Selenosugars targeting the infective stage of Trypanosoma brucei with high selectivity.

Earlier evidences showed that diglycosyl diselenides are active against the infective stage of African trypanosomes (top hits IC50 0.5 and 1.5 µM) but poorly selective (selectivity index <10). Here we extended the study to 33 new seleno-glycoconjugates with the aim to improve potency and selectivity. Three selenoglycosides and three glycosyl selenenylsulfides displayed IC50 against bloodstream Trypanosoma brucei in the sub-µM range (IC50 0.35-0.77 µM) and four of them showed an improved selectivity (selectivity index >38-folds vs. murine and human macrohages). For the glycosyl selenylsulfides, the anti-trypanosomal activity was not significantly influenced by the nature of the moiety attached to the sulfur atom. Except for a quinoline-, and to a minor extent a nitro-derivative, the most selective hits induced a rapid (within 60 min) and marked perturbation of the LMWT-redox homeostasis. The formation of selenenylsulfide glycoconjugates with free thiols has been identified as a potential mechanism involved in this process.

Orofacial Myofunctional Aspects of Nursing Infants and Preschoolers.

Introduction Clinical assessment in orofacial motricity is required for the speech therapist to diagnose and treat disorders involving the stomatognathic system. Validated tools can help establish a prognosis and outline intervention methods connected to human development. Objective The goal of the present study was to examine the domains of the oromyofunctional assessment of nursing infants and preschoolers according to sex and age group, as well as the application of the MMBGR Protocol - Nursing Infants and Preschool Children. Methods A quantitative technique was used to conduct an analytical and cross-sectional investigation. The present study included a total of 214 healthy breastfeeding infants and preschoolers of both sexes. The Mann-Whitney test was used to compare the medians. The Spearman correlation of each test domain was determined. R Core Team 2021 (R Foundation, Vienna, Austria) was used, and the significance threshold was set at 5%. Results In intraoral and extraoral examinations, there was a difference between sexes for tongue scores in nursing infants (d = - 0.428; p = 0.045), worse in males. When the orofacial functions were considered in nursing infants, there were differences between the sexes for the liquid/solid/semisolid deglutition scores (d = 0.479; p = 0.031), with females performing worse. There were sex differences in solid/semisolid deglutition (d = - 0.335; p = 0.043), and speech in preschoolers (d = - 0.478; p = 0.034), including the production of phones/phonemes (d = - 0.599; p = 0.007), which were always worse in males. Conclusion The research revealed sex disparities and related the domains of oromyofunctional assessment, according to scores, of the domains of myofunctional assessment, as recorded in a standardized oromyofunctional assessment protocol by age group.

Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro.

Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence. Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy -performed in a large and diverse chemolibrary- complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening. Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 µM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12-20 µM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7-45 µM). Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known "garbage in, garbage out" machine learning principle.

Murine colon organoids as a novel model to study Trypanosoma cruzi infection and interactions with the intestinal epithelium.

Chagas disease (CD) is a life-threatening illness caused by the parasite Trypanosoma cruzi (T. cruzi). With around seven million people infected worldwide and over 50,000 deaths per year, CD is a major public health issue in Latin America. The main route of transmission to humans is through a triatomine bug (vector-borne), but congenital and oral transmission have also been reported. The acute phase of CD presents mild symptoms but may develop into a long-lasting chronic illness, characterized by severely impaired cardiac, digestive, and neurological functions. The intestinal tissue appears to have a key role during oral transmission and chronic infection of CD. In this immune-privileged reservoir, dormant/quiescent parasites have been suggested to contribute to disease persistence, infection relapse, and treatment failure. However, the interaction between the intestinal epithelium and T. cruzi has not been examined in depth, in part, due to the lack of in vitro models that approximate to the biological and structural complexity of this tissue. Therefore, to understand the role played by the intestinal tissue during transmission and chronic infection, physiological models resembling the organ complexity are needed. Here we addressed this issue by establishing and characterizing adult stem cell-derived colonoid infection models that are clinically relevant for CD. 3D and 2D systems of murine intestinal organoids infected with T. cruzi Dm28c (a highly virulent strain associated with oral outbreaks) were analyzed at different time points by confocal microscopy. T. cruzi was able to invade and replicate in intestinal epithelial primary cells grown as intact organoids (3D) and monolayers (2D). The permissiveness to pathogen infection differed markedly between organoids and cell lines (primate and intestinal human cell lines). So far, this represents the first evidence of the potential that these cellular systems offer for the study of host-pathogen interactions and the discovery of effective anti-chagasic drugs.

Orofacial Myofunctional Aspects of Nursing Infants and Preschoolers

Abstract Introduction Clinical assessment in orofacial motricity is required for the speech therapist to diagnose and treat disorders involving the stomatognathic system. Validated tools can help establish a prognosis and outline intervention methods connected to human development. Objective The goal of the present study was to examine the domains of the oromyofunctional assessment of nursing infants and preschoolers according to sex and age group, as well as the application of the MMBGR Protocol - Nursing Infants and Preschool Children. Methods A quantitative technique was used to conduct an analytical and cross-sectional investigation. The present study included a total of 214 healthy breastfeeding infants and preschoolers of both sexes. The Mann-Whitney test was used to compare the medians. The Spearman correlation of each test domain was determined. R Core Team 2021 (R Foundation, Vienna, Austria) was used, and the significance threshold was set at 5%. Results In intraoral and extraoral examinations, there was a difference between sexes for tongue scores in nursing infants(d =-0.428; p = 0.045), worse in males. When the orofacial functions were considered in nursing infants, there were differences between the sexes for the liquid/solid/semisolid deglutition scores (d = 0.479; p = 0.031), with females performing worse. There were sex differences in solid/semisolid deglutition (d = -0.335; p = 0.043), and speech in preschoolers (d = - 0.478; p = 0.034), including the production of phones/phonemes (d = - 0.599; p = 0.007), which were always worse in males. Conclusion The research revealed sex disparities and related the domains of oromyofunctional assessment, according to scores, of the domains of myofunctional assessment, as recorded in a standardized oromyofunctional assessment protocol by age group.

Perfil dos fonoaudiólogos com formação em motricidade orofacial no Brasil / Profile of speech therapists trained in orofacial myology in Brazil

RESUMO Objetivo Caracterizar o perfil do fonoaudiólogo brasileiro com formação especializada em motricidade orofacial (MO). Métodos Estudo descritivo e exploratório, transversal, de abordagem quantitativa, realizado entre setembro 2022 e fevereiro 2023, com parceria do Conselho Federal de Fonoaudiologia. Participaram 87 fonoaudiólogos com formação em MO. Resultados Evidenciou-se predominância feminina, faixa etária entre 41 e 50 anos e tempo de formação especializada em MO entre 16 e 20 anos; maioria com título de especialista e da Região Sudeste do Brasil, atuando em consultórios/ambulatórios e/ou clínicas, com ações interdisciplinares com Medicina e Odontologia, abrangendo adultos e crianças, principalmente na rede privada. Prevaleceram os domínios da MO quanto à reabilitação de estruturas moles e hábito oral e maior uso de tecnologias: leve - acolhimento e assistência; leve-dura - avaliação e terapia e dura - fotobiomodulação. Conclusão Os fonoaudiólogos brasileiros com formação especializada em MO, participantes do estudo, são, em sua maioria, mulheres com mais de 41 anos de idade, que detêm titulação de especialista, com práticas nos vários domínios e níveis de tecnologia da área, principalmente em diagnóstico e reabilitação dos distúrbios miofuncionais orofaciais.

