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One of the main incentives for implementing video-based surveillance systems is the urban security. During the last years, several approaches for automatic detection of suspicious events have been proposed. Those methods usually require a training stage before starting their operation. This means that previous to run time a representative dataset of interest events, that may occur in the future, must be available. Nevertheless, most real surveillance systems lack of that information, so many of those proposals results impractical. In this paper, a context online learning scheme for detecting suspicious behaviors on surveillance videos is proposed. Contextual information, which is inferred from videos of people in a scenario, allows detecting suspicious behaviors before an eventual criminal's final attack occur. The main attribute of the proposed approach is the capacity to start up its operation with a reduced training dataset. By an incremental learning process, which uses new data obtained during the online operation, the proposed scheme improves the performance over time achieving a better adaptation to conditions of each scenario. The proposed scheme was validated on two datasets. The first of them includes threats against a parked truck and its driver. The second testing dataset is composed of night assault scenes recorded in an urban environment. The experimental results demonstrate that the proposed method is able to learn incrementally from a reduced initial dataset, achieving a performance similar to batch-type systems trained with all data simultaneously and outperforming five state-of-the-art algorithms over violence detection. • The context model allows to detect suspicious behaviors on surveillance videos. • Contextual information to detect suspicious behaviors before criminal attack occur • Capacity to start up the system operation with a reduced training dataset • Performance improvements by using incremental learning during the online operation [ABSTRACT FROM AUTHOR]

Silicone oil (SO) still represents the main choice for long‐term intraocular tamponade in complicated vitreoretinal surgery. This review compared the complications associated with the use of SO and other vitreous substitutes after pars plana vitrectomy in patients with different underlying diseases. Meta‐analysis was conducted in accordance with PRISMA guidelines. We retrieved randomized clinical trials (RCTs), retrospective case–control and cohort studies evaluating the risk of using SO, published between 1994 and 2020, conducting a computer‐based search of the following databases: PubMed, Web of Science, Scopus and Embase. Primary outcome was the rate of complications such as intraocular hypertension, retinal re‐detachment, unexpected vision loss or hypotony. Secondary outcome was to compare the rate of adverse events of different SO viscosities, especially emulsification. Forty‐three articles were included. There were significant differences in intraocular hypertension (p = 0.0002, OR = 1.66; 95% CI = 1.27–2.18) and the rate of retinal re‐detachment (p < 0.0009, OR = 0.65; 95% CI = 0.50–0.64) between SO and other agents, including placebo. However, there were no differences in other complication rates. Silicone oil (SO)‐emulsification rate was non‐significantly higher in low than high SO viscosity, and results from other complications were comparable in both groups. The high quality of most of the studies included in this study is noteworthy, which provides some certainty to the conclusions. Among them is the high variability of the SO residence time. The fact that ocular hypertension and not hypotension is related to SO use. A clear relationship is not found for the so‐called unexplained vision loss, which affects a significant percentage of eyes. Re‐detachment cases are less if SO is used and that surprisingly there does not seem to be a relationship in the percentage of emulsification between the low‐ and high‐viscosity silicones. All these data warrant more standardized prospective studies. [ABSTRACT FROM AUTHOR]

This work presents the proposal of a multilevel framework for building remote access laboratories for experimentation in robotics. This framework provides the communication infrastructure for the designing of a remote access laboratory, which is carried out through the implementation of three layers: link layer, web layer and client layer. Likewise, the software architecture on how these layers should be built is defined, so that this is responsible for controlling communication between them. In addition, the implementation of the remote access laboratory is presented for the industrial robot Mitsubishi RV-2AJ from Universidad del Quindio, where the multilevel architecture proposed by the framework is used. The website of the framework is available online and can be downloaded from http://www.flarer.net. [ABSTRACT FROM AUTHOR]

