Brain clocks capture diversity and disparity in aging and dementia.

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of multimodal diversity (geographical, socioeconomic, sociodemographic, sex, neurodegeneration) on the brain age gap (BAG) is unknown. Here, we analyzed datasets from 5,306 participants across 15 countries (7 Latin American countries -LAC, 8 non-LAC). Based on higher-order interactions in brain signals, we developed a BAG deep learning architecture for functional magnetic resonance imaging (fMRI=2,953) and electroencephalography (EEG=2,353). The datasets comprised healthy controls, and individuals with mild cognitive impairment, Alzheimer's disease, and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (fMRI: MDE=5.60, RMSE=11.91; EEG: MDE=5.34, RMSE=9.82) compared to non-LAC, associated with frontoposterior networks. Structural socioeconomic inequality and other disparity-related factors (pollution, health disparities) were influential predictors of increased brain age gaps, especially in LAC (R2=0.37, F2=0.59, RMSE=6.9). A gradient of increasing BAG from controls to mild cognitive impairment to Alzheimer's disease was found. In LAC, we observed larger BAGs in females in control and Alzheimer's disease groups compared to respective males. Results were not explained by variations in signal quality, demographics, or acquisition methods. Findings provide a quantitative framework capturing the multimodal diversity of accelerated brain aging.

Gaming expertise induces meso­scale brain plasticity and efficiency mechanisms as revealed by whole-brain modeling.

Video games are a valuable tool for studying the effects of training and neural plasticity on the brain. However, the underlying mechanisms related to plasticity-associated brain structural changes and their impact on brain dynamics are unknown. Here, we used a semi-empirical whole-brain model to study structural neural plasticity mechanisms linked to video game expertise. We hypothesized that video game expertise is associated with neural plasticity-mediated changes in structural connectivity that manifest at the meso­scale level, resulting in a more segregated functional network topology. To test this hypothesis, we combined structural connectivity data of StarCraft II video game players (VGPs, n = 31) and non-players (NVGPs, n = 31), with generic fMRI data from the Human Connectome Project and computational models, to generate simulated fMRI recordings. Graph theory analysis on simulated data was performed during both resting-state conditions and external stimulation. VGPs' simulated functional connectivity was characterized by a meso­scale integration, with increased local connectivity in frontal, parietal, and occipital brain regions. The same analyses at the level of structural connectivity showed no differences between VGPs and NVGPs. Regions that increased their connectivity strength in VGPs are known to be involved in cognitive processes crucial for task performance such as attention, reasoning, and inference. In-silico stimulation suggested that differences in FC between VGPs and NVGPs emerge in noisy contexts, specifically when the noisy level of stimulation is increased. This indicates that the connectomes of VGPs may facilitate the filtering of noise from stimuli. These structural alterations drive the meso­scale functional changes observed in individuals with gaming expertise. Overall, our work sheds light on the mechanisms underlying structural neural plasticity triggered by video game experiences.

Elevating understanding: Linking high-altitude hypoxia to brain aging through EEG functional connectivity and spectral analyses.

High-altitude hypoxia triggers brain function changes reminiscent of those in healthy aging and Alzheimer's disease, compromising cognition and executive functions. Our study sought to validate high-altitude hypoxia as a model for assessing brain activity disruptions akin to aging. We collected EEG data from 16 healthy volunteers during acute high-altitude hypoxia (at 4,000 masl) and at sea level, focusing on relative changes in power and aperiodic slope of the EEG spectrum due to hypoxia. Additionally, we examined functional connectivity using wPLI, and functional segregation and integration using graph theory tools. High altitude led to slower brain oscillations, that is, increased δ and reduced α power, and flattened the 1/f aperiodic slope, indicating higher electrophysiological noise, akin to healthy aging. Notably, functional integration strengthened in the θ band, exhibiting unique topographical patterns at the subnetwork level, including increased frontocentral and reduced occipitoparietal integration. Moreover, we discovered significant correlations between subjects' age, 1/f slope, θ band integration, and observed robust effects of hypoxia after adjusting for age. Our findings shed light on how reduced oxygen levels at high altitudes influence brain activity patterns resembling those in neurodegenerative disorders and aging, making high-altitude hypoxia a promising model for comprehending the brain in health and disease.

