Repositorio Institucional Fleni
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Meditation Increases the Entropy of Brain Oscillatory Activity
We address the hypothesis that the entropy of neural dynamics indexes the intensity and quality of conscious content. Previous work established that serotonergic psychedelics can have a dysregulating effect on brain activity, leading to subjective effects that present a considerable overlap with the phenomenology of certain meditative states. Here we propose that the prolonged practice of meditation results in endogenous increased entropy of brain oscillatory activity. We estimated the entropy of band-specific oscillations during the meditative state of traditions classified as 'focused attention' (Himalayan Yoga), 'open monitoring' (Vipassana), and 'open awareness' (Isha Shoonya Yoga). Among all traditions, Vipassana resulted in the highest entropy increases, predominantly in the alpha and low/high gamma bands. In agreement with previous studies, all meditation traditions increased the global coherence in the gamma band, but also stabilized gamma-range dynamics by lowering the metastability. Finally, machine learning classifiers could successfully generalize between certain pairs of meditation traditions based on the scalp distribution of gamma band entropies. Our results extend previous findings on the spectral changes observed during meditation, showing how long-term practice can lead to the capacity for achieving brain states of high entropy. This constitutes an example of an endogenous, self-induced high entropy state.Fil: Martínez Vivot, Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina. Instituto de Física de Buenos Aires; Argentina. Instituto de Investigaciones Biomédicas UCA-CONICET (BIOMED); Argentina.Fil: Pallavicini, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina. Instituto de Física de Buenos Aires; Argentina. Instituto de Investigaciones Biomédicas UCA-CONICET (BIOMED); Argentina. Fleni; Argentina.Fil: Zamberlan, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina. Instituto de Física de Buenos Aires; Argentina.Fil: Vigo, Daniel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Investigaciones Biomédicas UCA-CONICET (BIOMED); Argentina.Fil: Tagliazucchi, Enzo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina. Instituto de Física de Buenos Aires; Argentina
New Tools for Quantitative Diagnosis of Parkinson's Disease Based on Scale Invariance of Acceleration Signals
Background: Movement disorders are neurologic syndromes that produce abnormal movements, being Parkinson’s disease (PD) the most frequent. Current diagnosis of Parkinson’s disease is clinical: it is based on expertise, which can result in diagnostic errors and treatment deficits. Quantitative diagnosis is reached searching objective parameters, a quantity that correlates with the phenomenon we want to quantify. Quantitative measures of movement are a novel approach to assist physicians in the
diagnosis of Parkinson’s disease. Objective: To find a quantitative feature in accelerometery signals that distinguishes parkinsonian patients from age-matched control subjects. Method: We designed and developed an ergonomic wristband with proper electronics attached, including inertial sensors and control logic to manage the data signals. Additionally, we developed a mobile app for logging and administration of data signals. We measured limb acceleration in two groups of people: a group of patients with Parkinson’s disease (n = 11) and an age-matched control group (n = 10). Acceleration signals were measured during the evaluation of finger tapping (from the motor subscore of the Unified Parkinson’s Disease Rating Scale - UPDRS part III). To characterize the signals, we developed mathematical tools based on the analysis of temporal and frequency patterns. Power spectrum analysis of the signals exhibited a power law relationship between variables with different frequency ranges. Results: Interpreting the finger tapping task as an input to the motor system, variations in the scale invariance bandwidth can be related to the mechanic system's control response. Analyzing the power spectrum of the patient group signals, a statistical relevant reduction (p<0.005) is found in the frequency range that follows a power law (Linear Invariance Range, LIR) compared to the control group. LIR quantity calculated correlates with the gold standard clinical diagnosis MDS-UPDRS-III. Conclusion: The LIR quantity allows proposing a reduction of the scale. The quantity LIR found is proposed as a possible signal related biomarker of Parkinson’s disease.Fil: Bianchi, Gianfranco. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Laboratorio de Neuroingeniería; Argentina. Fleni. Departamento de Neurología. Servicio de Movimientos Anormales; Argentina.Fil: Ameghino, Lucía. Fleni. Departamento de Neurología. Servicio de Movimientos Anormales; Argentina.Fil: Tela, Marcela. Fleni. Departamento de Neurología. Servicio de Movimientos Anormales; Argentina.Fil: Terroba Chambi, Cinthia. Fleni. Departamento de Neurología. Servicio de Movimientos Anormales; Argentina.Fil: Rossi, Malco. Fleni. Departamento de Neurología. Servicio de Movimientos Anormales; Argentina.Fil: Merello, Marcelo. Fleni. Departamento de Neurología. Servicio de Movimientos Anormales; Argentina.Fil: Andrés, Daniela S. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Laboratorio de Neuroingeniería; Argentina
Environmental factors between normal and superagers in an Argentine cohort
Normal aging usually brings age-related cognitive decline. However, there is a group of aged individuals who have exceptional memory performance: the superagers.
