A pilot study of closed-loop neuromodulation for treatment-resistant post-traumatic stress disorder.

The neurophysiological mechanisms in the human amygdala that underlie post-traumatic stress disorder (PTSD) remain poorly understood. In a first-of-its-kind pilot study, we recorded intracranial electroencephalographic data longitudinally (over one year) in two male individuals with amygdala electrodes implanted for the management of treatment-resistant PTSD (TR-PTSD) under clinical trial NCT04152993. To determine electrophysiological signatures related to emotionally aversive and clinically relevant states (trial primary endpoint), we characterized neural activity during unpleasant portions of three separate paradigms (negative emotional image viewing, listening to recordings of participant-specific trauma-related memories, and at-home-periods of symptom exacerbation). We found selective increases in amygdala theta (5-9 Hz) bandpower across all three negative experiences. Subsequent use of elevations in low-frequency amygdala bandpower as a trigger for closed-loop neuromodulation led to significant reductions in TR-PTSD symptoms (trial secondary endpoint) following one year of treatment as well as reductions in aversive-related amygdala theta activity. Altogether, our findings provide early evidence that elevated amygdala theta activity across a range of negative-related behavioral states may be a promising target for future closed-loop neuromodulation therapies in PTSD.

Noradrenergic modulation determines respiratory network activity during temperature changes in the in vitro brainstem of bullfrogs.

Among vertebrate ectotherms, air breathing frequency is generally constrained across warmer temperatures, but decreases during cooling. The brainstem mechanisms that give rise to this ventilatory strategy are unclear. Neuromodulation has recently been shown to stabilize motor circuit output across temperatures. Therefore, we tested the hypothesis that an important neuromodulatory system in respiratory control network, norepinephrine, produces this pattern of respiratory motor activity across temperatures. To this end, we used in vitro brainstem-spinal cord preparations from adult bullfrogs, Lithobates catesbeianus, to assess the role of noradrenergic signaling in shaping the frequency response of the respiratory network during temperature changes. We identified that noradrenergic signaling through the α1 adrenergic receptor constrains motor output from the respiratory network across warm temperatures. In contrast, the α2 adrenergic receptor actively inhibits respiratory motor output during cooling. These results indicate that noradrenergic tuning, rather than passive thermal responses, produces temperature responses of the respiratory circuits.

Synaptic up-scaling preserves motor circuit output after chronic, natural inactivity.

Neural systems use homeostatic plasticity to maintain normal brain functions and to prevent abnormal activity. Surprisingly, homeostatic mechanisms that regulate circuit output have mainly been demonstrated during artificial and/or pathological perturbations. Natural, physiological scenarios that activate these stabilizing mechanisms in neural networks of mature animals remain elusive. To establish the extent to which a naturally inactive circuit engages mechanisms of homeostatic plasticity, we utilized the respiratory motor circuit in bullfrogs that normally remains inactive for several months during the winter. We found that inactive respiratory motoneurons exhibit a classic form of homeostatic plasticity, up-scaling of AMPA-glutamate receptors. Up-scaling increased the synaptic strength of respiratory motoneurons and acted to boost motor amplitude from the respiratory network following months of inactivity. Our results show that synaptic scaling sustains strength of the respiratory motor output following months of inactivity, thereby supporting a major neuroscience hypothesis in a normal context for an adult animal.

Space and space-time distributions of dengue in a hyper-endemic urban space: the case of Girardot, Colombia.

BACKGROUND: Dengue is a widely spread vector-borne disease. Dengue cases in the Americas have increased over the last few decades, affecting various urban spaces throughout these continents, including the tourism-oriented city of Girardot, Colombia. Interactions among mosquitoes, pathogens and humans have recently been examined using different temporal and spatial scales in attempts to determine the roles that social and ecological systems play in dengue transmission. The current work characterizes the spatial and temporal behaviours of dengue in Girardot and discusses the potential territorial dynamics related to the distribution of this disease. METHODS: Based on officially reported dengue cases (2012-2015) corresponding to epidemic (2013) and inter-epidemic years (2012, 2014, 2015), space (Getis-Ord index) and space-time (Kulldorff's scan statistics) analyses were performed. RESULTS: Geocoded dengue cases (n = 2027) were slightly overrepresented by men (52.1%). As expected, the cases were concentrated in the 0- to 15-year-old age group according to the actual trends of Colombia. The incidence rates of dengue during the rainy and dry seasons as well as those for individual years (2012, 2013 and 2014) were significant using the global Getis-Ord index. Local clusters shifted across seasons and years; nevertheless, the incidence rates clustered towards the southwest region of the city under different residential conditions. Space-time clusters shifted from the northeast to the southwest of the city (2012-2014). These clusters represented only 4.25% of the total cases over the same period (n = 1623). A general trend was observed, in which dengue cases increased during the dry seasons, especially between December and February. CONCLUSIONS: Despite study limitations related to official dengue records and available fine-scale demographic information, the spatial analysis results were promising from a geography of health perspective. Dengue did not show linear association with poverty or with vulnerable peripheral spaces in intra-urban settings, supporting the idea that the pathogenic complex of dengue is driven by different factors. A coordinated collaboration of epidemiological, public health and social science expertise is needed to assess the effect of "place" from a relational perspective in which geography has an important role to play.

