Neurological manifestations of COVID-19 in patients: from path physiology to therapy.

Coronavirus is a family of ARN positive single-stranded belonging to the family of Coronaviridae. There are several families of coronavirus that transmit more or less serious diseases. However, the so-called coronavirus-19 (SARS-CoV2) is the one that is currently causing most of the problems; in fact, biological dysfunctions that this virus causes provoke damage in various organs, from the lung to the heart, the kidney, the circulatory system, and even the brain. The neurological manifestations caused by viral infection, as well as the hypercoagulopathy and systemic inflammation, have been reported in several studies. In this review, we update the neurological mechanisms by which coronavirus-19 causes neurological manifestation in patients such as encephalomyelitis, Guillain-Barré syndrome, lacunars infarcts, neuropsychiatry disorders such as anxiety and depression, and vascular alterations. This review explains (a) the possible pathways by which coronavirus-19 can induce the different neurological manifestations, (b) the strategies used by the virus to cross the barrier system, (c) how the immune system responds to the infection, and (d) the treatment than can be administered to the COVID-19 patients.

Bone union formation in the rat mandibular symphysis using hydroxyapatite with or without simvastatin: effects on healthy, diabetic, and osteoporotic rats.

OBJECTIVE: The objective is to compare new bone formation in critical defects in healthy, diabetic, and osteoporotic rats filled with hydroxyapatite (HA) alone and HA combined with simvastatin (SV). MATERIALS AND METHODS: A total of 48 adult female Sprague-Dawley rats were randomized into three groups (n = 16 per group): Group, 1 healthy; Group 2, diabetics; and Group 3, osteoporotics. Streptozotocin was used to induce type 1 diabetes in Group 2, while bilateral ovariectomy was used to induce osteoporosis in Group 3. The central portion of the rat mandibular symphysis was used as a physiological critical bone defect. In each group, eight defects were filled with HA alone and eight with HA combined with SV. The animals were sacrificed at 4 and 8 weeks, and the mandibles were processed for micro-computed tomography to analyze radiological union and bone mineral density (BMD); histological analysis of the bone union; and immunohistochemical analysis, which included immunoreactivity of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2). RESULTS: In all groups (healthy, diabetics, and osteoporotics), the defects filled with HA + SV presented greater radiological bone union, BMD, histological bone union, and more VEGF and BMP-2 positivity, in comparison with bone defects treated with HA alone. CONCLUSIONS: Combined application of HA and SV improves bone regeneration in mandibular critical bone defects compared with application of HA alone in healthy, diabetic, and osteoporotic rats. CLINICAL RELEVANCE: This study might help to patients with osteoporosis or uncontrolled diabetes type 1, but future studies should be done.

Synergistic effect of photodynamic therapy and alendronate on alveolar bone loss in rats with ligature-induced periodontitis.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) and antiresorptive drugs, such as alendronate (ALN), have been shown to reduce alveolar bone loss. The aim of this study was to evaluate the possible synergic effects of combining PDT and ALN on bone loss in periodontitis in rats. MATERIAL AND METHODS: Periodontitis was induced by ligature in 60 Wistar rats randomized into the following groups: control (Group 1); PDT (Group 2); ALN 0.01 mg/kg (Group 3); ALN 0.25 mg/kg (Group 4); PDT + ALN 0.01 mg/kg (Group 5); and PDT + ALN 0.25 mg/kg (Group 6). The rats were killed on day 12 and the mandibles were processed for macroscopic morphometric analysis, micro-computed tomography to analyze bone mineral density (BMD) and histological analysis. Gingival samples were collected to evaluate myeloperoxidase (MPO) and malonaldehyde (MDA) levels. RESULTS: Bone loss and inflammatory activity in histological studies, from the greatest to least was: control > ALN 0.01 mg/kg > PDT > ALN 0.25 mg/kg > PDT + ALN 0.01 mg/kg > PDT + ALN 0.25 mg/kg, while the order from least to greatest BMD was: control < ALN 0.01 mg/kg < PDT < ALN 0.25 mg/kg < PDT + ALN 0.01 mg/kg < PDT + ALN 0.25 mg/kg. The order of MPO and MDA activity from greatest to least was: control > ALN 0.01 mg/kg > PDT > ALN 0.25 mg/kg > PDT + ALN 0.01 mg/kg > PDT + ALN 0.25 mg/kg. The positive results obtained in the group treated with PDT + ALN 0.25 mg/kg showed statistically significant differences (P ≤ .05) compared with the other 5 groups for BMD, MPO and MDA. CONCLUSION: Combined approach therapy of PDT + ALN 0.25 mg/kg demonstrated a protective effect on alveolar bone loss.

