Optogenetic modulation of hippocampal oscillations ameliorates spatial cognition and hippocampal dysrhythmia following early-life seizures.

There is increasing human and animal evidence that brain oscillations play a critical role in the development of spatial cognition. In rat pups, disruption of hippocampal rhythms via optogenetic stimulation during the critical period for memory development impairs spatial cognition. Early-life seizures are associated with long-term deficits in spatial cognition and aberrant hippocampal oscillatory activity. Here we asked whether modulation of hippocampal rhythms following early-life seizures can reverse or improve hippocampal connectivity and spatial cognition. We used optogenetic stimulation of the medial septum to induce physiological 7 Hz theta oscillations in the hippocampus during the critical period of spatial cognition following early-life seizures. Optogenetic stimulation of the medial septum in control and rats subjected to early-life seizures resulted in precisely regulated frequency-matched hippocampal oscillations. Rat pups receiving active blue light stimulation performed better than the rats receiving inert yellow light in a test of spatial cognition. The improvement in spatial cognition in these rats was associated with a faster theta frequency and higher theta power, coherence and phase locking value in the hippocampus than rats with early-life seizures receiving inert yellow light. These findings indicate that following early life seizures, modification of hippocampal rhythms may be a potential novel therapeutic modality.

Estimation of Transfer Function Coefficients for Second-Order Systems via Metaheuristic Algorithms.

The present research develops the parametric estimation of a second-order transfer function in its standard form, employing metaheuristic algorithms. For the estimation, the step response with a known amplitude is used. The main contribution of this research is a general method for obtaining a second-order transfer function for any order stable systems via metaheuristic algorithms. Additionally, the Final Value Theorem is used as a restriction to improve the velocity search. The tests show three advantages in using the method proposed in this work concerning similar research and the exact estimation method. The first advantage is that using the Final Value Theorem accelerates the convergence of the metaheuristic algorithms, reducing the error by up to 10 times in the first iterations. The second advantage is that, unlike the analytical method, it is unnecessary to estimate the type of damping that the system has. Finally, the proposed method is adapted to systems of different orders, managing to calculate second-order transfer functions equivalent to higher and lower orders. Response signals to the step of systems of an electrical, mechanical and electromechanical nature were used. In addition, tests were carried out with simulated signals and real signals to observe the behavior of the proposed method. In all cases, transfer functions were obtained to estimate the behavior of the system in a precise way before changes in the input. In all tests, it was shown that the use of the Final Value Theorem presents advantages compared to the use of algorithms without restrictions. Finally, it was revealed that the Gray Wolf Algorithm has a better performance for parametric estimation compared to the Jaya algorithm with an error up to 50% lower.

Sensorless Estimation Based on Neural Networks Trained with the Dynamic Response Points.

In the present work, a neuronal dynamic response prediction system is shown to estimate the response of multiple systems remotely without sensors. For this, a set of Neural Networks and the response to the step of a stable system is used. Six basic characteristics of the dynamic response were extracted and used to calculate a Transfer Function equivalent to the dynamic model. A database with 1,500,000 data points was created to train the network system with the basic characteristics of the dynamic response and the Transfer Function that causes it. The contribution of this work lies in the use of Neural Network systems to estimate the behavior of any stable system, which has multiple advantages compared to typical linear regression techniques since, although the training process is offline, the estimation can perform in real time. The results show an average 2% MSE error for the set of networks. In addition, the system was tested with physical systems to observe the performance with practical examples, achieving a precise estimation of the output with an error of less than 1% for simulated systems and high performance in real signals with the typical noise associated due to the acquisition system.

Inhibition of amyloid-ß aggregation by coumarin analogs can be manipulated by functionalization of the aromatic center.

Aggregation of the amyloid-ß protein (Aß) plays a pathogenic role in the progression of Alzheimer's disease, and small molecules that attenuate Aß aggregation have been identified toward a therapeutic strategy that targets the disease's underlying cause. Compounds containing aromatic structures have been repeatedly reported as effective inhibitors of Aß aggregation, but the functional groups that influence inhibition by these aromatic centers have been less frequently explored. The current study identifies analogs of naturally occurring coumarin as novel inhibitors of Aß aggregation. Derivatization of the coumarin structure is shown to affect inhibitory capabilities and to influence the point at which an inhibitor intervenes within the nucleation dependent Aß aggregation pathway. In particular, functional groups found within amyloid binding dyes, such as benzothiazole and triazole, can improve inhibition efficacy. Furthermore, inhibitor intervention at early or late stages within the amyloid aggregation pathway is shown to correlate with the ability of these functional groups to recognize and bind amyloid species that appear either early or late within the aggregation pathway. These results demonstrate that functionalization of small aromatic molecules with recognition elements can be used in the rational design of Aß aggregation inhibitors to not only enhance inhibition but to also manipulate the inhibition mechanism.

Disruption of hippocampal rhythms via optogenetic stimulation during the critical period for memory development impairs spatial cognition.

BACKGROUND: Hippocampal oscillations play a critical role in the ontogeny of allocentric memory in rodents. During the critical period for memory development, hippocampal theta is the driving force behind the temporal coordination of neuronal ensembles underpinning spatial memory. While known that hippocampal oscillations are necessary for normal spatial cognition, whether disrupted hippocampal oscillatory activity during the critical period impairs long-term spatial memory is unknown. Here we investigated whether disruption of normal hippocampal rhythms during the critical period have enduring effects on allocentric memory in rodents. OBJECTIVE/HYPOTHESIS: We hypothesized that disruption of hippocampal oscillations via artificial regulation of the medial septum during the critical period for memory development results in long-standing deficits in spatial cognition. METHODS: After demonstrating that pan-neuronal medial septum (MS) optogenetic stimulation (465 nm activated) regulated hippocampal oscillations in weanling rats we used a random pattern of stimulation frequencies to disrupt hippocampal theta rhythms for either 1Hr or 5hr a day between postnatal (P) days 21-25. Non-stimulated and yellow light-stimulated (590 nm) rats served as controls. At P50-60 all rats were tested for spatial cognition in the active avoidance task. Rats were then sacrificed, and the MS and hippocampus assessed for cell loss. Power spectrum density of the MS and hippocampus, coherences and voltage correlations between MS and hippocampus were evaluated at baseline for a range of stimulation frequencies from 0.5 to 110 Hz and during disruptive hippocampal stimulation. Unpaired t-tests and ANOVA were used to compare oscillatory parameters, behavior and cell density in all animals. RESULTS: Non-selective optogenetic stimulation of the MS in P21 rats resulted in precise regulation of hippocampal oscillations with 1:1 entrainment between stimulation frequency (0.5-110 Hz) and hippocampal local field potentials. Across bandwidths MS stimulation increased power, coherence and voltage correlation at all frequencies whereas the disruptive stimulation increased power and reduced coherence and voltage correlations with most statistical measures highly significant (p < 0.001, following correction for false detection). Rats receiving disruptive hippocampal stimulation during the critical period for memory development for either 1Hr or 5hr had marked impairment in spatial learning as measured in active avoidance test compared to non-stimulated or yellow light-control rats (p < 0.001). No cell loss was measured between the blue-stimulated and non-stimulated or yellow light-stimulated controls in either the MS or hippocampus. CONCLUSION: The results demonstrated that robust regulation of hippocampal oscillations can be achieved with non-selective optogenetic stimulation of the MS in rat pups. A disruptive hippocampal stimulation protocol, which markedly increases power and reduces coherence and voltage correlations between the MS and hippocampus during the critical period of memory development, results in long-standing spatial cognitive deficits. This spatial cognitive impairment is not a result of optogenetic stimulation-induced cell loss.

Comparative study of inhibition at multiple stages of amyloid-beta self-assembly provides mechanistic insight.

The "amyloid cascade hypothesis," linking self-assembly of the amyloid-beta protein (Abeta) to the pathogenesis of Alzheimer's disease, has led to the emergence of inhibition of Abeta self-assembly as a prime therapeutic strategy for this currently unpreventable and devastating disease. The complexity of Abeta self-assembly, which involves multiple reaction intermediates related by nonlinear and interconnected nucleation and growth mechanisms, provides multiple points for inhibitor intervention. Although a number of small-molecule inhibitors of Abeta self-assembly have been identified, little insight has been garnered concerning the point at which these inhibitors intervene within the Abeta assembly process. In the current study, a julolidine derivative is identified as an inhibitor of Abeta self-assembly. To gain insight into the mechanistic action of this inhibitor, the inhibition of fibril formation from monomeric protein is assessed quantitatively and compared with the inhibition of two distinct mechanisms of growth for soluble Abeta aggregation intermediates. This compound is observed to significantly inhibit soluble aggregate growth by lateral association while having little effect on soluble aggregate elongation via monomer addition. In addition, inhibition of soluble Abeta aggregate association exhibits an IC(50) with a somewhat lower stoichiometric ratio than the IC(50) determined for inhibition of fibril formation from monomeric Abeta. This quantitative comparison of inhibition within multiple Abeta self-assembly assays suggests that this compound binds the lateral surface of on-pathway intermediates exhibiting a range of sizes to prevent their association with other aggregates, which is required for further assembly into mature fibrils.

FMRI correlates of olfactory processing in typically-developing school-aged children.

Human olfactory processing is understudied relative to other sensory modalities, despite its links to neurodevelopmental and neurodegenerative disorders. To address this limitation, we developed a fast, robust fMRI odor paradigm that is appropriate for all ages and levels of cognitive functioning. To test this approach, thirty-four typically developing children aged 7-12 underwent fMRI during brief, repeated exposure to phenylethyl alcohol, a flower-scented odor. Prior to fMRI scanning, olfactory testing (odor detection and identification) was conducted. During fMRI stimulus presentation, odorant release was synchronized to each participant's inspiratory phase to ensure participants were inhaling during the odorant exposure. Between group differences and correlations between activation and odor detection threshold scores were tested using the FMRIB Software Library. Results demonstrated that our 2-min paradigm significantly activated primary and secondary olfactory regions. In addition, a significant relationship between odor detection threshold and higher activation in the right amygdala and lower activation in the left frontal, insular, occipital, and cerebellar regions was observed, suggesting that this approach is sensitive to individual differences in olfactory processing. These findings demonstrate the feasibility of studying olfactory function in children using brain imaging techniques.

Soluble aggregates of the amyloid-beta protein activate endothelial monolayers for adhesion and subsequent transmigration of monocyte cells.

Increasing evidence suggests that the deposition of amyloid plaques, composed primarily of the amyloid-beta protein (Abeta), within the cerebrovasculature is a frequent occurrence in Alzheimer's disease and may play a significant role in disease progression. Accordingly, the pathogenic mechanisms by which Abeta can alter vascular function may have therapeutic implications. Despite observations that Abeta elicits a number of physiological responses in endothelial cells, ranging from alteration of protein expression to cell death, the Abeta species accountable for these responses remains unexplored. In the current study, we show that isolated soluble Abeta aggregation intermediates activate human brain microvascular endothelial cells for both adhesion and subsequent transmigration of monocyte cells in the absence of endothelial cell death and monolayer disruption. In contrast, unaggregated Abeta monomer and mature Abeta fibril fail to induce any change in endothelial adhesion or transmigration. Correlations between average Abeta aggregate size and observed increases in adhesion illustrate that smaller soluble aggregates are more potent activators of endothelium. These results support previous studies demonstrating heightened neuronal activity of soluble Abeta aggregates, including Abeta-derived diffusible ligands, oligomers, and protofibrils, and further show that soluble aggregates also selectively exhibit activity in a vascular cell model.

Soluble aggregates of the amyloid-beta protein selectively stimulate permeability in human brain microvascular endothelial monolayers.

Cerebral amyloid angiopathy associated with Alzheimer's disease is characterized by cerebrovascular deposition of the amyloid-beta protein (Abeta). Abeta elicits a number of morphological and biochemical alterations in the cerebral microvasculature, which culminate in hemorrhagic stroke. Among these changes, compromise of the blood-brain barrier has been described in Alzheimer's disease brain, transgenic animal models of Alzheimer's disease, and cell culture experiments. In the current study, presented data illustrates that isolated soluble Abeta(1-40) aggregates, but not unaggregated monomer or mature fibril, enhance permeability in human brain microvascular endothelial monolayers. Abeta(1-40)-induced changes in permeability are paralleled by both a decrease in transendothelial electrical resistance and a re-localization of the tight junction-associated protein zonula occludin-1 away from cell borders and into the cytoplasm. Small soluble Abeta(1-40) aggregates are confirmed to be the most potent stimulators of endothelial monolayer permeability by establishing an inverse relationship between average aggregate size and stimulated changes in diffusional permeability coefficients. These results support previous findings demonstrating that small soluble Abeta(1-40) aggregates are also primarily responsible for endothelial activation, suggesting that these same species may elicit other changes in the cerebrovasculature associated with cerebral amyloid angiopathy and Alzheimer's disease.

The influence of 5-HTTLPR transporter genotype on amygdala-subgenual anterior cingulate cortex connectivity in autism spectrum disorder.

