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The diversity of sustainable certifications raises questions about the credibility, intentions, and impacts of Voluntary Sustainability Standards (VSS) on Global Value Chains (GVC). Few studies show the impacts of VSS on different sustainable dimensions in sectors such as the non-timber forest product (NTFP) sector. This paper aims to investigate in the value chain of the most important NTFP in the Amazon, açaí, whether VSS contributes to sustainable outcomes in the Governance, Environmental, Economic, and Social dimensions. Using case studies in enterprises of the açaí chain and the use of tools and indicators was possible to generate information that is currently scarce for NTFPs in the Amazon from the VSS perspective. The results show that there is a great distance that the weakest links of the GVC (Micro, Small, and Medium Enterprises - MSMEs) must walk to adopt VSS and be inserted into the global market. The requirements are based on bureaucratic management activities, which are extraordinarily complex and involve many issues and indicators. The VSS lacks supplements that evaluate and validate the results reported by the companies as sustainable. Finally, the VSS is still far from ensuring an inclusive and fully sustainable chain by itself.
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Satellite-based land use monitoring and farm-level traceability offer opportunities for targeted zero-deforestation interventions on private lands. Brazil's Rural Environmental Registry (Cadastro Ambiental Rural, or "CAR"), a land cadaster based on self-declaration of property boundaries, was created to monitor compliance with national forest laws. It has become an important enabling measure for sustainable supply chain initiatives like the Amazon Soy Moratorium. However, CAR enrollment is increasingly used to bolster illegal land claims, putting it at the heart of land grabbing dynamics. Self-declaration of properties in the CAR offers a unique situation to study land conflicts and their impact on land use decisions on a large scale. We quantified competing land claims among 846,420 registrations in the Brazilian Legal Amazon and applied a series of generalized linear mixed-effects models. We determined that CAR overlaps are more prevalent on larger registrations, in more densely settled areas, and in areas with less secure land tenure. We tested how landholders respond to land conflicts, finding significantly more deforestation and declared legal forest reserve on lands with multiple claims. CAR overlap results in an overestimation of forest reserves by up to 9.7 million hectares when considering double-counted and deforested areas of reserves, highlighting an overlooked form of Forest Code noncompliance. While the CAR continues to be used as evidence of land tenure, we conclude that the formalization of land claims through self-declarations is inadequate to decrease conflicts. CAR overlap information provides objective evidence of land conflict that authorities can leverage with field inspection to ensure peaceful occupation before issuing land titles.
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Conservação dos Recursos Naturais , Brasil , Florestas , Humanos , Agricultura , Sistema de Registros , População Rural , Monitoramento Ambiental/métodosRESUMO
Different resources, such as environmental enrichment, are being evaluated in order to minimize animal stress and promote better conditions during the life cycle of animals, as consumers are increasingly concerned about animal welfare issues. Lairage represents an important stage in the swine production chain and is directly related to animal welfare. The aim of this study was to evaluate the effect of lairage time in the slaughterhouse and environmental enrichment on the level of skin lesions and behavioral responses in pigs. A total of 648 finishing pigs of both sexes were assessed before and after lairage at the slaughterhouse with a five-point scale (0 = none, to 4 = ≥16 superficial lesions or >10 deep lesions). After lairage (after slaughter), lesions were also classified according to their source (mounting, fighting, and handling). Pigs were distributed into two treatments groups during lairage: with environmental enrichment (EE) on the pen, with hanging metal chains, and with no enrichment (NE). Behavior was monitored during the first four hours of lairage. Proportional odds, mixed linear model for longitudinal data, and non-parametric Wilcoxon signed rank tests were used to analyze the relation between treatments, skin lesions, and behavior. The simple metal chains did not affect skin lesion score or pigs' behavior (p > 0.05), whereas lairage duration influenced standing (SA), sitting (S), lying (L), idleness (I), and drinking water (D) (p < 0.001). The main source of skin lesions was handling, which did not differ between treatments (EE and NE) (p > 0.05). It was observed that the severity of the lesions (highest scores of 3, 4, and 5) increased in the different anatomical regions of the pigs when compared before and after slaughter, with the exception of the frontal area, which was the same (p = 0.7547). Lairage time has a proportional relation with skin lesions, and hanging chains at the slaughterhouse pens was not enough to reduce the number of lesions and to change pig behavior.
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Enhancing the initial stages of plant growth by using polymeric gels for seed priming presents a significant challenge. This study aimed to investigate a microgel derived from polyetheramine-poly(propylene oxide) (PPO) and a bisepoxide (referred to as micro-PPO) as a promising alternative to optimize the seed germination process. The micro-PPO integrated with an iron micronutrient showed a positive impact on seed germination compared with control (Fe solutions) in which the root length yield improved up to 39%. Therefore, the element map by synchrotron-based X-ray fluorescence shows that the Fe intensities in the seed primers with the micro-PPO-Fe gel are about 3-fold higher than those in the control group, leading to a gradual distribution of Fe species through most internal embryo tissues. The use of micro-PPO for seed priming underscores their potential for industrial applications due to the nontoxicity results in zebrafish assays and environmentally friendly synthesis of the water-dispersible monomers employed.