Review: Could neurotransmitters influence neurogenesis and neurorepair after stroke?

Brain ischaemia and reperfusion produce alterations in the microenvironment of the parenchyma, including ATP depletion, ionic homeostasis alterations, inflammation, release of multiple cytokines and abnormal release of neurotransmitters. As a consequence, the induction of proliferation and migration of neural stem cells is redirected towards the peri-infarct region. The success of new neurorestorative treatments for damaged brain implies the need to describe with greater accuracy the mechanisms in charge of regulating adult neurogenesis, under both physiological and pathological conditions. Recent evidence demonstrates that many neurotransmitters, glutamate in particular, control the subventricular zone (SVZ), thus being part of the complex signal network that exerts a remarkable influence on the production of new neurones. Neurotransmitters provide a link between brain activity and SVZ neurogenesis. Therefore, a deeper knowledge of the role of neurotransmitters systems, such as glutamate and its transporters, in adult neurogenesis, may prove a valuable tool to be utilized as a neurorestorative therapy in this pathology.

Escalas utilizadas para valorar el dolor en niños de 0-24 meses tras una intervención quirúrgica menor. Instrumentos de ayuda para la valoración en fisioterapia / Scales used to evaluate pain in infants aged 0-24 months after minor surgery. Instruments for help in physiotherapy evaluation

ObjetivoConocer, con base en los estudios publicados recientemente, el tipo de escalas que están siendo utilizadas para evaluar el dolor en niños.Búsqueda y selección de estudiosSe identificaron 75 publicaciones mediante la búsqueda electrónica en las bases de datos MEDLINE, ISI of Knowledge, Dialnet, Cochrane Library Plus y PEDro. Los criterios de inclusión fueron artículos en inglés o español publicados desde enero de 1995 hasta enero de 2012 que incluían escalas para evaluar el dolor de sujetos de hasta 24 meses de edad después de una intervención quirúrgica menor. Como criterio de exclusión se establecieron estudios que hacían referencia a sujetos con edades no comprendidas en el intervalo de edad estudiado.ResultadosSe incluyeron 4 estudios en la revisión con calidad metodológica variable y heterogeneidad en el tamaño de la muestra. Sus autores utilizan distintas escalas observacionales que muestran datos positivos con respecto a la detección del dolor.ConclusionesEs necesario un mayor número de estudios para determinar las escalas más utilizadas en la valoración del dolor en niños de hasta 24 meses de edad tras una intervención quirúrgica menor. Parece ser que la utilización de escalas observacionales puede detectar el dolor en esta tipología de pacientes(AU)

ObjectiveTo know, based on the most recent studies published, the scales that are being used to evaluate pain in infants.Search and study selectionSeventy-five publications were identified by electronic search using the databases MEDLINE, ISI of Knowledge, Dialnet, Cochrane Library Plus and PEDro. Inclusion criteria were articles published from January 1995 to January 2012 in English or Spanish that included scales to assess pain after minor surgery in infants of 0-24 months. Exclusion criteria established were articles on any other type of patients not included in the established age range.ResultsFour articles with variable methodological quality and sample size heterogeneity were included. Their authors used different observational scales that show positive data for pain detection.ConclusionsMore studies are needed to determine the scales used most in the evaluation of pain in infants from 0 to 24 months after minor surgery. It seems that the use of observational scales may detect pain in this type of patients (AU)

Power line interference filtering on surface electromyography based on the stationary wavelet packet transform.

Power line interference is one of the main problems in surface electromyogram signals (EMG) analysis. In this work, a new method based on the stationary wavelet packet transform is proposed to estimate and remove this kind of noise from EMG data records. The performance has been quantitatively evaluated with synthetic noisy signals, obtaining good results independently from the signal to noise ratio (SNR). For the analyzed cases, the obtained results show that the correlation coefficient is around 0.99, the energy respecting to the pure EMG signal is 98-104%, the SNR is between 16.64 and 20.40dB and the mean absolute error (MAE) is in the range of -69.02 and -65.31dB. It has been also applied on 18 real EMG signals, evaluating the percentage of energy respecting to the noisy signals. The proposed method adjusts the reduction level to the amplitude of each harmonic present in the analyzed noisy signals (synthetic and real), reducing the harmonics with no alteration of the desired signal.