ABSTRACT Purpose To characterize the profile of Brazilian speech therapists with specialized training in orofacial myology (OM). Methods Descriptive and exploratory, cross-sectional study, with a quantitative approach, carried out between September 2022 and February 2023, in partnership with CFFa. Eighty-seven speech therapists with specialized training in OM participated. Results showed female predominance, age between 41 and 50 years, and time of specialized training in OM between 16-20 years; most with specialist titles in the Southeast of Brazil. Most work in offices/outpatient clinics and/or clinics with interdisciplinary actions with Medicine and Dentistry; seeing adults and children, mainly in a private sector. As to OM domains there was a predominance of rehabilitation of soft structures and oral habits, and most use technologies: light - reception and assistance, light-hard - evaluation and therapy, and hard - photobiomodulation (40.2%). Conclusion The Brazilian speech therapists with specialized training in OM participating in the study are mostly women over 41 years old, who hold the title of specialists, and carry out practices in various domains and levels of technology in the area, with a predominance of diagnosis and rehabilitation of oromyofunctional disorders.

New multifunctional Ru(II) organometallic compounds show activity against Trypanosoma brucei and Leishmania infantum.

Human African trypanosomiasis (sleeping sickness) and leishmaniasis are prevalent zoonotic diseases caused by genomically related trypanosomatid protozoan parasites (Trypanosoma brucei and Leishmania spp). Additionally, both are co-endemic in certain regions of the world. Only a small number of old drugs exist for their treatment, with most of them sharing poor safety, efficacy, and pharmacokinetic profiles. In this work, new multifunctional Ru(II) ferrocenyl compounds were rationally designed as potential agents against these trypanosomatid parasites by including in a single molecule 1,1'-bis(diphenylphosphino)ferrocene (dppf) and two bioactive bidentate ligands: 8-hydroxyquinoline derivatives (8HQs) and polypyridyl ligands (NN). Three [Ru(8HQs)(dppf)(NN)](PF6) compounds were synthesized and fully characterized. They showed in vitro activity on bloodstream Trypanosoma brucei (IC50 140-310 nM) and on Leishmania infantum promastigotes (IC50 3.0-4.8 µM). The compounds showed good selectivity towards T. brucei in respect to J774 murine macrophages as mammalian cell model (SI 15-38). Changing hexafluorophosphate counterion by chloride led to a three-fold increase in activity on both parasites and to a two to three-fold increase in selectivity towards the pathogens. The compounds affect in vitro at least the targets of the individual bioactive moieties included in the new chemical entities: DNA and generation of ROS. The compounds are stable in solution and are more lipophilic than the free bioactive ligands. No clear correlation between lipophilicity, interaction with DNA or generation of ROS and activity was detected, which agrees with their overall similar anti-trypanosoma potency and selectivity. These compounds are promising candidates for further drug development.

Evaluation of the Anti-Leishmania mexicana and -Trypanosoma brucei Activity and Mode of Action of 4,4'-(Arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol).

Trypanosomiasis and leishmaniasis are neglected infections caused by trypanosomatid parasites. The first-line treatments have many adverse effects, high costs, and are prone to resistance development, hence the necessity for new chemotherapeutic options. In line with this, twenty five 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives were synthesized and evaluated in vitro for their anti-trypanosomatid activity. Ten and five compounds from this series showed IC50 ≤ 10 µM against the promastigote and the bloodstream stage of Leishmania mexicana and Trypanosoma brucei brucei, respectively. Overall, derivatives with pyrazole rings substituted with electron-withdrawing groups proved more active than those with electron-donating groups. The hits proved moderately selective towards L. mexicana and T. brucei (selectivity index, SI, compared to murine macrophages = 5−26). The exception was one derivative displaying an SI (>111−189) against T. brucei that surpassed, by >6-fold, the selectivity of the clinical drug nifurtimox (SI = 13−28.5). Despite sharing a common scaffold, the hits differed in their mechanism of action, with halogenated derivatives inducing a rapid and marked intracellular oxidative milieu in infective T. brucei. Notably, most of the hits presented better absorption, distribution, metabolism, and excretion (ADME) properties than the reference drugs. Several of the bioactive molecules herein identified represent a promising starting point for further improvement of their trypanosomatid potency and selectivity.

A Simple Bioluminescent Assay for the Screening of Cytotoxic Molecules Against the Intracellular Form of Leishmania infantum.