• A KD decreased SUDEP incidence in Scn1aR1407X/+ mice independent of ketosis. • A KD delayed the onset of audiogenic S-IRA in DBA/1 mice independent of ketosis. • The protective effect of a KD in DBA/1 mice required continuous treatment. • Mechanisms other than formation of ketones may have a protective effect against SUDEP. Patients with uncontrolled epilepsy have a high risk of sudden unexpected death in epilepsy (SUDEP). Seizure-induced respiratory arrest (S-IRA) is thought to be the determining cause of death in many cases of SUDEP. The goal of the present study was to use Scn1aR1407X/+ (Dravet Syndrome, DS) and DBA/1 mice to determine: (1) the effect of a ketogenic diet (KD) on S-IRA and (2) the relationship between serum ketones and the protective effect of a KD. Ketogenic diet treatment significantly decreased spontaneous seizure-induced mortality in DS mice compared to control (8% vs 39%, p = 0.0021). This protective effect was not abolished when ketosis was prevented by supplementing the KD with glucose (10% mortality, p = 0.0007). In DBA/1 mice, the latency to onset of S-IRA due to audiogenic seizures was delayed from 7.6 to 20.8 seconds by a KD on treatment day (TD) 7 compared to control (p < 0.0001), an effect that was reversed on TD14 when mice were crossed over to a control diet on TD7. β-Hydroxybutyrate (BHB) levels were significantly decreased in DBA/1 mice on a KD supplemented with glucose (p = 0.0038), but the protective effect was maintained. Our findings show that a KD decreases SUDEP in DS mice and increases the latency to audiogenic S-IRA in DBA/1 mice. In both mouse models, a KD was protective against S-IRA. This effect may be due in part to specific dietary components rather than generation of ketone bodies. [ABSTRACT FROM AUTHOR]

Planning and operation of smart energetic projects have increased in complexity and requires a deeper analysis. The inclusion of renewable energy and distributed generation sources lead to an inherent difficulty to define appropriate models for decision-making. Nowadays, decisions in planning and operation are made level by level due to a disarticulation of information within the electrical sector and the stakeholders. Therefore, here is proposed an architectural decision model of multilevel-multiobjective to solve this problem. In this scheme, the problem of energetic assets sizing is on the upper level, while the problem of operation and dispatch of unit power is on the lower level. Both levels are related through quantitative tools (key performance indicators (KPI)) and qualitative tools (quality function deployment (QFD) and hierarchical analytical process (AHP)). This model was applied in the Yucatán peninsula. As a result, an integral solution with a lower cost and better environmental factor than the baseline for the region was obtained. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged during the last months of 2019, spreading throughout the world as a highly transmissible infectious illness designated as COVID-19. Vaccines have now appeared, but the challenges in producing sufficient material and distributing them around the world means that effective treatments to limit infection and improve recovery are still urgently needed. This review focuses on the relevance of different glycobiological molecules that could potentially serve as or inspire therapeutic tools during SARS-CoV-2 infection. As such, we highlight the glycobiology of the SARS-CoV-2 infection process, where glycans on viral proteins and on host glycosaminoglycans have critical roles in efficient infection. We also take notice of the glycan-binding proteins involved in the infective capacity of virus and in human defense. In addition, we critically evaluate the glycobiological contribution of candidate drugs for COVID-19 therapy such as glycans for vaccines, anti-glycan antibodies, recombinant lectins, lectin inhibitors, glycosidase inhibitors, polysaccharides, and numerous glycosides, emphasizing some opportunities to repurpose FDA-approved drugs. For the nextgeneration drugs suggested here, biotechnological engineering of new probes to block the SARS-CoV-2 infection might be based on the essential glycobiological insight on glycosyltransferases, glycans, glycan-binding proteins, and glycosidases related to this pathology. [ABSTRACT FROM AUTHOR]

In recent years, there has been a transformation in the value chain of different industrial sectors, like the electricity networks, with the appearance of smart grids. Currently, the underlying knowledge in raw data coming from numerous devices can mark a significant competitive advantage for utilities. It is the case of the Advanced Metering Infrastructure (AMI). Such technology gets user consumption characteristics at levels of detail that were previously not possible. In this context, the terms big data and data analytics become relevant, which are tools that allow using large volumes of information and the generation of valuable knowledge from raw data that can support data-driven decisions for operating on the grid. This paper presents the results of the big data implementation and data analytics techniques in a case study with smart metering data from the city of London. Implemented big data and data analytic techniques to show how to understand user consumption patterns on a broader horizon, the relationships with seasonal variables identify behaviors related to specific events and atypical consumptions. This knowledge helps support decision making about improving demand response programs and, in general, the planning and operation of the Smart Grid. [ABSTRACT FROM AUTHOR]