Social deficits in autism spectrum disorder (ASD) are linked to amygdala functioning and functional connection between the amygdala and subgenual anterior cingulate cortex (sACC) is involved in the modulation of amygdala activity. Impairments in behavioral symptoms and amygdala activation and connectivity with the sACC seem to vary by serotonin transporter-linked polymorphic region (5-HTTLPR) variant genotype in diverse populations. The current preliminary investigation examines whether amygdala-sACC connectivity differs by 5-HTTLPR genotype and relates to social functioning in ASD. A sample of 108 children and adolescents (44 ASD) completed an fMRI face-processing task. Youth with ASD and low expressing 5-HTTLPR genotypes showed significantly greater connectivity than youth with ASD and higher expressing genotypes as well as typically developing (TD) individuals with both low and higher expressing genotypes, in the comparison of happy vs. baseline faces and happy vs. neutral faces. Moreover, individuals with ASD and higher expressing genotypes exhibit a negative relationship between amygdala-sACC connectivity and social dysfunction. Altered amygdala-sACC coupling based on 5-HTTLPR genotype may help explain some of the heterogeneity in neural and social function observed in ASD. This is the first ASD study to combine genetic polymorphism analyses and functional connectivity in the context of a social task.

Neural correlates of emotional inhibitory control in autism spectrum disorders.

Atypical inhibitory function is often present in individuals with autism spectrum disorder (ASD), who may have difficulty suppressing context-inappropriate behaviors. We investigated the neural correlates of inhibition in ASD in response to both emotional and non-emotional stimuli using an fMRI Go/NoGo inhibition task with human faces and letters. We also related neural activation to behavioral dysfunction in ASD. Our sample consisted of 19 individuals with ASD (mean age=25.84) and 22 typically developing (TD) control participants (mean age=29.03). As expected, no group differences in task performance (inhibition accuracy and response time) were found. However, adults with ASD exhibited greater angular gyrus activation in face response inhibition blocks, as well as greater fusiform gyrus activation than controls, in a condition comparing face inhibition to letter inhibition. In contrast, control participants yielded significantly greater anterior cingulate cortex (ACC) activation in letter inhibition blocks. A positive relationship between communication and language impairment and angular gyrus activation during face inhibition was also found. Group activation differences during inhibition tasks in the context of comparable task performance and the relationship between activation and dysfunction highlight brain regions that may be related to ASD-specific dysfunction.

Sensory Symptoms and Processing of Nonverbal Auditory and Visual Stimuli in Children with Autism Spectrum Disorder.

Atypical sensory responses are common in autism spectrum disorder (ASD). While evidence suggests impaired auditory-visual integration for verbal information, findings for nonverbal stimuli are inconsistent. We tested for sensory symptoms in children with ASD (using the Adolescent/Adult Sensory Profile) and examined unisensory and bisensory processing with a nonverbal auditory-visual paradigm, for which neurotypical adults show bisensory facilitation. ASD participants reported more atypical sensory symptoms overall, most prominently in the auditory modality. On the experimental task, reduced response times for bisensory compared to unisensory trials were seen in both ASD and control groups, but neither group showed significant race model violation (evidence of intermodal integration). Findings do not support impaired bisensory processing for simple nonverbal stimuli in high-functioning children with ASD.

Activation of brain endothelium by soluble aggregates of the amyloid-ß protein involves nuclear factor-κB.

Cerebrovascular accumulation of amyloid-ß protein (Aß) aggregates in Alzheimer's disease (AD) is proposed to contribute to disease progression and brain inflammation as a result of Aß-induced increases in endothelial monolayer permeability and stimulation of the endothelium for cellular adhesion and transmigration. These deficiencies facilitate the entry of serum proteins and monocyte-derived microglia into the brain. In the current study, a role for nuclear factor-κB (NF-κB) in the activation of cerebral microvascular endothelial cells by Aß is explored.Quantitative immunocytochemistry is employed to demonstrate that Aß(1-40) preparations containing isolated soluble aggregates elicit the most pronounced activation and nuclear translocation of NF-κB. This rapid and transient response is observed down to physiological Aß concentrations and parallels phenotypic changes in endothelial monolayers that are selectively elicited by soluble Aß(1-40) aggregates. While monomeric and fibrillar preparations of Aß(1-40) also activated NF-κB, this response was less pronounced, limited to a small cell population, and not coupled with phenotypic changes. Soluble Aß(1-40) aggregate stimulation of endothelial monolayers for adhesion and subsequent transmigration of monocytes as well as increases in permeability were abrogated by inhibition of NF-κB activation. Together, these results provide additional evidence indicating a role for soluble Aß aggregates in the activation of the cerebral microvascular endothelium and implicate the involvement of NF-κB signaling pathways in Aß stimulation of endothelial dysfunction associated with AD.