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Aminas , Cucumis sativus , Germinação , Ferro , Microgéis , Sementes , Germinação/efeitos dos fármacos , Sementes/química , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Cucumis sativus/metabolismo , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/química , Ferro/metabolismo , Ferro/química , Aminas/química , Aminas/metabolismo , Microgéis/química , Compostos de Epóxi/química , Compostos de Epóxi/metabolismo , Peixe-Zebra/metabolismo , AnimaisRESUMO
BACKGROUND: Anti-desmoglein (Dsg)1 is produced in pemphigus foliaceus (PF), affecting exclusively the skin. Pemphigus vulgaris (PV) shows the production of anti-Dsg3 in the mucosal form, and anti-Dsg1 and 3 in the mucocutaneous form. Anti-Dsg3 autoantibodies have been rarely reported in PF. OBJECTIVES: To determine the factors associated with the production and pathogenicity of anti-Dsg3 in PF. METHODS: Comparative analytical study of three patients groups: 16 PF-anti-Dsg3+, and 42 PF-anti-Dsg3(-) and 22 PV treatment-naïve cases. Serum was used in the anti-Dsg1 and 3 ELISA, and in immunoblotting (IB) with human epidermis extract. The expression of Dsg1 and 3 in paraffin sections was analyzed by immunohistochemistry (IHC). HLA-DRB1 alleles were compiled from a database. RESULTS: In the PF-anti-Dsg3+ group: age range similar to that of the PV group (pâ¯>â¯0.9999); predominance of the generalized form of PF (pâ¯=â¯0.002); anti-Dsg3 titers lower than those of PV (pâ¯<â¯0.0001); IB confirmed Dsg3 identification in one (8.33%) of 12 patients; IHC showed exclusive cytoplasmic internalization of Dsg1; HLA-DRB1 alleles of susceptibility to PF, with the absence of alleles associated with PV, in the five typed patients. STUDY LIMITATIONS: Most of the patients in the PF-anti-Dsg3+ group were undergoing treatment. CONCLUSION: The presence of anti-Dsg3 antibodies in PF was related to older age (comparable to that of PV) and the generalized form of PF. The non-pathogenicity of anti-Dsg3 antibodies in PF can be attributed to the low serum anti-Dsg3 titers, the lack of Dsg3 internalization as detected by IHC, and the absence of PV-associated HLA-DRB1 alleles.
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Autoanticorpos , Desmogleína 1 , Desmogleína 3 , Imuno-Histoquímica , Pênfigo , Humanos , Pênfigo/imunologia , Desmogleína 3/imunologia , Autoanticorpos/imunologia , Autoanticorpos/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Desmogleína 1/imunologia , Ensaio de Imunoadsorção Enzimática , Adulto Jovem , Immunoblotting , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Idoso de 80 Anos ou mais , AdolescenteRESUMO
Information theory explains how systems encode and transmit information. This article examines the neuronal system, which processes information via neurons that react to stimuli and transmit electrical signals. Specifically, we focus on transfer entropy to measure the flow of information between sequences and explore its use in determining effective neuronal connectivity. We analyze the causal relationships between two discrete time series, X:=Xt:t∈Z and Y:=Yt:t∈Z, which take values in binary alphabets. When the bivariate process (X,Y) is a jointly stationary ergodic variable-length Markov chain with memory no larger than k, we demonstrate that the null hypothesis of the test-no causal influence-requires a zero transfer entropy rate. The plug-in estimator for this function is identified with the test statistic of the log-likelihood ratios. Since under the null hypothesis, this estimator follows an asymptotic chi-squared distribution, it facilitates the calculation of p-values when applied to empirical data. The efficacy of the hypothesis test is illustrated with data simulated from a neuronal network model, characterized by stochastic neurons with variable-length memory. The test results identify biologically relevant information, validating the underlying theory and highlighting the applicability of the method in understanding effective connectivity between neurons.
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Argentina has a relevant international role as a producer of agricultural commodities. Buenos Aires is the province with the largest cultivated area of cereals and oilseeds of the country. Rainfed crops depend exclusively on green water, meaning a comparative advantage for Buenos Aires province. The green virtual water content in the crops produced in Buenos Aires has implications for water allocation at international level. A great amount of countries depends on the Argentinean rainfed agriculture. Therefore, it is important to understand the effects of climate variations on Argentinean crop production at local level and the role of rainfed crops in regional and international trade. We analysed the temporal and territorial variations of crops green water demand in a climatic variability context and their influence on the water footprint. The green water footprint of the main crops of Buenos Aires was assessed, including soybeans, maize, sunflower, wheat and barley, in different climatic conditions: for the period 2008-2018, which include a dry year, a humid year and an ordinary year. A dataset about the green water footprint at municipality level was provided, and the results were presented on maps for each crop and for the different climatic conditions. The relevance of green water of main crops in the world water-dependent supply chains was shown. This comprehensive green water footprint assessment provides a useful database for researchers, companies and policy makers in Argentina and beyond.
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Agricultura , Produtos Agrícolas , Argentina , Mudança Climática , Clima , Abastecimento de Água/estatística & dados numéricos , ChuvaRESUMO
Abstract Background Oligoclonal bands (OCBs) and Kappa free light chains (FLCs) in the cerebrospinal fluid (CSF) are sensitive markers of intrathecal immunoglobulin (Ig)G synthesis in patients with multiple sclerosis. Objective To evaluate the concordance rate between OCBCs and the Kappa index (KI) in patients with suspected multiple sclerosis (MS). Methods Patients with suspected MS were referred to a specialized CSF laboratory as part of their diagnostic investigation. Paired CSF and serum samples were collected and submitted to detection of OCBs and determination of the KI. Positive and negative results were determined with both methods, and the percentage of agreement between them was established. Results In total, 171 serum and CSF samples from 171 patients were included in the analysis. The mean age of the patients was of 40 ± 14.2 years; 18.9% of them were male, and 81.1% were female. The OCBs and KI presented concordant results in 161 (94.2%) samples: in 74 (43.3%), both were positive, and in 87 (50.9%), both were negative. In 10 cases, the results were discrepant: KI positive/OCB negative in 8 and OCB positive/KI negative in 2 cases. Conclusion The KI and OCBs presented high concordance level. Currently, the detection of OCBs in the CSF is the standard method for MS diagnosis, but it is time-consuming, and its visual interpretation can be difficult. The results suggest that the KI is a good alternative for the detection of intrathecal immunoproduction in cases of suspected MS.
Resumo Antecedentes Bandas oligoclonais (BOCs) e cadeias leves de imunoglobulina (free light chains, FLCs, em inglês) Kappa no líquido cefalorraquidiano (LCR) são marcadores sensíveis da síntese intratecal de imunoglobulina (Ig)G em pacientes com esclerose múltipla (EM). Objetivo Avaliar a taxa de concordância entre BOCs e o índice Kappa (IK) em pacientes com suspeita de EM. Métodos Pacientes com suspeita de EM foram encaminhados a um laboratório especializado em LCR como parte de sua investigação diagnóstica. Amostras pareadas de LCR e soro foram coletadas e investigadas quanto à presença de BOCs e submetidas à determinação do IK. Resultados positivos e negativos foram determinados com ambos os métodos, e estabeleceu-se o percentual de concordância entre eles. Resultados Ao todo, 171 amostras de soro e LCR de 171 pacientes foram incluídas na análise. A média de idade dos pacientes foi de 40 ± 14,2 anos; 18,9% deles eram do sexo masculino, e 81,1%, do sexo feminino. Resultados concordantes entre as BOCs e o IK foram observados em 161 (94,2%) amostras: em 74 (43,3%), ambos foram positivos, e em 87 (50,9%), ambos foram negativos. Em 10 casos, os resultados foram discrepantes: IK positivo/BOC negativo em 8, e BOC positivo/IK negativo em 2. Conclusão Observou-se alto nível de concordância entre o IK e as BOCs. A detecção de BOCs no LCR é atualmente o método padrão para o diagnóstico de EM, mas é demorado, e sua interpretação visual pode ser difícil. Os resultados sugerem que o IK pode ser uma alternativa para a detecção de imunoprodução intratecal em casos de suspeita de EM.
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Resumo O Projeto ArticulaFito realizou um amplo diagnóstico da base produtiva de espécies vegetais com valor medicinal, cosmético e alimentar, mapeando 26 cadeias de valor (CdV) de povos e comunidades tradicionais e de agricultores familiares (PCTAFs). O objetivo é definir critérios para priorização de ações de fortalecimento das CdV mapeadas, tendo como referência os desafios e oportunidades identificados. As metodologias de análise envoltória de dados e diagrama de Pareto foram aplicadas em dados quantitativos extraídos de cada mapa de CdV. Dessa forma, o conjunto de CdV foi dividido em quatro grupos de níveis de desempenho. Para cada grupo foi traçado um diagrama de ação que ordenou as ocorrências e suas origens, permitindo relacionar e indicar, em ordem de prioridade, as instituições e os atores a serem considerados no processo de fortalecimento. O grupo com o melhor desempenho apresentou dez espécies, sendo 70% no segmento cosmético, no bioma Amazônia e na região norte, 80% nativas sob regime de extrativismo e 20% exóticas sob regime de cultivo. O diagrama de ação gerado priorizou as ações e os investimentos, otimizando os recursos públicos aplicados para a inclusão produtiva dos PCTAFs por meio do uso sustentável da sociobiodiversidade.
Abstract The ArticulaFito Project conducted a broad analysis of the production base of plants with medicinal, cosmetic, and food value, mapping 26 value chains (CdV) of traditional peoples and communities and family farmers (PCTAFs). The objective is to define criteria to prioritize actions in order to strengthen the mapped CdV, maintaining the identified challenges and opportunities as a reference. Data Envelopment Analysis and Pareto Diagram methodologies were applied to quantitative data extracted from each CdV map. In this way, the CdV set was divided into four groups of performance levels. For each group, an action diagram was drawn, which, ordered the occurrences and their origins, enabling the reporting and indication, in order of priority, of the institutions and actors to be considered in the strengthening process. The group with the best performance had ten species, 70% in the cosmetic segment, in the Amazon biome, and in the northern region, with 80% native under an extractive regime and 20% exotic under a cultivation regime. The Action Diagram generated prioritized actions and investments, optimizing public resources in the productive inclusion of PCTAFs for the sustainable use of (socio) biodiversity.
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Resumo: Este estudo objetivou analisar as condições operacionais para conservação de imunobiológicos no Brasil. Trata-se de um estudo de método misto com delineamento explanatório sequencial, desenvolvido nas salas de vacinação de distintas regiões brasileiras entre 2021 e 2022. Na etapa quantitativa, desenvolveu-se um estudo transversal descritivo, com a aplicação da Escala de Avaliação da Conservação de Imunobiológicos aos profissionais de enfermagem. Os dados foram analisados por meio de estatística descritiva. Já na etapa qualitativa, desenvolveu-se um estudo descritivo-exploratório nas instâncias da cadeia de frio, com os respectivos responsáveis técnicos e profissionais de enfermagem. Analisou-se as entrevistas por meio da Análise de Conteúdo na Modalidade Temática. Os dados foram combinados mediante conexão, com elaboração de joint-displays e metainferências. Foram analisadas 280 salas, em que grande parte: era de uso exclusivo (79,6%); utilizava caixas de poliuretano (77,8%); e mantinha seus equipamentos distantes da incidência de luz solar/fontes de calor (73,5%). Apenas 27,5% dispunham de baterias/geradores e 26,5% de outros instrumentos de medição de temperatura. Sessenta por cento detinham câmaras refrigeradas e 67,6% ambientes climatizados. Revelaram-se fragilidades associadas a condições geográficas, infraestrutura, insumos materiais, recursos humanos e financeiros, organização e gestão do trabalho, rotatividade e capacitação. Os achados possibilitaram conhecer a pluralidade da cadeia de frio brasileira e permitiram a identificação de potencialidades e fragilidades na conservação de imunobiológicos relacionadas às estruturas e aos processos de trabalho que requerem aprimoramento.
Abstract: This study aimed to analyze the operational conditions to preserve immunobiological products in Brazil. This mixed-method study with a sequential explanatory design was developed in vaccination rooms in several Brazilian regions from 2021 to 2022. Its quantitative stage developed a descriptive cross-sectional study by applying the Immunobiological Conservation Assessment Scale to nursing professionals. Data were analyzed by descriptive statistics. Its qualitative stage developed a descriptive-exploratory study in cold chain instances with the respective technical managers and nursing professionals. The interviews were evaluated by thematic content analysis. The data were combined by connection, and joint-displays and meta-inferences were elaborated. Overall, 280 rooms were analyzed. Most were for exclusive use (79.6%), had polyurethane boxes (77.8%), and kept their equipment away from sunlight/heat (73.5%). Only 27.5% had batteries/generators and 26.5% had other temperature measuring instruments. In total, 60% had refrigerated rooms and 67.6%, air-conditioned rooms. This study found weaknesses associated with geographical conditions, infrastructure, material inputs, human and financial resources, work organization and management, turnover, and training. These findings showed the plurality of the Brazilian cold chain and identified the potentialities and weaknesses related to the structures and work processes in preserving immunobiological products, which require improvement.