Background: Impairments in activities of daily living (ADL) are a criterion for Alzheimer's disease (AD) dementia. However, ADL gradually decline in AD, impacting on advanced (a-ADL, complex interpersonal or social functioning), instrumental (IADL, maintaining life in community), and finally basic functions (BADL, activities related to physiological and self-maintenance needs). Information and communication technologies (ICT) have become an increasingly important aspect of daily functioning. Yet, the links of ADL, ICT, and neuropathology of AD dementia are poorly understood. Such knowledge is critical as it can provide biomarker evidence of functional decline in AD. Methods: ADL were evaluated with the Technology–Activities of Daily Living Questionnaire (T-ADLQ) in 33 patients with AD and 30 controls. ADL were divided in BADL, IADL, and a-ADL. The three domain subscores were covaried against gray matter atrophy via voxel-based morphometry. Results: Our results showed that three domain subscores of ADL correlate with several brain structures, with a varying degree of overlap between them. BADL score correlated mostly with frontal atrophy, IADL with more widespread frontal, temporal and occipital atrophy and a-ADL with occipital and temporal atrophy. Finally, ICT subscale was associated with atrophy in the precuneus. Conclusions: The association between ADL domains and neurodegeneration in AD follows a traceable neuropathological pathway which involves different neural networks. This the first evidence of ADL phenotypes in AD characterised by specific patterns of functional decline and well-defined neuropathological changes. The identification of such phenotypes can yield functional biomarkers for dementias such as AD. [ABSTRACT FROM AUTHOR]

Episodic memory tests with cued recall, such as the Free and Cued Selective Reminding Test (FCSRT), allow for the delineation of hippocampal and prefrontal atrophy contributions to memory performance in Alzheimer's disease (AD). Both Word and Picture versions of the test exist but show different profiles, with the Picture version usually scoring higher across different cohorts. One possible explanation for this divergent performance between the different modality versions of the test might be that they rely on different sets of neural correlates. The current study explores this by contrasting the neural correlates of the Word and Picture versions of the FCSRT with voxel-based morphometry (VBM) in AD and healthy subjects. We predicted that the Picture version would be associated with different cortical regions than the Word version, which might be more hippocampal-centric. When comparing 35 AD patients and 34 controls, AD patients exhibited impairments on both versions of the FCSRT and both groups performed higher in the Picture version. A region of interest analysis based on prior work revealed significant correlations between free recall of either version with atrophy of the temporal pole and hippocampal regions. Thus, contrary to expectations, performance on both the Word and the Picture version of the FCSRT is associated with largely overlapping networks. Free recall is associated with hippocampal volume and might be properly considered as an indicator of hippocampal structural integrity. [ABSTRACT FROM AUTHOR]

We present a system for dense tracking, 3D reconstruction, and object detection of desktop-like environments, using a depth camera; the Kinect sensor. The camera is moved by hand meanwhile its pose is estimated, and a dense model, with evolving color information of the scene, is constructed. Alternatively, the user can couple the object detection module (YOLO: you only look once [1]) for detecting and propagating to the model information of categories of objects commonly found over desktops, like monitors, keyboards, books, cups, and laptops, getting a model with color associated to object categories. The camera pose is estimated using a model-to-frame technique with a coarse-to-fine iterative closest point algorithm (ICP), achieving a drift-free trajectory, robustness to fast camera motion and to variable lighting conditions. Simultaneously, the depth maps are fused into the volumetric structure from the estimated camera poses. For visualizing an explicit representation of the scene, the marching cubes algorithm is employed. The tracking, fusion, marching cubes, and object detection processes were implemented using commodity graphics hardware for improving the performance of the system. We achieve outstanding results in camera pose, high quality of the model's color and geometry, and stability in color from the detection module (robustness to wrong detections) and successful management of multiple instances of the same category. [ABSTRACT FROM AUTHOR]

Background: Intracellular neurofibrillary tangles are part of the core pathology of Alzheimer's disease (AD), which are mainly composed of hyperphosphorylated tau protein.Objectives: The purpose of this study is to determine whether high molecular weight (HMW) or low molecular weight (LMW) tau protein levels, as well as the ratio HMW/LMW, present in platelets correlates with brain magnetic resonance imaging (MRI) structural changes in normal and cognitively impaired subjects.Methods: We examined 53 AD patients and 37 cognitively normal subjects recruited from two Memory Clinics at the Universidad de Chile. Tau levels in platelets were determined by immunoreactivity and the MRI scans were analyzed using voxel-based morphometry in 41 AD patients.Results: The HMW/LMW tau ratio was statistically different between controls and AD patients, and no associations were noted between HMW or LMW tau and MRI structures. In a multivariate analysis controlled for age and education level, the HMW/LMW tau ratio was associated with reduced volume in the left medial and right anterior cingulate gyri, right cerebellum, right thalamus (pulvinar), left frontal cortex, and right parahippocampal region.Conclusions: This exploratory study showed that HMW/LMW tau ratio is significantly higher in AD patients than control subjects, and that it is associated with specific brain regions atrophy. Determination of peripheral markers of AD pathology can help understanding the pathophysiology of neurodegeneration in AD. [ABSTRACT FROM AUTHOR]