[Operation of government policies for the prevention and control of dengue: The cases of Arauca and Armenia]. / Funcionamiento de las políticas gubernamentales para la prevención y el control del dengue: el caso de Arauca y Armenia en Colombia.

INTRODUCTION: Dengue is a growing public health problem in urban areas, given that its transmission is associated with the environment, as well as with the behaviour of individuals and communities. The model proposed by Ecohealth to study this problem includes the operation of government policies. OBJECTIVE: To describe the operation of policies to prevent and control dengue in two Colombian cities. MATERIALS AND METHODS: A qualitative study was conducted. Data was collected through interviews with officials who worked in the health and education sectors. The contents were processed with the Ethnograph software, using the proposals of the bottom-up model of implementation as analytical categories. RESULTS: A lack of coordination was identified between department and municipal offices, with few developments of the protocol for dengue and severe dengue in terms of community participation, communication strategies and studies of inhabitants´ knowledge, attitudes and practices. The integrated management strategy was limited by the instability of human resources, limited intra-institutional and cross-sectorial coordination and little emphasis on promotion interventions, both at the individual and population levels. CONCLUSIONS: Coordination between the departament and the municipality needs to be strengthened in the city of Arauca. Both here and in Armenia administration of human resources and interinstitutional coordination should be improved. Promotion of preventative measures should be strengthened to impact on the determinants of dengue.

Funcionamiento de las políticas gubernamentales para la prevención y el control del dengue: el caso de Arauca y Armenia en Colombia / Operation of government policies for the prevention and control of dengue: The cases of Arauca and Armenia

Introducción. El dengue es un problema de salud pública en aumento en las zonas urbanas, debido a que su transmisión está asociada con el ambiente y el comportamiento de las personas y las comunidades. El modelo propuesto por Ecosalud para su estudio, incluye el análisis del funcionamiento de las políticas gubernamentales. Objetivo. Describir el funcionamiento de las políticas para prevenir y controlar el dengue en dos ciudades colombianas. Materiales y métodos. Se adelantó un estudio cualitativo, para lo cual se recopiló información mediante entrevistas a funcionarios del sector de la salud y la educación, cuyos contenidos se procesaron en Ethnograph con base en las categorías de análisis propuestas en el modelo de ´implementación desde la base´. Resultados. Se encontró que había desarticulación entre el departamento y el municipio, así como un desarrollo escaso del protocolo de dengue y dengue hemorrágico en cuanto a la participación comunitaria, las estrategias de comunicación y los estudios de conocimientos, actitudes y prácticas de los pobladores. La estrategia de gestión integrada se ve limitada por la inestabilidad del recurso humano, la escasa coordinación entre instituciones y sectores, y la falta de énfasis en las intervenciones de promoción tanto a nivel individual como de la población. Conclusiones. En Arauca es necesario fortalecer la coordinación entre el departamento y el municipio. Tanto en Arauca como en Armenia se requiere mejorar la administración de los recursos humanos y la coordinación interinstitucional, así como fortalecer la promoción y la prevención, para lograr el efecto esperado sobre los factores determinantes del dengue.

Introduction: Dengue is a growing public health problem in urban areas, given that its transmission is associated with the environment, as well as with the behaviour of individuals and communities. The model proposed by Ecohealth to study this problem includes the operation of government policies. Objective: To describe the operation of policies to prevent and control dengue in two Colombian cities. Materials and methods: A qualitative study was conducted. Data was collected through interviews with officials who worked in the health and education sectors. The contents were processed with the Ethnograph software, using the proposals of the bottom-up model of implementation as analytical categories. Results: A lack of coordination was identified between department and municipal offices, with few developments of the protocol for dengue and severe dengue in terms of community participation, communication strategies and studies of inhabitants´ knowledge, attitudes and practices. The integrated management strategy was limited by the instability of human resources, limited intra-institutional and cross-sectorial coordination and little emphasis on promotion interventions, both at the individual and population levels. Conclusions: Coordination between the departament and the municipality needs to be strengthened in the city of Arauca. Both here and in Armenia administration of human resources and interinstitutional coordination should be improved. Promotion of preventative measures should be strengthened to impact on the determinants of dengue.

Territorial analysis of Aedes aegypti distribution in two Colombian cities: a chorematic and ecosystem approach.

A territorial analysis of Aedes aegypti density was conducted in two Colombian cities using an ecosystem and chorematic approach. Entomological and behavioral data (by cluster) and information on the urban context were used to analyze the relationship between territorial structures and dynamics and vector density. The results were represented in graphic (chorematic) models. Arauca showed higher vector density than Armenia. Higher density was related to unplanned urbanization, flood-prone areas, low socioeconomic strata, household water tanks, higher temperature, and recall of control measures for adult mosquitos. Zones with low density indices coincided with diverse socioeconomic, ecological, and behavioral conditions. The study found a relationship between territorial structures and dynamics and vector density in both Arauca and Armenia, where the interaction between ecological and social systems shape areas with high and low A. aegypti density.

Territorial analysis of Aedes aegypti distribution in two Colombian cities: a chorematic and ecosystem approach / Análise territorial da distribuição do Aedes aegypti em duas cidades da Colômbia: aproximação desde a coremática e a abordagem ecossistêmica / Análisis territorial de la distribución de Aedes aegypti en dos ciudades de Colombia: aproximación desde la coremática y el enfoque ecosistémico

A territorial analysis of Aedes aegypti density was conducted in two Colombian cities using an ecosystem and chorematic approach. Entomological and behavioral data (by cluster) and information on the urban context were used to analyze the relationship between territorial structures and dynamics and vector density. The results were represented in graphic (chorematic) models. Arauca showed higher vector density than Armenia. Higher density was related to unplanned urbanization, flood-prone areas, low socioeconomic strata, household water tanks, higher temperature, and recall of control measures for adult mosquitos. Zones with low density indices coincided with diverse socioeconomic, ecological, and behavioral conditions. The study found a relationship between territorial structures and dynamics and vector density in both Arauca and Armenia, where the interaction between ecological and social systems shape areas with high and low A. aegypti density.

Foi realizada uma análise territorial da densidade do Aedes aegypti em duas cidades da Colômbia, desde um enfoque ecossistêmico e da coremática. Com base em informação entomológica e comportamental (por conglomerados) e informação do contexto urbano, foi indagada a relação de estruturas dinâmicas do território com a densidade vetorial. Foram apresentados os resultados com modelos gráficos (coremática). Identificou-se maior densidade vetorial em Arauca do que na Armênia. Maiores densidades foram relacionadas à urbanização não planejada, zonas de alagamento, estratos socioeconômicos baixos, tanques baixos (reservatórios), maior temperatura e relatório de ações contra os mosquitos adultos. Zonas de densidades baixas coincidiram com diversas condições socioeconômicas, ecológicas e comportamentais. Foi encontrada uma relação das estruturas e dinâmicas do território com a densidade vetorial para Arauca e Armênia, onde a interação entre sistemas ecológicos e sociais configura zonas particulares de alta e baixa densidades de A. aegypti.

Se realizó un análisis territorial de la densidad de Aedes aegypti en dos ciudades de Colombia desde un enfoque ecosistémico y la coremática. A partir de información entomológica y comportamental (por conglomerados) e información del contexto urbano, se indagó la relación de estructuras y dinámicas del territorio con la densidad vectorial. Se representaron los resultados con modelos gráficos (coremática). Se identificó mayor densidad vectorial en Arauca que en Armenia. Mayores densidades se relacionaron con urbanización no planeada, zonas de inundación, estratos socioeconómicos bajos, tanques bajos (alberca), mayor temperatura y reporte de acciones hacia los mosquitos adultos. Zonas de densidades bajas coincidieron con diversas condiciones socioeconómicas, ecológicas y comportamentales. Se encontró relación de las estructuras y dinámicas del territorio con la densidad vectorial para Arauca y Armenia, donde la interacción entre sistemas ecológicos y sociales configuran zonas particulares de alta y baja densidad de A. aegypti.