Resumen: Este estudio tuvo como objetivo analizar las condiciones operativas para la conservación de inmunobiológicos en Brasil. Estudio de método mixto con diseño explicativo secuencial, desarrollado en las salas de vacunación de las distintas regiones brasileñas, entre 2021 y 2022. En la etapa cuantitativa se desarrolló un estudio transversal descriptivo, con la aplicación de la Escala de Evaluación de la Conservación de Inmunobiológicos a los profesionales de enfermería. Los datos fueron analizados mediante estadística descriptiva. En la etapa cualitativa se desarrolló un estudio descriptivo-exploratorio en las instancias de la cadena de frío, con los respectivos responsables técnicos y profesionales de enfermería. Las entrevistas se analizaron por medio del Análisis de Contenido en la Modalidad Temática. Los datos fueron combinados mediante conexión, con elaboración de joint-displays y metainferencias. Se analizaron 280 salas. Gran parte era de uso exclusivo (79,6%); utilizaba cajas de poliuretano (77,8%) y mantenía sus equipos alejados de la incidencia de la luz solar/fuentes de calor (73,5%). Solo el 27,5% disponía de baterías/generadores y el 26,5% de otros instrumentos de medición de temperatura. El 60% tenía cámaras refrigeradas y el 67,6% ambientes climatizados. Se revelaron debilidades asociadas a las condiciones geográficas, la infraestructura, los insumos de materiales, los recursos humanos y financieros, la organización y gestión del trabajo, la rotación y la capacitación. Los hallazgos posibilitaron conocer la pluralidad de la cadena de frío brasileña y permitieron la identificación de potencialidades y debilidades de la conservación de inmunobiológicos relacionadas con las estructuras y los procesos de trabajo que requieren mejoras.
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We derive asymptotic formulae in the limit when population size N tends to infinity for mean fixation times (conditional and unconditional) in a population with two types of individuals, A and B, governed by the Moran process. We consider only the case in which the fitness of the two types do not depend on the population frequencies. Our results start with the important cases in which the initial condition is a single individual of any type, but we also consider the initial condition of a fraction [Formula: see text] of A individuals, where x is kept fixed and the total population size tends to infinity. In the cases covered by Antal and Scheuring (Bull Math Biol 68(8):1923-1944, 2006), i.e. conditional fixation times for a single individual of any type, it will turn out that our formulae are much more accurate than the ones they found. As quoted, our results include other situations not treated by them. An interesting and counterintuitive consequence of our results on mean conditional fixation times is the following. Suppose that a population consists initially of fitter individuals at fraction x and less fit individuals at a fraction [Formula: see text]. If population size N is large enough, then in the average the fixation of the less fit individuals is faster (provided it occurs) than fixation of the fitter individuals, even if x is close to 1, i.e. fitter individuals are the majority.
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Frequência do Gene , Humanos , Densidade DemográficaRESUMO
La amiloidosis AL es una enfermedad debida al depósito, en órganos y tejidos, de fibrillas formadas por cadenas livianas producidas de forma patológica por plasmocitos clonales. Su tratamiento actualmente está orientado a erradicar el clon de células plasmáticas; este históricamente se extrapoló de tratamientos disponibles y estudiados para otras discrasias sanguíneas. En el año 2020, el Grupo de Estudio de Amiloidosis (GEA) confeccionó distintas guías de práctica clínica para el tratamiento de la amiloidosis AL. Desde entonces se han publicado ensayos clínicos que arrojan contundencia al conocimiento disponible hasta el momento, y están en desarrollo nuevas líneas de investigación que robustecen y estimulan el estudio en el área. En esta revisión se realiza una actualización de las guías existentes en lo que respecta al tratamiento de la amiloidosis por cadenas livianas.Como evidencia de relevancia, en el último año estuvieron disponibles resultados de ensayos clínicos que respaldan el uso de esquemas basados en daratumumab (un anticuerpo monoclonal anti-CD38+) para pacientes con diagnóstico reciente de amiloidosis AL como primera línea. Además, para el tratamiento de la amiloidosis AL refractaria o recaída, la disponibilidad de bibliografía respaldatoria es escasa y extrapolada del tratamiento del mieloma múltiple; sin embargo, actualmente existe evidencia de calidad para recomendar el uso de ixazomib, un inhibidor de proteosoma reversible por vía oral disponible en la Argentina desde 2020. Por último, se mencionan algunas líneas de investigación con otros anticuerpos monoclonales y terapéuticas basadas en el uso de CAR-T cells. (AU)
AL amyloidosis is a disease caused by the deposit in different organs and tissues of protein fibrils formed by light chains synthetized by pathological clonal plasma cells. Its treatment is currently aimed at eradicating this plasma cell clone and it has been historically extrapolated from available and validated treatments for other blood dyscrasias. In 2020, the Amyloidosis Study Group prepared different clinical practice guidelines for the treatment of AL amyloidosis.Since then, clinical trials have been published that confirm and strengthen the knowledge available up to now, and new lines of research are being developed that stimulate study in the area. In this review, an update of the existing guidelines regarding the treatment of AL amyloidosis is made. As relevant evidence, in the last year, results of clinical trials have been made available that support the use of regimens based on Daratumumab (an anti-CD38+ monoclonal antibody) for patients with newly diagnosed AL amyloidosis as first line therapy. In addition, for the treatment of refractory or relapsed AL amyloidosis, where the availability of supporting literature is scant and extrapolated from the treatment of multiple myeloma, there is currently quality evidence to recommend the use of ixazomib, an oral reversible proteasome inhibitor, only available in Argentina since 2020. Finally, some research lines exploring the efficacy of other monoclonal antibodies and therapeutic experiments based on the use of CAR-T cells are mentioned. (AU)
