Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2).

The mechanistic target of rapamycin (mTOR) exists in two complexes that regulate diverse cellular processes. mTOR complex 1 (mTORC1), the canonical target of rapamycin, has been well studied, whereas the physiological role of mTORC2 remains relatively uncharacterized. In mice in which the mTORC2 component Rictor is deleted in liver [Rictor-knockout (RKO) mice], we used genomic and phosphoproteomic analyses to characterize the role of hepatic mTORC2 in vivo. Overnight food withdrawal followed by refeeding was used to activate mTOR signaling. Rapamycin was administered before refeeding to specify mTORC2-mediated events. Hepatic mTORC2 regulated a complex gene expression and post-translational network that affects intermediary metabolism, ribosomal biogenesis, and proteasomal biogenesis. Nearly all changes in genes related to intermediary metabolic regulation were replicated in cultured fetal hepatocytes, indicating a cell-autonomous effect of mTORC2 signaling. Phosphoproteomic profiling identified mTORC2-related signaling to 144 proteins, among which were metabolic enzymes and regulators. A reduction of p38 MAPK signaling in the RKO mice represents a link between our phosphoproteomic and gene expression results. We conclude that hepatic mTORC2 exerts a broad spectrum of biological effects under physiological conditions. Our findings provide a context for the development of targeted therapies to modulate mTORC2 signaling.

COVID-19 vaccine hesitancy in Latin America and Africa: a scoping review. / Hesitação vacinal contra a COVID-19 na América Latina e África: uma revisão de escopo.

Vaccination has played an important role in the containment of COVID-19 pandemic advances. However, SARS-CoV-2 vaccine hesitancy has caused a global concern. This scoping review aims to map the scientific literature on COVID-19 vaccine hesitancy in Latin America and Africa from a Global Health perspective, observing the particularities of the Global South and using parameters validated by the World Health Organization (WHO). The review reporting observes the recommendations of the PRISMA for Scoping Reviews (PRISMA-ScR) model. Search was conducted in PubMed, Scopus, Web of Science, and Virtual Health Library (VHL) databases, selecting studies published from January 1, 2020 to January 22, 2022. Selected studies indicate that COVID-19 vaccine hesitancy involves factors such as political scenario, spread of misinformation, regional differences in each territory regarding Internet access, lack of access to information, history of vaccination resistance, lack of information about the disease and the vaccine, concern about adverse events, and vaccine efficacy and safety. Regarding the use of conceptual and methodology references from the WHO for vaccine hesitancy, few studies (6/94) use research instruments based on these references. Then, the replication in Global South of conceptual and methodological parameters developed by experts from the Global North contexts has been criticized from the perspective of Global Health because of it may not consider political and sociocultural particularities, the different nuances of vaccine hesitancy, and issues of access to vaccines.

A vacinação tem papel relevante para conter os avanços da pandemia de COVID-19. No entanto, a hesitação vacinal com os imunizantes que agem contra o SARS-CoV-2 tem causado preocupação em âmbito global. Esta revisão de escopo tem como objetivo mapear a literatura científica sobre a hesitação vacinal contra a COVID-19 na América Latina e África sob uma perspectiva da Saúde Global, observando as particularidades do Sul Global e o uso de parâmetros validados pela Organização Mundial da Saúde (OMS). O relato da revisão segue as recomendações do protocolo PRISMA para Revisões de Escopo (PRISMA-ScR). O levantamento foi realizado nas bases de dados PubMed, Scopus, Web of Science e Biblioteca Virtual em Saúde (BVS), selecionando estudos publicados entre 1º de janeiro de 2020 e 22 de janeiro de 2022, os quais indicam que a hesitação vacinal contra a COVID-19 envolve fatores como o cenário político, a disseminação de desinformação, diferenças regionais referentes ao acesso à Internet, falta de acesso à informação, o histórico de resistência à vacinação, falta de informações sobre a doença e a vacina, preocupação com eventos adversos, eficácia e segurança dos imunizantes. Quanto ao uso dos referenciais conceituais e metodológicos da OMS sobre hesitação vacinal, poucos estudos (apenas 6 de 94) utilizam instrumentos de pesquisa baseado neles. Desta forma, a replicação de parâmetros conceituais e metodológicos elaborados por expertises do Norte Global em contextos do Sul Global tem sido criticada pela perspectiva da Saúde Global, em decorrência da possibilidade de não considerar as especificidades políticas e socioculturais, as diferentes nuances de hesitação vacinal e questões de acesso às vacinas.