Exposure to high-altitude hypoxia, with reduced oxygen levels, can replicate brain function changes akin to aging and Alzheimer's disease. In our work, we propose high-altitude hypoxia as a possible reversible model of human brain aging. We gathered EEG data at high altitude and sea level, investigating the impact of hypoxia on brainwave patterns and connectivity. Our findings revealed that high-altitude exposure led to slower and noisier brain oscillations and produced altered brain connectivity, resembling some remarkable changes seen in the aging process. Intriguingly, these changes were linked to age, even when hypoxia's effects were considered. Our research unveils how high-altitude conditions emulate brain patterns associated with aging and neurodegenerative conditions, providing valuable insights into the understanding of both normal and impaired brain function.

Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole-brain modeling.

INTRODUCTION: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) lack mechanistic biophysical modeling in diverse, underrepresented populations. Electroencephalography (EEG) is a high temporal resolution, cost-effective technique for studying dementia globally, but lacks mechanistic models and produces non-replicable results. METHODS: We developed a generative whole-brain model that combines EEG source-level metaconnectivity, anatomical priors, and a perturbational approach. This model was applied to Global South participants (AD, bvFTD, and healthy controls). RESULTS: Metaconnectivity outperformed pairwise connectivity and revealed more viscous dynamics in patients, with altered metaconnectivity patterns associated with multimodal disease presentation. The biophysical model showed that connectome disintegration and hypoexcitability triggered altered metaconnectivity dynamics and identified critical regions for brain stimulation. We replicated the main results in a second subset of participants for validation with unharmonized, heterogeneous recording settings. DISCUSSION: The results provide a novel agenda for developing mechanistic model-inspired characterization and therapies in clinical, translational, and computational neuroscience settings.

Gaming expertise induces meso-scale brain plasticity and efficiency mechanisms as revealed by whole-brain modeling Gaming expertise, neuroplasticity and functional dynamics.

Video games are a valuable tool for studying the effects of training and neural plasticity on the brain. However, the underlaying mechanisms related to plasticity-induced brain structural changes and their impact in brain dynamics are unknown. Here, we used a semi-empirical whole-brain model to study structural neural plasticity mechanisms linked to video game expertise. We hypothesized that video game expertise is associated with neural plasticity-mediated changes in structural connectivity that manifest at the meso-scale level, resulting in a more segregated functional network topology. To test this hypothesis, we combined structural connectivity data of StarCraft II video game players (VGPs, n = 31) and non-players (NVGPs, n = 31), with generic fMRI data from the Human Connectome Project and computational models, with the aim of generating simulated fMRI recordings. Graph theory analysis on simulated data was performed during both resting-state conditions and external stimulation. VGPs' simulated functional connectivity was characterized by a meso-scale integration, with increased local connectivity in frontal, parietal and occipital brain regions. The same analyses at the level of structural connectivity showed no differences between VGPs and NVGPs. Regions that increased their connectivity strength in VGPs are known to be involved in cognitive processes crucial for task performance such as attention, reasoning, and inference. In-silico stimulation suggested that differences in FC between VGPs and NVGPs emerge in noisy contexts, specifically when the noisy level of stimulation is increased. This indicates that the connectomes of VGPs may facilitate the filtering of noise from stimuli. These structural alterations drive the meso-scale functional changes observed in individuals with gaming expertise. Overall, our work sheds light into the mechanisms underlying structural neural plasticity triggered by video game experiences.

Whole-brain modeling explains the context-dependent effects of cholinergic neuromodulation.

Integration and segregation are two fundamental principles of brain organization. The brain manages the transitions and balance between different functional segregated or integrated states through neuromodulatory systems. Recently, computational and experimental studies suggest a pro-segregation effect of cholinergic neuromodulation. Here, we studied the effects of the cholinergic system on brain functional connectivity using both empirical fMRI data and computational modeling. First, we analyzed the effects of nicotine on functional connectivity and network topology in healthy subjects during resting-state conditions and during an attentional task. Then, we employed a whole-brain neural mass model interconnected using a human connectome to simulate the effects of nicotine and investigate causal mechanisms for these changes. The drug effect was modeled decreasing both the global coupling and local feedback inhibition parameters, consistent with the known cellular effects of acetylcholine. We found that nicotine incremented functional segregation in both empirical and simulated data, and the effects are context-dependent: observed during the task, but not in the resting state. In-task performance correlates with functional segregation, establishing a link between functional network topology and behavior. Furthermore, we found in the empirical data that the regional density of the nicotinic acetylcholine α4ß2 correlates with the decrease in functional nodal strength by nicotine during the task. Our results confirm that cholinergic neuromodulation promotes functional segregation in a context-dependent fashion, and suggest that this segregation is suited for simple visual-attentional tasks.