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Humanos , Antígeno de Maturação de Linfócitos B/uso terapêutico , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Recidiva , Guias de Prática Clínica como Assunto , Transplante de Células-Tronco HematopoéticasRESUMO
Objetivo: Desenvolver uma análise de custo-utilidade da implementação do teste farmacogenético como uma ferramenta adicional para orientar a escolha do melhor tratamento medicamentoso para indivíduos com depressão. Métodos: Para a realização desta análise, criou-se um modelo analítico de decisão baseado em um modelo de Markov. A avaliação foi realizada sob a perspectiva do Sistema de Saúde Suplementar brasileiro, com horizonte temporal de 10 anos, incluindo custos médicos diretos e custos da tecnologia utilizada, além de ter como comparador o tratamento empírico tradicional para a depressão. As probabilidades de transição foram obtidas por meio de análise da literatura disponível. Também foram realizadas análises de sensibilidade probabilística e univariada. Adicionalmente, foi realizada uma avaliação sob a perspectiva da sociedade, incluindo os custos de tratamento medicamentoso realizados pelos pacientes. Resultados: De acordo com a análise realizada, o emprego do teste farmacogenético como guia do tratamento para depressão mostrou-se favorável, proporcionando economia de -R$ 3.439,97 por paciente e aumento de 0,39 QALY ao longo do horizonte temporal. Assim, evidencia-se uma economia significativa a favor do teste farmacogenético, correspondendo a -R$ 8.776,78 por QALY salvo. Além disso, a robustez do modelo foi comprovada por meio das análises de sensibilidade. No cenário sob perspectiva da sociedade, o resultado foi ainda mais favorável, proporcionando economia de -R$ 9.381,49 por paciente e aumento de 0,39 QALY, correspondendo a -R$ 23.936,05 por QALY salvo. Conclusão: Os resultados encontrados neste estudo demonstraram que o uso de testes farmacogenéticos no tratamento da depressão é economicamente vantajoso, com aumento no valor de QALY e redução nos custos médicos diretos, em comparação ao tratamento empírico tradicional. Essa descoberta alinha-se à tendência atual de personalização no cuidado da saúde mental, sugerindo implicações práticas na reavaliação de protocolos, com potencial incorporação dos testes farmacogenéticos como padrão de cuidado.
Objective: To evaluate the cost-utility of pharmacogenetic testing incorporation as an additional tool in guiding the selection of optimal drug treatments for individuals with depression. Methods: A decision analytical model was created based on the Markov model for this analysis. The evaluation was conducted from the perspective of the Brazilian Supplementary Health System, with a time horizon of 10 years. The study included direct medical and technology costs and a comparison with traditional empirical treatment for depression was performed. Transition probabilities were derived from an analysis of available literature. Probabilistic and univariate sensitivity analyses were also carried out. Additionally, an evaluation was conducted from the perspective of Society, including the costs of drug treatment carried out by patients. Results: The application of pharmacogenetic testing as a guide for depression treatment demonstrated favorable outcomes, yielding savings of -R$ 3,439.97 per patient and an increase of 0.39 QALY over the specified time frame. Thus, significant savings were evident, corresponding to -R$ 8,776.78 per QALY saved. The sensitivity analyses confirmed the model's robustness. In the Society's perspective scenario, the outcome was even more favorable, resulting in savings of -R$ 9,381.49 per patient and a 0.39 increase in QALYs, equivalent to -R$ 23,936.05 per QALY saved. Conclusion: The study findings reveal that incorporating harmacogenetic tests in depression treatment offers economic benefits, evidenced by an increase in QALY value and a decrease in direct medical costs compared to conventional empirical treatment. This aligns with the ongoing trend towards personalized mental health care, implying practical considerations for protocol reassessment and the possible integration of pharmacogenetic tests as a standard of care.
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Cadeias de Markov , Análise Custo-Benefício , Testes Farmacogenômicos , Análise de Custo-EfetividadeRESUMO
The objective of this study was to apply simulation and genetic algorithms for the economic and environmental optimization of the reverse network (manufacturers, waste managers, and recyclers in Sao Paulo, Brazil) of waste from electrical and electronic equipment (WEEE) to promote the circular economy. For the economic evaluation, the reduction in fuel, drivers, insurance, depreciation, maintenance, and charges was considered. For the environmental evaluation, the impact of abiotic, biotic, water, land, air, and greenhouse gases was measured. It was concluded that the optimized structure of the WEEE reverse chains for Sao Paulo, Brazil provided a reduction in the number of collections, thus making the most of cubage. It also generated economic and environmental gains, contributing to the strategic actions of the circular economy. Therefore, the proposed approach is replicable in organizational practice, which is mainly required to meet the 2030 agenda of reducing the carbon footprint generated by transport in large cities. Thus, this study can guide companies in structuring the reverse WEEE chains in Sao Paulo, Brazil, and other states and countries for economic and environmental optimization, which is an aspect of great relevance considering the exponential generation of WEEE.