[HIV-1 neuropathogenesis: therapeutic strategies against neuronal loss induced by gp120/Tat glycoprotein in the central nervous system]. / Neuropatogenesis inducida por el virus del sida: estrategias terapeuticas frente a la neurodegeneracion inducida por la glucoproteina gp120/Tat en el sistema nervioso central.

Neuroinflammation is a key process in the neuropathogenesis of AIDS virus since as a result of the aberrant activation of the chemokine receptors (CXCR4, CX3CR1 and CR5) produces proinflammatory cytokine release by infected cells, increases microglial neurotoxicity and generates lipoperoxides and reactive oxygen species (ROS) that eventually damage the neuron. Moreover, the neurotoxin Tat produces dendritic loss by interacting with the low-density lipoprotein receptor (LRP) and also overstimulates N-methyl D-aspartate receptors (NMDA). Furthermore, the aberrant interaction of glycoprotein gp120 with the CXCR4 chemokine receptor causes caspase-3-dependent apoptosis (ceramide is also released) activating apoptotic proteins (p53 and retinoblastoma), which are part of the neurotoxic mechanisms associated to neuronal dysfunction in neuroAIDS. Similarly, gliosis/microglial activation and the release of neurotoxic factors by infected monocytes with elevated amounts of certain chemokines in the cerebrospinal fluid (MCP-1 and fractalkine, among others) contribute to the neuropathogenesis of HIV-1. Alpha-synuclein and beta amyloid deposits have also been detected in post mortem brains of seropositives patients. In addition, there are studies have detected several systemic markers related with the degenerative effects of the virus and its neurotoxins on the central nervous system; such as osteopontin, CD163 and fractalkine, among others. Lastly, clinical trials have been conducted using protective strategies related that attempt to inhibit apoptotic proteins (GSK-3 beta), microglial activation inhibitors (minocycline), antioxidants (selegiline) or trophic factors (IGF-1, growth hormone or erythropoietin). These trials have shown that their treatments are beneficial and complementary to treat complications of HIV/AIDS.

Cognitive/personality pattern and triplet expansion size in adult myotonic dystrophy type 1 (DM1): CTG repeats, cognition and personality in DM1.

BACKGROUND: Although central nervous system (CNS) involvement in adult myotonic dystrophy type 1 (DM1) was described long ago, the large number of variables affecting the cognitive and personality profile have made it difficult to determine the effect of DM1 on the brain. The aim of this study was to define the cognitive and personality patterns in adult DM1 patients, and to analyse the relationship between these clinical patterns and their association with the underlying molecular defect. METHOD: We examined 121 adult DM1 patients with confirmed molecular CTG repeat expansion and 54 control subjects using comprehensive neuropsychological tests and personality assessments with the Millon Clinical Multiaxial Inventory (MCMI)-II. We used a multiple linear regression model to assess the effect of each variable on cognition and personality adjusted to the remainders. RESULTS: Patients performed significantly worse than controls in tests measuring executive function (principally cognitive inflexibility) and visuoconstructive ability. In the personality profile, some paranoid and aggressive traits were predominant. Furthermore, there was a significant negative correlation between the CTG expansion size and many of the neuropsychological and personality measures. The molecular defect also correlated with patients' daytime somnolence. CONCLUSIONS: Besides muscular symptomatology, there is significant CTG-dependent involvement of the CNS in adult DM1 patients. Our data indicate that the cognitive impairment predominantly affects the fronto-parietal lobe.

Tools for acquisition, processing and knowledge-based diagnostic of the electroencephalogram and visual evoked potentials.

The objective of our research is to develop computer-based tools to automate the clinical evaluation of the electroencephalogram (EEG) and visual evoked potentials (VEP). This paper describes a set of solutions to support all the aspects regarding the standard procedures of the diagnosis in neurophysiology, including: (1) acquisition and real-time processing and compression of EEG and VEP signals, (2) real-time brain mapping of spectral powers, (3) classifier design, (4) automatic detection of morphologies through supervised neural networks. (5) signal analysis through fuzzy modelling, and (6) a knowledge based approach to classifier design.

Effects of chronic stress on contextual fear conditioning and the hippocampal expression of the neural cell adhesion molecule, its polysialylation, and L1.

Chronic stress has been shown to induce time-dependent neurodegeneration in the hippocampus, ranging from a reversible damage to a permanent neuronal loss. This damage has been proposed to impair cognitive function in hippocampus-dependent learning tasks. In this study, we have used a 21-day restraint stress procedure in rats, previously reported to induce reversible atrophy of apical dendrites of CA3 pyramidal cells, to assess whether it may influence subsequent performance in the contextual fear conditioning task under experimental conditions involving high stress levels (1 mA shock intensity as the unconditioned stimulus). In addition, we were interested in the study of the possible cellular and molecular mechanisms involved in the reversible phase of neural damage. Cell adhesion molecules of the immunoglobulin superfamily, such as the neural cell adhesion molecule and L1, are cell-surface macromolecules that, through their recognition and adhesion properties, regulate cell-cell interactions and have been reported to play a key role in cognitive functioning. A second aim of this study was to evaluate whether chronic stress would modulate the expression of the neural cell adhesion molecule, its polysialylation, and L1 in the hippocampus. The results showed that chronic stress facilitated subsequent contextual fear conditioning. They also showed that chronically stressed rats displayed reduced hippocampal neural cell adhesion molecule, but increased polysialylated expression as well as a trend towards exhibiting increased L1 expression. In summary, these results support the view that a 21-day chronic stress regimen predisposes individuals to develop enhanced contextual fear conditioning responses. They also indicate that cell adhesion molecules might play a role in the structural remodelling that occurs in the hippocampus as a consequence of chronic stress exposure.

Regulation of hippocampal cell adhesion molecules NCAM and L1 by contextual fear conditioning is dependent upon time and stressor intensity.

Cell adhesion molecules (CAMs) of the immunoglobulin superfamily, NCAM and L1, as well as the post-translational addition of alpha-2, 8-linked polysialic acid (PSA) homopolymers to NCAM (PSA-NCAM), have been implicated in the neural mechanisms underlying memory formation. Given that the degree of stress elicited by the training situation is one of the key factors that influence consolidation processes, this study questioned whether training rats under different stressor intensities (0.2, 0.4, or 1 mA shock intensity) in a contextual fear conditioning task might regulate subsequent expression of NCAM, PSA-NCAM and L1 in the hippocampus, as evaluated immediately after testing rats for conditioning at 12 and 24 h after training. Behavioural inhibition (evaluated as a 'freezing' index) at testing and post-testing plasma corticosterone levels were also assessed. The results showed that 12 h post-training, conditioned animals displayed reduced NCAM, but increased L1, expression. At this time point, the group trained at the highest shock intensity (1 mA) also presented decreased PSA-NCAM expression. Analyses performed 24 h post-training indicated that the 1 mA group exhibited increased NCAM and L1 expression, but decreased expression of PSA-NCAM levels. In addition, L1 values that presented a shock intensity-dependent U-shaped pattern were also increased in the group trained at the lowest shock condition (0.2 mA) and remained unchanged in the intermediate shock condition (0.4 mA). Freezing and corticosterone values at both testing times were positively related with shock intensity experienced at training. Therefore, our results show a complex regulation of CAMs of the immunoglobulin superfamily in the hippocampus that depends upon stressor intensity and time factors. In addition, the pattern of CAMs expression found in the 1 mA group (which is the one that shows higher post-training corticosterone levels and develops the stronger and longer-lasting levels of fear conditioning) supports the view that, after a first phase of synaptic de-adherence during consolidation, NCAM and L1 might participate in the stabilization of selected synapses underlying the establishment of long-term memory for contextual fear conditioning, and suggests that glucocorticoids might play a role in the observed regulation of CAMs.

Correlational relationship between shock intensity and corticosterone secretion on the establishment and subsequent expression of contextual fear conditioning.

A role for corticosterone in the consolidation of contextual fear conditioning has previously been proposed. In this study, physiological evidence was found to support this view. The extent of conditioned fear and the levels of plasma corticosterone in rats, after context exposure at training and at different posttraining times (24 hr and 7 days), depended on the intensity of the unconditional stimulus (footshock). In each experimental session, a positive correlation was found between the magnitude of corticosterone levels and the fear-related behavioral inhibition exhibited in the context. Results support the involvement of corticosterone on the processes that occur during consolidation in determining the strength at which the contextual fear conditioning is stored as a long-term memory.

[Molecular bases of the programmed cell death process: implications of tumor suppressor protein p53 and other proteins in the control of cell cycle. Mechanisms of apoptotic action. Review]. / Bases moleculares del proceso de muerte celular programada: implicaciones de la proteína supresora de tumores p53 y otras proteínas en el control del ciclo celular. Mecanismos de acción apoptótica. Revisión.

