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Purpose Advances in functional imaging allowed us to visualize brain glucose metabolism in vivo and non-invasively with [18F]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) imaging. In the past decades, FDG-PET has been instrumental in the understanding of brain function in health and disease. The source of the FDG-PET signal has been attributed to neuronal uptake, with hypometabolism being considered as a direct index of neuronal dysfunction or death. However, other brain cells are also metabolically active, including astrocytes. Based on the astrocyte-neuron lactate shuttle hypothesis, the activation of the glutamate transporter 1 (GLT-1) acts as a trigger for glucose uptake by astrocytes. With this in mind, we investigated glucose utilization changes after pharmacologically downregulating GLT-1 with clozapine (CLO), an antipsychotic drug. Methods Adult male Wistar rats (control, n = 14; CLO, n = 12) received CLO (25/35mg kg−1) for six weeks. CLO effects were evaluated in vivo with FDG-PET and cortical tissue was used to evaluate glutamate uptake, GLT-1 and GLAST levels. CLO treatment effects were also assessed in cortical astrocyte cultures (glucose and glutamate uptake, GLT-1 and GLAST levels) and in cortical neuronal cultures (glucose uptake). Results CLO markedly reduced in vivo brain glucose metabolism in several brain areas, especially in the cortex. Ex vivo analyses demonstrated decreased cortical glutamate transport along with GLT-1 mRNA and protein downregulation. In astrocyte cultures, CLO decreased GLT-1 density as well as glutamate and glucose uptake. By contrast, in cortical neuronal cultures, CLO did not affect glucose uptake. Conclusion This work provides in vivo demonstration that GLT-1 downregulation induces astrocyte-dependent cortical FDG-PET hypometabolism - mimicking the hypometabolic signature seen in people developing dementia - and adds further evidence that astrocytes are key contributors of the FDG-PET signal.

As an indicator of surface moisture, TVDI has great potential for application in agriculture in different types of climates, but the best results have been obtained in arid climates, given the presence of areas with contrasting water conditions. Some studies under subtropical climate conditions have shown good results in the use of TVDI as an indicator of surface moisture but some uncertainties still need to be better understood. This study aimed to evaluate the coherence of temperature-vegetation dryness index (TVDI) values, obtained from sensors installed on the surface, compared to data obtained using orbital images in an agricultural area in southern Brazil under humid subtropical climate conditions. The analyses employed normalized difference vegetation index (NDVI) and surface temperature (TS) data obtained through sensors installed on the surface, with continuous monitoring, as well as Landsat OLI/TIRS images, covering the period of the soybean cycle. The TVDI values, obtained from NDVI and TS radiometric sensors installed in the field, indicated consistency of using Landsat-OLI/TIRS orbital images to map the surface moisture condition, representing the spatial and temporal variations of the water condition of soybean cultivations under subtropical climate conditions. Made available in DSpace on 2022-07-19T17:19:44Z (GMT). No. of bitstreams: 1 Surface.pdf: 1485818 bytes, checksum: bae2de48cb720087a875385b3c250846 (MD5) Previous issue date: 2022

Reactive astrogliosis is an early event in the continuum of Alzheimer’s disease (AD). Current advances in positron emission tomography (PET) imaging provide ways of assessing reactive astrogliosis in the living brain. In this review, we revisit clinical PET imaging and in vitro findings using the multi-tracer approach, and point out that reactive astrogliosis precedes the deposition of Aβ plaques, tau pathology, and neurodegeneration in AD. Furthermore, considering the current view of reactive astrogliosis heterogeneity—more than one subtype of astrocyte involved—in AD, we discuss how astrocytic body fluid biomarkers might fit into trajectories different from that of astrocytic PET imaging. Future research focusing on the development of innovative astrocytic PET radiotracers and fluid biomarkers may provide further insights into the heterogeneity of reactive astrogliosis and improve the detection of AD in its early stages.

Amyloid-β (Aβ) dysmetabolism is tightly associated with pathological processes in Alzheimer's disease (AD). Currently, it is thought that, in addition to Aβ fibrils that give rise to plaque formation, Aβ aggregates into non-fibrillar soluble oligomers (AβOs). Soluble AβOs have been extensively studied for their synaptotoxic and neurotoxic properties. In this review, we discuss physicochemical properties of AβOs and their impact on different brain cell types in AD. Additionally, we summarize three decades of studies with AβOs, providing a compelling bulk of evidence regarding cell-specific mechanisms of toxicity. Cellular models may lead us to a deeper understanding of the detrimental effects of AβOs in neurons and glial cells, putatively shedding light on the development of innovative therapies for AD.

A novel carboxylation radiosynthesis methodology is described starting from cyclotron-produced [11C]CO2 and fluoride-activated silane derivatives. Six carbon-11 labelled carboxylic acids were obtained from their corresponding trimethylsilyl and trialkoxysilyl precursors in a one-pot labelling methodology. The radiochemical yields ranged from 19% to 93% within 12 minutes post [11C]CO2 delivery with a trapping efficiency of 21-89%.

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10

Background Fungal infections are highly prevalent and are responsible for high rates of morbidity and mortality. In this context, the search for new treatment alternatives is very relevant. Objectives Analyse chemical compounds for antifungal potential against dermatomycosis fungi. Methods The antifungal activity of 121 compounds, intermediates or derivatives of 1,3-bis(aryloxy)propane substituted at C-2 (111 compounds) and isothiouronium derivatives (10 compounds) was investigated through susceptibility tests, mechanism of action, toxicity and hydrogel incorporation. Results The compound 1,3-bis(3,4-dichlorophenoxy)propan-2-aminium chloride (2j) was the most active fungicide against dermatophytes and Candida spp., at very low concentrations (0.39-3.12 µg/mL), including action on resistant and multidrug-resistant clinical strains. Compound 2j has presented a promising toxicity profile, showing selectivity index >10, relative to human lymphocytes. The compound was classified as non-irritant by the HET-CAM test and did not cause histopathological alterations in pig ear skin, thus presenting an excellent perspective for topical application. 2j targets the fungal cell wall, which was confirmed by scanning electron microscopy, which also indicated the additional ability of 2j to inhibit the Candida albicans pseudohyphae formation and biofilm of Microsporum canis. Compound 2j was incorporated in a hydrogel with bioadhesive potential. The results of the human skin permeation showed that 2j remained significantly in the epidermis, ideally for the dermatomycosis treatment. Conclusions Therefore, the compound 2j demonstrated the potential for antifungal drug development, with a action mechanism elucidated and already applied in a semisolid formulation as a new therapeutic option for fungal skin infections.

Astrocytes are highly efficient homeostatic glial cells playing a crucial role in optimal brain functioning and homeostasis. Astrocytes respond to changes in brain homoeostasis following central nervous system (CNS) injury/diseased state by a specific defence mechanism called reactive astrogliosis. Recent studies have implicated and placed reactive astrogliosis in the centre of pathophysiology of Alzheimer's disease (AD) and other neurodegenerative disorders. The AD biomarker field is evolving rapidly with new findings providing strong evidence which supports the notion that a reactive astrogliosis is an early event in the time course of AD progression which may precede other pathological hallmarks of AD. Clinical/translational in vivo PET and in vitro postmortem brain imaging studies demonstrated 'a first and second wave' of reactive astrogliosis in AD with distinct close-loop relationships with other pathological biomarkers at different stages of the disease. At the end stages, reactive astrocytes are found to be associated, or in proximity, with amyloid plaque and tau pathological deposits in postmortem AD brains. Several new PET-tracers, which are being in pipeline and validated at a very fast pace for mapping and visualising reactive astrogliosis in the brain, will provide further invaluable mechanistic insights into AD and other non-AD dementia pathologies. The complementary roles of microglia and astrocyte activation in AD progression, along with the clinical value of new fluid astrocytes biomarkers in the context of existing biomarkers, are the latest avenue that needs further exploration.

The small and medium Italian historical centres are characterized, among other things, by reconstruction that have occurred over the centuries after earthquakes. While earthquakes determine structural damages, human losses and loss of the functionality of an urban system above all, they may create, at the same time, new opportunities if the urban and socio-economical structures are improved during the reconstruction processes as a whole. These processes and the optimal implementation of planning models within them is not straightforward [1], due to that several issues emerge as a challenge of the reconstruction programmes (decision-making processes, general vision for the entire urban system for instance). According to the literature, although a unique definition has not still been coined, resilience can be defined as the capacity of a system (a city) to withstand and restore after a shocking episode (an earthquake). Mainly in the context of cities [2], some approaches have been framed and experimented by other authors [3, 4, 5]. Starting from a short literature review, focuses on theories and methodological approaches to evaluate urban resilience, this work analyses – through an interdisciplinary approach – the case study of Nocera Umbra twenty years after two devastating earthquakes occurred in 1997. The research represents a first attempt that aims at analysing if the implemented reconstruction strategies have made the urban system more resilient with respect to both the built and the socio-economic environment.

Introducao O Virus da Imunodeficiencia Humana (HIV) e uma infeccao transmissivel pelo sangue cuja triagem laboratorial de alta sensibilidade e obrigatoria para doacao de sangue, a fim de reduzir o risco transfusional. Porto Alegre, historicamente, e a capital brasileira com a maior frequencia de HIV na populacao geral. Objetivos Este estudo teve por objetivos verificar o perfil socio-epidemiologico e possivel alteracao na taxa de prevalencia de HIV entre doadores de sangue no Servico de Hemoterapia do Hospital de Clinicas de Porto Alegre (HCPA) nos ultimos anos. Material e metodos Um estudo transversal retrospectivo foi conduzido atraves de levantamento de dados no Sistema Realblood e nos registros sorologicos das doacoes realizadas de janeiro de 2015 a maio de 2021. Foram incluidos todos os casos de HIV positivos e confirmados com NAT (Teste de Acido Nucleico) ou Imunoblot. Os dados foram compilados e analisados no sistema SPSS v. 18. Resultados Durante o periodo analisado, foram realizadas 83.062 doacoes de sangue, sendo identificados 39 casos de HIV confirmado, o que resulta em uma prevalencia de 46,95/100.000 bolsas ou 1/2.129 doacoes. Individuos portadores de HIV nessa amostra eram na maioria do sexo masculino (56,4%), solteiros (69,2%), brancos (61,5%), com baixa escolaridade (53,9%), residentes em Porto Alegre e Regiao Metropolitana (82,1%), com idade media no diagnostico de 32,9 (DP ±8,8) anos. O principal tipo de doacao envolvida foi de reposicao (61,5%), sendo que 79,5% recoletaram amostra. Cerca de 15,4% dos casos possuia algum tipo de co-infecao e 18% se tratava de soroconversao, isto e, doadores que anteriormente apresentavam resultados negativos para HIV. Nao houve diferenca estatistica entre os sexos considerando os fatores idade de diagnostico, estado civil e tipo de doacao. Houve uma queda de 55,4% na prevalencia de HIV entre os doadores a partir de 2017 (73,2 versus 32,6/100.000; p = 0,021). Discussao O perfil socio-epidemiologico do doador de sangue com HIV positivo se assemelha aos dados de HIV na populacao geral brasileira quanto ao sexo, idade de diagnostico e escolaridade, diferindo quanto a etnia. Este dado acompanha as caracteristicas etnicas da populacao gaucha. Apesar da elevada frequencia de HIV em Porto Alegre, a taxa de prevalencia entre doadores de sangue no HCPA nos ultimos tres anos foi em media 44,2% inferior a populacao. Conclusao A reducao da prevalencia de HIV entre doadores de sangue, pode ser explicada devido ao perfil de doadores ser formado em sua maioria por individuos saudaveis e aos processos de captacao e triagem clinica em constante melhoria, que possivelmente influenciam na mitigacao deste risco transfusional.

Introducao A implementacao de novas tecnicas em Servicos de Hemoterapia deve ser precedida de avaliacao e validacao dos procedimentos para assegurar os criterios de qualidade. O objetivo deste trabalho e descrever o protocolo de Validacao para a triagem sorologica de doadores de sangue realizado no Servico de Hemoterapia do Hospital de Clinicas de Porto Alegre (HCPA). Material e metodos Foram validados dois equipamentos Cobas e411 e o conjunto de kits de eletroquimioluminescencia (Roche) para os marcadores: Imunodeficiencia Humana (HIV), virus T-Linfotropico Humano (HTLV), Doenca de Chagas, hepatite B (HBsAg e anti-HBc) e hepatite C (HCV) entre outubro de 2020 e janeiro 2021. As variaveis analisadas foram sensibilidade de 100%; especificidade maior que 99%; coeficiente de variacao (CV) de ate 10% na reprodutibilidade de amostras reagentes; ausencia de efeito pro-zona; produtividade e poder discriminatorio entre as amostras reagentes (R) e nao reagentes (NR). Os tipos de amostras testadas incluiram: cadavericas, sabidamente reagentes, com possiveis interferentes como hemolise e lipemia, doacoes com resultado desconhecido, paineis de performance e controles comerciais e internos, totalizando no minimo 800 testes/parâmetro. Resultados e discussao Os criterios de sensibilidade e especificidade foram considerados atingidos para todos os parâmetros. O CV das amostras e controles reagentes foi inferior a 10% em todos os parâmetros. Os resultados das amostras com possiveis interferentes e cadavericas nao apresentaram discrepâncias. O estudo de pro-zona mostrou que Chagas, HTLV, HCV, HIV e HBsAg apresentaram uma curva de diluicao e reatividade lineares e proporcionais. A curva do HBc nao apresentou a mesma linearidade, provavelmente por ser um teste competitivo. A partir dos testes das amostras R e NR (n > 100; n > 500), obtivemos o valor medio e o perfil de variacao das amostras, demonstrando alto poder discriminatorio entre as amostras R e NR para todos os parâmetros. Os equipamentos apresentaram boa produtividade processando sessenta doacoes em 3h:50m:19s. Da mesma forma, apresentou boa autonomia, processando 20 amostras sem interferencia ou carregamento. Conclusao Todos os criterios de avaliacao estabelecidos foram atingidos e o conjunto para triagem sorologica de doadores de sangue da marca Roche foi validado e aprovado para uso.

Integrated Plastic and Reconstructive Surgery residency programs may use medical school reputation to help fill the gap of a pass/fail USMLE Step 1 in the match. The main objective of this manuscript was to consider if this shifting emphasis is warranted. Herein, a cross-sectional analysis of academic plastic surgeons found that medical school reputation did not predict career achievement. In the absence of evidence demonstrating its worth, residency programs should exercise caution in using medical school reputation in the match.

The anti-oxidative potential of Rhamnidium elaeocarpum extract was assessed using a green chemical bottom-up approach to produce ~ 80 nm cubic Fe3O4 nanoparticles. The protocol makes use of FeCl3 as the only precursor of magnetite, and it allows the obtaining of the material using water as solvent, and urea as a pH regulator. Besides, since the bark extract functions as both the capping and reducing agents, no unfriendly extra chemicals are required to promote the Fe3+ reduction to Fe2+. For comparison purposes, we also obtained iron oxide materials in the absence of the biomass, and it was observed that urea alone could not reduce Fe3+ to promote the formation of magnetite nanoparticles. In that case, other forms of iron oxide materials, with very low magnetic response, such as hematite (α-Fe2O3) and maghemite (γ-Fe2O3) were obtained. The bio-inspired catalyst (Fe3O4) was applied in the degradation of Rhodamine-B using H2O2. Under the studied conditions, a single portion of the catalyst could promote the dye degradation for at least 5 cycles (degradation > 94%), and the material could be rapidly isolated in between batches using a small neodymium magnet. We also found out that the iron oxides obtained in the absence of extract and urea exhibited a lower degradation efficiency, and could not be recycled in successive runs. An investigation on the toxicity of this new catalyst was also carried out on three model organisms and no toxicity enhancement could be induced by the presence of the as-synthesized magnetite nanoparticles.