Epileptic seizure suppression: A computational approach for identification and control using real data.

Epilepsy affects millions of people worldwide every year and remains an open subject for research. Current development on this field has focused on obtaining computational models to better understand its triggering mechanisms, attain realistic descriptions and study seizure suppression. Controllers have been successfully applied to mitigate epileptiform activity in dynamic models written in state-space notation, whose applicability is, however, restricted to signatures that are accurately described by them. Alternatively, autoregressive modeling (AR), a typical data-driven tool related to system identification (SI), can be directly applied to signals to generate more realistic models, and since it is inherently convertible into state-space representation, it can thus be used for the artificial reconstruction and attenuation of seizures as well. Considering this, the first objective of this work is to propose an SI approach using AR models to describe real epileptiform activity. The second objective is to provide a strategy for reconstructing and mitigating such activity artificially, considering non-hybrid and hybrid controllers - designed from ictal and interictal events, respectively. The results show that AR models of relatively low order represent epileptiform activities fairly well and both controllers are effective in attenuating the undesired activity while simultaneously driving the signal to an interictal condition. These findings may lead to customized models based on each signal, brain region or patient, from which it is possible to better define shape, frequency and duration of external stimuli that are necessary to attenuate seizures.

Chaotic and stochastic dynamics of epileptiform-like activities in sclerotic hippocampus resected from patients with pharmacoresistant epilepsy.

The types of epileptiform activity occurring in the sclerotic hippocampus with highest incidence are interictal-like events (II) and periodic ictal spiking (PIS). These activities are classified according to their event rates, but it is still unclear if these rate differences are consequences of underlying physiological mechanisms. Identifying new and more specific information related to these two activities may bring insights to a better understanding about the epileptogenic process and new diagnosis. We applied Poincaré map analysis and Recurrence Quantification Analysis (RQA) onto 35 in vitro electrophysiological signals recorded from slices of 12 hippocampal tissues surgically resected from patients with pharmacoresistant temporal lobe epilepsy. These analyzes showed that the II activity is related to chaotic dynamics, whereas the PIS activity is related to deterministic periodic dynamics. Additionally, it indicates that their different rates are consequence of different endogenous dynamics. Finally, by using two computational models we were able to simulate the transition between II and PIS activities. The RQA was applied to different periods of these simulations to compare the recurrences between artificial and real signals, showing that different ranges of regularity-chaoticity can be directly associated with the generation of PIS and II activities.

Amazon rainforest rodents (Proechimys) are resistant to post-stroke epilepsy.

There are no clinical interventions to prevent post-injury epilepsy, a common and devastating outcome after brain insults. Epileptogenic events that run from brain injury to epilepsy are poorly understood. Previous studies in our laboratory suggested Proechimys, an exotic Amazonian rodent, as resistant to acquired epilepsy development in post-status epilepticus models. The present comparative study was conducted to assess (1) stroke-related brain responses 24-h and 30 days after cortical photothrombosis and (2) post-stroke epilepsy between Proechimys rodents and Wistar rats, a traditional animal used for laboratory research. Proechimys group showed smaller volume of ischemic infarction and lesser glial activation than Wistar group. In contrast to Wistar rats, post-stroke decreased levels of pro-inflammatory cytokines and increased levels of anti-inflammatory mediators and growth factors were found in Proechimys. Electrophysiological signaling changes assessed by cortical spreading depression, in vitro and in vivo, showed that Wistar's brain is most severely affected by stroke. Chronic electrocorticographic recordings showed that injury did not lead to epilepsy in Proechimys whereas 88% of the Wistar rats developed post-stroke epilepsy. Science gains insights from comparative studies on diverse species. Proechimys rodents proved to be a useful animal model to study antiepileptogenic mechanisms after brain insults and complement conventional animal models.

Characterization of adult patients with Guillain-Barré syndrome during the arboviral infection outbreaks in Honduras.

