Computational models of compound nerve action potentials: Efficient filter-based methods to quantify effects of tissue conductivities, conduction distance, and nerve fiber parameters.

BACKGROUND: Peripheral nerve recordings can enhance the efficacy of neurostimulation therapies by providing a feedback signal to adjust stimulation settings for greater efficacy or reduced side effects. Computational models can accelerate the development of interfaces with high signal-to-noise ratio and selective recording. However, validation and tuning of model outputs against in vivo recordings remains computationally prohibitive due to the large number of fibers in a nerve. METHODS: We designed and implemented highly efficient modeling methods for simulating electrically evoked compound nerve action potential (CNAP) signals. The method simulated a subset of fiber diameters present in the nerve using NEURON, interpolated action potential templates across fiber diameters, and filtered the templates with a weighting function derived from fiber-specific conduction velocity and electromagnetic reciprocity outputs of a volume conductor model. We applied the methods to simulate CNAPs from rat cervical vagus nerve. RESULTS: Brute force simulation of a rat vagal CNAP with all 1,759 myelinated and 13,283 unmyelinated fibers in NEURON required 286 and 15,860 CPU hours, respectively, while filtering interpolated templates required 30 and 38 seconds on a desktop computer while maintaining accuracy. Modeled CNAP amplitude could vary by over two orders of magnitude depending on tissue conductivities and cuff opening within experimentally relevant ranges. Conduction distance and fiber diameter distribution also strongly influenced the modeled CNAP amplitude, shape, and latency. Modeled and in vivo signals had comparable shape, amplitude, and latency for myelinated fibers but not for unmyelinated fibers. CONCLUSIONS: Highly efficient methods of modeling neural recordings quantified the large impact that tissue properties, conduction distance, and nerve fiber parameters have on CNAPs. These methods expand the computational accessibility of neural recording models, enable efficient model tuning for validation, and facilitate the design of novel recording interfaces for neurostimulation feedback and understanding physiological systems.

Color changing bioadhesive barrier for peripherally inserted central catheters.

Bacteria migration at catheter insertion sites presents a serious complication (bacteraemia) with high mortality rates. One strategy to mediate bacteraemia is a physical barrier at the skin-catheter interface. Herein a colorimetric biosensor adhesive (CathoGlu) is designed and evaluated for both colorimetric detection of bacterial infection and application as a bacteria barrier. The design intent combines viscous, hydrophobic bioadhesive with an organic pH indicator (bromothymol blue). Visual observation can then distinguish healthy skin at pH = ∼5 from an infected catheter insertion site at pH = ∼8. The liquid-to-biorubber transition of CathoGlu formulation occurs via a brief exposure to UVA penlight, providing an elastic barrier to the skin flora. Leachates from CathoGlu demonstrate no genotoxic and skin sensitization effect, assessed by OECD-recommended in vitro and in chemico assays. The CathoGlu formulation was found non-inferior against clinically approved 2-octyl-cyanoacrylate (Dermabond™), and adhesive tape (Micropore™) within an in vivo porcine model. CathoGlu skin adhesive provides new opportunities to prevent sepsis in challenging clinical situations.

Improved Methods for Preparing Transverse Sections and Unrolled Whole Mounts of Maize Leaf Primordia for Fluorescence and Confocal Imaging.

In maize (Zea mays) and other grasses (Poaceae), the leaf primordia are deeply ensheathed and rolled within the leaf whorl, making it difficult to study early leaf development. Here, we describe methods for preparing transverse sections and unrolled whole mounts of maize leaf primordia for fluorescence and confocal imaging. The first method uses a wire stripper to remove the upper portions of older leaves, exposing the tip of the leaf primordium and allowing its measurement for more accurate transverse section sampling. The second method uses clear, double-sided nano tape to unroll and mount whole-leaf primordia for imaging. We show the utility of the two methods in visualizing and analyzing fluorescent protein reporters in maize. These methods provide a solution to the challenges presented by the distinctive morphology of maize leaf primordia and will be useful for visualizing and quantifying leaf anatomical and developmental traits in maize and other grass species.

Spatiotemporal parameters for energy efficient kilohertz-frequency nerve block with low onset response.