Objective: Our aim was to identify the environmental factors that could influence exceptional memory performance in a cohort of Argentine individuals.
Methods: Forty healthy volunteers >80 years of age were classified into two groups, superagers (SA, n=20) and normal agers (NA, n=20), according to the Northwestern SuperAging Program criteria. Participants were neuropsychologically tested and evaluated on environmental aspects: working status, education, bilingualism, cognitive reserve, physical activity, social networking, clinical comorbidities, and longevity of parents and siblings.
Results: Both groups were highly educated (NA=16.3±3 years; SA 15.85±2.6; p=0.6), 11.8% of the sample was still working without differences between groups. There were no differences in cognitive reserve inventory (p=0.7), physical activity engagement (p=0.423), or social network index (p=0.73). As for longevity, 44% of the siblings lived longer than 80 years of age (p=0.432) and maternal longevity was linked to SA (NA=46.7%; SA=80%; p=0.045).
Conclusions: This study is a pilot approximation to the superaging population in Argentina. Our results suggest that environmental factors related to successful aging do not differentiate superaging. SA may depend on variables yet to be identified, probably of a genetic/metabolic order.Fil: Calandri, Ismael Luis. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Crivelli, Lucía. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Martín, María Eugenia. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Egido, Noelia. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Magrath Guimet, Nahuel. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina. Universidad de la Costa; Colombia
Thalamic tumors in children: case series from our institution and literature review
Purpose: To describe a case series of children with thalamic tumors treated at our institution in a 5-year period.
Method: A retrospective and observational study was performed. The records of 15 patients between 2013 and 2018 were analyzed.
Results: From 2013 to 2018, 15 patients were treated at our institution. The male to female index was 1.5, and the median age was 8.9 (IQR 4.75-13). Seven (46%) tumors were left-sided, seven (46%) were right-sided, and one (6%) was bilateral. All patients were symptomatic at the time of treatment. Motor deficit was the most common form of presentation (73%). Gross-total resection was performed in two (13.3%) patients, subtotal resection was performed in two other patients (13.3%), and for the rest of the patients (73.3%), the chosen surgical approach was a stereotactic-guided biopsy. The average of procedures was 3.4, mostly related to the treatment for hydrocephalus. Twelve patients (80%) received treatment for hydrocephalus. Nine patients (75%) were treated with ventriculoperitoneal shunts, and four patients (33%) underwent endoscopic third ventriculostomy. High-grade tumors predominated. Grade IV tumors were diagnosed in six patients (40%), followed by grade III in four patients (26.6%), grade II in three (20%) patients, and grade I in two (13.3%) patients. Chemotherapy was given in 93% of the cases, being temozolomide, the most used drug.
Conclusion: The clinical and surgical approaches for thalamic tumors in children have changed over time. At our institution, the lesser invasive surgical procedures are now being used more frequently.Fil: Giovannini, Sebastián Juan María. Hospital de Pediatría Juan P. Garrahan. Departamento de Neurocirugía Pediátrica; Argentina. Fleni. Departamento de Neurocirugía; Argentina.Fil: Renedo, Daniela. Hospital de Pediatría Juan P. Garrahan. Departamento de Neurocirugía Pediátrica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Neurocirugía; Argentina.Fil: Ferraro, Florencia. Hospital de Pediatría Juan P. Garrahan. Departamento de Neurocirugía Pediátrica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Neurocirugía; Argentina. Hospital Británico. Departamento de Neurocirugía; Argentina.Fil: Ruiz Johnson, Agustín. Hospital de Pediatría Juan P. Garrahan. Departamento de Neurocirugía Pediátrica; Argentina.Fil: Argañaraz, Romina. Hospital de Pediatría Juan P. Garrahan. Departamento de Neurocirugía Pediátrica; Argentina.Fil: Pérez Zabala, Joaquín. Hospital de Pediatría Juan P. Garrahan. Departamento de Neurocirugía Pediátrica; Argentina. Hospital Central de San Isidro. Departamento de Neurocirugía; Argentina.Fil: Zemma, Elena. Hospital de Pediatría Juan P. Garrahan. Departamento de Neurocirugía Pediátrica; Argentina.Fil: Mantese, Beatriz. Hospital de Pediatría Juan P. Garrahan. Departamento de Neurocirugía Pediátrica; Argentina
Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism
Human embryonic and induced pluripotent stem cells (hESCs and hiPSCs) are self-renewing human pluripotent stem cells (hPSCs) that can differentiate to a wide range of specialized cells. Notably, hPSCs enhance their undifferentiated state and self-renewal properties in hypoxia (5% O2). Although thoroughly analyzed, hypoxia implication in hPSCs death is not fully determined. In order to evaluate the effect of chemically mimicked hypoxia on hPSCs cell survival, we analyzed changes in cell viability and several aspects of apoptosis triggered by CoCl2 and dimethyloxalylglycine (DMOG). Mitochondrial function assays revealed a decrease in cell viability at 24 h post-treatments. Moreover, we detected chromatin condensation, DNA fragmentation and CASPASE-9 and 3 cleavages. In this context, we observed that P53, BNIP-3, and NOXA protein expression levels were significantly up-regulated at different time points upon chemical hypoxia induction. However, only siRNA-mediated downregulation of NOXA but not HIF-1α, HIF-2α, BNIP-3, and P53 did significantly affect the extent of cell death triggered by CoCl2 and DMOG in hPSCs. In conclusion, chemically mimicked hypoxia induces hPSCs cell death by a NOXA-mediated HIF-1α and HIF-2α independent mechanism.Fil: Sevlever, Gustavo Emilio. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Isaja, Luciana. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Mucci, Sofía. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Vera, Jonathan. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Rodríguez Varela, María Soledad. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Marazita, Mariela Claudia. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Morris-Hanon, Olivia. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Videla-Richardson, Guillermo Agustín. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Scassa, María Elida. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Romorini, Leonardo. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina
Bruton's tyrosine kinase inhibitors: a promising emerging treatment option for multiple sclerosis
Fil: Carnero Contentti, Edgar. Hospital Alemán de Buenos Aires; Argentina.Fil: Correale, Jorge. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina
Cervicodorsal extramedullary anaplastic ependymoma with intracranial metastasis
Fil: Marcó del Pont, Francisco. Fleni. Departamento de Neurocirugía; Argentina.Fil: Villamil, Facundo. Fleni. Departamento de Neurocirugía; Argentina.Fil: Lorefice, Fernando. Fleni. Departamento de Neurología; Argentina.Fil: Caffaratti, Guido. Fleni. Departamento de Neurología; Argentina.Fil: Ries Centeno, Tomás. Fleni. Departamento de Neurología; Argentina.Fil: Ruella, Mauro E. Fleni. Departamento de Neurología; Argentina.Fil: Mormandi, Rubén. Fleni. Departamento de Neurología; Argentina
LB82 Effect of Ofatumumab on Serum Immunoglobulin Levels and Infection Risk in Relapsing Multiple Sclerosis Patients from the Phase 3 ASCLEPIOS I and II Trials
Fil: Correale, Jorge. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina.Fil: de Seze, Jérôme. University Hospital of Strasbourg; Francia.Fil: Bar-Or, Amit. University of Pennsylvania. Perelman School of Medicine. Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology; Estados Unidos.Fil: Cross, Anne H. Washington University School of Medicine; Estados Unidos.Fil: Kappos, Ludwig. University Hospital and University of Basel. Departments of Medicine, Clinical Research,
Biomedicine and Biomedical Engineering. Neurologic Clinic and Policlinic; Suiza.Fil: Selmaj, Krzysztof. Center for Neurology; Polonia.Fil: Wiendl, Heinz. University of Muenster; Alemania.Fil: Kerloeguen, Cecile. Novartis Pharma AG; Suiza.Fil: Goodyear, Alexandra. Novartis Pharmaceuticals Corporation; Estados Unidos.Fil: Pingili, Ratnakar. Novartis Pharmaceuticals Corporation; Estados Unidos.Fil: Sullivan, Roseanne. Novartis Pharmaceuticals Corporation; Estados Unidos.Fil: Gupta, Ayan Das. Novartis Healthcare; India.Fil: Jehl, Valentine. Novartis Pharma AG; Suiza.Fil: Häring, Dieter A. Novartis Pharma AG; Suiza.Fil: Merschhemke, Martin. Novartis Pharma AG; Suiza.Fil: Hauser, Stephen L. University of California. UCSF Weill Institute for Neurosciences. Department of Neurology; Estados Unidos
Glioma del nervio óptico en paciente adulto con presentación hemorrágica tratado mediante abordaje endoscópico transesfenoidal extendido
The optic nerve glioma is a very uncommon entity in adult patients, with little information about its natural history and
therapeutical management. We report the case of a 27-year-old patient with acute involvement of the left optic nerve due
to intratumoral hemorrhage, a very uncommon form of presentation in this type of tumor. Resection was performed using
