Editorial: Women in veterinary experimental and diagnostic pathology: 2021

The percentage of women participating in different professional sectors has risen over the last decades. The gender dimension is attracting special attention worldwide, and special measures are being undertaken to promote the incorporation and recognition of the contribution of women to different fields and levels, including legislation and policies..

Beyond motor neurons: expanding the clinical spectrum in Kennedy's disease

Kennedy's disease, or spinal and bulbar muscular atrophy (SBMA), is an X-linked neuromuscular condition clinically characterised by weakness, atrophy and fasciculations of the limb and bulbar muscles, as a result of lower motor neuron degeneration. The disease is caused by an abnormally expanded triplet repeat expansions in the ubiquitously expressed androgen receptor gene, through mechanisms which are not entirely elucidated. Over the years studies from both humans and animal models have highlighted the involvement of cell populations other than motor neurons in SBMA, widening the disease phenotype. The most compelling aspect of these findings is their potential for therapeutic impact: muscle, for example, which is primarily affected in the disease, has been recently shown to represent a valid alternative target for therapy to motor neurons. In this review, we discuss the emerging study of the extra-motor neuron involvement in SBMA, which, besides increasingly pointing towards a multidisciplinary approach for affected patients, deepens our understanding of the pathogenic mechanisms and holds potential for providing new therapeutic targets for this disease

Synaptic Failure: Focus in an Integrative View of ALS

From early description by Charcot, the classification of the Amyotrophic Lateral Sclerosis (ALS) is evolving from a subtype of Motor Neuron (MN) Disease to be considered rather a multi-systemic, non-cell autonomous and complex neurodegenerative disease. In the last decade, the huge amount of knowledge acquired has shed new insights on the pathological mechanisms underlying ALS from different perspectives. However, a whole vision on the multiple dysfunctional pathways is needed with the inclusion of information often excluded in other published revisions. We propose an integrative view of ALS pathology, although centered on the synaptic failure as a converging and crucial player to the etiology of the disease. Homeostasis of input and output synaptic activity of MNs has been proved to be severely and early disrupted and to definitively contribute to microcircuitry alterations at the spinal cord. Several cells play roles in synaptic communication across the MNs network system such as interneurons, astrocytes, microglia, Schwann and skeletal muscle cells. Microglia are described as highly dynamic surveying cells of the nervous system but also as determinant contributors to the synaptic plasticity linked to neuronal activity. Several signaling axis such as TNFα/TNFR1 and CX3CR1/CX3CL1 that characterize MN-microglia cross talk contribute to synaptic scaling and maintenance, have been found altered in ALS. The presence of dystrophic and atypical microglia in late stages of ALS, with a decline in their dynamic motility and phagocytic ability, together with less synaptic and neuronal contacts disrupts the MN-microglia dialogue, decreases homeostatic regulation of neuronal activity, perturbs “on/off” signals and accelerates disease progression associated to impaired synaptic function and regeneration. Other hotspot in the ALS affected network system is the unstable neuromuscular junction (NMJ) leading to distal axonal degeneration. Reduced neuromuscular spontaneous synaptic activity in ALS mice models was also suggested to account for the selective vulnerability of MNs and decreased regenerative capability. Synaptic destabilization may as well derive from increased release of molecules by muscle cells (e.g. NogoA) and by terminal Schwann cells (e.g. semaphorin 3A) conceivably causing nerve terminal retraction and denervation, as well as inhibition of re-connection to muscle fibers. Indeed, we have overviewed the alterations on the metabolic pathways and self-regenerative capacity presented in skeletal muscle cells that contribute to muscle wasting in ALS. Finally, a detailed footpath of pathologic changes on MNs and associated dysfunctional and synaptic alterations is provided. The oriented motivation in future ALS studies as outlined in the present article will help in fruitful novel achievements on the mechanisms involved and in developing more target-driven therapies that will bring new hope in halting or delaying disease progression in ALS patients

Decoding Amyotrophic Lateral Sclerosis: Discovery of Novel Disease-Related Biomarkers and Future Perspectives in Neurodegeneration

Amyotrophic lateral sclerosis (ALS) belongs to the group of motor neuron diseases, in which the degeneration, the weakness of voluntary muscles, and death of motor neurons gradually spread along disease progression. ALS comes from Greek language and means “no muscle nourishment” (“amyotrophic”), “area of the spinal cord where affected nerve cells are localized” (“lateral”), and “the degeneration and hardening of the spinal cord” (“sclerosis”). The fundamental contributions of the celebrated neurologist Jean-Martin Charcot at the end of the nineteenth century provided the first description of ALS...