Structural Features of the Human Connectome That Facilitate the Switching of Brain Dynamics via Noradrenergic Neuromodulation.

The structural connectivity of human brain allows the coexistence of segregated and integrated states of activity. Neuromodulatory systems facilitate the transition between these functional states and recent computational studies have shown how an interplay between the noradrenergic and cholinergic systems define these transitions. However, there is still much to be known about the interaction between the structural connectivity and the effect of neuromodulation, and to what extent the connectome facilitates dynamic transitions. In this work, we use a whole brain model, based on the Jasen and Rit equations plus a human structural connectivity matrix, to find out which structural features of the human connectome network define the optimal neuromodulatory effects. We simulated the effect of the noradrenergic system as changes in filter gain, and studied its effects related to the global-, local-, and meso-scale features of the connectome. At the global-scale, we found that the ability of the network of transiting through a variety of dynamical states is disrupted by randomization of the connection weights. By simulating neuromodulation of partial subsets of nodes, we found that transitions between integrated and segregated states are more easily achieved when targeting nodes with greater connection strengths-local feature-or belonging to the rich club-meso-scale feature. Overall, our findings clarify how the network spatial features, at different levels, interact with neuromodulation to facilitate the switching between segregated and integrated brain states and to sustain a richer brain dynamics.

Cholinergic neuromodulation of inhibitory interneurons facilitates functional integration in whole-brain models.

Segregation and integration are two fundamental principles of brain structural and functional organization. Neuroimaging studies have shown that the brain transits between different functionally segregated and integrated states, and neuromodulatory systems have been proposed as key to facilitate these transitions. Although whole-brain computational models have reproduced this neuromodulatory effect, the role of local inhibitory circuits and their cholinergic modulation has not been studied. In this article, we consider a Jansen & Rit whole-brain model in a network interconnected using a human connectome, and study the influence of the cholinergic and noradrenergic neuromodulatory systems on the segregation/integration balance. In our model, we introduce a local inhibitory feedback as a plausible biophysical mechanism that enables the integration of whole-brain activity, and that interacts with the other neuromodulatory influences to facilitate the transition between different functional segregation/integration regimes in the brain.

Relación entre IPSS y uroflujometría en pacientes con síntomas urinarios / Relationship between IPSS and Uroflowmetry in Patients with Urinary Symptoms

Introducción Los cuestionarios clínicos para los síntomas urinarios se diseñaron para objetivar los síntomas urinarios y de esa forma evitar estudios invasivos y costosos, con la división entre síntomas urinarios de vaciado y llenado, sin embargo, los pacientes presentan síntomas que hacen difícil el discernimiento entre obstrucción infravesical, detrusor hipocontractil o incluso detrusor hiperactivo. Determinar la correlación entre la uroflujometría y la severidad de los síntomas usando el IPSS (International Prostate Symptom Score) en pacientes síntomas urinarios, comparados con urodinamia y determinar su correlación con el diagnostico de obstrucción infravesical, detrusor hipocontráctil o detrusor hipocontráctil Métodos Estudio retrospectivo en el cual se recolectaron 27 hombres que consultaron por síntomas urinarios de vaciado y asistieron al Hospital Universitario de la Samaritana en Bogotá, Colombia entre abril del 2016 y abril del 2017. El IPSS se realizó a todos los pacientes con el cuestionario autoadministrado. Adicionalmente se realizó uroflujometría y urodinamia con el equipo de urodinámia Medical Measurement System SN077116. Resultados La edad promedio fue 67,26 años (37­86), IPSS leve del 22%, moderado 59% y severo 19%, con patrones de uroflujometricos campana 26%, meseta 41% intermitente 33%, el 37% presentaron un Qmax menor del 10%, el cual se consideró obstructivo y una PdetQmax menor de 40, en un 37%, lo cual es congruente con los resultados de la uroflujometria, además de relacionarse con residuo postmiccional elevado. Conclusión Existe una correlación entre el IPSS y el Qmax, comparado con patrones urodinámicos, la utilización de los índices como métodos no invasivos para el ahorro de costos si es comparable con hallazgos urodinámicos. Sin embargo, existe un porcentaje no despreciable de pacientes con Qmax menor de 10 que no corresponden a obstrucción infravesical. Es necesario tener en cuenta que hasta el 23% de los pacientes pueden presentar IPSS moderado o severo sin que el origen sea obstructivo.