La vacunación tiene un papel relevante para frenar los avances de la pandemia de COVID-19. Sin embargo, la indecisión a las vacunas contra el SARS-CoV-2 ha causado preocupación a nivel global. Esta revisión de alcance tiene como objetivo mapear la literatura científica sobre la indecisión a las vacunas contra COVID-19 en América Latina y África desde una perspectiva de la Salud Global, observando las particularidades del Sur Global y el uso de parámetros validados por la Organización Mundial de la Salud (OMS). El informe de la revisión sigue las recomendaciones del protocolo PRISMA para Revisiones de Alcance (PRISMA-ScR). La encuesta se realizó en las bases de datos PubMed, Scopus, Web of Science e Biblioteca Virtual en Salud (BVS), seleccionando los estudios publicados entre 1º de enero de 2020 y 22 de enero de 2022. Los estudios seleccionados indican que la indecisión a las vacunas de COVID-19 involucra factores como el escenario político, la diseminación de desinformación, las diferencias regionales de cada territorio referente al acceso a Internet, la falta de acceso a la información, el historial de resistencia a la vacunación, la falta de informaciones sobre la enfermedad y la vacuna, la preocupación por los eventos adversos, la eficacia y la seguridad de los inmunizantes. En cuanto al uso de los referenciales conceptuales y metodológicos de la Organización Mundial de la Salud (OMS) sobre la indecisión a las vacunas, pocos estudios (6/94) utilizan instrumentos de investigación basados en esos referenciales. Así, la replicación de parámetros conceptuales y metodológicos elaborados por expertos del Norte Global en contextos del Sur Global ha sido criticada por la perspectiva de la Salud Global, por la posibilidad de no considerar las especificidades políticas y socioculturales, los diferentes matices de la indecisión a las vacunas y cuestiones de acceso a las vacunas.

Software Package for Transcranial Magnetic Stimulation Coil and Coil Array Analysis and Design.

Objective: This study aims to describe a MATLAB software package for transcranial magnetic stimulation (TMS) coil analysis and design. Approach: Electric and magnetic fields of the coils as well as their self- and mutual (for coil arrays) inductances are computed, with or without a magnetic core. Solid and stranded (Litz wire) conductors are also taken into consideration. The starting point is the centerline of a coil conductor(s), which is a 3D curve defined by the user. Then, a wire mesh and a computer aided design (CAD) mesh for the volume conductor of a given cross-section (circular, elliptical, or rectangular) are automatically generated. Self- and mutual inductances of the coil(s) are computed. Given the conductor current and its time derivative, electric and magnetic fields of the coil(s) are determined anywhere in space.Computations are performed with the fast multipole method (FMM), which is the most efficient way to evaluate the fields of many elementary current elements (current dipoles) comprising the current carrying conductor at a large number of observation points. This is the major underlying mathematical operation behind both inductance and field calculations. Main Results: The wire-based approach enables precise replication of even the most complex physical conductor geometries, while the FMM acceleration quickly evaluates large quantities of elementary current filaments. Agreement to within 0.74% was obtained between the inductances computed by the FMM method and ANSYS Maxwell 3D for the same coil model. Although not provided in this study, it is possible to evaluate non-linear magnetic cores in addition to the linear core exemplified. An experimental comparison was carried out against a physical MagVenture C-B60 coil; the measured and simulated inductances differed by only 1.25%, and nearly perfect correlation was found between the measured and computed E-field values at each observation point. Significance: The developed software package is applicable to any quasistatic inductor design, not necessarily to the TMS coils only.

Caudal and middle segmental mandibulectomies for the treatment of unilateral temporomandibular joint ankylosis in cats.