Arbovirus infections have been associated with a wide spectrum of neurological manifestations. Among these, Guillain-Barré syndrome (GBS) is one of the most common. This study describes the characteristics of GBS associated with arbovirus infections during the outbreak which occurred in Honduras from January 2016 to February 2019. This was an observational retrospective study of adult patients who were diagnosed with GBS during that time. The diagnosis of GBS was based upon the criteria first published by Asbury, et al. and subsequently revised as the Brighton Criteria. A total of 91 patients with GBS constituted the study population. RT-PCR tests for ZIKV, CHIKV, and DENV arboviruses were performed in 47 (52%) of the patients. Of the tested population, 8/47 were positive for one of the arboviruses (5/8 for ZIKV, 3/8 for CHIKV; 0/8 for DENV). The clinical profile of the eight cases with GBS and arboviral infection did not differ significantly from the GBS patients who tested negative for ZIKV and CHIKV. In the cases with GBS and ZIKV, a parainfectious onset of the disease was suggested. Although not a strikingly large number of patients with GBS and arbovirus infection were seen, the close temporal relationship in these eight cases suggests an arbovirus (ZIKV and CHIKV) etiology.

Deleterious effects of chronic mercury exposure on in vitro LTP, memory process, and oxidative stress.

Heavy metal contamination in aquatic environments plays an important role in the exposure of humans to these toxicants. Among these pollutants, mercury (Hg) is one main concern due to its high neurotoxicity and environmental persistence. Even in low concentrations, Hg bioaccumulation is a major threat to human health, with higher impact on populations whose diet has fish as chief consumption. Mercury compounds have high affinity for neuronal receptors and proteins, which gives Hg its cumulative feature and have the ability to cross cell membranes and blood-brain barrier to show their neurotoxicity. Intoxication with Hg increases levels of reactive oxygen species (ROS), thus depleting faster the resource of antioxidant proteins. To evaluate Hg-induced hippocampal ROS production, synaptic plasticity, anxiety, and memory, a total of 11 male Wistar rats were exposed to HgCl2 (Hg30 group) to produce a residual concentration of 8 ng/mL at the end of 30 days. Behavioral tests (plus-maze discriminative avoidance task), in vitro electrophysiology, and ROS assays were performed. Western blot assay showed decreased levels of antioxidant proteins GPx and SOD in Hg30 group. Increased ROS production was observed in the CA1 and CA3 regions in the Hg-exposed group. Plus-maze task detected long-term memory impairment in Hg30 group, linked to poorer in vitro long-term potentiation as compared to control group. Hg intoxication also promoted higher anxiety-like behavior in the exposed animals. In conclusion, our data suggests that low doses of HgCl2 resulted in impaired long-term memory and unbalance between decreased antioxidant protein expression and increased ROS production in the hippocampus.

Behavioral, electrophysiological and neuropathological characteristics of the occurrence of hypertension in pregnant rats.

Pre-eclampsia (PE) affects approximately 2 to 8% of pregnant women, causing blood pressure above 140 × 90 mmHg and proteinuria, normally after the 20th gestation week. If unsuccessfully treated, PE can lead to self-limited seizures (Eclampsia) that could eventually result in death of the mother and her fetus. The present study reports an experimental model of preeclampsia hypertension in pregnant (HP) and non-pregnant (H) Wistar rats by partially clamping one of their renal arteries. Pregnant (P) and non-pregnant (C) controls were provided. Differently from controls (C and P), H and HP animals presented a steady rise in BP two weeks after renal artery clamping. Injection of pentylenetetrazol (PTZ) induced behavioral and electroencephalographic seizures in all groups, which were increased in number, duration, amplitude and power accompanied by decreased latency in HP animals (p < 0.05). Consistent results were obtained in in vitro experimentation. Immunohistochemistry of hippocampus tissue in HP animals showed decreased density of neurons nuclei in CA1, CA3 and Hilus and increased density of astrocytes in CA1, CA3 and gyrus (p < 0.05). The present findings show that the clamping of one renal arteries to 0.15 mm and PTZ administration were able to induce signs similar to human PE in pregnant Wistar rats.