This chapter describes a viability assay for the intracellular (amastigote) and clinically relevant form of Leishmania infantum that is based on the detection of bioluminescence (BL) signal. The assay uses a reporter cell line of L. infantum that expresses constitutively a redshifted luciferase from Photinus pyralis and murine macrophages (cell line J774.A1) as host cells for infection. The host cell line was selected because it is a differentiated cell line, easy to manipulate in vitro, and advantageous for ethical reasons. This chapter introduces an assay designed for the screening of bioactive compounds/molecules employing a 96-well microplate and a 24 h treatment. The assay setup shows excellent balance between simplicity (cell culture manipulation/infection and timing) and quality parameters, as well as potential to detect drug-like molecules acting in a fast and cytotoxic manner.

MMBRG Protocol - Infants and Preschoolers: Myofunctional Orofacial Clinic Examination. / Protocolo MMBRG ­ Lactentes e Pré-Escolares: Exame Clínico Miofuncional Orofacial.

PURPOSE: To present the Myofunctional Orofacial Clinical Examination Protocol belonging to the MMBGR Protocol - Infants and Preschoolers, including its validation. METHODS: Initially, test content-based validity was evaluated from the MBGR Protocol to be used with the age group between 6 and 71 months based on the bibliography and experience between the authors (original and current). For the content and appearance analysis, 10 speech therapists specialized in Orofacial Motricity attended and filled out an electronic form with dichotic and Likert scale questions in two moments. We used the Content Validity Index and the Exact Binomial Test. Then there was a validity based on the response processes analysis followed by a reliability of the Clinical Examination with 155 participants by 7 experienced and calibrated speech therapists, and the examiners between and within agreement was verified by the Intraclass Correlation Coefficient. RESULTS: There were additions, modifications, and exclusions of items according to the age group, resulting in the Myofunctional Orofacial Clinical Examination Protocol for Infants and Preschoolers, which obtained 90.5% agreement; and 100% of the appropriate scores by at least 90% of the specialists. In reliability, most items of the Extraoral and Intraoral Examination and Chewing obtained a reasonable to good, or even excellent, agreement. CONCLUSION: The "Clinical Myofunctional Clinical Examination" was validated based on the test content, response process, and reliability and, along with the "Instructional" and the "Clinical History" is part of the "MMBGR Protocol - Infants and Preschoolers" for speech therapy activities in the age group between 6 and 71 months of age.

OBJETIVO: Apresentar Exame Clínico Miofuncional Orofacial pertencente ao Protocolo MMBGR - Lactentes e Pré-escolares, incluindo sua validação. MÉTODO: Inicialmente foi realizada a validade do conteúdo do teste adaptado do Protocolo MBGR, para faixa etária entre 6 e 71 meses, fundamentada na bibliografia e experiência entre autores (originais e atuais). Para análise de conteúdo e aparência participaram 10 fonoaudiólogos especialistas em Motricidade Orofacial, que preencheram formulário eletrônico com questões dicóticas e escala de Likert, em dois momentos. Foi calculado Índice de Validade de Conteúdo e Teste Binomial Exato. Na sequência houve análise da validade baseada nos processos de resposta, seguida da análise da confiabilidade do Exame Clínico, com 155 participantes, por 7 fonoaudiólogos experientes e calibrados, sendo verificada a concordância entre e intra examinadores pelo Coeficiente de Correlação Intraclasse. RESULTADOS: Houve acréscimos, modificações e exclusão de itens conforme faixa etária, concluindo-se o Protocolo Exame Clínico Miofuncional Orofacial para lactentes e pré-escolares, que obteve 90,5% com concordância; e 100% dos escores adequados por pelo menos 90% dos especialistas. Quanto à confiabilidade, a maioria dos itens dos Exames Extraoral e Intraoral e Mastigação obtiveram concordância razoável a boa, ou, até mesmo, excelente. CONCLUSÃO: O "Exame Clínico Miofuncional Orofacial" teve validação baseada no conteúdo do teste, nos processos de resposta e confiabilidade concluída, e junto ao "Instrutivo" e à "História Clínica" integra o "Protocolo MMBGR - Lactentes e Pré-escolares", para atuação fonoaudiológica na faixa etária entre 6 e 71 meses de idade.

MMBGR Protocol - infants and preschoolers: Instructive and Orofacial Myofunctional Clinical History. / Protocolo MMBRG ­ Lactentes e Pré-escolares: Instrutivo e História Clínica Miofuncional Orofacial.

PURPOSE: To present Myofunctional Orofacial Clinical History Instructive and Protocol belonging to the MMBGR Protocol - Infants and Preschoolers, including the adaptation and validation of content and appearance. METHODS: Validation, descriptive and cross-sectional study. Adaptation based on the MBGR Protocol, based on theoretical studies and the authors' experience. Infants between 6 and 23 months of age and preschoolers between 24 and 71 months were considered. Consent and consensus of the version adapted by the authors (original and current) was obtained. The appearance and content of the new instrument were analyzed by 10 speech therapists specialized in Orofacial Motricity. We performed two analysis rounds. First: an electronic form containing dichotic questions (yes / no), with justification for negative answers; Content Validity Index and Exact Binomial Test; Second: 5 points-Likert scale. RESULTS: We produced an unprecedented instructional and adapted Clinical History protocol maintaining 23 age group related items. We excluded information from 7 items and included information in 8. Initially, we achieved agreement in 70% instructional specialist items by at least 70% of the specialists; and 64% of Clinical History items, by at least 90% of specialists. In the second round, there were 100% of "I totally agree" responses from the experts. CONCLUSION: "Instructive" and "Myofunctional Clinical History, Orofacial" had validity of content and appearance concluded, and together with the "Clinical Examination" they integrate the "Protocol MMBGR - Infants and Preschoolers", being able to contribute to clinical practice and research in Motricity Orofacial area in the age group between 6 months and 5 years and 11 months of age.

OBJETIVO: Apresentar Instrutivo e Protocolo de História Clínica Miofuncional Orofacial pertencentes ao Protocolo MMBGR - Lactentes e Pré-escolares, incluindo adaptação e validação do conteúdo e aparência destes. MÉTODO: Estudo tipo validação, descritivo e transversal. Adaptação a partir do Protocolo MBGR, fundamentada em estudos teóricos e experiência dos autores. Considerados lactentes entre 6 e 23 meses de vida e pré-escolares entre 24 e 71 meses. Obtido consentimento e consenso da versão adaptada pelos autores (originais e atuais). Analisados aparência e conteúdo do novo instrumento por 10 fonoaudiólogos especialistas em Motricidade Orofacial. Realizadas duas rodadas de análise: Primeira com formulário eletrônico contendo questões dicóticas (sim/não), com espaço para justificar as respostas negativas; calculado Índice de Validade de Conteúdo e Teste Binomial Exato; e Segunda com escala Likert 5 posições. RESULTADOS: Produzido instrutivo inédito e adaptado o Protocolo de História Clínica, com manutenção de 23 itens pertinentes à faixa etária em questão. Excluídas informações em 7 itens e acrescidas em 8 itens. Inicialmente obteve-se concordâncias de 70% do instrutivo, por pelo menos 70% dos especialistas; e 64% dos itens da História Clínica, por ao menos 90% dos especialistas. Obteve-se na segunda rodada 100% de respostas "Concordo totalmente" dos especialistas. CONCLUSÃO: "Instrutivo" e "História Clínica Miofuncional Orofacial" tiveram validade de conteúdo e aparência concluída, e junto ao "Exame Clínico" integram o "Protocolo MMBGR - Lactentes e Pré-escolares", com potencial contribuição para atuação clínica e na pesquisa em Motricidade Orofacial na faixa etária de 6 meses a 5 anos e 11 meses de idade.

Protocolo MMBRG - Lactentes e Pré-Escolares: Exame Clínico Miofuncional Orofacial / MMBRG Protocol - Infants and Preschoolers: Myofunctional Orofacial Clinic Examination

RESUMO Objetivo Apresentar Exame Clínico Miofuncional Orofacial pertencente ao Protocolo MMBGR - Lactentes e Pré-escolares, incluindo sua validação. Método Inicialmente foi realizada a validade do conteúdo do teste adaptado do Protocolo MBGR, para faixa etária entre 6 e 71 meses, fundamentada na bibliografia e experiência entre autores (originais e atuais). Para análise de conteúdo e aparência participaram 10 fonoaudiólogos especialistas em Motricidade Orofacial, que preencheram formulário eletrônico com questões dicóticas e escala de Likert, em dois momentos. Foi calculado Índice de Validade de Conteúdo e Teste Binomial Exato. Na sequência houve análise da validade baseada nos processos de resposta, seguida da análise da confiabilidade do Exame Clínico, com 155 participantes, por 7 fonoaudiólogos experientes e calibrados, sendo verificada a concordância entre e intra examinadores pelo Coeficiente de Correlação Intraclasse. Resultados Houve acréscimos, modificações e exclusão de itens conforme faixa etária, concluindo-se o Protocolo Exame Clínico Miofuncional Orofacial para lactentes e pré-escolares, que obteve 90,5% com concordância; e 100% dos escores adequados por pelo menos 90% dos especialistas. Quanto à confiabilidade, a maioria dos itens dos Exames Extraoral e Intraoral e Mastigação obtiveram concordância razoável a boa, ou, até mesmo, excelente. Conclusão O "Exame Clínico Miofuncional Orofacial" teve validação baseada no conteúdo do teste, nos processos de resposta e confiabilidade concluída, e junto ao "Instrutivo" e à "História Clínica" integra o "Protocolo MMBGR - Lactentes e Pré-escolares", para atuação fonoaudiológica na faixa etária entre 6 e 71 meses de idade.

ABSTRACT Purpose To present the Myofunctional Orofacial Clinical Examination Protocol belonging to the MMBGR Protocol - Infants and Preschoolers, including its validation. Methods Initially, test content-based validity was evaluated from the MBGR Protocol to be used with the age group between 6 and 71 months based on the bibliography and experience between the authors (original and current). For the content and appearance analysis, 10 speech therapists specialized in Orofacial Motricity attended and filled out an electronic form with dichotic and Likert scale questions in two moments. We used the Content Validity Index and the Exact Binomial Test. Then there was a validity based on the response processes analysis followed by a reliability of the Clinical Examination with 155 participants by 7 experienced and calibrated speech therapists, and the examiners between and within agreement was verified by the Intraclass Correlation Coefficient. Results There were additions, modifications, and exclusions of items according to the age group, resulting in the Myofunctional Orofacial Clinical Examination Protocol for Infants and Preschoolers, which obtained 90.5% agreement; and 100% of the appropriate scores by at least 90% of the specialists. In reliability, most items of the Extraoral and Intraoral Examination and Chewing obtained a reasonable to good, or even excellent, agreement. Conclusion The "Clinical Myofunctional Clinical Examination" was validated based on the test content, response process, and reliability and, along with the "Instructional" and the "Clinical History" is part of the "MMBGR Protocol - Infants and Preschoolers" for speech therapy activities in the age group between 6 and 71 months of age.

Protocolo MMBRG - Lactentes e Pré-escolares: Instrutivo e História Clínica Miofuncional Orofacial / MMBGR Protocol - infants and preschoolers: Instructive and Orofacial Myofunctional Clinical History

RESUMO Objetivo Apresentar Instrutivo e Protocolo de História Clínica Miofuncional Orofacial pertencentes ao Protocolo MMBGR - Lactentes e Pré-escolares, incluindo adaptação e validação do conteúdo e aparência destes. Método Estudo tipo validação, descritivo e transversal. Adaptação a partir do Protocolo MBGR, fundamentada em estudos teóricos e experiência dos autores. Considerados lactentes entre 6 e 23 meses de vida e pré-escolares entre 24 e 71 meses. Obtido consentimento e consenso da versão adaptada pelos autores (originais e atuais). Analisados aparência e conteúdo do novo instrumento por 10 fonoaudiólogos especialistas em Motricidade Orofacial. Realizadas duas rodadas de análise: Primeira com formulário eletrônico contendo questões dicóticas (sim/não), com espaço para justificar as respostas negativas; calculado Índice de Validade de Conteúdo e Teste Binomial Exato; e Segunda com escala Likert 5 posições. Resultados Produzido instrutivo inédito e adaptado o Protocolo de História Clínica, com manutenção de 23 itens pertinentes à faixa etária em questão. Excluídas informações em 7 itens e acrescidas em 8 itens. Inicialmente obteve-se concordâncias de 70% do instrutivo, por pelo menos 70% dos especialistas; e 64% dos itens da História Clínica, por ao menos 90% dos especialistas. Obteve-se na segunda rodada 100% de respostas "Concordo totalmente" dos especialistas. Conclusão "Instrutivo" e "História Clínica Miofuncional Orofacial" tiveram validade de conteúdo e aparência concluída, e junto ao "Exame Clínico" integram o "Protocolo MMBGR - Lactentes e Pré-escolares", com potencial contribuição para atuação clínica e na pesquisa em Motricidade Orofacial na faixa etária de 6 meses a 5 anos e 11 meses de idade.

ABSTRACT Purpose To present Myofunctional Orofacial Clinical History Instructive and Protocol belonging to the MMBGR Protocol - Infants and Preschoolers, including the adaptation and validation of content and appearance. Methods Validation, descriptive and cross-sectional study. Adaptation based on the MBGR Protocol, based on theoretical studies and the authors' experience. Infants between 6 and 23 months of age and preschoolers between 24 and 71 months were considered. Consent and consensus of the version adapted by the authors (original and current) was obtained. The appearance and content of the new instrument were analyzed by 10 speech therapists specialized in Orofacial Motricity. We performed two analysis rounds. First: an electronic form containing dichotic questions (yes / no), with justification for negative answers; Content Validity Index and Exact Binomial Test; Second: 5 points-Likert scale. Results We produced an unprecedented instructional and adapted Clinical History protocol maintaining 23 age group related items. We excluded information from 7 items and included information in 8. Initially, we achieved agreement in 70% instructional specialist items by at least 70% of the specialists; and 64% of Clinical History items, by at least 90% of specialists. In the second round, there were 100% of "I totally agree" responses from the experts. Conclusion "Instructive" and "Myofunctional Clinical History, Orofacial" had validity of content and appearance concluded, and together with the "Clinical Examination" they integrate the "Protocol MMBGR - Infants and Preschoolers", being able to contribute to clinical practice and research in Motricity Orofacial area in the age group between 6 months and 5 years and 11 months of age.

Protocolos fonoaudiológicos de história clínica: revisão integrativa / Clinical history speech-language pathology protocols: integrative review

RESUMO Objetivo identificar, coletar e analisar, na literatura científica, evidências da existência de protocolos fonoaudiológicos de levantamento da história clínica, conforme classificação de risco, especialmente para distúrbios oromiofuncionais, em lactentes e pré-escolares. Estratégia de pesquisa foram selecionados estudos publicados, sem delimitação temporal, nas bases de dados eletrônicas LILACS, SciELO e PubMed e na literatura cinza (Google Acadêmico). Critérios de seleção estudos disponíveis na íntegra nas línguas portuguesa e inglesa, que identificassem protocolos fonoaudiológicos de história clínica aplicáveis a lactentes (6 a 23 meses de vida) e pré-escolares (24 a 71 meses de vida). Foram excluídas as revisões narrativas e de literatura (integrativa, sistêmica e escopo). Resultados foram encontradas 1371 publicações brasileiras no período de 1980 a 2022. Destas, foram identificadas apenas cinco que tratavam de protocolos fonoaudiológicos para levantamento de dados pregressos a partir da história clínica da faixa etária de 6 a 71 meses. Apenas um desses protocolos possuía classificação de risco para distúrbios fonoaudiológicos, distribuídos na área de linguagem e fluência. Os outros três eram da área de motricidade orofacial (MO) e não continham classificação de risco para distúrbio miofuncional orofacial. Conclusão existem poucos protocolos fonoaudiológicos para levantamento da história clínica de lactentes e pré-escolares que contenham, ou não, classificação de risco, publicados em revistas de acesso aberto e que passaram por processos completos de validação, sendo necessário ampliar estudos e publicações desses instrumentos, inclusive na área de MO.