The walls of the blood vessels involved with cerebral aneurysms present different mechanical properties, when compared with those of normal artery. Consequently the models which may describe then predict an aneurysm rupture need as input their mechanical properties. This paper describes the experimental determination of the mechanical properties of the tissues of the blood vessels affected with a cerebral aneurysm. In particular, we determine and discuss the critical elongation and the rupture strength. The affected tissues were obtained from surgical clipping and extraction; six specimens were tested. The mechanical tests were performed in a tensile device. The experimental data was fitted numerically with a Mooney-Rivlin hyper elastic model. The model was compared with previous published data. [ABSTRACT FROM AUTHOR]

We describe two cases of aneurysmal rupture in moyamoya-like vessels in middle cerebral artery occlusion. This phenomenon was previously described in severe steno-occlusive disease and accounts for the hemorrhagic presentation. To our knowledge, these are the second and third clinical cases published in modern neuroradiological literature. [ABSTRACT FROM AUTHOR]

A sensitivity study of the results provided by computational fluid dynamics (CFD) in models of cerebral aneurysms including fluid structure interaction (FSI) was performed. With 83 reconstructed models of cerebral aneurysms, a geometrical study was done and one case was selected for a detailed study of the computational fluid dynamics. In this model the number of carotid siphon used for the CFD simulations was varied. In the FSI study, five simulations were conducted varying the elastic modulus of the artery and the arterial wall thickness, and the effect of hypertension on the results was reported. The FSI simulations have shown that the most important parameter that affects the aneurysm wall stress state is the arterial hypertension with maximum stress of around 900 kPa. It is concluded that FSI simulations must be used to simultaneously determine the wall stress and the fluid dynamics inside cerebral aneurysm. [ABSTRACT FROM AUTHOR]

Abstract: Solid mechanics plays an important role in the progression and rupture of cerebral aneurysms. The hypothesis is that the mechanism that control aneurysm enlargement is the wall remodeling under the effect of time dependent arterial pressure. When the aneurysm enlarges, the characteristics of the collagen fibers change, increasing the risk of rupture. The current work describes the solid dynamics in 30 patient-specific models of cerebral aneurysms. An area based index shows important difference between unruptured and ruptured aneurysms. The effective wall stress and displacement showed large variations depending on aneurysm size and form. The effects of hypertension were reported and correlations between the maximal effective stress and displacement with geometrical indices were found. [Copyright &y& Elsevier]

Abstract: Hemodynamics plays an important role in the progression and rupture of cerebral aneurysms. The temporal and spatial variations in wall shear stress (WSS) within the aneurysmal sac are hypothesized to be correlated with the growth and rupture of the aneurysm. The current work describes the blood flow dynamics in 34 patient-specific models of saccular aneurysms located in the region of the anterior and posterior circulation of the circle of Willis. The models were obtained from three-dimensional rotational angiography image data and blood flow dynamics was studied under a physiologically representative waveform of inflow. The three-dimensional continuity and momentum equations for unsteady laminar flow were solved with commercial software using non-structured fine grid sizes. The vortex structure, the wall pressure, and the WSS showed large variations, depending on the morphology of the artery, size of the aneurysm, and form. A correlation existed between the mean WSS on the aneurysmal sac for lateral unruptured and ruptured aneurysms with an aneurysm surface index, which is defined as the ratio between the aneurysm area and the artery area at model inlet, respectively. [Copyright &y& Elsevier]

Sudden unexpected death in epilepsy (SUDEP) has been linked to respiratory dysfunction, but the mechanisms underlying this association remain unclear. Here we found that both focal and generalized convulsive seizures (GCSs) in epilepsy patients caused a prolonged decrease in the hypercapnic ventilatory response (HCVR; a measure of respiratory CO 2 chemoreception). We then studied Scn1a R1407X /+ (Dravet syndrome; DS) and Scn8a N1768D /+ (D/+) mice of both sexes, two models of SUDEP, and found that convulsive seizures caused a postictal decrease in ventilation and severely depressed the HCVR in a subset of animals. Those mice with severe postictal depression of the HCVR also exhibited transient postictal hypothermia. A combination of blunted HCVR and abnormal thermoregulation is known to occur with dysfunction of the serotonin (5-hydroxytryptamine; 5-HT) system in mice. Depleting 5-HT with para -chlorophenylalanine (PCPA) mimicked seizure-induced hypoventilation, partially occluded the postictal decrease in the HCVR, exacerbated hypothermia, and increased postictal mortality in DS mice. Conversely, pretreatment with the 5-HT agonist fenfluramine reduced postictal inhibition of the HCVR and hypothermia. These results are consistent with the previous observation that seizures cause transient impairment of serotonergic neuron function, which would be expected to inhibit the many aspects of respiratory control dependent on 5-HT, including baseline ventilation and the HCVR. These results provide a scientific rationale to investigate the interictal and/or postictal HCVR as noninvasive biomarkers for those at high risk of seizure-induced death, and to prevent SUDEP by enhancing postictal 5-HT tone. SIGNIFICANCE STATEMENT There is increasing evidence that seizure-induced respiratory dysfunction contributes to the pathophysiology of sudden unexpected death in epilepsy (SUDEP). However, the cellular basis of this dysfunction has not been defined. Here, we show that seizures impair CO 2 chemoreception in some epilepsy patients. In two mouse models of SUDEP we found that generalized convulsive seizures impaired CO 2 chemoreception, and induced hypothermia, two effects reported with serotonergic neuron dysfunction. The defects in chemoreception and thermoregulation were exacerbated by chemical depletion of serotonin and reduced with fenfluramine, suggesting that seizure-induced respiratory dysfunction may be due to impairment of serotonin neuron function. These findings suggest that impaired chemoreception because of transient inhibition of serotonergic neurons may contribute to the pathophysiology of SUDEP., (Copyright © 2023 the authors.)