Nanopartículas de oro como vector de terapia genética en el tratamiento de la Esclerosis Lateral Amiotrófica

El descubrimiento de mutaciones de la enzima superóxido-dismutasa 1 (SOD1) en pacientes con Esclerosis Lateral Amiotrófica (ELA) como causa de la enfermedad ha abierto la puerta a nuevas investigaciones con el objetivo de encontrar un tratamiento eficiente. El principal problema se encuentra en el direccionamiento de las terapias a las motoneuronas, afectadas en la ELA, por lo que se buscan vectores biocompatibles que cumplan cuatro objetivos: una carga eficiente del fármaco, atravesar la barrera hematoencefálica, la internalización celular y la liberación del fármaco. En el presente trabajo se propone caracterizar los efectos de nanopartículas de oro en la viabilidad y ciclo celular de las neuronas motoras, para posteriormente ser utilizadas como transporte de RNA de interferencia (siRNA). El objetivo que se busca es una reducción en la expresión de la proteína mutada por degradación del RNA mensajero (mRNA) que la codifica en una línea celular de motoneuronas NSC-34. Los resultados muestran una unión muy eficiente de siRNA con las nanopartículas Au-PEI-PEG para todas las concentración evaluadas. Respecto a la viabilidad celular, se obtiene un incremento de la dosis subcitotóxica del 300% tras la conjugación con el siRNA y una buena internalización a partir de las 24 horas de tratamiento. Sin embargo se precisa indagar más en los mecanismos moleculares que desencadenan los cambios observados en el ciclo celular y granularidad tras el tratamiento. Finalmente, se ha concluido que las nanopartículas de oro presentan un alto potencial como vector de moléculas en terapia génica para tratamiento de enfermedades neurodegenerativas.<br /

Activation of C-fiber nociceptors by low-power diode laser

Objective: The evaluation of selective activation of C-fibers to record evoked potentials using the association of low-power diode laser (810 nm), tiny-area stimulation and skin-blackening. Method: Laser-evoked potentials (LEPs) were obtained from 20 healthy young subjects. An aluminum plate with one thin hole was attached to the laser probe to provide tiny-area stimulation of the hand dorsum and the stimulated area was covered with black ink. Results: The mean intensity used for eliciting the ultra-late laser-evoked potential (ULEP) was 70 +/- 32 mW. All subjects showed a clear biphasic potential that comprised a negative peak (806 +/- 61 ms) and a positive deflection (1033 +/- 60 ms), corresponding to the ULEP related to C-fiber activation. Conclusion: C-fiber-evoked responses can be obtained using a very low-power diode laser when stimulation is applied to tiny areas of darkened skin. This strategy offers a non-invasive and easy methodology that minimizes damage to the tissue.Univ Fed Sao Paulo, Dept Psicobiol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Setor Neurofisiol Clin, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Psicobiol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Setor Neurofisiol Clin, Sao Paulo, SP, BrazilWeb of Scienc

Diseño de un modelo de gestión de atención al ciudadano para la Demarcación Hidrográfica de Pastaza de la Secretaria del Agua, durante el período 2014 – 2015

En esta investigación se realiza un Modelo de Gestión de Atención al Ciudadano que es una herramienta y conjunto de directrices que permite el desarrollo de la institución. Las instituciones públicas actualmente consideran indispensable cubrir las necesidades y expectativas de los usuarios respecto al servicio que brindan, es necesario identificar la fundamentación teórica en la cual se sustenta el modelo, para establecer los requisitos que se consideran en la implementación y elaboración de dicho modelo para garantizar el cumplimiento de la propuesta. Utilizando el Método inductivo- deductivo, planteamos las causas que originan el problema, con el método analítico-sintético tendremos una visión completa tanto interna y externa de todo el proceso en la identificación de los factores que influyen en la atención a los usuarios. Dentro de la investigación se observa una atención deficiente, clientes insatisfechos, carencia de estrategias y falta de capacitación al personal sobre atención al cliente. Evidentemente la ausencia de un Modelo de Gestión de Atención al Ciudadano dentro de la Demarcación Hidrográfica de Pastaza ha dificultado el desenvolvimiento eficiente de los funcionarios de la institución. Implementar el Modelo de Gestión de Atención al Ciudadano dentro de la Demarcación permitirá dar respuesta a los problemas identificados a fin de mejorar la calidad del servicio al usuario.In this research A Management Model of the Citizen Attention is carried out being a tool and a set of guidelines that allows the institution development. Currently the public institutions are considered indispensable to covert the user needs and expectations regarding to the service offered, it is necessary to identify the theoretical foundation which the model is based, for establishing the requirements considered in the implementation and elaborate the model ensuring compliance of the proposal. Using the Inductive - Deductive method, the causes are posed that problem caused, with the analytic and synthetic method we will have a clear vision both internal and external of the whole process in the identification of factors influencing in the users attention. Within the investigation is observed a poor attention, unsatisfied customer, lack of strategies and lack of training to the personnel about customer service. Obviously the lack of Management Model of the Citizen Attention in Hydrographical Demarcations from Pastaza has hampered the efficient development by the institution’s officials. To implement the Management Model of the Citizen Attention within the Hydrographical Demarcations allowing response development to the problems identified in order to improve the user service quality

Evaluating Membranes for Bone Regeneration

This work was supported by: 1)the Ministry of Economy and Competitiveness and European Regional Development Fund [Project MAT2017-85999-P MINECO/AEI/FEDER/UE],2) University of Granada/Regional Government of Andalusia Research Fund from Spain and European Regional Development Fund (A-BIO-157-UGR-18/FEDER).This research is part of M.T-O.’s PhD research study.Objectives:Maxillofacial bone defectsare the main hindering conditions for traditional dental implant strategies. Guided Bone Regeneration (GBR) is used to handle this situation. The principle of GBR is to use a membrane to prevent the colonization of soft tissue cells of the bone defect and favors the migration of osteogenic linages. Currentmembranes do not completely fulfill the requirements that an optimal membrane should have, sometimes resulting in non-predictable results. Thus, the need to develop an ideal membrane to perform this duty is clear. Recent developments in bio-manufacturing are driving innovations in membranes technology permitting the active participation of the membrane in the healing and regenerative process trough native tissue mimicking, drug-delivery and cells interaction, away from being a passive barrier. New membranes features need specific evaluation techniques, beyond the International Standard for membrane materials (last reviewed in 2004), being this the rationale for the present review.Nanotechnology application has completely shifted the way of analyzing structural characterization. New progresses on osteoimmmunomodulation have also switched the understanding of cells-membranes interaction. Data and Sources:To propose an updated protocol for GBR membranes evaluation, critical reading of therelevant published literature was carried out after a MEDLINE/PubMed database search. Conclusions:The main findings are that a potential active membrane should be assessed in its nanostructure, physicochemical and nanomechanical properties,bioactivityand antibacterial,osteoblasts proliferation, differentiation and mineralization. Immunomodulationtesting for macrophages recruitmentand M2 phenotype promotion in osteoblasts co-culture has to beachieved to completely analyze membranes/tissue interactions.Ministry of Economy and Competitiveness and European Regional Development Fund [Project MAT2017-85999-P MINECO/AEI/FEDER/UE]University of Granada/Regional Government of Andalusia Research Fund from Spain and European Regional Development Fund (A-BIO-157-UGR-18/FEDER

Amyotrophic Lateral Sclerosis: A Focus on Disease Progression

Since amyotrophic lateral sclerosis (ALS) was discovered and described in 1869 as a neurodegenerative disease in which motor neuron death is induced, a wide range of biomarkers have been selected to identify therapeutic targets. ALS shares altered molecular pathways with other neurodegenerative diseases, such as Alzheimer’s, Huntington’s, and Parkinson’s diseases. However, the molecular targets that directly influence its aggressive nature remain unknown.What is the first link in the neurodegenerative chain of ALS that makes this disease so peculiar? In this review, we will discuss the progression of the disease from the viewpoint of the potential biomarkers described to date in human and animal model samples. Finally, we will consider potential therapeutic strategies for ALS treatment and future, innovative perspectives