A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors

Alcohol produces both stimulant and sedative effects in humans and rodents. In humans, alcohol abuse disorder is associated with a higher stimulant and lower sedative responses to alcohol. Here, we show that this association is conserved in mice and demonstrate a causal link with another liability factor: low expression of striatal dopamine D2 receptors (D2Rs). Using transgenic mouse lines, we find that the selective loss of D2Rs on striatal medium spiny neurons enhances sensitivity to ethanol stimulation and generates resilience to ethanol sedation. These mice also display higher preference and escalation of ethanol drinking, which continues despite adverse outcomes. We find that striatal D1R activation is required for ethanol stimulation and that this signaling is enhanced in mice with low striatal D2Rs. These data demonstrate a link between two vulnerability factors for alcohol abuse and offer evidence for a mechanism in which low striatal D2Rs trigger D1R hypersensitivity, ultimately leading to compulsive-like drinkingFil: Bocarsly, Miriam E.. National Institutes of Health; Estados UnidosFil: da Silva e Silva, Daniel. National Institutes of Health; Estados UnidosFil: Kolb, Vanessa. National Institutes of Health; Estados UnidosFil: Luderman, Kathryn D.. National Institutes of Health; Estados UnidosFil: Shashikiran, Sannidhi. National Institutes of Health; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sibley, David R.. National Institutes of Health; Estados UnidosFil: Dobbs, Lauren K.. National Institutes of Health; Estados Unidos. University of Texas at Austin; Estados UnidosFil: Álvarez, Verónica Alicia. National Institutes of Health; Estados Unido

Parametric Analysis of a Heavy Metal Sorption Isotherm Based on Fractional Calculus

Heavy metals are widely recognized as being hazardous to human health and environmentally aggressive. The literature reports different approaches for lead removal, for example, water hyacinths. Heavy metal sorption isotherm modeling represents an important tool towards the study of equilibrium conditions. Fractional calculus represents a novel approach and a growing research field for process modeling, based on derivatives of arbitrary order. Recently, a novel isotherm based on fractional calculus was proposed for lead sorption using water hyacinth (Eichhornia crassipes). This paper reports a general procedure on error analysis and its influence on parameter estimation. It was applied to mathematical models based on fractional differential equations, focusing on a heavy metal novel isotherm sorption model. Parameter variance was calculated by using two different approaches (with the complete Hessian matrix and with a simplified Hessian matrix), and joint parameter confidence regions were generated, being successfully able to show that the fractional nature of the model is statistically valid

Caracterização química e avaliação das atividades antibacteriana, antifúngica, antimicobacteriana e citotóxica de Talinum paniculatum

In this study, the bioactivity of Talinum paniculatum was evaluated, a plant widely used in folk medicine. The extract from the T. paniculatum leaves (LE) was obtained by percolation with ethanol-water and then subjecting it to liquid-liquid partitions, yielding hexane (HX), ethyl acetate (EtOAc), butanol (BuOH), and aqueous (Aq) fractions. Screening for antimicrobial activity of the LE and its fractions was evaluated in vitro through broth microdilution method, against thirteen pathogenic and non-pathogenic microorganisms, and the antimycobacterial activity was performed through agar diffusion assay. The cytotoxic concentrations (CC90) for LE, HX, and EtOAc were obtained on BHK-21 cells by using MTT reduction assay. The LE showed activity against Serratia marcescens and Staphylococcus aureus, with Minimum Inhibitory Concentration (MIC) values of 250 and 500 µg/mL, respectively. Furthermore, HX demonstrated outstanding activity against Micrococcus luteus and Candida albicans with a MIC of 31.2 µg/mL in both cases. The MIC for EtOAc also was 31.2 µg/mL against Escherichia coli. Conversely, BuOH and Aq were inactive against all tested microorganisms and LE proved inactive against Mycobacterium tuberculosisand Mycobacterium bovisas well. Campesterol, stigmasterol, and sitosterol were the proposed structures as main compounds present in the EF and HX/EtOAc fractions, evidenced by mass spectrometry. Therefore, LE, HX, and EtOAc from T. paniculatumshowed potential as possible sources of antimicrobial compounds, mainly HX, for presenting low toxicity on BHK-21 cells with excellent Selectivity Index (SI = CC90/MIC) of 17.72 against C. albicans.Neste estudo foi avaliada a bioatividade de Talinum paniculatum, planta amplamente utilizada na medicina popular. O extrato das folhas (EF) de T. paniculatum foi obtido por percolação com etanol-água e, em seguida, submetido à partição líquido-líquido, obtendo-se as frações hexânica (HX), acetato-etílica (AcOEt), butanólica (BuOH) e aquosa (Aq). A triagem para a atividade antimicrobiana do EF e de suas frações foram avaliadas in vitro através do método de microdiluição em caldo contra treze micro-organismos patogênicos e não-patogênicos e, a atividade antimicobacteriana, foi avaliada através do teste de difusão em ágar. As concentrações citotóxicas (CC90) do EF e das frações HX e AcOEt foram obtidas sobre células da linhagem BHK-21 através do ensaio de redução do MTT. O EF mostrou atividade contra Serratia marcescens e Staphylococcus aureus, com valores de concentração inibitória mínima (CIM) de 250 e 500 µg/mL, respectivamente. Além disso, HX demonstrou excelente atividade contra Micrococcus luteus e Candida albicans com uma CIM de 31,2 µg/mL, em ambos os casos. Contra Escherichia coli, a CIM para AcOEt foi também de 31,2 µg/mL. Por outro lado, as frações BuOH e Aq foram inativas contra todos os micro-organismos testados, assim como o EF contra Mycobacterium tuberculosis e Mycobacterium bovis. Campesterol, estigmasterol e sitosterol foram as estruturas propostas como principais compostos presentes no EF e nas frações HX e AcOEt, evidenciadas através de espectrometria de massas. Portanto, o extrato da folha e as frações HX e AcOEt provenientes de T. paniculatum apresentaram potencial como possíveis fontes de compostos antimicrobianos, HX principalmente, por ter apresentado uma baixa toxicidade sobre células BHK-21 com um bom índice de seletividade (IS = CC90/MIC) de 17,72 contra C. albicans