Case series summary: Three cats affected by unilateral temporomandibular joint ankylosis underwent segmental mandibulectomy, while one cat with bilateral ankylosis underwent right temporomandibular joint gap arthroplasty and left segmental mandibulectomy. Minimal intraoperative complications were linked to the segmental mandibulectomies in the cases reported. All cats recovered their ability to open the mouth, and the vertical range of motion was unaltered during the postoperative period. Mandibular drift and dental malocclusion were the main postoperative complications related to the segmental mandibulectomies. Relevance and novel information: Surgical excision of ankylotic tissue at the temporomandibular joint region may be technically challenging and associated with severe iatrogenic trauma of surrounding tissues. The results of this case series suggest that middle or caudal segmental mandibulectomy is a safe, feasible and effective surgical procedure to treat unilateral temporomandibular ankylosis in cats and could be considered as an alternative surgical technique to surgical excision of ankylotic tissue at the temporomandibular joint.

Direct detection of a magnetic field in the innermost regions of an accretion disk.

Models predict that magnetic fields play a crucial role in the physics of astrophysical accretion disks and their associated winds and jets. For example, the rotation of the disk twists around the rotation axis the initially vertical magnetic field, which responds by slowing down the plasma in the disk and by causing it to fall towards the central star. The magnetic energy flux produced in this process points away from the disk, pushing the surface plasma outwards, leading to a wind from the disk and sometimes a collimated jet. But these predictions have hitherto not been supported by observations. Here we report the direct detection of the magnetic field in the core of the protostellar accretion disk FU Orionis. The surface field reaches strengths of about 1 kG close to the centre of the disk, and it includes a significant azimuthal component, in good agreement with recent models. But we find that the field is very filamentary and slows down the disk plasma much more than models predict, which may explain why FU Ori fails to collimate its wind into a jet.

Hesitação vacinal contra a COVID-19 na América Latina e África: uma revisão de escopo / La indecisión a las vacunas contra COVID-19 en América Latina y África: una revisión de alcance / COVID-19 vaccine hesitancy in Latin America and Africa: a scoping review

Resumo: A vacinação tem papel relevante para conter os avanços da pandemia de COVID-19. No entanto, a hesitação vacinal com os imunizantes que agem contra o SARS-CoV-2 tem causado preocupação em âmbito global. Esta revisão de escopo tem como objetivo mapear a literatura científica sobre a hesitação vacinal contra a COVID-19 na América Latina e África sob uma perspectiva da Saúde Global, observando as particularidades do Sul Global e o uso de parâmetros validados pela Organização Mundial da Saúde (OMS). O relato da revisão segue as recomendações do protocolo PRISMA para Revisões de Escopo (PRISMA-ScR). O levantamento foi realizado nas bases de dados PubMed, Scopus, Web of Science e Biblioteca Virtual em Saúde (BVS), selecionando estudos publicados entre 1º de janeiro de 2020 e 22 de janeiro de 2022, os quais indicam que a hesitação vacinal contra a COVID-19 envolve fatores como o cenário político, a disseminação de desinformação, diferenças regionais referentes ao acesso à Internet, falta de acesso à informação, o histórico de resistência à vacinação, falta de informações sobre a doença e a vacina, preocupação com eventos adversos, eficácia e segurança dos imunizantes. Quanto ao uso dos referenciais conceituais e metodológicos da OMS sobre hesitação vacinal, poucos estudos (apenas 6 de 94) utilizam instrumentos de pesquisa baseado neles. Desta forma, a replicação de parâmetros conceituais e metodológicos elaborados por expertises do Norte Global em contextos do Sul Global tem sido criticada pela perspectiva da Saúde Global, em decorrência da possibilidade de não considerar as especificidades políticas e socioculturais, as diferentes nuances de hesitação vacinal e questões de acesso às vacinas.