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BACKGROUND: Microvasculature dysfunction is a common finding in pathologic remodeling of the heart and is thought to play an important role in the pathogenesis of hypertrophic cardiomyopathy (HCM), a disease caused by sarcomere gene mutations. We hypothesized that microvascular dysfunction in HCM was secondary to abnormal microvascular growth and could occur independent of ventricular hypertrophy. METHODS: We used multimodality imaging methods to track the temporality of microvascular dysfunction in HCM mouse models harboring mutations in the sarcomere genes Mybpc3 (cardiac myosin binding protein C3) or Myh6 (myosin heavy chain 6). We performed complementary molecular methods to assess protein quantity, interactions, and post-translational modifications to identify mechanisms regulating this response. We manipulated select molecular pathways in vivo using both genetic and pharmacological methods to validate these mechanisms. RESULTS: We found that microvascular dysfunction in our HCM models occurred secondary to reduced myocardial capillary growth during the early postnatal time period and could occur before the onset of myocardial hypertrophy. We discovered that the E3 ubiquitin protein ligase MDM2 (murine double minute 2) dynamically regulates the protein stability of both HIF1α (hypoxia-inducible factor 1 alpha) and HIF2α (hypoxia-inducible factor 2 alpha)/EPAS1 (endothelial PAS domain protein 1) through canonical and noncanonical mechanisms. The resulting HIF imbalance leads to reduced proangiogenic gene expression during a key period of myocardial capillary growth. Reducing MDM2 protein levels by genetic or pharmacological methods normalized HIF protein levels and prevented the development of microvascular dysfunction in both HCM models. CONCLUSIONS: Our results show that sarcomere mutations induce cardiomyocyte MDM2 signaling during the earliest stages of disease, and this leads to long-term changes in the myocardial microenvironment.
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Cardiomiopatia Hipertrófica , Proteínas Proto-Oncogênicas c-mdm2 , Camundongos , Animais , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Sarcômeros/metabolismo , Mutação , Hipertrofia , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismoRESUMO
In Honduras, as in many settings between 2020 and 2022, food security was affected by the COVID-19 pandemic, climate change, and conflicts-what some refer to as "The Three Cs." These challenges have had overlapping impacts on food supply chains, food assistance programs, food prices, household purchasing power, physical access to food, and food acceptability. This article applies a food system disruption analysis-adapted from a fault tree analysis originally developed for a municipal context in the United States-to the context of Honduras to systematically examine how the Three Cs affected food availability, accessibility, and acceptability. This article demonstrates the value of approaching food security through a disruption analysis, especially for settings impacted by multiple, interconnected, ongoing crises.
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Productive and behavioral responses of finishing pigs with and without access to environmental enrichment (EE) were evaluated. A total of 432 pigs, male and female, Hampshire line, initial and final weight of 22-27 kg and 110-125 kg, respectively, were studied for 112 days. The study design was in random blocks, with 6 treatments, distributed in a factorial scheme 2 × 3 (sex × treatment) and 12 repetitions/treatment, totalling 72 pens. The animals were weighed and distributed in 3 blocks-light (20.3 to 24.8 kg), medium weight (24.8 to 27.7 kg), and heavy (27.7 to 33.8 kg). The treatments were as follows: branched chains for males (T1); branched sisal ropes for males (T2), males without EE (T3); branched chains for females (T4); branched sisal ropes for females (T5) and females without EA (T6). There was no effect (P > 0.05) of interaction (enrichment × sex) and sex on performance. Daily consumption and daily weight gain were lower (P < 0.05) in the chain group compared to the sisal rope and control groups. Feed conversion was similar (P > 0.05) between treatments under study. There was no interaction between gender and enrichment for behavioral responses (P = 0.8986). However, there was an environmental enrichment (P = 0.0017; P < 0.001) and gender (P = 0.0251; P < 0.001) effect in relation to the animals' behavior in the morning and in the afternoon, respectively. Calmer animals, regardless of sex, were observed for groups without enrichment (control) and morning and afternoon periods. The animals interacted with the types of enrichment under study, given the higher probabilities of interaction with the object for males and females in the morning and afternoon shifts. It was observed, regardless of the shifts, that the control treatment for males and females was different when compared to the other enrichments for males and females. In general, the pigs' behaviors were expressed more in the afternoon when compared to the morning. It was observed that the animal interaction and aggression (afternoon shift) behaviors are more related to the control group, while object interaction is more related to the enriched treatments. The use of sisal ropes and branched chains guarantees the performance and behavior of pigs in the finishing phase, but we recommend the use of branched chains, as this enrichment increased the profitability of the farmer by reducing feed consumption, maintaining feed conversion and animal welfare, besides being a more durable material than sisal rope.