The management of COVID-19 cases through telemedicine in Brazil.

In Dec 2020 Brazil became one of the worldwide epicenters of the COVID-19 pandemic with more than 7.2M reported cases. Brazil has a large territory with unequal distribution of healthcare resources including physicians. Resource limitation has been one of the main factors hampering Brazil's response to the COVID-19 crisis. Telemedicine has been an effective approach for COVID-19 management as it allows to reduce the risk of cross-contamination and provides support to remote rural locations. Here we present the analyses of teleconsultations from a countrywide telemedicine service (TelessáudeRS-UFRGS, TRS), that provides physician-to-physician remote support during the COVID-19 pandemic in Brazil. We performed a descriptive analysis of the teleconsultation incoming calls and a text analysis from the call transcripts. Our findings indicate that TRS teleconsultations in Brazil experienced an exponential increment of 802.% during a period of 6 days, after the first death due to COVID-19 was reported. However, the number of teleconsultations cases decreased over time, despite the number of reported COVID-19 cases continuously increasing. The results also showed that physicians in low-income municipalities, based on GDP per capita, are less likely to consult the telemedicine service despite facing higher rates of COVID-19 cases. The text analysis of call transcripts from medical teleconsultations showed that the main concern of physicians were "asymptomatic" patients. We suggest an immediate reinforcement of telehealth services in the regions of lower income as a strategy to support COVID-19 management

The management of COVID-19 cases through telemedicine in Brazil

In Dec 2020 Brazil became one of the worldwide epicenters of the COVID-19 pandemic with more than 7.2M reported cases. Brazil has a large territory with unequal distribution of healthcare resources including physicians. Resource limitation has been one of the main factors hampering Brazil’s response to the COVID-19 crisis. Telemedicine has been an effective approach for COVID-19 management as it allows to reduce the risk of cross-contamination and provides support to remote rural locations. Here we present the analyses of teleconsultations from a countrywide telemedicine service (Telessa´udeRS-UFRGS, TRS), that provides physician-to-physician remote support during the COVID-19 pandemic in Brazil. We performed a descriptive analysis of the teleconsultation incoming calls and a text analysis from the call transcripts. Our findings indicate that TRS teleconsultations in Brazil experienced an exponential increment of 802.% during a period of 6 days, after the first death due to COVID-19 was reported. However, the number of teleconsultations cases decreased over time, despite the number of reported COVID-19 cases continuously increasing. The results also showed that physicians in low-income municipalities, based on GDP per capita, are less likely to consult the telemedicine service despite facing higher rates of COVID-19 cases. The text analysis of call transcripts from medical teleconsultations showed that the main concern of physicians were “asymptomatic” patients. We suggest an immediate reinforcement of telehealth services in the regions of lower income as a strategy to support COVID-19 management.Telemedicin

Assessing Depth Perception in Virtual Environments: A Comprehensive Framework

Understanding humans’ perception of depth and how they interact with virtual environments is a challenging task. This context involves investigating how features of these environments affect depth perception, which is crucial for tasks like object manipulation and navigation that require interpreting spatial information. This article presents a comprehensive (general, extensible and flexible) framework to assess depth perception in different virtual environments to support the development of more effective and immersive virtual experiences. This approach can assist developers in decision-making regarding different approaches for assessing depth perception in virtual environments, considering stereoscopic and monoscopic techniques for visualization. The framework considers parameters such as the distance between the user and virtual objects and the sizes of virtual objects. Metrics such as hit rate, response time, and presence questionnaire responses were utilized to assess depth perception. The previous experiments are presented (anaglyph and shutter glasses), as well as the new experiments, considering cave environments with and without anaglyph glasses

Integrated proteomics identified up-regulated focal adhesion-mediated proteins in human squamous cell carcinoma in an orthotopic murine model

Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules.Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by co95e98208FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2009/54067-3; 2010/19278-0; 2011/22421-2; 2009/53839-2; 2011/02267-9470567/2009-0; 470549/2011-4; 301702/2011-0; 470268/2013-1; 505413/2013-