PSS) group differed from patients with negative spot sign (NSS) in terms of etiology: 8 PSS cases (29.6%) had a major cardioembolic cause, 4 (14.8%) a large vessel atheromatous disease, 15 (55.6%) an undetermined cause. Some 21 (77.8%) PSS patients had some minor cardioembolic cause, mainly calcifications of the left valves. In the NSS group, 2 (22%) were diagnosed with giant cell arteritis (GCA). In CRAO, the ultrasound spot sign could be a guide for the detection of embolic sources. Its absence makes it necessary to consider more strongly the possibility of arteritis. Furthermore, our findings suggest a key role of calcium embolism in PSS patients.

This historical cohort study evaluated clinical characteristics of progression and prognosis in adults with thymidine kinase 2 deficiency (TK2d). Records were available for 17 untreated adults with TK2d (mean age of onset, 32 years), including longitudinal data from 6 patients (mean follow-up duration, 26.5 months). Pearson's correlation assessed associations between standard motor and respiratory assessments, clinical characteristics, and laboratory values. Longitudinal data were assessed by linear regression mixed models. Respiratory involvement progressed at an annual rate of 8.16% decrement in forced vital capacity (FVC). Most patients under noninvasive ventilation (NIV) remained ambulant (12/14, 86%), reduced FVC was not associated with concomitant decline in 6-minute walk test (6MWT), and 6MWT results were not correlated with FVC. Disease severity, assessed by age at NIV onset, correlated most strongly at diagnosis with: creatinine levels (r = 0.8036; P = 0.0009), followed by FVC (r = 0.7265; P = 0.0033), mtDNA levels in muscle (r = 0.7933; P = 0.0188), and age at disease onset (r = 0.7128; P = 0.0042). This population of adults with TK2d demonstrates rapid deterioration of respiratory muscles, which progresses independently of motor impairment. The results support FVC at diagnosis, mtDNA levels in muscle, and age at disease onset as prognostic indicators. Creatinine levels may also be potentially prognostic, as previously reported in other neuromuscular disorders.

[Background and objective] TK2 deficiency (TK2d) is a rare mitochondrial disorder that manifests predominantly as a progressive myopathy with a broad spectrum of severity and age of onset. The rate of progression is variable, and the prognosis is poor due to early and severe respiratory involvement. Early and accurate diagnosis is particularly important since a specific treatment is under development. This study aims to evaluate the diagnostic value of lower limb muscle MRI in adult patients with TK2d., [Methods] We studied a cohort of 45 genetically confirmed patients with mitochondrial myopathy (16 with mutations in TK2, 9 with mutations in other nuclear genes involved in mitochondrial DNA [mtDNA] synthesis or maintenance, 10 with single mtDNA deletions, and 10 with point mtDNA mutations) to analyze the imaging pattern of fat replacement in lower limb muscles. We compared the identified pattern in patients with TK2d with the MRI pattern of other non-mitochondrial genetic myopathies that share similar clinical characteristics., [Results] We found a consistent lower limb muscle MRI pattern in patients with TK2d characterized by involvement of the gluteus maximus, gastrocnemius medialis, and sartorius muscles. The identified pattern in TK2 patients differs from the known radiological involvement of other resembling muscle dystrophies that share clinical features., [Conclusions] By analyzing the largest cohort of muscle MRI from patients with mitochondrial myopathies studied to date, we identified a characteristic and specific radiological pattern of muscle involvement in patients with TK2d that could be useful to speed up its diagnosis., This work was supported in part by the Instituto de Salud Carlos III and FEDER (PI18/01374 to MA.M and PMP15/00025 to CP, MO and MAM.). CD-G, CP, NM and MO are members of the European Reference Network for Neuromuscular Diseases (EURO-NMD) and MO is member of XUECs (Xarxes d'Unitats d'Expertesa Clínica en Malalties Minoritàries de Catalunya).

RESUMEN Introducción: El término trastornos del neurodesarrollo incluye diferentes combinaciones de deficiencias en las habilidades esperadas para la edad cronológica de un niño, considerando las esferas motoras, del lenguaje, la socialización, sensorial y el control de esfínter, y en los pacientes afectados pueden asociarse algunas enfermedades (comorbilidad). Objetivo: Examinar las principales comorbilidades crónicas que pueden presentarse en pacientes con trastornos del neurodesarrollo. Métodos: Las fuentes de búsquedas fueron las bases de datos computarizadas: PubMed, Ebsco, SciELO. Además, referencias identificadas en los artículos revisados y que se consideraron importantes y con validez científica. con diez años o menos de publicación, 42/59 se publicaron en los últimos cinco años. Se utilizaron para la búsqueda las palabras clave: trastornos del neurodesarrollo, desarrollo infantil, comorbilidad, trastorno autístico; en idioma español, inglés, o francés, en dependencia de la fuente Resultados: Las comorbilidades más frecuentes, o importantes por su implicación en la vida de los pacientes con trastornos del neurodesarrollo son: la epilepsia, los trastornos de la audición y la visión, las enfermedades mentales, las dificultades en la deglución y el estado nutricional deficiente. Consideraciones finales: La ocurrencia de comorbilidad en pacientes con trastornos del neurodesarrollo es frecuente, puede presentarse en el sistema nervioso o en otros sistemas del organismo y contribuye a que la calidad de vida de estos pacientes se afecte en mayor cuantía.

Autosomal dominant mutations in the TWNK gene, which encodes a mitochondrial DNA helicase, cause adult-onset progressive external ophthalmoplegia (PEO) and PEO-plus presentations. In this retrospective observational study, we describe clinical and complementary data from 25 PEO patients with mutations in TWNK recruited from the Hospital 12 de Octubre Mitochondrial Disorders Laboratory Database. The mean ages of onset and diagnosis were 43 and 63 years, respectively. Family history was positive in 22 patients. Ptosis and PEO (92% and 80%) were the most common findings. Weakness was present in 48%, affecting proximal limbs, neck, and bulbar muscles. Exercise intolerance was present in 28%. Less frequent manifestations were cardiac (24%) and respiratory (4%) involvement, neuropathy (8%), ataxia (4%), and parkinsonism (4%). Only 28% had mild hyperCKemia. All 19 available muscle biopsies showed signs of mitochondrial dysfunction. Ten different TWNK mutations were identified, with c.1361T>G (p.Val454Gly) and c.1070G>C (p.Arg357Pro) being the most common. Before definitive genetic confirmation, 56% of patients were misdiagnosed (36% with myasthenia, 20% with oculopharyngeal muscle dystrophy). Accurate differential diagnosis and early confirmation with appropriately chosen complementary studies allow genetic counseling and the avoidance of unnecessary treatments. Thus, mitochondrial myopathies must be considered in PEO/PEO-plus presentations, and particularly, TWNK is an important cause when positive family history is present.

Introduction: The histological composition of the clot influences its mechanical properties, affects the efficacy of endovascular treatment (EVT), and could determine the clinical outcome of patients with acute ischemic stroke (AIS). Insights into clot composition may guide therapeutic decision-making prior to EVT and facilitate revascularization therapies.Material and Methods: Consecutive patients with AIS recorded in a prospective single-center reperfusion registry from December 2015 to December 2019 and treated with EVT were included. Baseline, laboratory [including post-procedural C-reactive protein (CRP)], radiological, and angiographic variables were analyzed. We aimed to study the relationship between histological composition of the clot with basal neuroimaging, laboratory markers, and recanalization technique. The secondary outcome was to analyze the correlation between clot composition and functional outcome at 3 months assessed by the modified Rankin scale (mRS).Results: From the study period, 360 AIS patients treated with EVT were included, of whom 189 (53%) fulfilled the inclusion criteria. One hundred (53%) cases of fibrin-predominant clot (FPC) were recorded. Full recanalization in FPC cases was achieved with higher probability when stent retrievers (SR) were selected as the first-line device (68.2%, p = 0.039). Patients with FPC had higher levels of CRP (p = 0.02), lower frequency of the hyperdense middle cerebral artery (HMCA) in baseline imaging (p = 0.039), and higher rates of mortality (p = 0.012). The multivariate analysis showed that the absence of HMCA (OR = 0.420; 95% CI 0.197–0.898; p = 0.025) and higher levels of CRP (OR = 1.01; 95% CI 1.003–1.019; p = 0.008) were predictors of FPC. Leukocytes and platelet counts were not associated with clot histology.Conclusions: The absence of HMCA and higher levels of CRP were markers of FPC. In patients with FPC, complete recanalization was most likely to be achieved when a SR was selected as first line of treatment. Mortality was higher in patients within this histologic group.

Este trabajo explica cómo los costos de comerciar (protección y otros costos) desestimulan las exportaciones manufactureras y por qué Colombia exporta mayoritariamente productos primarios. Para esto, además de una revisión de literatura y una descripción del desempeño exportador colombiano, se presenta una metodología que mide la protección total causada por el arancel y las medidas no arancelarias (MNA) y que permite generar una serie de la protección verdadera para el período 1950-2019. Los resultados muestran que el país no ha explotado su potencial exportador de manufacturas porque los incentivos para hacerlo han sido magros, un resultado de la alta protección a la producción local, de una infraestructura escasa y de unos servicios logísticos costosos.

ObjectiveThe coronavirus disease 2019 (COVID-19) has spread worldwide since December 2019. Neurologic symptoms have been reported as part of the clinical spectrum of the disease. We aimed to determine whether neurologic manifestations are common in hospitalized patients with COVID-19 and to describe their main characteristics.MethodsWe systematically reviewed all patients diagnosed with COVID-19 admitted to the hospital in a Spanish population during March 2020. Demographic characteristics, systemic and neurologic clinical manifestations, and complementary tests were analyzed.ResultsOf 841 patients hospitalized with COVID-19 (mean age 66.4 years, 56.2% men), 57.4% developed some form of neurologic symptom. Nonspecific symptoms such as myalgias (17.2%), headache (14.1%), and dizziness (6.1%) were present mostly in the early stages of infection. Anosmia (4.9%) and dysgeusia (6.2%) tended to occur early (60% as the first clinical manifestation) and were more frequent in less severe cases. Disorders of consciousness occurred commonly (19.6%), mostly in older patients and in severe and advanced COVID-19 stages. Myopathy (3.1%), dysautonomia (2.5%), cerebrovascular diseases (1.7%), seizures (0.7%), movement disorders (0.7%), encephalitis (n = 1), Guillain-Barré syndrome (n = 1), and optic neuritis (n = 1) were also reported, but less frequent. Neurologic complications were the main cause of death in 4.1% of all deceased study participants.ConclusionsNeurologic manifestations are common in hospitalized patients with COVID-19. In our series, more than half of patients presented some form of neurologic symptom. Clinicians need to maintain close neurologic surveillance for prompt recognition of these complications. The mechanisms and consequences of severe acute respiratory syndrome coronavirus type 2 neurologic involvement require further studies.

RESUMEN Objetivo: Describir los aspectos de mayor relevancia en niños y adolescentes con crisis sintomáticas agudas o diagnóstico de epilepsia, en tiempo de pandemia de la COVID-19. Métodos: La información se obtuvo de las bases de datos PubMed/Medline, Scielo, y Clinical Key utilizando palabras clave incluidas en el Descriptor de Ciencias de la Salud en idioma inglés o español, sin límite de tiempo, y todo tipo de publicación; se seleccionaron los artículos relacionados con epilepsia, crisis epilépticas, y COVID-19. Resultados: En la literatura se justifica la ocurrencia de crisis epilépticas por varias causas en enfermos con la COVID-19 y se insiste en la conducta terapéutica y la necesidad de vigilancia de las interacciones farmacológicas entre los medicamentos indicados para la prevención de recurrencia de las crisis epilépticas y los específicos para esta nueva enfermedad. Basado en estos criterios, presentamos una propuesta para la conducta a seguir en cada situación. Consideraciones finales: Esta comprobada la posibilidad de que ocurran complicaciones neurológicas en pacientes con la COVID-19 y específicamente en las crisis epilépticas y la epilepsia. El uso de interferón y lopinavir/ritonavir, en caso de estar indicado en los protocolos de actuación, y el mantenimiento del tratamiento previo con los medicamentos para prevenir la recurrencia de crisis en los epilépticos, considerando las posibles interacciones y la vigilancia requerida en cada caso, parece ser la mejor opción en la mayoría de los niños y adolescentes con COVID-19.

BackgroundImproper regulation of apoptosis has been postulated as one of the main factors that contributes to the etiology and/or progression of several prevalent diseases, including ischemic stroke and neurodegenerative pathologies. Consequently, in the last few years, there has been an ever-growing interest in the in vivo study of apoptosis. The clinical application of the tissue sampling and imaging approaches to analyze apoptosis in neurological diseases is, however, limited. Since apoptotic bodies are membrane vesicles that are released from fragmented apoptotic cells, it follows that the presence of these vesicles in the bloodstream is likely due to the apoptotic death of cells in tissues. We therefore propose to use circulating apoptotic bodies as biomarkers for measuring apoptotic death in patients with ischemic stroke and neurodegenerative diseases.ResultsSince there is no scientific literature establishing the most appropriate method for collecting and enumerating apoptotic bodies from human blood samples. Authors, here, describe a reproducible centrifugation-based method combined with flow cytometry analysis to isolate and quantify plasma apoptotic bodies of patients with ischemic stroke, multiple sclerosis, Parkinson’s disease and also in healthy controls. Electron microscopy, dynamic light scattering and proteomic characterization in combination with flow cytometry studies revealed that our isolation method achieves notable recovery rates of highly-purified intact apoptotic bodies.ConclusionsThis easy, minimally time consuming and effective procedure for isolating and quantifying plasma apoptotic bodies could help physicians to implement the use of such vesicles as a non-invasive tool to monitor apoptosis in patients with cerebrovascular and neurodegenerative diseases for prognostic purposes and for monitoring disease activity.

Background: The coronavirus disease 2019 (COVID-19) has spread worldwide since December 2019 Spain is one of the most affected countries, with high incidence a

BackgroundMutations in the metalloendopeptidase (MME) gene were initially identified as a cause of autosomal recessive Charcot-Marie-Tooth disease type 2 (CMT2). Subsequently, variants in MME were linked to other late-onset autosomal dominant polyneuropathies. Thus, our goal was to define the phenotype and mode of inheritance of patients carrying changes in MME.MethodsWe screened 197 index cases with a hereditary neuropathy of the CMT type or distal hereditary motor neuropathy (dHMN) and 10 probands with familial amyotrophic lateral sclerosis (fALS) using a custom panel of 119 genes. In addition to the index case subjects, we also studied other clinically and/or genetically affected and unaffected family members.ResultsWe found 17 variants in MME in a total of 20 index cases, with biallelic MME mutations detected in 13 cases from nine families (three in homozygosis and six in compound heterozygosis) and heterozygous variants found in 11 families. All patients with biallelic variants had a similar phenotype, consistent with late-onset axonal neuropathy. Conversely, the phenotype of patients carrying heterozygous mutations was highly variable [CMT type 1 (CMT1), CMT2, dHMN and fALS] and mutations did not segregate with the disease.ConclusionMME mutations that segregate in an autosomal recessive pattern are associated with a late-onset CMT2 phenotype, yet we could not demonstrate that MME variants in heterozygosis cause neuropathy. Our data highlight the importance of establishing an accurate genetic diagnosis in patients carrying MME mutations, especially with a view to genetic counselling.

Resumen: Objetivos: Comprobar si han existido variaciones en la etiología del ictus isquémico en los últimos años e investigar las posibles causas que lo justifiquen. Pacientes y métodos: Análisis de los antecedentes epidemiológicos y factores de riesgo vascular de los pacientes diagnosticados de ictus isquémico en el Complejo Hospitalario Universitario de Albacete (CHUA) entre 2009 y 2014. La clasificación etiológica del ictus isquémico se realizó según los criterios TOAST. Se compararon los resultados con los de la clásica Stroke Data Bank (SDB) y se contrastaron ambas series con otros registros hospitalarios publicados en el periodo que las separa. Resultados: Se analiza a 1.664 pacientes, 58% varones, mediana de edad 74 años. Según la clasificación etiológica los resultados obtenidos son (CHUA/SDB): aterotrombóticos (12%/9%), lacunares (13%/25%), cardioembólicos (32%/19%), causa infrecuente (3%/4%) e indeterminados (40%/44%). El 63% de los pacientes del CHUA era mayor de 70 años, en la SDB solo el 42% superaba esa edad. En ambos registros el subtipo cardioembólico era más prevalente en mayores de 70 años. La HTA no tratada era más frecuente en la SDB (SDB = 31% vs. CHUA = 10%). El análisis de otras bases de datos muestra una tendencia progresiva a escala mundial al aumento en la prevalencia del ictus cardioembólico. Conclusiones: Nuestro estudio muestra tanto en nuestro centro como a escala mundial una disminución del porcentaje de ictus lacunares y un aumento del de cardioembólicos respecto a la SDB. Estas diferencias pudieran justificarse por el envejecimiento de los pacientes, el mejor control de la HTA actualmente y mayor capacidad para detectar arritmias cardioembólicas en las Unidades de Ictus. Abstract: Objectives: We aimed to determine whether the aetiology of ischaemic stroke has changed in recent years and, if so, to ascertain the possible reasons for these changes. Patients and methods: We analysed the epidemiological history and vascular risk factors of all patients diagnosed with ischaemic stroke at Complejo Hospitalario Universitario de Albacete (CHUA) from 2009 to 2014. Ischaemic stroke subtypes were established using the TOAST criteria. Our results were compared to data from the classic Stroke Data Bank (SDB); in addition, both series were compared to those of other hospital databases covering the period between the two. Results: We analysed 1664 patients (58% were men) with a mean age of 74 years. Stroke aetiology in both series (CHUA, SDB) was as follows: atherosclerosis (12%, 9%), small-vessel occlusion (13%, 25%), cardioembolism (32%, 19%), stroke of other determined aetiology (3%, 4%), and stroke of undetermined aetiology (40%, 44%). Sixty-three percent of the patients from the CHUA and 42% of the patients from the SDB were older than 70 years. Cardioembolic strokes were more prevalent in patients older than 70 years in both series. Untreated hypertension was more frequent in the SDB (SDB = 31% vs CHUA = 10%). The analysis of other databases shows that the prevalence of cardioembolic stroke is increasing worldwide. Conclusions: Our data show that the prevalence of lacunar strokes is decreasing worldwide whereas cardioembolic strokes are increasingly more frequent in both our hospital and other series compared to the SDB. These differences may be explained by population ageing and the improvements in management of hypertension and detection of cardioembolic arrhythmias in stroke units. Palabras clave: Base de Datos de Ictus, Etiología del ictus, Subtipos de ictus, TOAST, Factores de riesgo vascular, Fibrilación auricular, Keywords: Stroke Data Bank, Stroke aetiology, Stroke subtypes, TOAST, Vascular risk factors, Atrial fibrillation

Recent studies based on experimental animal models of stroke have suggested that uncoupling protein 2 (UCP2), an inner mitochondrial membrane protein that is thought to regulate energy metabolism and reduce reactive oxygen species generation, provides protection against reperfusion damage. We aimed to investigate whether -866G/A polymorphism in the promoter of the UCP2 gene, which enhances its transcriptional activity, is associated with functional prognosis in patients with embolic ischemic stroke after early recanalization. We investigate a hospital-based prospective cohort of patients with acute ischemic stroke due to occlusion of the middle cerebral artery diagnosed by transcranial Doppler who obtained a partial/complete recanalization 24 h after administration of intravenous thrombolysis. The main end point of the study was functional independence defined as modified Rankin Scale 0-2 on day 90. A total of 80 patients were enrolled. The UCP2-866G/A polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism technique (14 genotype A/A (18%), 45 genotype A/G (56%) and 21 genotype G/G (26%). The percentage of patients with good functional outcome at 3 months was significantly higher in patients harboring the A/A genotype than in those with A/G or G/G genotypes (85 vs 41%, p = 0.01). The A/A genotype was found to be an independent marker of good prognosis after adjustment for secondary variables (age, sex, glucose level, NIHSS score at baseline, complete recanalization and early neurological improvement) in a logistic regression analysis (OR 0.05, 95% CI 0.01-0.48, p = 0.01). Our results suggest that the AA genotype of UCP2-866 may predict a better functional outcome in ischemic stroke after recanalization of proximal MCA occlusion.

El libro examina el desempeno del sector externo colombiano desde 1950 con enfasis en las politicas de comercio exterior, las instituciones que disenan y ejecutan la politica, y los efectos de la proteccion sobre los costos de participar en el comercio internacional, , la productividad de la economia, y los incentivos para exportar. La publicacion desarrolla estos temas en tres secciones. La primera examina la historia de la politica comercial, las instituciones del sector externo y la participacion de Colombia en el comercio mundial. La segunda parte cuantifica los costos de comerciar y el monto de la proteccion a la produccion local, esencialmente la manufacturera, en el periodo 1950-2016. La tercera parte cuantifica los desincentivos para exportar y el impacto del proteccionismo sobre la productividad del sector manufacturero. A lo largo del libro se explica como durante setenta anos la economia colombiana experimento cambios importantes en su politica comercial y en las instituciones que gobiernan el sector externo. Aunque en distintas epocas se busco liberalizar el comercio, el proteccionismo reino durante todo el periodo. Casi siempre, las razones coyunturales determinaron los intentos de libera lizacion, y en muy contadas ocasiones puede decirse que la busqueda de una apertura a la competencia externa obedecio a un proposito genuino de liberalizar el comercio con el fin de hacer mas productiva y eficiente a la economia colombiana. Al tiempo que los instrumentos de control crecieron y cambiaron en el tiempo, volcandose hacia un uso intensivo de las medidas no arancelarias, el andamiaje institucional y regulatorio se torno mas extenso y complejo, afectando la calidad de las instituciones del sector. En resumen, el libro concluye que Colombia no ha explotado su potencial exportador porque los incentivos para hacerlo han sido magros, un resultado de la alta proteccion a la produccion nacional, de una infraestructura y de unos servicios logisticos ineficientes y costosos. Una apertura verdadera de la economia contribuiria a a reducir los costos de comerciar, a aumentar la productividad en forma significativa y a crear incentivos para exportar bienes de mayor valor agregado, todo ello en beneficio de una participacion mas intensiva de Colombia en las redes de comercio internacional.

Dysregulation of apoptosis may contribute to the etiology and/or progression of several prevalent diseases, including stroke and neurodegenerative pathologies. So, detection of the apoptotic processes in patients would be useful in daily clinical practice, However, thein vivoanalysis of apoptosis that occurs in tissue has limitations. We therefore propose to use circulating apoptotic bodies as biomarkers for measuring apoptotic death in patients. Since there is no scientific literature establishing the most appropriate method for measuring apoptotic bodies from human blood samples, we here describe a reproducible centrifugation-based method combined with electron microscopy, dynamic light scattering and flow cytometry studies to isolate, characterize and quantify plasma apoptotic bodies of patients with ischemic stroke, multiple sclerosis and Parkinson’s disease. The analysis revealed that our isolation protocol achieves notable recovery rates of highly-purified intact apoptotic bodies. This easy and rapid procedure would help physicians to implement the use of plasma apoptotic bodies analysis as a non-invasive tool to monitor apoptotic death in neurological patients for prognostic purposes and for following disease activity and assessing drug effectiveness.

Objectives The best revascularization technique for tandem carotid occlusions is not clearly defined. The primary objective of this study is to describe our technical and clinical results, analyzing the main predictors of functional independence. The secondary objective is the analysis of stent reocclusion rate. Methods A single-center series of 250 mechanical thrombectomies in the anterior circulation was studied. A subsequent analysis of 40 carotid occlusions was performed. The demographics, etiology, angiographic results, antithrombotic drugs, and 3-month follow-up were registered. A bivariate analysis was performed to establish the association of the study variables with major clinical complications (death, symptomatic hemorrhagic transformation and early recurrence) and the functional prognosis. In addition, the relationship between the preprocedure antiaggregation regimen and the reocclusions was studied, as well as its clinical impact. Independent predictive factors were studied using a multivariate logistic regression model. Results Complete recanalization was achieved in 30 cases (75%). Simultaneous stent placement was decided in 32 cases (80%). Functional independence was reached in 19 cases (47.5%), and 3 (7.5%) died at 3 months. Seven major complications were reported (17.5%). In patients with satisfactory revascularization where a carotid stent was used, 9 reocclusions (28.1%) were detected during the follow-up, 2 of them symptomatic. The only factor related independently with functional independence was the administration of single antiaggregation (odds ratio = .31; 95% confidence interval .002-.595; P = .021). Conclusions Urgent endovascular treatment of tandem carotid occlusions has shown to be effective and safe in our series. The administration of single antiaggregation is a predictor of functional independence. In patients treated with carotid stent, the reocclusion rate is high, but generally asymptomatic.