Apoptosis is a mechanism of cell death that occurs in normal development and on the regulation of vertebrate tissues and organ cellularity. Neurons undergo p53-dependent and p53-independent apoptosis, depending upon the stimulus that triggers DNA fragmentation. Many neurons in the developing nervous system suffer apoptosis, with the cyclin D1 being an essential mediator of neuronal cell death. Other characteristics of apoptosis are: condensation of the nucleus, fragmentation of chromatin at nucleosome linkage sites, membrane blebbing, and the formation of apoptotic bodies. Among the possible molecular mechanisms are: (a) activation of proteases, as ICE (Il-1 beta converting enzyme); (b) calpain is activated in several cells, with PARP (Poly-ADP-ribose polymerase) and a small U1 Ribonucleoprotein, being substrates for ICE and its homologs such as ICH and others proteins. The p53 gene encodes a transcription factor that contributes to several different cellular activities, including apoptosis, the cellular response to radiation, and the activation of proteins such as GADD, Bcl-2 (represses to apoptosis) and Bax. P53 exerts a role as inductor of apoptosis by transactivating expression of the Bax gene. The p53 gene tumor suppressor limits cellular proliferation by including either the arrest of cell cycle in G1, or apoptosis, depending on the cellular context. The p21 is an inhibitor of cyclin-dependent kinase, which is transactivated by p53. During apoptosis, there is an activation of both, c-myc, and the transcription factor NF-kB, which is a important regulator of apoptosis. As an example of signalization of apoptosis we have selected to illustrate the problem related to the system Fas/APO in thymocytes.

[The combined application of visual evoked potentials and the quantified electroencephalogram improve discrimination of cerebral maturity]. / La aplicación conjunta del potencial evocado visual y el electroencefalograma cuantificado mejora la discriminación de la maduración cerebral.

INTRODUCTION AND OBJECTIVE: The aim of this job is to evaluate brain maturation by means of Electroencephalogram (EEG) and Visual Evoked Potentials stimulated with flash (VEP-flash) quantitative analysis techniques. MATERIAL AND METHODS: The transversal study is made on a sample of 96 subjects in which EEG and VEP-flash, first isolated and then joining both, are analyzed. The selection of spectral parameters was done taking care of all the subjects were selected in the sense of maximizing brain maturation discrimination. Multivariate analysis techniques for classifying subjects were used. EEG and VEP-flash variables were selected with the linear discriminant analysis. In the EEG case the variables take into account, as a reference, either the median of the power spectrum or either the time instant in which the spectral power in every band reaches its maximum value. In the joined EEG-VEP-flash the VEP variables which give more information were related with the slopes and distances between the basic peaks of the evoked response (N1, P1 and N2) and age. For brain maturation evaluation the variables in the occipital channels are sufficient, being those of the right hemisphere the most diagnostic significative ones. CONCLUSION: The joined use of EEG and VEP-flash means an improvement in the maturative level discrimination regarding to the isolated consideration of any of them. Variables obtained from the EEG-VEP-flash are enough for brain maturation evaluation.

[A study of cerebral maturity by means of quantitative analysis of the electroencephalogram]. / Estudio de la maduración cerebral mediante el análisis cuantitativo del electroencefalograma.

INTRODUCTION AND OBJECTIVE: The objective of this study is to evaluate cerebral maturity by means of quantitative analysis techniques applied to the electroencephalogram (EEG). MATERIAL AND METHODS: A transversal study of cerebral maturity was carried out in 403 persons who had undergone an EEG. A previous pilot study had been carried out of 103 persons. A series of spectral parameters of the EEG were selected so that all those studied were in the most similar conditions possible. Different frequency bands were analyzed choosing the one with best discrimination of the maturity aspect. Classification of the different levels of cerebral maturity was done with the help of multivariant analysis. The value of the median of the frequencies and the spectrum of relative potencies at the moment when a frequency band is at a maximum are the parameters which evolve best with age and best discriminate maturity Spectral analysis allows selection of the frequency bands most suitable to the problem. Working with two frequency bands is sufficient to evaluate cerebral maturity. RESULTS: The variables obtained in the occipital channels were sufficient for evaluation of cerebral maturity. Those of the right hemisphere were more significant for diagnosis. The occipital channels are the most relevant in the study of cerebral maturity. CONCLUSIONS: The neuronal network is the most efficient classifier for classification of different groups of maturity The next most efficient method is by quadratic discriminant analysis. Consideration of the variables, taking into account the factors of stability and regularity of the EEG signals improves discrimination with respect to the average of those recorded during the entire procedure.