Background: COVID-19 requires an early diagnosis to optimize management and limit transmission. SARS-CoV-2 is able to spread effectively. Infected asymptomatic individuals have been found to be contagious. RT-qPCR is the currently recommended laboratory method for diagnosing acute infection. However, rapid antigen detection (RAD) tests are not only fast, but require less specialized training. The possibility of using RAD tests to identify asymptomatic patients is attractive, as it could effectively contribute to minimizing the hospital spread of SARS-CoV-2. The objective of the study was to determine the performance of RAD vs. RT-qPCR for the detection of asymptomatic cases in INER health personnel., Methods: In order to follow WHO guidelines, generalized tests, a test station for health care workers was implemented on demand. A rapid test was carried out and a second sample was taken to be processed by RT-qPCR. With the results of both tests we conducted a retrospective study. Sensitivity, specificity, positive predictive value, negative predictive value and negative likelihood ratios were calculated., Results: A total of 1640 RAD tests were performed in health care workers (mean age was 39, 69, 47% with a self-reported comorbidity). Participants provided 1,640 valid RAD/RT-qPCR test pairs with 2% testing positive via RT-qPCR. 12 RAD samples were positive for SARS-CoV-2. Overall sensitivity of the PANBIO ™ COVID-19 Ag Rapid Test test was 35.2%., Conclusions: RADs are not recommended for the detection of asymptomatic cases due to low performance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Becerril Vargas, Cojuc-Konigsberg, Alberto Mujica Sánchez, García Colín, Alfredo Camacho Corral, Hansel Chávez Morales, Aguirre Pineda, Martínez Bravo, Ortiz Martínez, Martínez Orozco, Rodríguez-Sánchez, Ochoa, Pantoja Jiménez, Morales Lozada and Cuevas Rodriguez.)

The knowledge of rainfall regimes is a relevant requirement for many activities such as water resources planning, risk management, agriculture activities management, and other hydrologic applications. The present study has consisted of validating four techniques (one linear, one non-linear, and two hybrids) that allow identifying homogenous regions. We take the monthly rainfall in the Southwestern Colombia (Nariño), an area of 33,268 km2 characterized by complex topography and local factors that can influence the rainfall behavior, to test all techniques. The results showed overall the best performance for the approach related to non-linear principal component analysis and self-organizing map. However, in all mainly prevail two regions: the Andean Region and Pacific Region with a bimodal and unimodal regime, respectively. The bimodal one dominates over the Andes mountains range and the unimodal one the coastal zone. The application of non-linear approaches provided a better understanding of the seasonality of rainfall, and the results may be useful for water resource management.