[Background] TK2 gene encodes for mitochondrial thymidine kinase, which phosphorylates the pyrimidine nucleosides thymidine and deoxycytidine. Recessive mutations in the TK2 gene are responsible for the ‘myopathic form’ of the mitochondrial depletion/multiple deletions syndrome, with a wide spectrum of severity., [Methods] We describe 18 patients with mitochondrial myopathy due to mutations in the TK2 gene with absence of clinical symptoms until the age of 12., [Results] The mean age of onset was 31 years. The first symptom was muscle limb weakness in 10/18, eyelid ptosis in 6/18, and respiratory insufficiency in 2/18. All patients developed variable muscle weakness during the evolution of the disease. Half of patients presented difficulty in swallowing. All patients showed evidence of respiratory muscle weakness, with need for non-invasive Mechanical Ventilation in 12/18. Four patients had deceased, all of them due to respiratory insufficiency. We identified common radiological features in muscle magnetic resonance, where the most severely affected muscles were the gluteus maximus, semitendinosus and sartorius. On muscle biopsies typical signs of mitochondrial dysfunction were associated with dystrophic changes. All mutations identified were previously reported, being the most frequent the in-frame deletion p.Lys202del. All cases showed multiple mtDNA deletions but mtDNA depletion was present only in two patients., [Conclusions] The late-onset is the less frequent form of presentation of the TK2 deficiency and its natural history is not well known. Patients with late onset TK2 deficiency have a consistent and recognizable clinical phenotype and a poor prognosis, due to the high risk of early and progressive respiratory insufficiency., This work was supported by research grants of Plan Nacional de I + D + I and Instituto de Salud Carlos III (ISCIII), Subdirección General de Evaluación y Fomento de la Investigación Sanitaria”, project PI16–01843 (CP), PI16/00579 and CP09/00011 for CJM and the European Regional Development Fund (FEDER a way to achieve Europe). MAM has received funding from the Spanish ISCIII (grant PI 15/00431). A multicentric grant funded by the ISCIII (PMP15/00025 to MAM, RM, MO, CP).

Esta nota explica en detalle la forma como calculamos la magnitud de las medidas no arancelarias que se aplicaron al comercio exterior colombiano en el periodo 1991-2014 y cuyos resultados fueron publicados en el Borrador de Economia Numero 817 de 2014: “Una vision general de la politica comercial colombiana entre 1950 y 2012”. La informacion original que usamos para este trabajo se anexa a esta nota en un archivo electronico a disposicion del publico, pues parte de esta informacion ya no se encuentra disponible en el sitio donde originalmente se publico. Como complemento de lo anterior, se describe la politica de restricciones cuantitativas antes de 1991.

ResumenLa neurocisticercosis es la enfermedad parasitaria más frecuente del sistema nervioso central. Es causada por las larvas de Taenia solium, las cuales pueden estar alojadas en distintas localizaciones anatómicas. En países como España existe una prevalencia en ascenso debido, principalmente, a la inmigración desde regiones endémicas. Las formas extraparenquimatosas son menos frecuentes, pero más graves por su tendencia a producir complicaciones. La neuroimagen desempeña un papel primordial en el diagnóstico y seguimiento de esta enfermedad, apoyada en la serología y un contexto clínico-epidemiológico compatible. El tratamiento de elección son los fármacos cisticidas albendazol y praziquantel, habitualmente se asocian a estos corticoides y, cuando corresponde, la cirugía. Se presenta un caso de neurocisticercosis con afectación simultánea intraventricular y subaracnoidea en su forma racemosa gigante.AbstractNeurocysticercosis is the most frequent parasitic disease of the central nervous system. It is caused by the larvae of Taenia solium, which can affect different anatomical sites. In Spain there is an increasing prevalence mainly due to immigration from endemic areas. The extraparenchymal forms are less common, but more serious because they usually develop complications. Neuroimaging plays a major role in the diagnosis and follow-up of this disease, supported by serology and a compatible clinical and epidemiological context. First-line treatments are cysticidal drugs such as albendazole and praziquantel, usually coadministered with corticosteroids, and in some cases surgery is indicated. We here report a case of neurocysticercosis with simultaneous intraventricular and giant racemose subarachnoid involvement.

Este trabajo presenta la estimacion de costos y tiempos de comerciar en Colombia para cada eslabon de la cadena logistica. Los resultados se derivan de la encuesta aplicada por el Banco de la Republica a agentes especializados en la logistica de comercio exterior afiliados a la Federacion Colombiana de Agentes Logisticos en Comercio Internacional (FITAC). La colaboracion de FITAC y sus miembros fue fundamental para generar esta informacion, dado su conocimiento sobre las actividades de importacion y exportacion y su papel estrategico en integrar los eslabones de la cadena logistica. Para las importaciones los costos se calculan para 13 categorias de servicios logisticos desde el puerto de embarque en el pais de procedencia hasta la bodega del importador, y en el caso de las exportaciones desde la bodega del productor hasta el puerto colombiano donde se embarca la mercancia. Adicionalmente, se presentan cifras sobre el tiempo que toma importar y exportar una mercancia.