Resumen: La vacunación tiene un papel relevante para frenar los avances de la pandemia de COVID-19. Sin embargo, la indecisión a las vacunas contra el SARS-CoV-2 ha causado preocupación a nivel global. Esta revisión de alcance tiene como objetivo mapear la literatura científica sobre la indecisión a las vacunas contra COVID-19 en América Latina y África desde una perspectiva de la Salud Global, observando las particularidades del Sur Global y el uso de parámetros validados por la Organización Mundial de la Salud (OMS). El informe de la revisión sigue las recomendaciones del protocolo PRISMA para Revisiones de Alcance (PRISMA-ScR). La encuesta se realizó en las bases de datos PubMed, Scopus, Web of Science e Biblioteca Virtual en Salud (BVS), seleccionando los estudios publicados entre 1º de enero de 2020 y 22 de enero de 2022. Los estudios seleccionados indican que la indecisión a las vacunas de COVID-19 involucra factores como el escenario político, la diseminación de desinformación, las diferencias regionales de cada territorio referente al acceso a Internet, la falta de acceso a la información, el historial de resistencia a la vacunación, la falta de informaciones sobre la enfermedad y la vacuna, la preocupación por los eventos adversos, la eficacia y la seguridad de los inmunizantes. En cuanto al uso de los referenciales conceptuales y metodológicos de la Organización Mundial de la Salud (OMS) sobre la indecisión a las vacunas, pocos estudios (6/94) utilizan instrumentos de investigación basados en esos referenciales. Así, la replicación de parámetros conceptuales y metodológicos elaborados por expertos del Norte Global en contextos del Sur Global ha sido criticada por la perspectiva de la Salud Global, por la posibilidad de no considerar las especificidades políticas y socioculturales, los diferentes matices de la indecisión a las vacunas y cuestiones de acceso a las vacunas.

Abstract: Vaccination has played an important role in the containment of COVID-19 pandemic advances. However, SARS-CoV-2 vaccine hesitancy has caused a global concern. This scoping review aims to map the scientific literature on COVID-19 vaccine hesitancy in Latin America and Africa from a Global Health perspective, observing the particularities of the Global South and using parameters validated by the World Health Organization (WHO). The review reporting observes the recommendations of the PRISMA for Scoping Reviews (PRISMA-ScR) model. Search was conducted in PubMed, Scopus, Web of Science, and Virtual Health Library (VHL) databases, selecting studies published from January 1, 2020 to January 22, 2022. Selected studies indicate that COVID-19 vaccine hesitancy involves factors such as political scenario, spread of misinformation, regional differences in each territory regarding Internet access, lack of access to information, history of vaccination resistance, lack of information about the disease and the vaccine, concern about adverse events, and vaccine efficacy and safety. Regarding the use of conceptual and methodology references from the WHO for vaccine hesitancy, few studies (6/94) use research instruments based on these references. Then, the replication in Global South of conceptual and methodological parameters developed by experts from the Global North contexts has been criticized from the perspective of Global Health because of it may not consider political and sociocultural particularities, the different nuances of vaccine hesitancy, and issues of access to vaccines.

Comparative study between the effects of photodynamic therapy and conventional therapy on microbial reduction in ligature-induced peri-implantitis in dogs.

BACKGROUND: Progressive peri-implant bone losses, which are accompanied by inflammatory lesions in the soft tissues, are referred to as peri-implantitis. The aim of this study was to compare the effects of photodynamic therapy (PDT) and conventional technique on microbial reduction in ligature-induced peri-implantitis in dogs. METHODS: Eighteen third premolars from nine Labrador retriever dogs were extracted and the implants were submerged. After osseointegration, peri-implantitis was induced. After 4 months, ligature was removed and natural bacterial plaque was allowed to form for another 4 months. The animals were then randomly divided into two groups. In the conventional group, they were treated using mucoperiosteal flaps for scaling the implant surface and chlorexidine (conventional) irrigation. In the PDT group, only mucoperiosteal scaling was carried out before photodynamic therapy. Inside the peri-implant pocket, a paste-based azulene photosensitizer was placed and then a GaAlAs low-power laser (lambda=660 nm, P=40 mW, E=7.2 J for 3 minutes) was used. Microbiological samples were obtained before and immediately after treatment. Before treatment, one implant was removed and analyzed by scanning electron microscopy to validate the contamination. RESULTS: The results of this study showed that Prevotella sp., Fusobacterium sp., and S. Beta-haemolyticus were significantly reduced for both groups. After treatment, no significant differences were observed between the groups. CONCLUSION: These findings suggest that photodynamic therapy is a non-invasive method that could be used to reduce microorganisms in peri-implantitis.