Introduction Clinical questionnaires for urinary symptoms were designed to perform an objective evaluation of urinary symptoms and thus avoid invasive and expensive studies. However, patients present symptoms that make difficult the discernment between infravesical obstruction and hypocontractile detrusor. The aim of this study is to determine the correlation between uroflowmetry and symptom severity using the IPSS (International Prostate Symptom Score) in patients with urinary symptoms, compared with urodynamics and to determine its correlation with the diagnosis of infra-vesical obstruction or hypocontractile detrusor. Methods Observational retrospective study in which the clinical records of the patients who consulted for urinary emptying symptoms at La Samaritana University Hospital in Bogotá, Colombia, between April 2016 and April 2017 were reviewed. The IPSS was performed in all patients. Additionally, uroflowmetry and urodynamics were documented with the Medical Measurement System SN077116. Results A total of 27 patients were included in the study. The average age was 67.26 years. The mild IPSS was found in 22% of the patients, moderate 59% and severe 19%. Patterns were identified in uroflowmetry with bell curves in 26% of patients, plateau 41% and intermittent in 33%. 37% of the patients had a Qmax lower than 10 mL/s which was considered obstructive and a PdetQmax less than 40 cm H2O in 37%, which is consistent with the results of uroflowmetry, in addition to being related to high postvoid residual volume. Conclusion There is a correlation between IPSS and Qmax associated with urodynamic patterns. The use of indices as non-invasive methods to reduce costs is comparable with the urodynamic findings; however, there is a non-negligible percentage of patients with Qmax less than 10 mL/s who do not correspond to infravesical obstruction. It is necessary to take into account that up to 23% of patients can have moderate or severe IPSS without the origin of the symptoms being obstructive.

Prenatal exposure to ketamine in rats: Implications on animal models of schizophrenia.

Schizophrenia is a complex neuropsychiatric disorder characterized by hallucinations, delusions, anhedonia, flat affect and cognitive impairments. The aim of this study was to propose a prenatal treatment with ketamine, a psychedelic drug that acts as a non-competitive inhibitor of glutamate NMDA receptors, as a neurodevelopmental animal model of schizophrenia. The drug was applied (i.m. 60 mg.kg-1 h-1 ) in pregnant Sprague-Dawley rats on gestational Day 14. Offspring behavior was studied on pubertal (4 weeks old) and adult (10 weeks old) stages. Also, hippocampal CA1-CA3 morphology was assessed in adult animals through a Nissl stain. Results showed a disinhibition and hyperactive behavior in pubertal animals exposed to ketamine, followed in adulthood with cognitive impairments, social withdrawal, anxiety, depression, and aggressive-like behaviors. In the hippocampus, a reduction of the CA3 layer thickness was observed, without changes in cell density. These results strongly suggest a robust link between prenatal pharmacologic manipulation of NMDA receptors and schizophrenia.

Sensor Fusion of a Mobile Device to Control and Acquire Videos or Images of Coffee Branches and for Georeferencing Trees.