Epilepsy is one of the most common chronic neurologic diseases, with a prevalence of 1% in the US population. Many people with epilepsy live normal lives, but are at risk of sudden unexpected death in epilepsy (SUDEP). This mysterious comorbidity of epilepsy causes premature death in 17%-50% of those with epilepsy. Most SUDEP occurs after a generalized seizure, and patients are typically found in bed in the prone position. Until recently, it was thought that SUDEP was due to cardiovascular failure, but patients who died while being monitored in hospital epilepsy units revealed that most SUDEP is due to postictal central apnea. Some cases may occur when seizures invade the amygdala and activate projections to the brainstem. Evidence suggests that the pathophysiology is linked to defects in the serotonin system and central CO 2 chemoreception, and that there is considerable overlap with mechanisms thought to be involved in sudden infant death syndrome (SIDS). Future work is needed to identify biomarkers for patients at highest risk, improve ascertainment, develop methods to alert caregivers when SUDEP is imminent, and find effective approaches to prevent these fatal events., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Children with cerebral palsy have difficulty to sit, stand, walk, run and jump independently. Therapy is an important factor in improving these aspects, and if applied in early intervention treatments, when the child is growing, it could have many benefits. These therapies require intensive and extended sessions, which in turn demand dedication and effort. New strategies that provide interesting and motivating interventions are often incorporated to improve the participation and performance of the children in the therapies. Therapies using social assistive robots can be alternative and complementary methods to promote the participation and motivation of children with cerebral palsy. Methods: The objective of this work is to validate the effectiveness of a 16-session physical therapy program to improve the participation and fulfillment of therapeutic objectives on an 8 year-old boy with dyskinetic cerebral palsy for motor learning to walk using a social assistive robot. The therapy program was carried out through a methodological proposal that uses SMART objectives (Specific, Measurable, Achievable, Realistic and Timed), Goal-Directed Therapy (GDT) and its evaluation through Goal Attainment Scaling (GAS). Results: A NAO robot was used as a social assistive robot to support a physical therapy for a child with cerebral palsy. In this work, it was observed that the motivation generated by the interaction with the social assistive robot facilitated the persistence in the walking and the fulfillment of the objectives. Conclusion: Using humanoid robots as social assistive robots may benefit therapeutic processes on children with motor disabilities. The methodology developed provides a formal way to achieve objectives in therapeutic processes for children with cerebral palsy.Implications for rehabilitationIt requires researchers to conduct more studies to validate the potential of the use of social robots in therapeutic interventions that promote development in children with motor disabilities, such as cerebral palsy.Promoting the use of new technologies in therapeutic processes such as humanoid robots allows us to create new strategies to know the impact of this technology in the area of rehabilitation.The use of formal methodologies focused on the patient, along with multidisciplinary teams, could increase the possibilities of using social robots to improve cognitive and motor outcomes in children with cerebral palsy.The formulation of SMART objectives and their quantification through the GAS scale can be used as recommendations to improve the formulation of goals in therapeutic interventions for children with cerebral palsy.

Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality in patients with drug-resistant epilepsy. Most SUDEP cases occur in bed at night and are preceded by a generalized tonic-clonic seizure (GTCS). Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly caused by mutations in the SCN1A gene. Affected individuals suffer from refractory seizures and an increased risk of SUDEP. Here, we demonstrate that mice with the Scn1a R1407X /+ loss-of-function mutation (DS) experience more spontaneous seizures and SUDEP during the early night. We also evaluate effects of long-term ketogenic diet (KD) treatment on mortality and seizure frequency. DS mice showed high premature mortality (44% survival by P60) that was associated with increased spontaneous GTCSs 1-2 days prior to SUDEP. KD treated mice had a significant reduction in mortality (86% survival by P60) compared to mice fed a control diet. Interestingly, increased survival was not associated with a decrease in seizure frequency. Further studies are needed to determine how KD confers protection from SUDEP. Moreover, our findings implicate time of day as a factor influencing the occurrence of seizures and SUDEP. DS mice, though nocturnal, are more likely to have SUDEP at night, suggesting that the increased incidence of SUDEP at night in may not be solely due to sleep.

Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly due to mutations of the sodium channel gene SCN1A. Patients with DS have a high risk of sudden unexplained death in epilepsy (SUDEP), widely believed to be due to cardiac mechanisms. Here we show that patients with DS commonly have peri-ictal respiratory dysfunction. One patient had severe and prolonged postictal hypoventilation during video EEG monitoring and died later of SUDEP. Mice with an Scn1aR1407X/+ loss-of-function mutation were monitored and died after spontaneous and heat-induced seizures due to central apnea followed by progressive bradycardia. Death could be prevented with mechanical ventilation after seizures were induced by hyperthermia or maximal electroshock. Muscarinic receptor antagonists did not prevent bradycardia or death when given at doses selective for peripheral parasympathetic blockade, whereas apnea, bradycardia, and death were prevented by the same drugs given at doses high enough to cross the blood-brain barrier. When given via intracerebroventricular infusion at a very low dose, a muscarinic receptor antagonist prevented apnea, bradycardia, and death. We conclude that SUDEP in patients with DS can result from primary central apnea, which can cause bradycardia, presumably via a direct effect of hypoxemia on cardiac muscle.