Robust Network Inhibition and Decay of Early-Phase LTP in the Hippocampal CA1 Subfield of the Amazon Rodent Proechimys.

Background: Diverse forms of long-term potentiation (LTP) have been described, but one of the most investigated is encountered in the glutamatergic synapses of the hippocampal cornu Ammonis (CA1) subfield. However, little is known about synaptic plasticity in wildlife populations. Laboratory animals are extremely inbred populations that have been disconnected from their natural environment and so their essential ecological aspects are entirely absent. Proechimys are small rodents from Brazil's Amazon rainforest and their nervous systems have evolved to carry out specific tasks of their unique ecological environment. It has also been shown that long-term memory duration did not persist for 24-h in Proechimys, in contrast to Wistar rats, when both animal species were assessed by the plus-maze discrimination avoidance task and object recognition test. Methods: In this work, different protocols, such as theta burst, single tetanic burst or multiple trains of high frequency stimulation (HFS), were used to induce LTP in hippocampal brain slices of Proechimys and Wistar rats. Results: A protocol-independent fast decay of early-phase LTP at glutamatergic synapses of the CA1 subfield was encountered in Proechimys. Long-term depression (LTD) and baseline paired-pulse facilitation (PPF) were investigated but no differences were found between animal species. Input/output (I/O) relationships suggested lower excitability in Proechimys in comparison to Wistar rats. Bath application of d-(-)-2-amino-5-phosphonopentanoicacid (D-AP5) and CNQX prevented the induction of LTP in both Proechimys and Wistar. However, in marked contrast to Wistar rats, LTP induction was not facilitated by the GABAA antagonist in the Amazon rodents, even higher concentrations failed to facilitate LTP in Proechimys. Next, the effects of GABAA inhibition on spontaneous activity as well as evoked field potentials (FPs) were evaluated in CA1 pyramidal cells. Likewise, much lower activity was detected in Proechimys brain slices in comparison to those of the Wistar rats. Conclusions: These findings suggest a possible high inhibitory tone in the CA1 network mediated by GABAA receptors in the Amazon rodents. Currently, neuroscience research still seeks to reveal molecular pathways that control learning and memory processes, Proechimys may prove useful in identifying such mechanisms in complement to traditional animal models.

Different patterns of epileptiform-like activity are generated in the sclerotic hippocampus from patients with drug-resistant temporal lobe epilepsy.

Human hippocampal slice preparations from patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) are excellent material for the characterization of epileptiform-like activity. However, it is still unknown if hippocampal regions as cornu Ammonis (CA) 1, CA3 and CA4, generate population epileptiform-like activity. Here, we investigated epileptiform activities of the subiculum, CA1, CA2, CA3, CA4 (induced by elevation of extracellular potassium concentration) and the dentate gyrus (induced with hilar stimulation and elevation of potassium concentration) from sclerotic hippocampi of patients with drug-resistant TLE. Five types of epileptiform-like activity were observed: interictal-like events; periodic ictal spiking; seizure-like events; spreading depression-like events; tonic seizure-like events and no activity. Different susceptibilities to generate epileptiform activity among hippocampal regions were observed; the dentate gyrus was the most susceptible region followed by the subiculum, CA4, CA1, CA2 and CA3. The incidence of epileptiform activity pattern was associated with specific regions of the hippocampal formation. Moreover, it was observed that each region of the hippocampal formation exhibits frequency-specific ranges in each subfield of the sclerotic human tissue. In conclusion, this study demonstrates that epileptiform-like activity may be induced in different regions of the hippocampal formation, including regions that are severely affected by neuronal loss.

Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil's Amazon Rainforest.

Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed that LTP decays rapidly over time reaching basal levels at 90 min after theta-burst stimulation in Proechimys, contrasting to the stable LTP found in the Wistar rats which was observed throughout 3-h recording period. These findings suggest a link between the LTP decay and the lack of 24-h long-lasting memory process in Proechimys. Nevertheless, why early-phase LTP in Proechimys decays very rapidly remains to be elucidated.