BACKGROUND: Electrical nerve conduction block has great potential for treatment of disease through reversible and local inactivation of somatic and autonomic nerves. However, the relatively high energy requirements and the presence of undesired excitation at the onset of the kilohertz-frequency (KHF) signals used for block pose obstacles to effective translation. Frequency, electrode geometry, and waveform shape are known to influence block threshold and onset response, but available data provide a limited understanding of how to select these parameters to optimize nerve block. METHODS: We evaluated KHF nerve block in rat tibial nerve across frequencies (5-60 kHz), electrode geometries (monopolar, bipolar, and tripolar), and waveform shapes. We present a novel Fourier-based method for constructing composite signals that systematically sample the KHF waveform design space. RESULTS: The lowest frequencies capable of blocking (5-16 kHz) were not the most energy-efficient among the tested frequencies. Further, bipolar cuffs required the largest current and power to block, monopolar cuffs required the lowest current, and both tripolar and monopolar cuffs required the lowest power. Tripolar cuffs produced the smallest onset response across frequencies. Composite signals comprised of a first harmonic sinusoid at fundamental frequency (f0) superposed on a second harmonic sinusoid at 2f0 could block at lower threshold and lower onset response compared to the constituent sinusoids alone. This effect was strongly dependent on the phase of the second harmonic and on the relative amplitudes of the first and second harmonics. This effect was also dependent on electrode geometry: monopolar and tripolar cuffs showed clear composite signal effects in most experiments; bipolar cuffs showed no clear effects in most experiments. CONCLUSIONS: Our data provide novel information about block threshold and onset response at the boundary of frequencies that can block. Our results also show an interaction between spatial (cuff geometry) and temporal (frequency and waveform shape) parameters. Finally, while previous studies suggested that temporal parameters could reduce onset response only in exchange for increased block threshold (or vice versa), our results show that waveform shape influences KHF response in ways that can be exploited to reduce both energy and onset responses.

Establishment of a Captive Cave Nectar Bat (Eonycteris spelaea) Breeding Colony in Singapore.

Bats are known natural reservoirs of several highly pathogenic zoonotic viruses, including Hendra virus, Nipah virus, rabies virus, SARS-like coronaviruses, and suspected ancestral reservoirs of SARS-CoV-2 responsible for the ongoing COVID-19 pandemic. The capacity to survive infections of highly pathogenic agents without severe disease, together with many other unique features, makes bats an ideal animal model for studying the regulation of infection, cancer, and longevity, which is likely to translate into human health outcomes. A key factor that limits bat research is lack of breeding bat colonies. To address this need, a captive bat colony was established in Singapore from 19 wild-caught local cave nectar bats. The bats were screened for specific pathogens before the start of captive breeding. Custom-made cages and an optimized diet inclusive of Wombaroo dietary formula, liquid diet, and supplement of fruits enabled the bats to breed prolifically in our facility. Cages are washed daily and disinfected once every fortnight. Bats are observed daily to detect any sick bat or abnormal behavior. In addition, bats undergo a thorough health check once every 3 to 4 mo to check on their overall wellbeing, perform sampling, and document any potential pregnancy. The current colony houses over 80 bats that are successfully breeding, providing a valuable resource for research in Singapore and overseas.

A Porcine Model Using Adipose Stem Cell-Loaded Scaffolds for Alveolar Ridge Augmentation.

Tooth loss greatly affects a person's quality of life and many turn to dental implants to replace lost teeth. The success of a dental implant depends on the amount of alveolar bone supporting the implant, and thus, bone augmentation is often necessary to preserve or build up bone volume in the alveolar ridge. Bone can be augmented with autogenous bone, allografts, or xenografts, but the limitations of such natural bone grafts prompt researchers to develop synthetic scaffolds supplemented with cells and/or bioactive agents as alternative bone grafts. The translation of these combination scaffolds from the laboratory to the clinic requires reliable experimental models that can simulate the clinical conditions in human patients. In this article, we describe the use of a porcine alveolar defect model as a platform to evaluate the efficacy of a novel combination of a three-dimensional-printed polycaprolactone-tricalcium phosphate (PCL-TCP) scaffold and adipose-derived mesenchymal stem cells (AD-MSCs) in lateral alveolar augmentation. The surgical protocol for the defect creation and regenerative surgery, as well as analytical methods to determine the extent of tissue regeneration, are described and discussed.

Individual Magnetoencephalography Response Profiles to Short-Duration L-Dopa in Parkinson's Disease.

Clinical responses to dopamine replacement therapy for individuals with Parkinson's disease (PD) are often difficult to predict. We characterized changes in MDS-UPDRS motor factor scores resulting from a short-duration L-Dopa response (SDR), and investigated how the inter-subject clinical differences could be predicted from motor cortical magnetoencephalography (MEG). MDS-UPDRS motor factor scores and resting-state MEG recordings were collected during SDR from twenty individuals with a PD diagnosis. We used a novel subject-specific strategy based on linear support vector machines to quantify motor cortical oscillatory frequency profiles that best predicted medication state. Motor cortical profiles differed substantially across individuals and showed consistency across multiple data folds. There was a linear relationship between classification accuracy and SDR of lower limb bradykinesia, although this relationship did not persist after multiple comparison correction, suggesting that combinations of spectral power features alone are insufficient to predict clinical state. Factor score analysis of therapeutic response and novel subject-specific machine learning approaches based on subject-specific neuroimaging provide tools to predict outcomes of therapies for PD.

Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance.

