Clinical implications of T-Cells CX3CR1+, Toll-like Receptor 4 signaling pathway, and immune checkpoints in Non-Muscle Invasive Bladder Cancer

Background: This study characterized and compared the molecular profiles of CX3C chemokine receptor 1 (CX3CR1, a marker of T-cell differentiation), Toll-like receptor 4 (TLR4)-mediated interferon signaling pathway, and immune checkpoints in the different histological stages of non-muscle invasive bladder cancer (NMIBC), aiming the investigation of these biomarkers as a criterion of clinical response to immunotherapy. Methods: Seventy-five formalin-fixed paraffin-embedded samples of bladder were obtained from 34 to 96-year-old patients (mean 65 years) with NMIBC diagnosis in University of Campinas (UNICAMP) and Paulinia Municipal Hospital/ Brazil. Subsequently, the samples were divided into 3 groups (n= 25 samples per group): pTis group, high-grade pTa group, and pT1 group; and submitted to immunohistochemistry analysis: TLR4-mediated IFN-γ production signaling pathway (TRIF, TBK1, IRF-3, IFN-γ), CX3CR1+CD8+ T-cells, immune checkpoints (PD-1/PD-L1 and CTLA-4), and regulatory T (Treg) cells (FOXP3). The retrospective anonymous study was approved by the local ethics committee (Clinical Trial: RBR-6swqd2). Results: pTis group showed the lowest activation of TLR4-mediated IFN-γ signaling pathway when compared (p<0.01) to high-grade pTa and pT1 groups. Both the immunoreaction intensity and positive cells percentage were lower (p<0.01) for TLR4, TRIF, IRF-3, and IFN-γ in the pTis group with respect to other groups. No statistical difference was found between high-grade pTa and pT1 groups for these biomarkers. Likewise, CX3CR1 immunoreactivities were remarkably lower (p<0.01) in the pTis group in comparison with high-grade pTa and pT1 groups, which did not show statistical differences between them. Furthermore, immune checkpoints (PD-1/PD-L1 and CTLA4) and FOXP3+ Treg cells immunoreactivities were significantly higher (p<0.01) in the high-grade pTa and pT1 compared to the pTis group. Conclusions: Our data demonstrated that pTis stage was characterized by an immunosuppressive microenvironment in comparison with pTa and pT1 stages, showing decreased TLR4-mediated interferon signaling pathway and low activation of CX3CR1+CD8+ T-cells; which implies in low sensitivity to immunotherapy. The larger number of FOXP3+ Treg cells in pTa and pT1 was correlated with intensified immune checkpoints immunoreactivities, indicating higher sensitivity to immunotherapy. Finally, these biomarkers may be useful in the clinical management of patients with NMIBC