Influence of parental education on Honduran medical students' labour perspectives: rural work and emigration.

INTRODUCTION: We sought to evaluate the intentions of Honduran medical students to emigrate or to work in a rural setting, and their association with parental education. METHODS: We performed a cross-sectional, analytic study at a Honduran medical school. Student participants completed a structured questionnaire, which assessed their intentions to emigrate or work in a rural setting after finishing medical school and the highest level of education achieved by their parents. We calculated crude and adjusted prevalence ratios with their respective 95% confidence intervals. RESULTS: Of 868 surveys distributed, 564 were completed. The mean age of the participants was 21 (standard deviation 3) years, and 62.2% were female. Of the respondents, 16.6% intended to emigrate to work and 11.2% intended to work in a rural setting. Higher paternal education (i.e., technical, university and postgraduate training) was associated with a higher rate of intention to emigrate. Students whose fathers underwent postgraduate education were less likely to intend to work in a rural setting. For maternal education, only the postgraduate level was associated with the outcomes in some of the tested models. CONCLUSION: The frequency of students intending to emigrate was relatively low. However, the frequency of students being willing to work in rural settings was also low. Students whose parents had higher levels of education were more likely to intend to work abroad and less likely to intend to work in a rural area. These factors should be considered in medical schools' selection processes to improve retention and ensure adequate distribution of physicians.

INTRODUCTION: Nous avons voulu évaluer les intentions d'étudiants en médecine honduriens d'émigrer ou de travailler en milieu rural et le rapport entre leurs intentions et le degré de scolarité de leurs parents. MÉTHODES: Nous avons effectué une étude analytique transversale dans une faculté de médecine du Honduras. Les étudiants participants ont répondu à un questionnaire structuré qui évaluait leurs intentions d'émigrer ou de travailler en milieu rural à la fin de leurs études de médecine et le plus haut degré de scolarité atteint par leurs parents. Nous avons calculé les rapports de prévalence brute et ajustée, ainsi que leurs intervalles de confiance de 95 % respectifs. RÉSULTATS: Sur les 868 questionnaires distribués, 564 ont été remplis. L'âge moyen des participants était de 21 ans (écart-type 3 ans) et 62,2 % étaient de sexe féminin. Parmi les répondants, 16,6 % avaient l'intention d'émigrer pour travailler et 11,2 % avaient l'intention de travailler en milieu rural. Un niveau de scolarité paternel plus élevé (c'est-à-dire, formation technique, universitaire ou études supérieures) était associé à un taux plus élevé d'intention d'émigrer. Les étudiants dont les pères avaient fait des études supérieures étaient moins susceptibles d'avoir l'intention de travailler en milieu rural. En ce qui concerne l'éducation maternelle, seules les études supérieures ont été associées aux résultats pour certains modèles testés. CONCLUSION: Le nombre d'étudiants ayant l'intention d'émigrer était relativement bas. Toutefois, le nombre d'étudiants acceptant de travailler en milieu rural était également bas. Les étudiants dont les parents avaient un niveau de scolarité plus élevé étaient plus susceptibles d'avoir l'intention de travailler à l'étranger et moins susceptibles d'avoir l'intention de travailler en milieu rural. Ces facteurs doivent entrer en ligne de compte lors du processus de sélection des étudiants admis dans les facultés de médecine pour améliorer la rétention et la distribution adéquate des effectifs médicaux.