Transcriptional response to dietary restriction in Drosophila melanogaster.

Dietary restriction (DR) extends lifespan in a wide variety of organisms. Although several genes and pathways associated with this longevity response have been identified, the specific mechanism through which DR extends lifespan is not fully understood. We have recently developed a novel methodology to screen for transcriptional changes in response to acutely imposed DR upon adult Drosophila melanogaster and identified groups of genes that switch their transcriptional patterns from a normal diet pattern to a restricted diet pattern, or 'switching genes'. In this current report we extend our transcriptional data analysis with gene set enrichment analysis to generate a pathway-centered perspective. The pattern of temporal behavior in response to the diet switch is strikingly similar within and across pathways associated with mRNA processing and protein translation. Furthermore, most genes within these pathways display an initial spike in activity within 6-8h from the diet switch, followed by a coordinated, partial down-regulation after 24h. We propose this represents a stereotypical response to DR, which ultimately leads to a mild but widespread inhibition of transcriptional and translational activity. Inhibition of the protein synthesis pathway has been observed in DR in other studies and has been shown to extend lifespan in several model organisms.

Avaliação da resposta inflamatória periapical em dentes de cães obturados com diferentes cimentos resinosos e técnicas obturadoras / Evaluation of periapical inflamation response from coronal leakage in dog´s teeth obturated using different resin-based sealers and different obturation techniques

Introdução: Este estudo avalia as respostas inflamatórias periapicais resultantes da infiltração coronária em dentes de cães obturados com diferentes cimentos resinosos (AH Plus®, RealSeal® e RealSeal SE®) e técnicas obturadoras (condensação lateral e termoplástica). Método: Para tanto, pré-molares de 5 cães tiveram o tratamento endodôntico realizado e foram obturados de acordo com os grupos experimentais: GI- AHPlus/ condensação lateral, GII-AHPlus/termoplástificação, GIII-RealSeal/condensação lateral, GIV-RealSeal/termoplástificação, GV-RealSeal SE/condensação lateral, GVI-RealSeal SE/ termoplástificação, Grupo controle positivo e Grupo-controle negativo. As cavidades coronárias ficaram então expostas ao meio bucal por um período de 75 dias e, passado esse período experimental, os cães foram eutanasiados, e se realizou a remoção cirúrgica dos dentes e periápices, a fixação e a desmineralização. Posteriormente, realizou-se a rotina histológica, digitalização e analise em relação à existência de patologia periapical com auxílio do teste de Kruskal-Wallis. Resultados: Observou-se que, em relação às técnicas, a termoplastificação por ondas contínuas de condensação associada à técnica de injeção mostrou melhores condições periapicais quando comparada à técnica de condensação lateral (p=0.0055), sendo que a utilização dessa técnica resultou em reações inflamatórias mais intensas para o cimento RealSeal SE (p=0.002). Em relação aos cimentos avaliados, o RealSeal SE mostrou-se menos eficaz em evitar a percolação, produzindo maiores níveis de inflamação crônica independentemente do sistema de obturação (p=0.0088). Conclusão: o sistema termoplástico proporcionou melhores respostas inflamatórias e o cimento RealSeal comportou-se igualmente ao cimento AH Plus.