ESTRATÉGIA DE FIDELIZAÇÃO COMO PRÁTICA EMPRESARIAL PARA CONQUISTA DE CLIENTES

Nowadays, adopting loyalty programs through relationship marketing has become an important strategy for organizations. The purpose of the article is to analyze business strategies regarding the importance and use of customer loyalty programs. In this way, bibliographic sources were used, such as books and scientific articles. As a research method, data collect were made with managers from cities in the interior of Paraná through the application of 107 questionnaires, sent via Google Forms. Among the variables analyzed, the main findings point out that 91.2% agree that the company seeks to have a good relationship with its customers, a fact that corroborates that only 9.8% consider that the company lost customers that were previously loyal. About 78.4% affirm that the company is aware of the importance of customer loyalty, although 65.7% claim that they have loyalty strategies, and the use of social networks to win new customers is made by 64.7% of managers , an important fact due to the constant growth of communication technologies. On the other hand, 59.8% agree that the company has loyalty and relationship programs, and 40.2% agree that the company has effective control over who are the loyal customers. As for indicators with less agreement, only 33.3% mention that the company trains employees, and only 26.5% have a CRM system, an indispensable tool to streamline processes and help with customer management. As a result, this research made major contribution to greater knowledge about customer loyalty and how it can be important for positive results in organizations.Hoy en día, la adopción de programas de fidelización a través del marketing relacional se ha convertido en una estrategia importante para las organizaciones. El propósito del artículo es analizar las estrategias comerciales sobre la importancia y el uso de los programas de fidelización de clientes. De esta forma se utilizaron fuentes bibliográficas, como libros y artículos científicos. método de investigación, se realizaron recolecciones junto con los administradores municipales del interior de Paraná mediante la aplicación de 107 cuestionarios, enviados a través de Google Forms. Entre las variables analizadas, los principales hallazgos señalan que el 91,2% está de acuerdo en que la empresa busca tener una buena relación con sus clientes, hecho que corrobora que solo el 9,8% considera que la empresa perdió clientes que antes eran leales. Alrededor del 78,4% afirma que la empresa es consciente de la importancia de la fidelización de los clientes, aunque solo el 65,7% afirma tener estrategias de fidelización; El 64,7% de los directivos hace uso de las redes sociales para captar nuevos clientes, hecho importante debido al constante crecimiento de las tecnologías de la comunicación. Por otro lado, el 59,8% coincide en que la empresa cuenta con programas de fidelización y relación; y el 40,2% está de acuerdo en que la empresa tiene un control efectivo sobre quiénes son los clientes fieles. Como resultado, esta investigación ha hecho una contribución importante a un mayor conocimiento sobre la lealtad del cliente y cómo puede ser importante para obtener resultados positivos en las organizaciones.Em tempos atuais, adotar programas de fidelização mediante marketing de relacionamento tornou-se uma estratégia importante para as organizações. O objetivo do artigo é analisar as estratégias empresariais quanto à importância e o uso de programas de fidelização de clientes. Deste modo, foram utilizadas fontes de natureza bibliográfica, tais como livros e artigos científicos. Como método de pesquisa, foram realizadas coletas juntos aos gestores de cidades do interior do Paraná por meio da aplicação de 107 questionários, enviados via Google Forms. Entre as variáveis analisadas, os principais achados apontam que 91,2% concordam que a empresa procura ter um bom relacionamento com seus clientes, fato que corrobora que apenas 9,8% consideram que a empresa perdeu clientes que antes eram fiéis. Cerca de 78,4% afirmam que a empresa tem consciência da importância da fidelização de clientes, apesar de apenas 65,7% alegarem que possuem estratégias de fidelização; o uso das redes sociais é feito por 64,7% dos gestores para conquistar novos clientes, fato importante devido ao crescimento constante de tecnologias de comunicação. Por outro lado, 59,8% concordam que a empresa possui programas de fidelidade e relacionamento; e 40,2% concordam que a empresa possui controle efetivo de quais são os clientes fiéis. Já indicadores de menor concordância, somente 33,3% citam que a empresa treina funcionários; e apenas 26,5% tem sistema de CRM, ferramenta indispensável para agilizar processos e auxiliar na gestão de clientes. Como resultado, a pesquisa tem contribuição para conhecimento da fidelização de clientes e como pode ser importante para resultados positivos nas organizações.&nbsp

Acute Exposure to Two Biocides Causes Morphological and Molecular Changes in the Gill Ciliary Epithelium of the Invasive Golden Mussel Limnoperna fortunei (Dunker, 1857)

Limnoperna fortunei, the golden mussel, is a bivalve mollusk considered an invader in South America. This species is responsible for ecological and economic damages due to its voluminous fouling capability. Chemical biocides such as MXD-100™ and sodium dichloroisocyanurate (NaDCC) are often used to control L. fortunei infestations in hydraulic systems. Thus, we proposed to investigate the effects of different periods (24, 48 and 72 h) of exposure to MXD-100™ (0.56 mg L−1) and NaDCC (1.5 mg L−1) on the gills of L. fortunei through morphological and molecular analyses. NaDCC promoted progressive morphological changes during the analyzed periods and only an upregulation of SOD and HSP70 expression during the first 24 h of exposure. MXD-100™ led to severe morphological changes from the first period of exposure, in addition to an upregulation of SOD, CAT, HSP70 and CYP expression during the first 24 h. In contrast, MXD-100™ led to a downregulation of CAT transcription between 24 and 48 h. In static conditions, NaDCC causes lethal damage after 72 h of exposure, and that exposure needs to be continuous to achieve the control of the species. Meanwhile, the MXD-100™ treatment presented several effects during the first 24 h, showing acute toxicity in a shorter period of time

Turner syndrome, Hashimoto's thyroiditis and Crohn's disease in sisters: case report