Serotonin (5-HT) neurons contribute to respiratory chemoreception in adult mice, but it is unclear whether they play a similar role in neonatal mice. We studied breathing during development in Lmx1b f/f/p mice, which lack 5-HT neurons. From postnatal days 1-7 (P1-P7), ventilation of Lmx1b f/f/p mice breathing room air was 50% of WT mice (p<0.001). By P12, baseline ventilation increased to a level equal to WT mice. In contrast, the hypercapnic ventilatory response (HCVR) of neonatal Lmx1b f/f/p and WT mice was equal to each other, but were both much less than adult WT mice. By P21 the HCVR of WT mice increased to near adult levels, but the HCVR of Lmx1b f/f/p mice had not changed, and was 42% less than WT mice. Primary cell cultures were prepared from the ventromedial medulla of neonatal mice, and patch-clamp recordings were made from neurons identified as serotonergic by expression of a reporter gene. In parallel with developmental changes of the HCVR in vivo, 5-HT neurons had little chemosensitivity to acidosis until 12days in vitro (DIV), after which their response increased to reach a plateau around 25 DIV. Neonatal Lmx1b f/f/p mice displayed high mortality and decreased growth rate, and this worsened in hypoxia. Mortality was decreased in hyperoxia. These results indicate that maturation of 5-HT neurons contributes to development of respiratory CO 2 /pH chemoreception during the first few weeks of life in mice in vivo. A defect in the 5-HT system in early postnatal life decreases survival due in part to hypoxia., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Intracellular neurofibrillary tangles are part of the core pathology of Alzheimer's disease (AD), which are mainly composed of hyperphosphorylated tau protein., Objectives: The purpose of this study is to determine whether high molecular weight (HMW) or low molecular weight (LMW) tau protein levels, as well as the ratio HMW/LMW, present in platelets correlates with brain magnetic resonance imaging (MRI) structural changes in normal and cognitively impaired subjects., Methods: We examined 53 AD patients and 37 cognitively normal subjects recruited from two Memory Clinics at the Universidad de Chile. Tau levels in platelets were determined by immunoreactivity and the MRI scans were analyzed using voxel-based morphometry in 41 AD patients., Results: The HMW/LMW tau ratio was statistically different between controls and AD patients, and no associations were noted between HMW or LMW tau and MRI structures. In a multivariate analysis controlled for age and education level, the HMW/LMW tau ratio was associated with reduced volume in the left medial and right anterior cingulate gyri, right cerebellum, right thalamus (pulvinar), left frontal cortex, and right parahippocampal region., Conclusions: This exploratory study showed that HMW/LMW tau ratio is significantly higher in AD patients than control subjects, and that it is associated with specific brain regions atrophy. Determination of peripheral markers of AD pathology can help understanding the pathophysiology of neurodegeneration in AD.

Background: Chile is one of the countries with the highest prevalence of cholelithiasis worldwide, considering the Mapuche ethnicity as a risk factor for developing this pathology. Moreover, cholelithiasis is the main risk factor for developing gallbladder cancer, being the fifth cause of cancer death in Chile. The purpose of this study was to compare the frequency of cholelithiasis and biliary pathology among the population belonging to Rapanui ethnicity and non-Rapanui population living on Easter Island., Materials and Methods: In this retrospective case-control study, a total of 609 abdominal ultrasonographs performed consecutively in Hanga Roa Hospital during the period August 2012 to January 2015 were analyzed. Multiple logistic regression was used to obtain odds ratio (OR) and 95% confidence intervals (95% CI) of cholelithiasis and biliary pathology, adjusting for age, gender and referral diagnostic hypothesis., Results: In the Rapanui population the frequency for cholelithiasis and biliary pathology was 6.4% and 13%, meanwhile for the non-Rapanui population it was 13% and 22% respectively. Compared to the non-Rapanui Chilean population, the Rapanui ethnicity presented an OR of 0.53 (95% CI: 0.29-0.95) for cholelithiasis and OR of 0.52 (95% CI: 0.33-0.82) for biliary pathology., Conclusions: We found statistically significant ethnic differences in the frequency of cholelithiasis and biliary disease among the population of Rapanui and non-Rapanui ethnicity, so that this could be a protective factor for the development of biliary pathology, given the Chilean population context. Other studies including community population to determine the real prevalence of cholelithiasis and analyze the protective role of Rapanui ethnicity on this disease are necessary.