Caracterización clínica y hematológica de pacientes pediátricos con Dengue en Honduras / Clinical and hematological characterization of pediatric patients with Dengue in Honduras

Objetivo: Caracterizar de forma clínica y hematológica los casos de dengue en población pediátrica, en el año 2010. Lugar del estudio: Hospital Escuela Universitario (HEU), Tegucigalpa, Honduras. Diseño: estudio descriptivo. Pacientes: Pediátricos hospitalizados en HEU con diagnóstico de dengue. Mediciones: Se evaluaron variables demográficas, clínicas y hematológicas. Resultados: De un total de 2.428 pacientes, 1.220 (50,2%) fueron masculinos. Los grupos etarios predominantes fueron escolares 793 (32,7%) y adolescentes 1.164 (47,9%). Según el tipo de dengue fueron clasificados en dengue sin signos de alarma; 1.107 (45,6%), dengue con signos de alarma; 836 (34,4%) y dengue grave; 485 (20,0%). Las manifestaciones clínicas más frecuentes fueron fiebre 1956 (80,6%), mialgias 1.506 (62,0%), artralgias 1.351 (55,6%) y cefalea 1.242 (51,2%). Se confirmaron 48 (1,9%) fallecidos. Conclusión: El cuadro clínico mostró sintomatología muy inespecífica lo que dificulta un acertado diagnóstico, la trombocitopenia fue la prueba hematológica que podría ser útil para la evaluación inicial de los casos sospechosos dengue.

Objective: Characterize cases of dengue in clinic and hematological form of pediatric population in 2010. Place of study: Hospital Escuela Universitario, Tegucigalpa, Honduras. Design Study: Observational Descriptive retrospective. Measurements: Were evaluated demographic, clinic and hematologic variables. Results: Out of a total of 2428 patients, 1220 (50.2%) were males. For kind of dengue, were classificated without warnings signs 1107 (45.6%), with warnings signs 836 (34.4%) and severe dengue 485 (20.0%). The mostly frequent clinic manifestations were fever 1956 (80.6%), myalgia 1.506 (62.0%), arthralgia 1.351 (55.6%) and headache 1.242 (51.2%). Were confirmed 48 (1.9%) deaths. Conclusion: The clinic evaluation shown nonspecific symptoms, thereby is difficult get a good diagnostic, the thrombocytopenia was it hematologic test that could be useful in the initial evaluation with suspected cases of dengue.

Complicaciones temibles en un paciente con VIH/SIDA criptococosis, tuberculosis miliar, meningoencefalitis / Fearsome Complications in a Patient with HIV/AIDS: Cryptococcosis, Miliary Tuberculosis, Meningoencephalitis

Los criptococos son un grupo de hongos que se encuentran en el suelo donde hay aves, fundamentalmente palomas. De las diversas especies de criptococo, solamente resulta patógeno para el hombre Cryptoccocus neoformans. La manifestación más frecuente de esta infección es la meningoencefalitis, que afecta principalmente a pacientes inmuno comprometidos. La tuberculosis miliar representa una entidad poco frecuente dentro de las formas de presentación extrapulmonar de la tuberculosis, en pacientes inmunocompetentes. Sin embargo, en los pacientes infectados por el virus de la inmunodeficiencia humana, esta cifra oscila alrededor de 10%. Se presenta un reporte de caso, donde el paciente cursó con esta forma de Tuberculosis. Caso Clínico: Paciente masculino de 53 años, con cuadro de evacuaciones diarreicas crónicas intermitentes, fiebre diaria, vómitos postprandiales 4 a 5 veces al día, de 3 meses de evolución, cefalea intensa de 10 días, concomitantemente presentó una convulsión tónico clónica hace una semana. Además tos crónica con expectoración blanquecina y hemoptisis. Al examen físico se observó microadenopatías cervicales bilaterales, hipoventilación pulmonar bilateral, desviación de la lengua y comisura labial hacia lado derecho, disminución de fuerza en ambos miembros inferiores y superior derecho. Se realiza prueba para la detección de VIH, la cual resulta positiva, con conteo de 10 células CD4, punción lumbar en donde se obtiene líquido cefalorraquídeo ligeramente turbio, tinta china y antígena para criptococo positivo. Paciente es diagnosticado con VIH y SIDA, criptococosis del sistema nervioso central, tuberculosis miliar por rayos X, y meningoencefalitis. Se inicia cobertura antibiótica y antifímica a la cual el paciente respondió favorablemente...