Smartphones show potential for controlling and monitoring variables in agriculture. Their processing capacity, instrumentation, connectivity, low cost, and accessibility allow farmers (among other users in rural areas) to operate them easily with applications adjusted to their specific needs. In this investigation, the integration of inertial sensors, a GPS, and a camera are presented for the monitoring of a coffee crop. An Android-based application was developed with two operating modes: (i) Navigation: for georeferencing trees, which can be as close as 0.5 m from each other; and (ii) Acquisition: control of video acquisition, based on the movement of the mobile device over a branch, and measurement of image quality, using clarity indexes to select the most appropriate frames for application in future processes. The integration of inertial sensors in navigation mode, shows a mean relative error of ±0.15 m, and total error ±5.15 m. In acquisition mode, the system correctly identifies the beginning and end of mobile phone movement in 99% of cases, and image quality is determined by means of a sharpness factor which measures blurriness. With the developed system, it will be possible to obtain georeferenced information about coffee trees, such as their production, nutritional state, and presence of plagues or diseases.

Disease burden and medical cost-analysis of acute respiratory infections in a low-income district of Bogotá / Análisis del costo médico y la carga de enfermedad de las infecciones respiratorias agudas en una localidad de ingresos bajos de Bogotá

Objective To estimate the burden of disease and related direct medical cost of Acute Respiratory Infections (ARI) for the health-care system in a low-income district of Bogota, generated by children under age five and senior population over age sixty. Methods A cross-sectional, retrospective, patient level study was conducted in San Cristobal district from 2008 to 2012 among the subsidized population. All inpatients and outpatients with ARI from three hospitals were reported. The total and average direct medical costs were estimated and are reported in International Dollars (Int$). Results It is estimated that, for children, ambulatory incidence rate for ARI varied between 54.4 % and 66.3 % and hospitalization rate between 9.2 % and 12.3 %. The mortality rate in the district oscillated between 18.1 and 27.7 deaths per 100 000. The main medical costs were attributed to hospitalizations, and the total medical hospitalization cost per year estimated ranged between Int$ 1 334 352 and Int$ 2 139 597. In the case of senior population, the ambulatory incidence rate fluctuated between 7.6 % and 10.0 %, and the hospitalization rates between 0.6 % and 2.1 %; the mortality rate ranged between 8.9 and 47.8 deaths per 100 000. Hospitalization cost per year was estimated to be between Int$ 88 957 and Int$ 373 382. Conclusion Direct medical costs due to ARI have an important disease and direct medical cost burden in this low-income district.(AU)

Objetivo Estimar la carga de enfermedad y los costos médicos directos relacionados con las Infecciones Respiratorias Agudas (IRA) para el sistema de salud en una localidad de bajos ingresos de Bogotá, en niños menores de cinco años y adultos mayores de sesenta años. Métodos Se realizó un estudio retrospectivo transversal a nivel de paciente en la localidad de San Cristóbal desde 2008 y 2012 en la población subsidiada. Se reportaron todos los pacientes hospitalizados y ambulatorios de tres hospitales públicos debido a IRA. Se estimaron los costos médicos directos relacionados. Los costos fueron convertidos en dólares internacionales (Int$). Resultados En niños. Se estimó que la incidencia ambulatoria para IRA varió entre 54,4 % y 66,3 % y la tasa de hospitalización varió entre 9,2 % y 12,3 %. La tasa de mortalidad en el distrito osciló entre 18,1 y 27,7 muertes por 100 000 niños. Se estimó que el costo de las hospitalizaciones oscilaron anualmente entre Int$ 1 334 352 y Int$ 2 139 597 representado la más importante carga financiera. En adultos, la incidencia ambulatoria fluctuó entre 7,6 % y 10 %. Las tasas de hospitalización variaron entre el 0,6 % y el 2,1 %. Mientras que la tasa de mortalidad varió entre 8,9 y 47,8 muertes por 100 000. Para hospitalizaciones se estimó un costo total por año entre Int$ 88 957 y Int$ 373 382. Conclusión Los costos médicos debido a IRA tienen una carga económica importante para el sistema de salud y los hogares en esta localidad.(AU)

Disease burden and medical cost-analysis of Acute Respiratory Infections in a low-income district of Bogotá.