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Comportamento Animal , Aumento de Peso , Suínos , Animais , Feminino , Masculino , Agressão , Bem-Estar do Animal , Ração Animal/análiseRESUMO
Resumen La amiloidosis primaria o de cadenas livianas (AL) es la forma más común de amiloidosis y se caracteriza por presentar una población clonal de células plasmáticas que producen una cadena ligera monoclonal de tipo lambda o kappa. En algunos sujetos, dicha cadena se deposita en forma de amiloide en los órganos y tejidos, dando lugar a manifestaciones clínicas, como proteinuria o síndrome nefrótico, miocardiopatía restrictiva y hepatomegalia. Aunque se considera una enfermedad rara, datos recientes sugieren que la amiloidosis cardíaca se subestima como una causa de enfermedades o síndromes cardíacos comunes. En la amiloidosis AL, tanto la respuesta hematológica como la de los órganos después del tratamiento son importantes para mejorar el resultado clínico, especialmente, si mejora la función cardíaca que es uno de los aspectos clave en el pronóstico de la amiloidosis AL. Se presenta el caso y la revisión de un paciente de sexo femenino, de 67 años de edad, que en la pesquisa diagnóstica de anemia e insuficiencia cardiaca (IC) se concluye en el diagnóstico de mieloma múltiple y amiloidosis cardiaca (AC) por depósito de cadenas livianas.
Abstract Primary or light chain (AL) amyloidosis is the most common form of amyloidosis and is characterized by a clonal population of plasma cells that produce a monoclonal lambda or kappa-type light chain, which in some subjects this chain is deposited as amyloid in the organs and tissues, giving rise to clinical manifestations such as proteinuria or nephrotic syndrome, restrictive cardiomyopathy and hepatomegaly. Although considered a rare disease, recent data suggest cardiac amyloidosis is underestimated as cause of common heart diseases or syndromes. In AL amyloidosis, both the hematologic and organ response after treatment, are important to improve clinical outcome. Especially if it improves cardiac function is one of the key aspects in the prognosis of AL amyloidosis. We present the case and review of a 67-year-old female patient, who in the investigation diagnoses anemia and heart failure concludes in the diagnosis of multiple myeloma and cardiac amyloidosis due to light chain deposition.
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The COVID-19 pandemic has brought negative impacts to global supply chains, in particular to the agricultural sector. Although these companies have been developing programs to mitigate the impacts caused by COVID-19, researchers have been worried about a possible weakening of the adoption of sustainable initiatives due to a focus on dealing with the consequences of the pandemic. Grounded on the Resource Orchestration Theory, the goal of this study was to assess the effects of the COVID-19 outbreak on sustainable (environmental, social, and economic) performance in the context of agri-food supply chains. To do so, a questionnaire survey was used to collect data from 349 different medium and large agri-food companies in Brazil. Data were analyzed using Structural Equation Modeling-Partial Least Squares technique. This study has found out that, under the impacts arising from COVID-19 pandemic (1) supply management and transportation and logistics management had a positive impact on food supply chains' sustainable performance; (2) the effects of relationship management and supply chain wide impact management were found to be negative on sustainable performance; and (3) the effects of demand and production management on sustainable performance were not considered significant. We propose a framework that clearly represents the relationship between the disrupted supply chain areas and sustainable performance through the development of orchestration capabilities. By knowing which kinds of impacts produce the most significant effects on sustainable performance, policy makers and managers will be able to make decisions and take actions to avoid negative effects and to improve firms' sustainable performance.
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The global value chain (GVC) literature has recognized the regional linkages of global production sharing while overlooking some regions across the globe. This gap may leave unanswered the question of how South American countries' regional trade linkages have changed amid the acceleration of globalization. This study, thus, investigates the regional linkages of global production sharing of South America by relying on value-added trade measures. Additionally, we develop a pioneering value-added hubness measure to illustrate the degree of relative market dependence between countries. The findings suggest that intra-regional forward linkages in South America have increased over time, but there are signs of a re-orientation towards Asia. China's influence extended beyond Asia, and together with the United States, China became an important hub-nation for South America. Brazil appears as a potential regional hub, mainly through its domestic market and not domestic production. Therefore, the study adds to GVC literature with insights about a missing region, reveals signs of changes in the interconnections between regional blocs, and enriches the research on the hub-and-spoke trade systems.