Reversible block of nerve conduction using kilohertz frequency electrical signals has substantial potential for treatment of disease. However, the ability to block nerve fibers selectively is limited by poor understanding of the relationship between waveform parameters and the nerve fibers that are blocked. Previous in vivo studies reported non-monotonic relationships between block signal frequency and block threshold, suggesting the potential for fiber-selective block. However, the mechanisms of non-monotonic block thresholds were unclear, and these findings were not replicated in a subsequent in vivo study. We used high-fidelity computational models and in vivo experiments in anesthetized rats to show that non-monotonic threshold-frequency relationships do occur, that they result from amplitude- and frequency-dependent charge imbalances that cause a shift between kilohertz frequency and direct current block regimes, and that these relationships can differ across fiber diameters such that smaller fibers can be blocked at lower thresholds than larger fibers. These results reconcile previous contradictory studies, clarify the mechanisms of interaction between kilohertz frequency and direct current block, and demonstrate the potential for selective block of small fiber diameters.

Enfermedades de transmisión hídricas en el cantón Penipe, Ecuador 2016-2017 / Waterborne diseases in cantón Penipe, Ecuador, 2016-2017

Introducción: La reemergencia y el control de algunas enfermedades de transmisión hídrica continúan siendo motivos de interés para los gobiernos sanitarios. Objetivo: Desarrollar acciones intersectoriales dirigidas al mejoramiento de la situación ambiental, el saneamiento básico y la calidad del agua. Métodos: Se desarrolló una investigación-acción participativa, con enfoque mixto. Se conformó un equipo multidisciplinario integrado por profesionales de la salud, miembros de la comunidad y del Gobierno Autónomo Descentralizado de Penipe, Chimborazo, Ecuador. La población estuvo constituida por 2089 habitantes que residían de forma permanente en el área urbana de la cabecera cantonal durante septiembre de 2016 y septiembre de 2017. La muestra (494 personas) se seleccionó por muestreo no probabilístico, la integraron individuos con edades entre 15 y 60 años, mentalmente aptos y que en el momento de la aplicación del instrumento se encontraban en su vivienda. Estas personas ofrecieron su consentimiento informado de participación y declararon residir de forma permanente en esa localidad. Para la recolección de los datos se empleó un cuestionario diseñado y validado por criterio de especialistas. Resultados: Predominaron las féminas de 21-30 años de edad y la autoidentificación étnica de mestiza. El consumo de agua hervida y su cloración constituyeron las prácticas más referidas por los encuestados, lo que resulta insuficiente para evitar la transmisibilidad de las enfermedades de transmisión hídrica. Conclusiones: La presencia de las enfermedades de transmisión hídricas en el cantón Penipe, Ecuador es un problema de la salud pública local que aún no ha sido resuelto, lo que justifica una intervención intersectorial que permita una educación para la salud incluyente, renovada y de carácter comunitario(AU)

Introduction: Re-emergence and control of some waterborne diseases are still an interest for sanitary governments. Objective: To develop intersectoral actions addressed to the improvement of the environmental situation, the basic sanitation and water quality. Methods: It was developed a participative research-action, with mixed approach. It was formed a multidisciplinary team made up by health professionals, members of the community and the Decentralized Autonomous Government of Penipe, Cimborazo, Ecuador. The population was formed by 2089 inhabitants living permanently in the urban area of the cantonal administrative center in the period from September 2016 to September 2017. The sample (494 people) was selected by non-probabilistic sampling, and it was made up by individuals in the ages from 15 to 60 years, mentally fit and that at the moment of the instrument's implementation were at their house. These people gave their informed consent for participating and declared to live permanently in that area. For data collection, it was used the questionnaire designed and validated by specialists criterion. Results: Females in the ages from 21 to 30 years and the ethnic auto-identification as mixed race predominated. Consumption of boiled water and its chlorination were the most common practices referred by those polled, which is insufficient to avoid transmissibility of waterborne diseases. Conclusions: The presence of water transmission diseases in cantón Penipe, in Ecuador is an unsolved local public health problem which justifies an intersectoral intervention that allows an inclusive, renewed and community focused health education(AU)

Quantitative comparisons of block thresholds and onset responses for charge-balanced kilohertz frequency waveforms.

OBJECTIVE: There is growing interest in delivering kilohertz frequency (KHF) electrical signals to block conduction in peripheral nerves for treatment of various diseases. Previous studies used different KHF waveforms to achieve block, and it remains unclear how waveform affects nerve block parameters. APPROACH: We quantified the effects of waveform on KHF block of the rat tibial nerve in vivo and in computational models. We compared block thresholds and onset responses across current-controlled sinusoids and charge-balanced rectangular waveforms with different asymmetries and duty cycles. MAIN RESULTS: Sine waves had higher block thresholds than square waves, but used less power at block threshold. Block threshold had an inverse relationship with duty cycle of rectangular waveforms irrespective of waveform asymmetry. Computational model results were consistent with relationships measured in vivo, although the models underestimated the effect of duty cycle on increasing thresholds. The axonal membrane substantially filtered waveforms, the filter transfer function was strikingly similar across waveforms, and filtering resulted in post-filtered rms block thresholds that were approximately constant across waveforms in silico and in vivo. Onset response was not consistently affected by waveform shape, but onset response was smaller at amplitudes well above block threshold. Therefore, waveforms with lower block thresholds (e.g. sine waves or square waves) could be more readily increased to higher amplitudes relative to block threshold to reduce onset response. We also observed a reduction in onset responses across consecutive trials after initial application of supra-block threshold amplitudes. SIGNIFICANCE: Waveform had substantial effects on block thresholds, and the amplitude relative to block threshold had substantial effects on onset response. These data inform choice of waveform in subsequent studies and clinical applications, enhance effective use of block in therapeutic applications, and facilitate the design of parameters that achieve block with minimal onset responses.

Dimensiones de calidad de vida afectadas en pacientes diabéticos / Quality of Life Dimensions Affected in Diabetic Patients

Introducción: La diabetes mellitus, segunda causa de mortalidad a nivel mundial, es una enfermedad crónica con elevada incidencia en adultos. La calidad de vida puede verse modificada con la sintomatología que afecta el estado de salud del paciente. Objetivo: Describir las dimensiones de calidad de vida afectadas en pacientes adultos y adultos mayores diabéticos. Métodos: Estudio descriptivo, transversal en unidades operativas del Distrito de Salud Chambo-Riobamba, Ecuador, desde noviembre 2017 a enero 2018. Universo de 138 pacientes con diabetes mellitus. Se realizó un muestreo no probabilístico por conveniencia, la muestra quedó constituida por 101 pacientes. Para obtener los datos se empleó la escala de calidad de vida y satisfacción en pacientes. Resultados: Predominó el sexo femenino en edades de 50 a 79 años (76,20 por ciento), religión católica (79,20 por ciento), casados (62,37 por ciento) y nivel de instrucción básica (60,39 por ciento). La hipertensión arterial, la artritis y los problemas de visión conformaron las características clínicas con mayor incidencia. Entre las dimensiones de calidad de vida frecuentemente afectadas se reportaron los cambios en su apariencia y las limitaciones para desarrollar actividades físicas. Conclusiones: Los cambios en su vida personal, la capacidad individual para adaptarse a la enfermedad, las limitaciones para el desarrollo de las actividades diarias, el descanso y los problemas económicos, se encuentran entre las dimensiones de calidad de vida más afectadas, las que generan en el enfermo dificultades para el mantenimiento de su salud(AU)

Introduction: Diabetes mellitus, the second leading cause of mortality worldwide, is a chronic disease with a high incidence in adults. The quality of life can be modified with the symptoms that affect the patient's state of health. Objective: To describe the dimensions of quality of life that are affected in diabetic adult and elderly patients. Methods: Descriptive, cross-sectional study with operational units of the Chambo-Riobamba Health District, Ecuador, from November 2017 to January 2018. The study group was made up of 138 patients with diabetes mellitus. A non-probabilistic sampling was carried out for convenience, and the sample finally consisted of 101 patients. To obtain the data, the scale of quality of life and satisfaction in patients was used. Results: There was a predominance of the female sex prevailed at ages 50 to 79 (76.20 percent), together with the Catholic religion (79.20 percent), married as a status (62.37 percent), and basic education level (60.39 percent). Hypertension, arthritis and vision problems formed the clinical features with the highest incidence. Among the dimensions of quality of life frequently affected, changes in their appearance and limitations to develop physical activities were reported. Conclusions: Changes in personal life, the individual capacity to adapt to the disease, limitations for the development of daily activities, rest, and economic problems are among the most affected dimensions of quality of life, which generate difficulties for the patients' maintaining their health(AU)

Algunas variables epidemiológicas relacionadas con la toxoplasmosis en mujeres en edad fértil en Riobamba / Some epidemiological variables associated to toxoplasmosis in women of childbearing age from Riobamba

Introducción: la toxoplasmosis adquirida durante por la mujer en edad fértil es un problema aun sin comprender por la comunidad y decisores de los sistemas de salud. En Ecuador existen datos pocos consistentes de la circulación de esta parasitosis, por lo que, ampliar el conocimiento sobre las variables que favorecen su adquisición es de gran interés. Objetivo: determinar la seroprevalencia de la toxoplasmosis en mujeres jóvenes y su relación con variables epidemiológicas. Métodos: Se ensayaron 403 muestras de sueros de estudiantes de la Facultad de Ciencias de la Salud de la Universidad Nacional de Chimborazo, se evaluó el comportamiento serológico de Toxoplasma gondii mediante la determinación de IgG anti Toxoplasma gondii utilizando un método inmunoenzimática, se determinó su relación con hábitos alimentarios, convivencia con animales y conocimiento del riesgo de ser seronegativas al momento de decidir de tener hijos. Resultados: El 26,8 por ciento (108/403) de la muestra resultó seropositivas al Toxoplasma gondii; la vía oral, la forma de adquirir la enfermedad más significativa, se demuestra la relación entre seroprevalencia y convivencia con animales de corral y mascotas. El 73,9 por ciento (298/403) de las encuestadas desconocen que las seronegativas durante el embarazo representan un riesgo potencial. Conclusiones: Se demuestra anticuerpos anti Toxoplasma gondii en sangre de las muestras estudiadas, lo que orienta a infecciones anteriores con Toxoplasma gondii y la influencia de variables estudiadas(AU)

Introduction: Toxoplasmosis acquired by women of childbearing age is a problem still not understood by the community and decision makers from health systems. Few consistent data are available in Ecuador about the circulation of this parasitic infection. Therefore, it is of great interest to broaden knowledge about the variables leading to its acquisition. Objective: Determine the seroprevalence of toxoplasmosis among young women and its relationship to epidemiological variables. Methods: A study was conducted of 403 serum samples from students attending the School of Health Sciences of the National University of Chimborazo. Serological behavior of Toxoplasma gondii was evaluated by determination of anti-Toxoplasma gondii IgG using an enzyme immunoassay. Identification was made of its relationship to eating habits, keeping animals at home, and knowledge about the risk of being seronegative when deciding to have children. Results: Of the total sample, 26.8 percent (108/403) were seropositive for Toxoplasma gondii. The oral route was the most significant mode of acquisition of the disease. A relationship was found between seroprevalence and keeping yard animals and pets. 73.9 percent (298/403) of the respondents were not aware that seronegative results during pregnancy constitute a potential risk. Conclusions: Anti-Toxoplasma gondii antibodies were found in blood of the samples studied, pointing to the existence of previous Toxoplasma gondii infections and the influence of the variables analyzed(AU)

Caracterización de pacientes hipertensos del Distrito de Salud Chambo-Riobamba / Characterization of hypertensive patients from Chambo-Rioamba Health District

RESUMEN Introducción: La hipertensión arterial afecta la salud individual a nivel mundial. En el Distrito de Salud Chambo-Riobamba del Ecuador, se evidenció incremento del número de adultos hipertensos. Objetivo: Describir las características sociodemográficas y clínicas de los pacientes adultos y adultos mayores hipertensos atendidos. Métodos: Investigación descriptiva transversal en el área de influencia del Distrito de Salud Chambo-Riobamba, Ecuador, entre noviembre 2017-marzo 2018. La población estuvo conformada por 287 individuos con diagnóstico de hipertensión arterial reportados por los Centros de Salud, y la muestra, de 188 pacientes, se determinó mediante muestreo no probabilístico. Se empleó el cuestionario "Escala de calidad de vida y satisfacción en pacientes". Resultados: Las características sociodemográficas observadas en esta población evidencian predominio de individuos con edades comprendidas entre 65 y 79 años (42,56 por ciento); el género femenino (69,15 por ciento), la religión católica (82,46 por ciento), la etnia mestiza (76,07 por ciento), el estado civil casado (48,40 por ciento), la convivencia con su esposo/a (42,02 por ciento), el nivel de instrucción básica (47,35 por ciento) y la profesión ama de casa (43,62 por ciento). Conclusiones: Prevaleció el rango de adultos mayores hipertensos, con predominio del sexo femenino, religión católica, autoidentificación mestiza, estado civil casado y nivel de instrucción básica. Las características clínicas mayormente referidas fueron problemas de visión, edemas en miembros inferiores, cefalea, cansancio, mareo, insuficiencia cardiaca, artritis y dolor articular. Los factores de riesgo modificables observados fueron la exposición a hábitos tóxicos como el consumo de café, tabaco y alcohol(AU)

ABSTRACT Introduction: High blood pressure affects individual health worldwide. In Chambo-Riobamba Health District of Ecuador, there was an increase in the number of hypertensive adults. Objective: To describe the sociodemographic and clinical characteristics of hypertensive adult and elderly patients treated in health centers of Chambo-Riobamba Health District, Ecuador. Methods: Cross-sectional descriptive research carried out in the area of influence of Chambo-Riobamba Health District, Ecuador, between November 2017 and March 2018. The study population consisted of 287 individuals with a diagnosis of arterial hypertension reported by the health centers; the sample was made up by 188 patients and determined by non-probabilistic sampling. The questionnaire "Scale of quality of life and patient satisfaction" was used. Results: The sociodemographic characteristics observed in this population show a predominance of individuals aged between 65 and 79 years (42.56 percent), the feminine gender (69.15 percent), the Catholic religion (82.46 percent), the mestizo ethnic group (76.07 percent), the married marital status (48.40 percent), the coexistence with his/her spouse (42.02 percent), the level of basic education (47.35 percent), and the profession of housewife (43.62 percent). Conclusions: The rank of hypertensive elderlies prevailed, with female sex, the Catholic religion, the mixed race self-identification, married marital status and basic education level. The clinical features mostly referred to were vision problems, edema in the lower limbs, headache, tiredness, dizziness, heart failure, arthritis, and joint pain. The modifiable risk factors observed were exposure to toxic habits, such as coffee, and tobacco and alcohol consumption(AU)

Multi-objective particle swarm optimization for postoperative deep brain stimulation targeting of subthalamic nucleus pathways.

OBJECTIVE: The effectiveness of deep brain stimulation (DBS) therapy strongly depends on precise surgical targeting of intracranial leads and on clinical optimization of stimulation settings. Recent advances in surgical targeting, multi-electrode designs, and multi-channel independent current-controlled stimulation are poised to enable finer control in modulating pathways within the brain. However, the large stimulation parameter space enabled by these technologies also poses significant challenges for efficiently identifying the most therapeutic DBS setting for a given patient. Here, we present a computational approach for programming directional DBS leads that is based on a non-convex optimization framework for neural pathway targeting. APPROACH: The algorithm integrates patient-specific pre-operative 7 T MR imaging, post-operative CT scans, and multi-objective particle swarm optimization (MOPSO) methods using dominance based-criteria and incorporating multiple neural pathways simultaneously. The algorithm was evaluated on eight patient-specific models of subthalamic nucleus (STN) DBS to identify electrode configurations and stimulation amplitudes to optimally activate or avoid six clinically relevant pathways: motor territory of STN, non-motor territory of STN, internal capsule, superior cerebellar peduncle, thalamic fasciculus, and hyperdirect pathway. MAIN RESULTS: Across the patient-specific models, single-electrode stimulation showed significant correlations across modeled pathways, particularly for motor and non-motor STN efferents. The MOPSO approach was able to identify multi-electrode configurations that achieved improved targeting of motor STN efferents and hyperdirect pathway afferents than that achieved by any single-electrode monopolar setting at equivalent power levels. SIGNIFICANCE: These results suggest that pathway targeting with patient-specific model-based optimization algorithms can efficiently identify non-trivial electrode configurations for enhancing activation of clinically relevant pathways. However, the results also indicate that inter-pathway correlations can limit selectivity for certain pathways even with directional DBS leads.

Clinical deep brain stimulation strategies for orientation-selective pathway activation.

OBJECTIVE: This study investigated stimulation strategies to increase the selectivity of activating axonal pathways within the brain based on their orientations relative to clinical deep brain stimulation (DBS) lead implants. APPROACH: Previous work has shown how varying electrode shape and controlling the primary electric field direction through preclinical electrode arrays can produce orientation-selective axonal stimulation. Here, we significantly extend those results using computational models to evaluate the degree to which clinical DBS leads can direct stimulus-induced electric fields and generate orientation-selective activation of fiber pathways in the brain. Orientation-selective pulse paradigms were evaluated in conceptual models and in patient-specific models of subthalamic nucleus (STN)-DBS for treating Parkinson's disease. MAIN RESULTS: Single-contact monopolar or two-contact bipolar stimulation through clinical DBS leads with cylindrical electrodes primarily activated axons orientated parallel to the lead. Conversely, multi-contact monopolar stimulation with a cathode-leading pulse waveform selectively activated axons perpendicular to the DBS lead. Clinical DBS leads with segmented rows of electrodes and a single current source provided additional angular resolution for activating axons oriented 0°, ±22.5°, ±45°, ±67.5°, or 90° relative to the lead shaft. Employing multiple independent current sources to deliver unequal amounts of current through these leads further increased the angular resolution of activation relative to the lead shaft. The patient-specific models indicated that multi-contact cathode configurations, which are rarely used in clinical practice, could increase activation of the hyperdirect pathway collaterals projecting into STN (a putative therapeutic target), while minimizing direct activation of the corticospinal tract of internal capsule, which can elicit sensorimotor side-effects when stimulated. SIGNIFICANCE: When combined with patient-specific tissue anisotropy and patient-specific anatomical morphologies of neural pathways responsible for therapy and side effects, orientation-selective DBS approaches show potential to significantly improve clinical outcomes of DBS therapy for a range of existing and investigational clinical indications.

Early Regenerative Capacity in the Porcine Heart.

BACKGROUND: The adult mammalian heart has limited ability to repair itself after injury. Zebrafish, newts, and neonatal mice can regenerate cardiac tissue, largely by cardiac myocyte (CM) proliferation. It is unknown whether hearts of young large mammals can regenerate. METHODS: We examined the regenerative capacity of the pig heart in neonatal animals (ages 2, 3, or 14 days postnatal) after myocardial infarction or sham procedure. Myocardial scar and left ventricular function were determined by cardiac magnetic resonance imaging and echocardiography. Bromodeoxyuridine pulse-chase labeling, histology, immunohistochemistry, and Western blotting were performed to study cell proliferation, sarcomere dynamics, and cytokinesis and to quantify myocardial fibrosis. RNA-sequencing was also performed. RESULTS: After myocardial infarction, there was early and sustained recovery of cardiac function and wall thickness in the absence of fibrosis in 2-day-old pigs. In contrast, older animals developed full-thickness myocardial scarring, thinned walls, and did not recover function. Genome-wide analyses of the infarct zone revealed a strong transcriptional signature of fibrosis in 14-day-old animals that was absent in 2-day-old pigs, which instead had enrichment for cytokinesis genes. In regenerating hearts of the younger animals, up to 10% of CMs in the border zone of the myocardial infarction showed evidence of DNA replication that was associated with markers of myocyte division and sarcomere disassembly. CONCLUSIONS: Hearts of large mammals have regenerative capacity, likely driven by cardiac myocyte division, but this potential is lost immediately after birth.

Parasitismo intestinal en escolares de la Unidad Educativa del Milenium. Cantón Penipe, Ecuador / Intestinal parasitosis in students of Unidad Educativa del Milenio. Town of Penipe, Ecuador

La población infantil tiene mayor probabilidad de ser afectada por enteroparasitosis, debido a la inmadurez inmunológica y que sus hábitos higiénicos aún se encuentran en desarrollo. Se realizó un estudio observacional, descriptivo, con enfoque mixto; cuya población objeto de investigación estuvo constituida por 382 escolares de la Unidad Educativa del Milenium. Cantón Penipe, Ecuador, cuyas edades oscilaron entre 5 y 11 años. Se realizó un muestreo no probabilístico por conveniencia, a partir del cual se seleccionaron 133 alumnos matriculados desde el primero a séptimo año de educación básica, durante el periodo octubre 2017 ­ febre-ro 2018, los que se habían realizado exámenes de heces fecales en los últimos seis meses, y cuyos tutores legales emitieron el consentimiento informado. Entre los individuos estudiados prevaleció el género femenino. La mayoría de los pacientes no presentaban parasitismo intes-tinal (53,38%). La incidencia parasitaria es más frecuente en niños con edades comprendidas entre los 8 y 10 años, para un 54,13%. Entre los informes con positividad, se observó un predominio del reporte de Entamoeba coli (48%) y Entamoeba histolytica con un 42%. La mayoría de los casos positivos mostraron poliparasitosis.

The infant population is more likely to be affected by enteroparasitosis due to immunological immaturity and their hygienic habits that are still in development. An observational and descriptive study with a mixed approach was carried out. The study population was constitu-ted by 382 students ranged between 5 and 11 years of age from Unidad Educativa del Mile-nio, town of Penipe, Ecuador. A non-probabilistic sampling was done for convenience, 133 students enrolled from the first to seventh year of basic education were selected, during the period October 2017 - February 2018. They had had the stool exams in the last six months. Legal tutors of students signed the informed consent. The female gender prevailed among the individuals studied. The majority of patients did not have intestinal parasitism (53.38%). The parasitic incidence is more frequent in children aged between 8 and 10 years, for 54.13%. It was observed a predominance of the report of Entamoeba coli (48%) and Entamoeba histolytica with 42% among the reports with positivity. Most of the positive cases showed polyparasitosis.

Aspectos clínicos y epidemiológicos de las enfermedades diarreicas agudas secretoras. Hospital General Docente "Juan B. Viñas González". 2014 / Clinical and epidemiological aspects of acute diarrheal secretory diseases. General Hos-pital "Juan B. Viñas González". 2014

Se realizó un estudio observacional, descriptivo, de corte transversal, con una población de estudio compuesta por 634 pacientes pediátricos con cuadro de diarrea aguda secretoria, que fueron ingresados en el Hospital General Docente "Juan B. Viñas González" de Palma Soria-no, Cuba, durante el período enero-diciembre, 2014. Los resultados arrojaron un predominio del rango de edades de 1 a 4 años, para un 30.4%; la mayoría de ellos, residentes en zonas rurales (64.5%), donde la calidad del agua de consumo no era la adecuada (46.8%) y la dispo-sición de las excretas tenían deficiencias en un 45.1% de los casos. Los síntomas predomi-nantes fueron fiebre y vómitos para un 47.4% y 45 % respectivamente y los signos fueron: los ojos hundidos en un 57.4% y sequedad de las mucosas (45.1%), como complicaciones se reportó: la deshidratación con 55.2%, la hipoglucemia (50.9%) y la acidosis metabólica (34.9%), presentando en ocasiones, un niño más de una complicación, lo que motivó un 35% de ingresos en los servicios de cuidados progresivos; sin embargo, no hubo fallecidos por esta causa en el tiempo estudiado.

An observational, descriptive, and cross-sectional study was carried out. 634 pediatric patients with acute diarrhea were the study population who were admitted to the General Hospital "Juan B. Viñas González" of Palma Soriano, Cuba, during the period January-De-cember 2014. The results showed a predominance of the age range between 1 and 4 years (30.4%); most of them, residents in rural areas (64.5%) where the quality of drinking water was not adequate (46.8%) and the disposal of excreta were deficient in 45.1% of cases. The predominant symptoms were fever and vomiting 47.4% and 45% respectively and the signs were: the sunken eyes (57.4%) and dryness of the mucous membranes (45.1%). There were some complications such as: dehydration (55.2%), hypoglycaemia (50.9%) and metabolic acidosis (34.9%); it was sometimes presented a child with more than one complication, which motivated a 35% of income in the progressive care services. However, there were no deaths due to this cause in the time studied.

Prevalencia de toxoplasmosis en estudiantes de la Universidad Nacional de Chimborazo en Ecuador / Prevalence of toxoplasmosis in students of the National University of Chimborazo in Ecuador

Introducción: La infección por Toxoplasma gondii durante la edad fértil de la mujer, es un problema de salud no bien entendido en la población, círculos médicos y decisores dentro de los sistemas de salud; al no considerar importante las formas de adquirirla y el riesgo que implica infectarse durante el embarazo. En Ecuador no existen datos consistentes de la circulación y endemicidad de esta parasitosis, siendo esta la situación problémica el motivo de este trabajo. Objetivo: Conocer la seroprevalencia de Toxoplasma gondii en mujeres jóvenes en edad fértil y su relación con el nivel de conocimiento sobre la enfermedad. Métodos: Se evaluó el comportamiento serológico de T. gondii en 105 muestras de sueros de alumnas de la Universidad Nacional de Chimborazo de la Carrera de Laboratorio Clínico e Histopatológico, mediante la determinación de IgG anti T. gondii utilizando la Técnica de Quimioluminiscencia. Resultados: 38 alumnas (36,0 por ciento) resultaron ser positivas para anticuerpos contra T. gondii, lo que indica el contacto con el parásito en algún momento de su vida. La falta de conocimiento sobre las principales vías de contagio puede ser la causa de la seropositividad demostrada, lo que representa un riesgo para las seronegativas durante el embarazo. Conclusiones: Se demuestra seroprevalencia de la infección por T. gondii en la población estudiada y la endemicidad del parásito(AU)

Introduction : Toxoplasma gondii is the infection that occurs during the fertile age of women and is a health problem not well understood by the people, doctors and leaders of the health systems of some countries; as it does not consider important the ways of acquiring it and the risk involved in becoming infected during pregnancy. In Ecuador there aren´t consistent data on the circulation and endemicity of this parasitosis, being this problematic situation the reason for this work. Objective : The purpose of the present study was to determine the seroprevalence of Toxoplasma gondii in young women of childbearing age and their relation with the level of knowledge about the disease. Methods: The serological behavior of T. gondii was evaluated in 105 samples of sera from the National University of Chimborazo of the Clinical and Histopathological Laboratory, by the determination of IgG anti T. gondii using the Chemiluminescence Technique. Results: Of the study population, 38 students (36.0 percent) were found to be positive for antibodies to T. gondii, indicating contact with the parasite at some point in their life. The demonstrated seropositivity may be due to the lack of knowledge about the main routes of infection, the risk of being seronegative during pregnancy and the high endemicity of the parasite. Conclusions : The seroprevalence of T. gondii infection in the studied population were demonstrated(AU)

Durable engraftment of genetically modified FVIII-secreting autologous bone marrow stromal cells in the intramedullary microenvironment.

Genetically modified FVIII-expressing autologous bone marrow-derived mesenchymal stromal cells (BMSCs) could cure haemophilia A. However, culture-expanded BMSCs engraft poorly in extramedullary sites. Here, we compared the intramedullary cavity, skeletal muscle, subcutaneous tissue and systemic circulation as tissue microenvironments that could support durable engraftment of FVIII-secreting BMSC in vivo. A zinc finger nuclease integrated human FVIII transgene into PPP1R12C (intron 1) of culture-expanded primary canine BMSCs. FVIII-secretory capacity of implanted BMSCs in each dog was expressed as an individualized therapy index (number of viable BMSCs implanted × FVIII activity secreted/million BMSCs/24 hours). Plasma samples before and after implantation were assayed for transgenic FVIII protein using an anti-human FVIII antibody having negligible cross-reactivity with canine FVIII. Plasma transgenic FVIII persisted for at least 48 weeks after implantation in the intramedullary cavity. Transgenic FVIII protein levels were low after intramuscular implantation and undetectable after both intravenous infusion and subcutaneous implantation. All plasma samples were negative for anti-human FVIII antibodies. Plasma concentrations and durability of transgenic FVIII secretion showed no correlation with the therapy index. Thus, the implantation site microenvironment is crucial. The intramedullary microenvironment, but not extramedullary tissues, supported durable engraftment of genetically modified autologous FVIII-secreting BMSCs.