Objective To estimate the burden of disease and related direct medical cost of Acute Respiratory Infections (ARI) for the health-care system in a low-income district of Bogota, generated by children under age five and senior population over age sixty. Methods A cross-sectional, retrospective, patient level study was conducted in San Cristobal district from 2008 to 2012 among the subsidized population. All inpatients and outpatients with ARI from three hospitals were reported. The total and average direct medical costs were estimated and are reported in International Dollars (Int$). Results It is estimated that, for children, ambulatory incidence rate for ARI varied between 54.4 % and 66.3 % and hospitalization rate between 9.2 % and 12.3 %. The mortality rate in the district oscillated between 18.1 and 27.7 deaths per 100 000. The main medical costs were attributed to hospitalizations, and the total medical hospitalization cost per year estimated ranged between Int$ 1 334 352 and Int$ 2 139 597. In the case of senior population, the ambulatory incidence rate fluctuated between 7.6 % and 10.0 %, and the hospitalization rates between 0.6 % and 2.1 %; the mortality rate ranged between 8.9 and 47.8 deaths per 100 000. Hospitalization cost per year was estimated to be between Int$ 88 957 and Int$ 373 382. Conclusion Direct medical costs due to ARI have an important disease and direct medical cost burden in this low-income district.

Factores de riesgo y diagnóstico de salud del adolescente venezolano: estudio piloto / Risk factors and health diagnosis of Venezuelan adolescent: pilot study

El internista venezolano esta trabajando en la definición de su área de trabajo en este grupo poblacional. Conocer los factores de riesgo en general del adolescente. Estudio transversal, multicéntrico de adolescentes que asisten a consulta de medicina interna.Procedimiento: 1) Autorización escrita, 2) Explicación de los objetivos, 3) Encuesta de factores de riesgo, 4) Diagnósticos. El análisis fue descriptivo y comparativo. 75 individuos estudiados; 69 por ciento mujeres. 11 por ciento tenían alteración de la figura paterna; el 27 por ciento habían sufrido repitencia escolar; 64 por ciento no comparte con la familia; 43 por ciento inició la ingesta alcohólica con amigos. La violencia fue: 39 por ciento en el hogar y 55 por ciento fuera del hogar; 43 por ciento eran sexualmente activos; 28 por ciento de las mujeres tenían historia de embarazos, 1 de cada 12 había sido abusado sexualmente; 7 reconocieron el uso de drogas. Se definen áreas de trabajo: la comunicación familiar, educación sexual, historia de abuso sexual, educación antiviolencia y educación preventiva general. Se propone utilizar los resultados del presente estudio para incluir en la historia clínica diaria en forma permanente áreas de orientación para los adolescentes y sus padres

Toxoplasmosis en embarazadas en el Hospital Dr. Pedro E. de Marchena, Bonao, R. D. en el período julio-septiembre 1995 / Toxoplasmosis in pregnancy patients at the \"Dr. Pedro E. de Marchena\" Hospital, Bonao, July-September 1995

Realizamos un estudio retrospectivo de tipo descriptivo, de incidencia de toxoplasmosis en embarazadas en el Hospital Dr. Pedro E. Marchena, Bonao, R.D. en el período julio-septiembre 1995. El objetivo principal del estudio fue determinar que porcentaje de las pacientes embarazadas que acuden a la consulta de obstetricia presentan esta patología. Además determinar el comportamiento epidemiológico de la patología en cuestión y pa proporción en pacientes embarazadas que resultaron positivas al test de toxoplasmosis. De un universo de 616 pacientes obstétricas, se escogieron 25 de ellas que presentaron la sintomatología que se asocia a la toxoplasmosis, para aplicarle el método TOXO-I-H-A (IGG), de los cuales 20 (80//) resultaron positivos. Fueron mayormente afectadas el grupo de pacientes con edades comprendidas entre los 25-29 años (56//), los demás grupos oscilan 15 a 4//. El área urbana tiene mayor número de casos, 18 con (72//), las empleadas públicas con 04 (16//), las demás no sobrepasó 12//. En cuanto a la educación, 17 pacientes (68//) tiene un nivel educacional medio, 5 (20//) un nivel bajo y 3 (12//) un nivel alto. Se pudo notar que 80// tiene animales domésticos en el hogar, los más frecuentes fueron perros y gatos. Existen dos posibilidades de presentación epidémicas y endémicas, la distribución es mundial y afecta a mamíferos, las aves y el hombre, en este invade cualquier célula del organismo y ha podido demostrarse inequivocadamente la infección congénita. Los medios de transmisión más frecuentes según tipo de animales en el hogar y de esta contribuir con posibles soluciones preventivas