A Síndrome de Turner é caracterizada citogeneticamente pela presença de um cromossomo X e perda total ou parcial do segundo cromossomo sexual, ocorrendo em aproximadamente 1:2.130 nascidos vivos do sexo feminino. A Tireoidite de Hashimoto é um distúrbio autoimune decorrente de resposta imune anormal à glândula tireoide, tanto do ponto de vista humoral como celular. A doença de Crohn é uma doença crônica recidivante que afeta todas as partes do tubo digestivo, sendo multifatorial, em que fatores de ordem genética, imunológica e ambientais têm uma relevância preponderante no início e na perpetuação da lesão tecidual imunomediada. O objetivo deste trabalho foi relatar o caso de três pacientes de uma mesma família. Caso 1, primeira gemelar (dizigótica), 8 anos de idade, sexo feminino, com diagnóstico de Tireoidite de Hashimoto. Caso 2 (segunda gemelar), sexo feminino, com o diagnóstico de Síndrome de Turner. Caso 3 (primogênita), sexo feminino, com diagnóstico de Doença de Crohn.  Duas filhas de um casal hígido manifestaram doenças autoimunes, as quais têm incidência aumentada na síndrome de Turner. Doenças endócrinas autoimunes possuem mecanismos complexos com a participação de vários fatores, como a susceptibilidade genética, eventos ambientais e resposta autoimune, porém, neste caso, não se encontrou história familiar positiva além da geração estudada. Outros estudos familiares, como este que se propõe, com múltiplos membros acometidos, poderão identificar associações cada vez mais consistentes entre essas doenças, além daquelas ainda não suspeitadas.   Palavras-chave: Síndrome de Turner, Tireoidite de Hashimoto, Doença de Crohn, Hereditariedade. ABSTRACT Turner syndrome is characterized cytogenetically by the presence of an X chromosome and total or partial loss of the second sex chromosome, occurring in approximately 1:2,130 live female births. Hashimoto's Thyroiditis is an autoimmune disorder resulting from an abnormal immune response to the thyroid gland, both from a humoral and cellular point of view. Crohn's disease is a chronic recurrent disease that affects all parts of the digestive tract, being multifactorial, in which genetic, immunological and environmental factors have a preponderant relevance at the beginning and the perpetuation of immune-mediated tissue injury. The objective of this study was to report the case of three patients from the same family. Case 1, first twin (dizygotic), 8 years old, female, with diagnosis of Hashimoto's Thyroiditis. Case 2 (second twin), female, with the diagnosis of Turner Syndrome. Case 3 (first-born), female, with diagnosis of Crohn's Disease. Two daughters of a healthy couple have manifested autoimmune diseases, which have an increased incidence in Turner syndrome. Autoimmune endocrine diseases have complex mechanisms with the participation of several factors, such as genetic susceptibility, environmental events and autoimmune response, but in this case, no positive family history was found beyond the generation studied. Other family studies, such as this one proposed, with multiple affected members, will be able to identify increasingly consistent associations between these diseases, in addition to those not yet suspected. Keywords: Turner syndrome, Hashimoto's thyroiditis, Crohn's disease, Heredity

Tetralogia de Fallot no Brasil: compreendendo a existência

Introduction: Tetralogy of Fallot involves four specific heart problems. Firstly, there is pulmonary stenosis, characterized by the narrowing of the pathway that carries blood from the heart to the lungs, hindering blood flow. Right ventricular hypertrophy is another characteristic, where the muscle of the right ventricle of the heart becomes thicker due to increased workload caused by pulmonary stenosis. Methodology: The present study adopted a descriptive epidemiological approach with the aim of analyzing cases of Tetralogy of Fallot among live births in Brazil from 2012 to 2021. Data collection utilized the Live Birth Information System (SINASC), made available by DATASUS. Results: In the group of individuals born with Tetralogy of Fallot, the analysis of variables reveals valuable information about demographic characteristics and perinatal conditions. Regarding the "Race/Ethnicity" variable, out of the 943 cases registered, 588 (62.35%) were classified as white, 51 (5.41%) as black, 10 (1.06%) as yellow, 267 (28.31%) as brown, and 27 (2.86%) had race/ethnicity recorded as unknown. Conclusion: A profound understanding of congenital heart diseases not only saves lives but also significantly improves the quality of life for affected individuals.Introdução: A Tetralogia de Fallot envolve quatro problemas cardíacos específicos. Em primeiro lugar, há a estenose pulmonar, caracterizada pelo estreitamento da via que conduz o sangue do coração para os pulmões, dificultando o fluxo sanguíneo. A hipertrofia ventricular direita é outra característica, onde o músculo do ventrículo direito do coração torna-se mais espesso devido ao aumento da carga de trabalho provocado pela estenose pulmonar. Metodologia: O presente estudo adotou uma abordagem epidemiológica descritiva com o objetivo de analisar os casos de Tetralogia de Fallot entre os nascidos vivos no Brasil no período de 2012 a 2021. Para a coleta de dados, utilizou-se o Sistema de Informações sobre Nascidos Vivos (SINASC), disponibilizado pelo DATASUS Resultado: No grupo de nascidos com Tetralogia de Fallot, a análise das variáveis revela informações valiosas sobre características demográficas e condições perinatais. Em relação à variável "Cor/Raça", dos 943 casos registrados, 588 (62,35%) eram classificados como brancos, 51 (5,41%) como pretos, 10 (1,06%) como amarelos, 267 (28,31%) como pardos, e 27 (2,86%) tiveram a cor/raça registrada como ignorada Conclusão: A compreensão profunda das cardiopatias congênitas não apenas salva vidas, mas também melhora significativamente a qualidade de vida dos indivíduos afetados

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio