Joint actions of diverse transcription factor families establish neuron-type identities and promote enhancer selectivity.

To systematically investigate the complexity of neuron specification regulatory networks, we performed an RNA interference (RNAi) screen against all 875 transcription factors (TFs) encoded in Caenorhabditis elegans genome and searched for defects in nine different neuron types of the monoaminergic (MA) superclass and two cholinergic motoneurons. We identified 91 TF candidates to be required for correct generation of these neuron types, of which 28 were confirmed by mutant analysis. We found that correct reporter expression in each individual neuron type requires at least nine different TFs. Individual neuron types do not usually share TFs involved in their specification but share a common pattern of TFs belonging to the five most common TF families: homeodomain (HD), basic helix loop helix (bHLH), zinc finger (ZF), basic leucine zipper domain (bZIP), and nuclear hormone receptors (NHR). HD TF members are overrepresented, supporting a key role for this family in the establishment of neuronal identities. These five TF families are also prevalent when considering mutant alleles with previously reported neuronal phenotypes in C. elegans, Drosophila, and mouse. In addition, we studied terminal differentiation complexity focusing on the dopaminergic terminal regulatory program. We found two HD TFs (UNC-62 and VAB-3) that work together with known dopaminergic terminal selectors (AST-1, CEH-43, CEH-20). Combined TF binding sites for these five TFs constitute a cis-regulatory signature enriched in the regulatory regions of dopaminergic effector genes. Our results provide new insights on neuron-type regulatory programs in C. elegans that could help better understand neuron specification and evolution of neuron types.

Transcriptional regulation of neuronal identity.

Neuronal diversity is an intrinsic feature of the nervous system. Transcription factors (TFs) are key regulators in the establishment of different neuronal identities; how are the actions of different TFs coordinated to orchestrate this diversity? Are there common features shared among the different neuron types of an organism or even among different animal groups? In this review, we provide a brief overview on common traits emerging on the transcriptional regulation of neuron type diversification with a special focus on the comparison between mouse and Caenorhabditis elegans model systems. In the first part, we describe general concepts on neuronal identity and transcriptional regulation of gene expression. In the second part of the review, TFs are classified in different categories according to their key roles at specific steps along the protracted process of neuronal specification and differentiation. The same TF categories can be identified both in mammals and nematodes. Importantly, TFs are very pleiotropic: Depending on the neuron type or the time in development, the same TF can fulfil functions belonging to different categories. Finally, we describe the key role of transcriptional repression at all steps controlling neuronal diversity and propose that acquisition of neuronal identities could be considered a metastable process.

Thinking out of the box: revisiting health surveillance based on medical records.

Despite the considerable advances in the last years, the health information systems for health surveillance still need to overcome some critical issues so that epidemic detection can be performed in real time. For instance, despite the efforts of the Brazilian Ministry of Health (MoH) to make COVID-19 data available during the pandemic, delays due to data entry and data availability posed an additional threat to disease monitoring. Here, we propose a complementary approach by using electronic medical records (EMRs) data collected in real time to generate a system to enable insights from the local health surveillance system personnel. As a proof of concept, we assessed data from São Caetano do Sul City (SCS), São Paulo, Brazil. We used the "fever" term as a sentinel event. Regular expression techniques were applied to detect febrile diseases. Other specific terms such as "malaria," "dengue," "Zika," or any infectious disease were included in the dictionary and mapped to "fever." Additionally, after "tokenizing," we assessed the frequencies of most mentioned terms when fever was also mentioned in the patient complaint. The findings allowed us to detect the overlapping outbreaks of both COVID-19 Omicron BA.1 subvariant and Influenza A virus, which were confirmed by our team by analyzing data from private laboratories and another COVID-19 public monitoring system. Timely information generated from EMRs will be a very important tool to the decision-making process as well as research in epidemiology. Quality and security on the data produced is of paramount importance to allow the use by health surveillance systems.

The influence of ultrasonic activation on the setting time and flow of four endodontic sealers / A influência da ativação ultrassônica no tempo de ajuste e no fluxo de quatro vedadores endodônticos / La influencia de la activación ultrasónica en el tiempo de ajuste y flujo de cuatro selladores endodónticos

The aim of the present study was to evaluate the influence of ultrasonic activation (UA) on the setting time and flow of four endodontic sealers: AH Plus (AH), Sealer Plus (SP), MTA Fillapex (MTAF), and BioRoot RCS (BIO). Properties were evaluated as required by ANSI/ADA Specification N° 57 (2008); only the size of the specimens was modified. UA was applied using a smooth tapered ultrasonic tip coupled to a piezoelectric ultrasonic device (30% power) on the freshly mixed materials in two cycles of 20 seconds. The results were statistically analyzed using the ANOVA and Kruskal-Wallis tests, followed by the Tukey and Dunn posthoc tests, respectively, depending on the normality of the data. The shortest setting times, initial and final, were, 115 (BIO/UA) and 148.6 (BIO/UA) min, whereas the longest were 1215 (AH) and 1928 (AH) min. The MTAF sealer did not set throughout the experimental period (2880 minutes). Significant differences were observed between BIO and MTAF and the other sealers, with or without UA, both in the initial and final setting time (P < 0.05). UA did not change the initial setting times; however, it reduced the final setting of BIO (P < 0.05). The highest and lowest flow values observed were 25.52 mm (AH/UA) and 18.66 mm (BIO/UA), respectively. The AH sealer, regardless of UA, exhibited higher flow values compared to the other sealers (P < 0.05), except for the MTAF/UA group, which was the only sealer in which UA promoted a significant flow increase (P < 0.05). Under the conditions of the study, it can be concluded that the BIO, under UA, presented the lowest setting time; however, it exhibited the lowest flow values. The MTAF sealer did not reach its final setting. Moreover, the SP groups exhibited intermediate results in all analyses. In summary, only the final setting time of the BIO group and the flow values of the MTAF group were influenced by UA.

O objetivo do presente estudo foi avaliar a influência da ativação ultrassônica (UA) no tempo e fluxo de ajuste de quatro selantes endodônticos: AH Plus (AH), Sealer Plus (SP), MTA Fillapex (MTAF) e BioRoot RCS (BIO). As propriedades foram avaliadas conforme exigido pela Especificação N° 57 (2008) da ANSI/ADA; apenas o tamanho dos espécimes foi modificado. O UA foi aplicado usando uma ponta de ultrassom suave cônica acoplada a um dispositivo ultrassônico piezoelétrico (30% de potência) nos materiais recém-misturados em dois ciclos de 20 segundos. Os resultados foram analisados estatisticamente usando os testes ANOVA e Kruskal-Wallis, seguidos pelos testes póstticos de Tukey e Dunn, respectivamente, dependendo da normalidade dos dados. Os tempos de ajuste mais curtos, iniciais e finais, foram 115 (BIO/UA) e 148,6 (BIO/UA) min, enquanto os mais longos foram 1215 (AH) e 1928 (AH) min. O selador da MTAF não foi colocado durante todo o período experimental (2880 minutos). Foram observadas diferenças significativas entre o BIO e o MTAF e os demais seladores, com ou sem UA, tanto no tempo de ajuste inicial quanto final (P < 0,05). A UA não alterou os tempos de ajuste inicial; no entanto, reduziu o ajuste final da BIO (P < 0,05). Os valores de fluxo mais alto e mais baixo observados foram 25,52 mm (AH/UA) e 18,66 mm (BIO/UA), respectivamente. O selador AH, independentemente do UA, apresentou valores de fluxo mais elevados em comparação com os outros seladores (P < 0,05), exceto para o grupo MTAF/UA, que foi o único selador no qual o UA promoveu um aumento significativo do fluxo (P < 0,05). Nas condições do estudo, pode-se concluir que o BIO, sob UA, apresentou o menor tempo de ajuste; no entanto, exibiu os menores valores de fluxo. O selador MTAF não atingiu seu ajuste final. Além disso, os grupos de SP apresentaram resultados intermediários em todas as análises. Em resumo, apenas o tempo de ajuste final do grupo BIO e os valores de fluxo do grupo MTAF foram influenciados pelo UA.

El objetivo del presente estudio fue evaluar la influencia de la activación ultrasónica (AU) sobre el tiempo de ajuste y flujo de cuatro selladores endodónticos: AH Plus (AH), Sealer Plus (SP), MTA Fillapex (MTAF) y BioRoot RCS (BIO). Las propiedades se evaluaron según lo requerido por la especificación ANSI/ADA N° 57 (2008), sólo se modificó el tamaño de los ejemplares. El AU se aplicó utilizando una punta ultrasónica cónica lisa acoplada a un dispositivo piezoeléctrico ultrasónico (30% de potencia) sobre los materiales recién mezclados en dos ciclos de 20 segundos. Los resultados se analizaron estadísticamente mediante las pruebas ANOVA y Kruskal- Wallis, seguidas de las pruebas postcográficas de Tukey y Dunn, respectivamente, dependiendo de la normalidad de los datos. Los tiempos de fraguado más cortos, inicial y final, fueron 115 (BIO/UA) y 148,6 (BIO/UA) min, mientras que los más largos fueron 1215 (AH) y 1928 (AH) min. El sellador MTAF no se ajustó durante todo el período experimental (2880 minutos). Se observaron diferencias significativas entre BIO y MTAF y los demás selladores, con o sin AU, tanto en el tiempo de ajuste inicial como final (P < 0,05). La AU no modificó los tiempos de ajuste inicial, pero redujo el ajuste final de BIO (P < 0,05). Los valores más altos y más bajos de caudal observados fueron 25,52 mm (AH/UA) y 18,66 mm (BIO/UA), respectivamente. El sellador AH, independientemente del AU, presentó valores de caudal más altos en comparación con los demás selladores (P < 0,05), excepto para el grupo MTAF/AU, que fue el único sellador en el que el AU promovió un incremento significativo del caudal (P < 0,05). Bajo las condiciones del estudio, se puede concluir que el BIO, bajo AU, presentó el menor tiempo de fraguado, sin embargo, presentó los menores valores de caudal. El sellador MTAF no alcanzó su ajuste final. Por otra parte, los grupos SP presentaron resultados intermedios en todos los análisis. En resumen, solo el tiempo de ajuste final del grupo BIO y los valores de flujo del grupo MTAF fueron influenciados por el AU.

A arte da diferenciação do modo humano: Nise da Silveira: o elo perdido entre duas tradições / The art of differentiating the human way: Nise da Silveira: the missing link between two traditions / El arte de diferenciar el modo humano: Nise da Silveira: el eslabón perdido entre dos tradiciones

Neste artigo, elaboramos um diálogo entre a psicologia analítica de Carl Jung e a filosofia da imanência de Baruch Spinoza a partir das "Cartas a Spinoza" de Nise da Silveira. Principalmente através da análise das três primeiras cartas, propomo-nos uma visada ao pensamento da Dra. Nise focada na epistemologia das ciências da mente humana e na gênese dos conceitos da psicologia analítica, tais como o processo de individuação. Tais cartas constituem um verdadeiro exercício de imaginação ativa. ■

In this article, we elaborated a dialogue between the analytical psychology of Carl Jung and the immanence philosophy of Baruch Spinoza based on "Letters to Spinoza" of Nise da Silveira. Mainly through the analysis of the first three letters, we propose a view to the thinking of Dra. Nise focused on the epistemology of the sciences of the human mind and on the genesis of the concepts of analytical psychology, such as the individuation process. Such letters constitute a real exercise of active imagination. ■

En este artículo, elaboramos un diálogo entre la psicología analítica de Carl Jung y la filosofía de la inmanencia de Baruch Spinoza basada en las "Cartas a Spinoza" de Nise da Silveira. Principalmente a través del análisis de las tres primeras letras, proponemos una mirada al pensamiento de la Dra. Nise centrada en la epistemología de las ciencias de la mente humana y en la génesis de los conceptos de psicología analítica, como el proceso de individuación. Estas cartas son un verdadero ejercicio de imaginación activa. ■

Photodynamic therapy as an aiding in the endodontic treatment: case report / Terapia fotodinâmica em Endodontia: relato de caso

ABSTRACT This article describes the application of Photodynamic Therapy as an aid to the endodontic treatment performed on a permanent tooth iatrogenically perforated and with pulp necrosis. After clinical and radiographic examination, the coronary access, curettage of the drilling area and mechanized preparation with the Reciproc System were performed. The drilling area was sealed with Mineral Trioxide Aggregate after prior alkalinization and decontamination by a calcium hydroxide buffer. After successive intracanal medication changes, the remission of the fistula, a clinical sign of endodontic infection, was not observed. Photodynamic therapy was then performed to reduce bacterial load in the root canal system, which resulted in fistula suppression. Then, it was possible to end the treatment with the obturation of the ducts by the Tagger Hybrid thermomechanical technique. After a year of proservation, the tooth presents no symptomatology and it is concluded that the Photodynamic Therapy was an effective solution in this case.

RESUMO Neste artigo descreve-se a aplicação da Terapia Fotodinâmica (PDT) como coadjuvante ao tratamento endodôntico realizado em dente permanente perfurado iatrogenicamente e portador de necrose pulpar. Após exame clínico e radiográfico, realizou-se a abertura coronária, curetagem da área da perfuração e preparo mecanizado com o sistema Reciproc (VDW/Alemanha). A área da perfuração foi selada com agregado trióxido mineral (MTA) depois de prévia alcalinização e descontaminação por um tampão de hidróxido de cálcio (HC). Após sucessivas trocas de medicação intracanal (MI) a fístula, sinal clínico de infeção endodôntica, não desaparecia. A terapia fotodinâmica então foi executada para reduzir a carga bacteriana do sistema de canais radiculares (SCR), o que resultou na remissão da fístula, propiciando a finalização do tratamento, com a obturação dos condutos pela técnica termomecânica Híbrida de Tagger e sucesso clínico com 1 ano de proservação.

Revascularização pulpar em dentes permanentes imaturos sem vitalidade pulpar: uma revisão integrativa / Pulp revascularization in immature permanent teeth without pulp vitality: an integrative review

Introdução: Dentes permanentes imaturos que evoluem para necrose pulpar representam um desafio para tratamento endodôntico. A endodontia regenerativa e técnicas de revascularização pulpar surgem como um campo dinâmico e potencialmente ideal para terapia clínica em dentes com desenvolvimento radicular incompleto. Objetivo: Revisar a literatura sobre as técnicas de revascularização pulpar no tratamento de dentes com ausência de vitalidade pulpar com ápice radicular imaturo. Métodos: Os descritores "pulp revascularization", "pulp necrosis", "immature permanent tooth", "revascularization", "revitalization", "dental pulp", "regeneration" foram utilizados para obtenção de artigos em língua inglesa, que apresentassem conteúdo disponibilizado na íntegra e publicados nos últimos 15 anos. Foram excluídos os trabalhos de relatos de caso e/ou séries de casos. Conclusão: Artigos revisados apresentaram uma heterogeneidade de resultados quanto à efetividade da técnica de revascularização pulpar, visto que os critérios estabelecidos para determinação do sucesso variavam entre os autores. O material mais comumente utilizado na técnica empregada consiste no Agregado Trióxido Mineral (MTA) em consistência pastosa aplicada sobre coágulo sanguíneo com formação induzida no interior do canal. Foi observada escassez de estudos laboratoriais e clínicos sobre as técnicas e materiais em revascularização pulpar, que suportem sua indicação, o que representa uma lacuna em potencial na literatura e requer cautela na indicação desta técnica.

Introduction: Immature permanent teeth that evolve to pulp necrosis represent a challenge for endodontic treatment. Regenerative endodontics and pulp revascularization techniques appear as a dynamic and potentially ideal field for clinical therapy in teeth with incomplete root development. Objective: To review the literature on pulpal revascularization techniques in the treatment of teeth with absence of pulp vitality with immature root apex. Methods: The descriptors "pulp revascularization", "pulp necrosis", "immature permanent tooth", "revascularization", "revitalization", "dental pulp" and "regeneration" were used to obtain articles in English that presented content available in full and published in the last 15 years. Works of case reports and/or series of cases were excluded. Conclusion: Reviewed articles presented a heterogeneity of results regarding the effectiveness of the pulp revascularization technique, since the established criteria for determining success varied among the authors. The material most commonly used in the technique used consists of the Mineral Trioxide Aggregate (MTA) in paste consistency applied on blood clot with induced formation inside the canal. A shortage of laboratory and clinical studies on pulp revascularization techniques and materials that support its indication has been observed, which represents a potential gap in the literature and requires caution in the indication of this technique.