Neuropathology of Traumatic Brain Injury and Its Role in the Development of Alzheimer’s Disease

The devastating deficiencies that result from brain injury stem from multiple overlapping mechanisms, exacerbated by the fact that there are no effective treatments. Traumatic brain injury (TBI) is recognized as the most influential environmental risk factor for neurodegenerative disease later in life, including dementia of Alzheimer’s disease (AD)-type. However, exactly how TBI triggers and strengthens the neurodegenerative cascade of events in AD remains controversial. Amyloid deposits and fibril precursor protein are extracellular in systemic amyloid A (AA) amyloidosis. In this chapter, I will discuss the neuropathology following TBI connected to AD. Additionally, I critically review recent animal and human studies regarding how brain trauma affects the potential risks factors for AD progression. Furthermore, it will be shown investigate the principal pathological features of dementia or AD, specifically focusing on axonal damage and consequent cleavage of the amyloid precursor protein (APP), amyloid β plaque formation, or phosphorylation and aggregation of tau, neurofibrillary tangles formation, and TDP-43 accumulation. In summary, despite recent progress more studies are required to (1) further understanding of the basic mechanisms and pathophysiology of TBI, (2) elucidate the precise association between TBI and neurodegenerative disease, and (3) to identify treatments and therapies that can mitigate long-term consequences

VALUE CO-CREATION AND OPPORTUNITIES IN HEALTH CARE AND WELLBEING: THE CASE OF THE GREEN PRESCRIPTION

The Green Prescription (GRx) is a health and wellbeing service that aims to manage the in-creasing obesity rates in the New Zealand population by providing free advice and support to at-risk patients. We evaluate the GRx service ecosystem using a qualitative approach and apply-ing a value co-creation framework. The resulting mapping allows us to identify new value co-creation opportunities and implications for practitioners. The research contributes a mapping of customer, supplier and encounter processes to a healthcare ecosystem and identifies existing and new value co-creation opportunities within the GRx ecosystem. We suggest that the GRx provider design a technological solution that allows the actors within the ecosystem to collabo-rate and create value. We also suggest that the service supplier could facilitate value co-creation by considering patients’ extrinsic motivators. The service supplier could improve the health-related intervention delivery by the use of Web 2.0 facilities, and enhance resource-sharing relationship experiences by making transparent a larger range of resources. Our study shows how the healthcare service provider may benefit from understanding active customer involvement in the relationship experience. We suggest that innovative research approaches such as the one applied may be useful when studying active customers and co-creation practices

Modelado del establecimiento de la conexión entre dos dispositivos bluetooth usando las redes de petri coloreadas

Bluetooth es una tecnología de comunicación que proporciona comunicación entre dispositivos vía radio frecuencias en un área de alrededor de los 10 metros. La especificación de Bluetooth incluye un conjunto de protocolos, adoptados y propios, organizados de forma jerárquica. Uno de los protocolos propios de esta tecnología es el bandabase. El establecimiento de una conexión es parte de la funciones de dicho protocolo. La especificación de este procedimiento es poco clara y ambigua y hace poco uso de herramientas para la descripción de protocolos tales como las tablas de estado. En este trabajo, las Redes de Petri Coloreadas (Coloured Petri Nets, CPNs), las cuales son una técnica formal, se utilizan para modelar el establecimiento de una conexión entre dos dispositivos Bluetooth, uno maestro y otro esclavo. Dicho modelo es entonces validado y depurado usando la técnica del grafo de estado. El análisis inicial muestra que el modelo se comporta acorde a lo esperado dadas las asunciones del modelo y las hechas para fines del análisis. La mayor contribución de este trabajo es el haber logrado una especificación clara y precisa del procedimiento a través del uso de la CPNs

Smad3 deficiency increases cortical and hippocampal neuronal loss following traumatic brain injury

Transforming growth factor-β (TGF-β) signaling is involved in pathological processes following brain injury. TGF-β signaling through Smad3 contributes significantly to the immune response and glial scar formation after brain injury. However, TGF-β is also neuroprotective, suggesting that Smad3 signaling may also be involved in neuroprotection after injury. We found expression of the TGF-β type II receptor (TβRII) and Smad3 protein to be strongly and rapidly induced in neurons in the ipsilateral cortex and CA1 region of the hippocampus after stab wound injury. In contrast, astrocytic expression of TβRII and Smad3 was induced more slowly. Comparison of the response of wild-type and Smad3 null mice to cortical stab wound injury showed a more pronounced loss of neuronal viability inSmad3 null mice. Neuronal density was more strongly reduced in Smad3 null mice than in wild-type mice at 1 and 3days post lesion in both the ipsilateral cortex and hippocampal CA1 region. Fluoro-Jade B, TUNEL staining, and cleaved caspase-3 staining also demonstrated increased neuronal degeneration at early time points after injury in the ipsilateral hemisphere in Smad3 null mice. Taken together, our results suggest that TGF-β cytokine family signaling through Smad3 protects neurons in the damaged cortex and hippocampus at early time points after injury

Temporal Changes in Cortical and Hippocampal Expression of Genes Important for Brain Glucose Metabolism Following Controlled Cortical Impact Injury in Mice