an extended transsphenoidal endoscopic approach, with functional preservation of the contralateral optic pathway. The
histopathology confirmed positive pilocytic astrocytoma with KIAA 1549-BRAF rearrangement and without BRAFV600E
mutation. Considering the histopathology and molecular biology, the contralateral visual stability and the wide surgical
resection, it was decided not to perform further treatment. The purpose of this decision was to avoid additional damage to the
chiasm, contralateral optic nerve and/or hypothalamus. Given the limited data available in medical literature, the report of this
case could contribute with additional information on the management and therapeutic approach of this type of tumors.Fil: Diez, Blanca. Fleni. Departamento de Neurología. Servicio de Neurooncología; Argentina.Fil: Rabadán, Alejandra T. Instituto Argentino de Diagnóstico y Tratamiento IADT. Neurocirugía; Argentina.Fil: Hernández, Diego. Instituto Argentino de Diagnóstico y Tratamiento IADT. Diagnóstico por Imágenes; Argentina.Fil: Varela, Analía. Instituto Argentino de Diagnóstico y Tratamiento IADT. Diagnóstico por Imágenes; Argentina.Fil: Rubianes, Javier. Instituto Argentino de Diagnóstico y Tratamiento IADT. Terapia Intensiva; Argentina
The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma
Background: Clear cell renal cell carcinoma (ccRCC), the most aggressive renal cancer, is characterized by early lymph node metastases and bad prognosis. Most therapies targeting advanced or metastatic ccRCC are based, as first-line treatment, on the administration of the vascular endothelial growth factor (VEGF) neutralizing antibody termed Bevacizumab. Despite proven benefits, the expected results were not obtained for the majority of patients. The possibility that an intricate interplay between angiogenesis and immune-checkpoints might exist lead us to evaluate tumor angiogenesis, by means of VEGF expression together with the immune checkpoint HLA-G/ILT4.
Methods: Tumor specimens were obtained from patients from two separate cohorts: One from "Evita Pueblo" Hospital from Berazategui, (Buenos Aires, Argentina) and the second includes patients surgically operated at the Urology Department of Saint-Louis Hospital (Paris, France) with a confirmed ccRCC diagnosis. Immunohistochemistry was performed with specific antibodies directed against HLA-G, VEGF-A, VEGF-C, D240, CD34, ILT4 and Ca-IX. In addition, gene expression levels were measured in a cell line derived from a ccRCC patient by semi-quantitative RT-PCR.
Results: Our results show that the highly vascularized tumors of ccRCC patients express high levels of VEGF and the immune-checkpoint HLA-G. In addition, ILT4, one of the HLA-G receptors, was detected on macrophages surrounding tumor cells, suggesting the generation of an immune-tolerant microenvironment that might favor tumorigenesis. Notably, RT-qPCR analysis provided the first evidence on the transcriptional relationship between HLA-G/ILT4 and the VEGF family. Namely, in the presence of HLA-G or ILT4, the levels of VEGF-A are diminished whereas those of VEGF-C are increased.
Conclusions: In an effort to find new therapeutic molecules and fight against metastasis dissemination associated with the poor survival rates of ccRCC patients, these findings provide the rationale for co-targeting angiogenesis and the immune checkpoint HLA-G.Fil: Miriuka, Santiago Gabriel. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: García, Marcela N. Universidad Nacional de La Plata. Faculty of Medical Sciences. Chair of Cytology, Histology and Embryology; Argentina.Fil: Palma, María Belen. Universidad Nacional de La Plata. Faculty of Medical Sciences. Chair of Cytology, Histology and Embryology; Argentina. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Verine, Jerome. Saint-Louis AP-HP Hospital. Department of Pathology; Francia. DRF-Francois Jacob Institute. CEA. Research Division in Hematology and Immunology (SRHI); Francia.Fil: Inda, Ana María. Universidad Nacional de La Plata. Faculty of Medical Sciences. Chair of Cytology, Histology and Embryology; Argentina. Comisión de Investigaciones Científicas (CIC); Argentina.Fil: Errecalde, Ana L. Universidad Nacional de La Plata. Faculty of Medical Sciences. Chair of Cytology, Histology and Embryology; Argentina.Fil: Desgrandchamps, François. DRF-Francois Jacob Institute. CEA. Research Division in Hematology and Immunology (SRHI); Francia. Saint-Louis Hospital. AP-HP. Department of Urology; Francia.Fil: Carosella, Edgardo D. DRF-Francois Jacob Institute. CEA. Research Division in Hematology and Immunology (SRHI); Francia. University of Paris; Francia.Fil: Tronik-Le Roux, Diana. DRF-Francois Jacob Institute. CEA. Research Division in Hematology and Immunology (SRHI); Francia. University of Paris; Francia