Nicotine may link maternal cigarette smoking with respiratory dysfunctions in sudden infant death syndrome (SIDS). Prenatal-perinatal nicotine exposure blunts ventilatory responses to hypercapnia and reduces central respiratory chemoreception in mouse neonates at Postnatal Days 0 (P0) to P3. This suggests that raphe neurons, which are altered in SIDS and contribute to central respiratory chemoreception, may be affected by nicotine. We therefore investigated whether prenatal-perinatal nicotine exposure affects the activity, electrical properties, and chemosensitivity of raphe obscurus (ROb) neurons in mouse neonates. Osmotic minipumps, implanted subcutaneously in 5- to 7-day-pregnant CF1 mice, delivered nicotine bitartrate (60 mg kg(-1) d(-1)) or saline (control) for up to 28 days. In neonates, ventilation was recorded by head-out plethysmography, c-Fos (neuronal activity marker), or serotonin autoreceptors (5HT1AR) were immunodetected using light microscopy, and patch-clamp recordings were made from raphe neurons in brainstem slices under normocarbia and hypercarbia. Prenatal-perinatal nicotine exposure decreased the hypercarbia-induced ventilatory responses at P1-P5, reduced both the number of c-Fos-positive ROb neurons during eucapnic normoxia at P1-P3 and their hypercapnia-induced recruitment at P3, increased 5HT1AR immunolabeling of ROb neurons at P3-P5, and reduced the spontaneous firing frequency of ROb neurons at P3 without affecting their CO2 sensitivity or their passive and active electrical properties. These findings reveal that prenatal-perinatal nicotine reduces the activity of neonatal ROb neurons, likely as a consequence of increased expression of 5HT1ARs. This hypoactivity may change the functional state of the respiratory neural network leading to breathing vulnerability and chemosensory failure as seen in SIDS.

Easter Island is a small island of 180 km2, located 3,800 km from the Chilean coast and one of the most isolated inhabited places in the world. Since the mid-twentieth century, it has been undergoing an epidemiological transition in relation to the causes of death, from a predominance of infectious to non-communicable diseases (NCDs) such as cardiovascular ailments and cancer. The aim of this study is to describe the causes of death to Easter Island between 2000 and 2012, so the statistical records of Hanga Roa Hospital and death certificates were reviewed. The period under review of 13 years there was a total of 252 deaths, an average to 19.3 deaths per year. The most frequent causes of death found in the general population of Easter Island were cardiovascular diseases (25.4%), followed by neoplasms (23.4%), accidents (18.6%). Related to Rapa Nui people, cardiovascular and neoplastic diseases (both 26.7%) predominate, while in the population without belonging to the ethnic group the main causes were traumatic (25%) and cardiovascular (22.2%). Comparing the leading causes of death of Easter Island with mainland Chile, it can be seen how they resemble. Taking the island death profile, it is necessary to work on public health strategies aimed to this, considering that some of the causes are completely preventable.

In this work, we introduce a model for predicting multivariate time series data. This model was obtained by partitioning the state space with joint permutations. We review the theoretical framework of the previous works, show a simple extension to multivariate data, and compare its performance to the previous model obtained by permutations for predicting scalar time series data.

Hemodynamically induced stress plays an important role in the progression and rupture of cerebral aneurysms. The current work describes computational fluid dynamics (CFD) simulations in anatomically realistic models of cerebral aneurysms. Twenty lateral aneurysms models were investigated. The models were obtained from three-dimensional rotational angiographic imaging data and CFD were studied under the same physiologically representative waveform of inflow. The flow was assumed to be laminar, non-Newtonian, and incompressible. The CFD models were solved with the finite elements package ADINA. Predictions of velocity field and wall shear stress (WSS) on the aneurysms were compared for the different cases. Linear correlations between the WSS on the aneurysm fundus at peak systole for lateral aneurysms with an area index were found.

1. Maternal tobacco smoking is the principal risk factor associated with sudden infant death syndrome (SIDS), a leading cause of death of infants under 1 year of age. Victims of SIDS show a higher incidence of respiratory control abnormalities, including central apnoeas, delayed arousal responses and diminished ventilatory chemoreflexes. 2. Nicotine is likely the link between maternal tobacco smoking and SIDS. Prenatal nicotine exposure can alter the breathing pattern and can reduce hypoxia- and hypercarbia-induced ventilatory chemoreflexes. In vitro approaches have revealed that prenatal nicotine exposure impairs central chemosensitivity, switching the cholinergic contribution from a muscarinic to a nicotinic receptor-based drive. In addition, serotonergic, noradrenergic, GABAergic, glycinergic and glutamatergic, among others, are affected by prenatal nicotine. 3. Here we propose that prenatal nicotine affects the respiratory network through two main processes: (i) reorganization of neurotransmitter systems; and (ii) remodelling of neural circuits. These changes make breathing more vulnerable to fail in early postnatal life, which could be related to the pathogenesis of SIDS.