Soluble aggregates of the amyloid-beta peptide are trapped by serum albumin to enhance amyloid-beta activation of endothelial cells.

BACKGROUND: Self-assembly of the amyloid-beta peptide (Abeta) has been implicated in the pathogenesis of Alzheimer's disease (AD). As a result, synthetic molecules capable of inhibiting Abeta self-assembly could serve as therapeutic agents and endogenous molecules that modulate Abeta self-assembly may influence disease progression. However, increasing evidence implicating a principal pathogenic role for small soluble Abeta aggregates warns that inhibition at intermediate stages of Abeta self-assembly may prove detrimental. Here, we explore the inhibition of Abeta1-40 self-assembly by serum albumin, the most abundant plasma protein, and the influence of this inhibition on Abeta1-40 activation of endothelial cells for monocyte adhesion. RESULTS: It is demonstrated that serum albumin is capable of inhibiting in a dose-dependent manner both the formation of Abeta1-40 aggregates from monomeric peptide and the ongoing growth of Abeta1-40 fibrils. Inhibition of fibrillar Abeta1-40 aggregate growth is observed at substoichiometric concentrations, suggesting that serum albumin recognizes aggregated forms of the peptide to prevent monomer addition. Inhibition of Abeta1-40 monomer aggregation is observed down to stoichiometric ratios with partial inhibition leading to an increase in the population of small soluble aggregates. Such partial inhibition of Abeta1-40 aggregation leads to an increase in the ability of resulting aggregates to activate endothelial cells for adhesion of monocytes. In contrast, Abeta1-40 activation of endothelial cells for monocyte adhesion is reduced when more complete inhibition is observed. CONCLUSION: These results demonstrate that inhibitors of Abeta self-assembly have the potential to trap small soluble aggregates resulting in an elevation rather than a reduction of cellular responses. These findings provide further support that small soluble aggregates possess high levels of physiological activity and underscore the importance of resolving the effect of Abeta aggregation inhibitors on aggregate size.

Cáncer de pulmón en el Hospital Nacional Rosales serie de casos del año 2010 / Lung cancer in the Rosales National Hospital case series of the year 2010

El cáncer de pulmón ha sido el cáncer más común a nivel mundial por varias décadas, y para el año 2012 contabilizaba un estimado de 1.8 millones de casos nuevos, representando el 12.9% de todos los nuevos cánceres. Ocupa el primer lugar de las muertes por cáncer contabilizando por sí mismo con 1.59 millones de muertes (Seguido por el cáncer hepático con 745,000 muertes). Se realizó un estudio Epidemiológico, descriptivo observacional de seguimiento de casos con cáncer de pulmón (serie de casos), y análisis de sobrevida. Se realizó con base de fuentes documentales de expedientes de pacientes que consultaron y fueron tratados en el HNR en el año 2010. 45 pacientes fueron enrolados en el estudio, en el periodo comprendido entre Enero y Diciembre del 2010.la incidencia fue mayor en el sexo masculino (62,2%), la edad promedio oscilo en 62.09 años. El hábito tabáquico estuvo presente en el 75% de la población, con mayor prevalencia en hombres (89,29%) 15 pacientes (33.3%) reportaron contacto con humo producto de la combustión de biomasa y 9 casos reportaron exposición a ambos. El 80% presentaron tos y disnea. La estirpe histológica más frecuente fue el adenocarcinoma en el 68,9%, seguido por el carcinoma epidermoide (20%), el 54% (22/41) se diagnosticaron en estadío III y 19/41 caos (46%) en estadío IV. Al relacionar la asociación de fumar y la estirpe se encontró que el 88,88% de adenocarcinomas se daba en fumadores hombres con OR para sexo por tabaquismo de 6,85 (IC 95% 1,10 ­ 42,75) con p= 0,043. En el 84,4% de los casos el método de diagnóstico fue la fibrobroncoscopia. Para la estadificación, el método más frecuente fue a través de TC de tórax en 68,88% de casos. Recibieron tratamiento con quimioterapia sistémica el 68,9% de los casos, y el tratamiento fue indistinto del estadio de la enfermedad. La sobrevida media global fue de 5,84 meses con error estándar de 1.069, IC 95% 3.74-7.94. No hubo diferencias entre la sobrevida según estadio o estirpe histológica, obteniendo un Log Rank de 0.209 y 0.449, respectivamente. Conclusión: en nuestro estudio, encontramos que la mayoría de nuestros pacientes llegan al hospital en estadios avanzados de su enfermedad; es más frecuente en hombres que en mujeres a una razón de 2:1; existe una fuerte relación entre el hábito de tabaco y cáncer de pulmón. Adenocarcinoma fue la estirpe histológica más diagnosticada; finalmente encontramos que la sobrevida fue muy bajo en nuestros pacientes

Manifestaciones paraneoplásicas cutáneas en pacientes con carcinoma pulmonar / Paraneoplastic cutaneous manifestations in patients with lung cancer

Un tumor maligno puede manifestarse externamente en piel y su reconocimiento puede conducir al diagnóstico de una neoplasia previamente no sospechada. Es difícil determinar la frecuenticia exacta de todos los síndromes paraneoplásicos debido a: distintas definiciones, etiologías desconocidas y la falta de estudios controlados sistemáticos. Se presenta un estudio clínico descriptivo sobre las manifestaciones cutáneas paraneoplásicas en pacientes con carcinoma pulmonar; para ello se evaluaron los pacientes que ingresaron con el diagnóstico de cáncer de pulmón o a quienes se les hizo este diagnóstico durante su hospitalización en el Hospital José Ignacio Baldó en el lapso noviembre/92-junio/94 y que presentaran alguna dermatosis. La muestra estuvo compuesta por 48 pacientes de los cuales 5 presentaron manifestaciones paraneoplásicas, a saber: tromboflebitis superficial (2 casos), ictiosis adquirida, esclerodermia y prurito generalizado con un caso cada uno. Estas condiciones son discutidas con amplitud

Curso: gestión ambiental en el sector salud / Course: environmental administration in the sector health

Comprende Curso de Gestión Ambiental en el Sector Salud, realizado por el Msc arq. Francisco Mendoza Velasquez para obtener el diplomado Gestión Ambiental y Desarrollo del Sector Salud, bajo la responsabilidad de la Universidad Nacional de Ingenieria en la Facultad de Arquitectura y el Programa de Estudios Ambientales Urbanos/Territoriales, Managua, Nicaragua. Aborda los principios y definiciones de lo que es la planificación ambiental, la gestión, el logro en que esta basado la gestión como son las acciones concretas y correcta realizadas para el mejoramiento físico y técnico del territorio y de la calidad de vida de sus ciudanos. Analiza el instrumento de la gestión ambiental, desde la perspectiva de la Ley General del Medio Ambiente y los Recursos Naturales. Incluye la Salud Pública y la Gestión Ambiental y explica las cuatro áreas fundamentales de ésta como es el 1)Fomento de la Vitalidad y Salud Integral; 2)Prevención de lesiones de enfermedades infecciosas y no infecciosas; 3) Organización y provision de servicos para el diagnóstico y tratamiento de enfermedaes, y 4) Rehabilitación de personas enfermas o incapacitadas para el alcance el grado mas alto posible de actividad por si misma. También informa sobre procediminetos e instrumento del sistema de gestión ambiental del FISE, su misión y visión institucional

Curso: legislación ambiental expresa para el desarrollo del sector salud / Course: environmental expressed legislation for the development of the sector health

Comprende Curso de legislación expresa para el desarrollo del sector salud, impartido por el Profesor Dr. Arq. Francisco Mendoza Velasquez, durante el diplomado Gestión Ambiental y Desarrollo del Sector Salud, bajo la responsabilidad de la Universidad Nacional de Ingenieria en la Facultad de Arquitectura y el Programa de Estudios Ambientales Urbanos/Territoriales, Managua, Nicaragua. El documento aborda el marco conceptual, la convención internacional para la protección de la flora, fauna y de la belleza escénica naturales de los países de américa, la misión y visión del sector salud. Define estrategias institucional para la prevención y control de la contaminación, asi mismo la Ley geneal del medio ambiente y los recursos naturales. Esta dividido en secciones donde detallan la planificación, legislación, la biodiversidad y el patrimonio genético nacional, los suelos, las aguas continentales, maritimas y costeras. Incluye al final las normas, decretos y reglamentos para la gestión ambiental