Introduction: This study aims to evaluate the periapical inflammatory responses resulting from coronary infiltration in dog?s teeth obturated using different resin sealers (AH Plus, RealSeal and RealSeal SE) and different obturation techniques (lateral condensation and thermoplastic). Method: For this study, premolars, from five dogs had endodontic treatment and were obturated according to their experimental groups as follows: GI-AHPlus/lateral condensation, GII-AH Plus/thermoplastic, GIII-RealSeal/lateral condensation, GIV-RealSeal/thermoplastic, GV-RealSeal SE/lateral condensation, GVI-RealSeal SE/ thermoplastic, a positive control group and a negative control group. The coronal access was left exposed to the oral environment for a period of 75 days, and after this experimental period, the dogs were euthanized, teeth and periapical tissue were removed, fixed and demineralized. The histological routine was made and each cut was digitalized and compared using the Kruskal-Wallis test. Results: thermoplastification by continuous wave of condensation associated with the injection technique showed better periapical conditions than what was seen for the lateral condensation technique (p=0.0055). On the other hand, for the sealers evaluated, the condensation technique resulted in more intense inflammatory reactions when the sealer RealSeal SE was used (p=0.002). In relation to the sealers evaluated, RealSeal SE was seen to be less effective against percolation, thus producing greater levels of chronic inflammation irrespective of the obturation system employed (p=0.0088). Warm vertical condensation showed better sealing properties, and AH Plus behave as Real Seal sealer.

The effect of timing temporary cements to treat induced pulp necrosis in the teeth of dogs

During endodontic therapy (pulpectomy, root canal debridement and root canal filling) microbiological management is a major concern. Bacteria present in dentine tubules, apical foramina and apical delta are causally related to failure of the procedure. Studies have shown that during single session endodontic treatment bacteria remain within dental structures. The aim of the present study was to evaluate endodontic treatment performed as two sessions, using temporary endodontic dressing materials for different periods in four groups of experimental dogs. A total of 80 roots of second and third upper premolar teeth and second, third and fourth lower premolar teeth were divided into four groups. The pulp chamber was opened with burrs and the pulp exposed for 60 days to induce pulpal inflammation and necrosis. Groups II, III and IV were treated with calcium hydroxide plus camphorated paramono-chlorophenol (PMCC) for 7, 15 and 30 days, respectively. In all groups, the root canals were filled with zinc oxide-eugenol and gutta-percha cones. Clinical and radiographical measurements were performed every 2 weeks. After 60 days a small block section containing the teeth, surrounding periapical tissues and the periodontium was removed for histological and microbiological study. Histological analysis revealed intense inflammatory response in all groups. Microbiological analysis showed microbial reduction inversely proportional to the period of time that the intracanal temporary medicament was left in place.

Em um tratamento endodôntico, a microbiota é o ponto primordial a ser levado em consideração, pois as bactérias presentes nos túbulos dentinários, nas foraminas e no delta apical em cães estão relacionadas aos insucessos do procedimento. Estudos revelam que tratamentos realizados em uma única sessão ainda permitem a permanência de bactérias nas estruturas dentárias, portanto propõe-se a execução em duas sessões, com diferentes tempos de "curativo de demora", para verificação da eficácia do protocolo em cães. Foram utilizados no total quatro cães, num total de 80 raízes, provenientes dos 2os e 3os pré-molares superiores e 2os, 3os e 4os pré-molares inferiores, divididas em quatro grupos de estudo. Nestes foi realizada abertura coronária, onde a polpa ficou exposta por 60 dias. Os Grupos II, III e IV foram tratados. O hidróxido de cálcio com p-monoclorofenol canforado, isto é, a pasta Calen/PMCC (S.S. White Artigos Dentários Ltda, RJ), foi utilizada como "curativo de demora". O Grupo II permaneceu com "curativo de demora" por sete dias, o Grupo III permaneceu por 15 dias e o Grupo IV por 30 dias, todos os grupos foram obturados com cimento à base de óxido de zinco e eugenol - Herodent (Vigodent S.A. Indústria e Comércio, SP) e guta-percha. Todos os grupos tiveram controle clínico e radiográfico quinzenal e após 60 dias os dentes foram extraídos em bloco (dente e periodonto) e passaram por processamento laboratorial para realização das análises histopatológica e histomicrobiológica. A análise histopatológica de forma geral mostrou intensa reação inflamatória em todos os grupos estudados, já na análise histomicrobiológica pode-se observar uma diminuição no número de microrganismos proporcional ao tempo de "curativo de demora" deixado intra-canal, portanto a permanência do "curativo" por 30 dias foi a mais eficaz.