Traumatic brain injury (TBI) causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n = 6/group) underwent sham or unilateral controlled cortical impact (CCI) injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6 h, 1, 3, 7, 14, 21, and 28 days after injury. Expressions of several genes important for brain glucose utilization were determined by qRT-PCR. In results, (1) mRNA levels of three key enzymes in glucose metabolism [hexo kinase (HK) 1, pyruvate kinase, and pyruvate dehydrogenase (PDH)] were all increased 6 h after injury in the contralateral cortex, followed by decreases at subsequent times in the ipsilateral cortex and hippocampus; (2) capillary glucose transporter Glut-1 mRNA increased, while neuronal glucose transporter Glut-3 mRNA decreased, at various times in the ipsilateral cortex and hippocampus; (3) astrocyte lactate transporter MCT-1 mRNA increased, whereas neuronal lactate transporter MCT-2 mRNA decreased in the ipsilateral cortex and hippocampus; (4) HK2 (an isoform of hexokinase) expression increased at all time points in the ipsilateral cortex and hippocampus. GPR81 (lactate receptor) mRNA increased at various time points in the ipsilateral cortex and hippocampus. These temporal alterations in gene expression corresponded closely to the patterns of impaired brain glucose utilization reported in both TBI patients and experimental TBI rodents. The observed changes in hippocampal gene expression were delayed and prolonged, when compared with those in the cortex. The patterns of alterations were specific to different brain regions and exhibited different recovery periods following TBI. Oral administration of telmisartan (1 mg/kg, for 7 days, n = 10 per group) ameliorated cortical or hippocampal mRNA for Glut-1/3, MCT-1/2 and PDH in CCI mice. These data provide molecular evidence for dynamic alteration of multiple critical factors in brain glucose metabolism post-TBI and can inform further research for treating brain metabolic disorders post-TBI

Traumatic Brain Injury in Mice Induces Acute Bacterial Dysbiosis Within the Fecal Microbiome

The secondary injury cascade that is activated following traumatic brain injury (TBI) induces responses from multiple physiological systems, including the immune system. These responses are not limited to the area of brain injury; they can also alter peripheral organs such as the intestinal tract. Gut microbiota play a role in the regulation of immune cell populations and microglia activation, and microbiome dysbiosis is implicated in immune dysregulation and behavioral abnormalities. However, changes to the gut microbiome induced after acute TBI remains largely unexplored. In this study, we have investigated the impact of TBI on bacterial dysbiosis. To test the hypothesis that TBI results in changes in microbiome composition, we performed controlled cortical impact (CCI) or sham injury in male 9-weeks old C57BL/6J mice. Fresh stool pellets were collected at baseline and at 24 h post-CCI. 16S rRNA based microbiome analysis was performed to identify differential abundance in bacteria at the genus and species level. In all baseline vs. 24 h post-CCI samples, we evaluated species-level differential abundances via clustered and annotated operational taxonomic units (OTU). At a high-level view, we observed significant changes in two genera after TBI, Marvinbryantia, and Clostridiales. At the species-level, we found significant decreases in three species (Lactobacillus gasseri, Ruminococcus flavefaciens, and Eubacterium ventriosum), and significant increases in two additional species (Eubacterium sulci, and Marvinbryantia formatexigens). These results pinpoint critical changes in the genus-level and species-level microbiome composition in injured mice compared to baseline; highlighting a previously unreported acute dysbiosis in the microbiome after TBI

Analysis of the Dynamic Service Flow Management Transactions Protocol for MAC IEEE 802.16. An Aproach

In this work the WiMax MAC Protocol for Dynamic Service Flow management and their transactions is analyzed by showing this several pitfalls of the specification and how this can affect the implementation of the protocol using Colored Petri Nets (CPNs). A detailed description of the protocol is developed at level of transactions it supports, and at level of service flows. The modeling and analysis of the protocol are important to improve the current specification and to support the reuse of the concepts in emerging networks. We show the potentialities of using a transaction oriented approach in the description of this kind of protocols. The contributions of this paper are focused on providing a clear description of the protocol, presentation of the model, validation and analysis of the model according to the generation of the Dynamic Service Flow management transactions protocol language, as well as the determination of regular expressions Language.Sociedad Argentina de Informática e Investigación Operativa (SADIO

Noteworthy new records of squamate reptiles (Reptilia: Squamata) from various Venezuelan Caribbean islands, including a new addition to the herpetofauna of Venezuela

The occurrence of Gymnophthalmus lineatus in Venezuela is established for the first time based on a specimen collected on Las Aves Archipelago. We also document the first records of Phyllodactylus ventralis from Los Frailes Archipelago, Amphisbaena alba from Isla de Margarita, and report the occurrence of Thecadactylus cf. rapicauda on Las Aves Archipelago. Additionally we expand the distribution of the snake Leptophis ahaetulla on Isla de Margarita and report the third specimen known from that island. We also present information on the lepidosis and coloration for all species when pertinent

Vaccinate fast but leave no one behind: a call to action for COVID-19 vaccination in Spain

During the first five months of 2021, Spains COVID-19 vaccination campaign progressed slowly and failed to reach marginalised populations. Here, we discuss how, despite recent improvements, it remains important to further engage key stakeholders to ensure nobody is left behind