ABSTRACT Purpose to identify, collect and analyze in the scientific literature evidence of the existence of speech therapy protocols for collecting clinical history, according to risk classification, especially for oromyofunctional disorders, in infants and preschoolers. Research Strategy We selected published studies, without temporal delimitation, in the electronic databases LILACS, SciELO and PUBMED; and in the gray literature (Google Academic). Selection criteria available in full in Portuguese and English, which identify speech-language pathology protocols of clinical history applicable to infants (6 to 23 months of age) and preschoolers (24 to 71 months of age). Narrative and literature reviews (integrative, systemic, and scope) were excluded. Results 1371 Brazilian publications were found in the period from 1980 to 2022. Of these, only five publications on speech therapy protocols were identified for collecting previous data from the clinical history of the age group between 6 and 71 months. Only two of these protocols have a risk classification for speech-language disorders, distributed in the areas of language and fluency. The other three are from the Orofacial Motricity (OM) area and do not carry a risk classification for orofacial myofunctional disorder. Conclusion There are few speech therapy protocols for surveying the clinical history of infants and preschoolers, whether or not they contain risk classification, published in open access journals that have a complete validation process.Therefore there is a need for more research and publication of these instruments, including in the area of OM.

Percepção das puérperas de um hospital materno infantil sobre a violência obstétrica no estado de Roraima / Perception of puerperal women in a maternal and children's hospital about obstetric violence in the State of Roraima / Percepción de mujeres puerperales en hospital materno e infantil sobre la violencia obstétrica en el Estado de Roraima

Objetivo: analisar a percepção das puérperas sobre condutas que soam como agressão durante o trabalho de parto, na visão das puérperas, em Boa Vista, Estado de Roraima. Métodos: pesquisa-ação com abordagem qualitativa e exploratória. A pesquisa foi realizada no Hospital Materno Infantil Nossa Senhora de Nazareth. A amostra foi de 50 participantes puérperas internadas no período da coleta de dados. Resultados: os resultados apontaram que 72% das mulheres não possuem conhecimento do que é violência obstétrica, 90% relataram que durante o pré-natal não foram informadas sobre violência obstétrica. 38% das mulheres responderam já ter sofrido violência obstétrica. 34% não tiveram direito ao acompanhante durante seu trabalho de parto e 20% responderam que durante seu trabalho de parto, alguém apertou/subiu na sua barriga para ajudar a saída do bebê. Conclusão: muitas dessas ações não são compreendidas por essas mulheres como violência obstétrica, ajudando a manter esses tipos posturas

Objective: to analyze the perception of postpartum women about behaviors that sound like aggression during labor, from the point of view of postpartum women, in State of Roraima. Methods: action research with a qualitative and exploratory approach. The research was carried out at the Hospital Nossa Senhora de Nazareth. The sample consisted of 50 postpartum participants hospitalized during the data collection period. Results: the results showed that 72% of women are not aware of what obstetric violence is, 90% reported that during prenatal care they were not informed about obstetric violence. 38% of women responded that they had already suffered obstetric violence. 34% were not entitled to a companion during their labor and 20% responded that during their labor, someone pressed/climbed their belly to help the baby come out. Conclusion: many of these actions are not understood by these women as obstetric violence, helping to maintain these types of postures

Objetivo: analizar la percepción de puérperas sobre durante el trabajo de parto, en el Estado de Roraima. Métodos: investigación acción con enfoque cualitativo y exploratorio. La investigación se llevó a cabo en el Hospital Nossa Senhora de Nazareth. La muestra estuvo compuesta por 50 participantes posparto hospitalizadas. Resultados: el 72% de las mujeres no tienen conocimiento de lo que es la violencia obstétrica, el 90% refirió que durante el control prenatal no fueron informadas sobre la violencia obstétrica. El 38% de las mujeres respondieron que ya habían sufrido violencia obstétrica. El 34% no tenía derecho a un acompañante durante el trabajo de parto y el 20% respondió que durante el trabajo de parto alguien le apretó/subió el vientre para ayudar a que el bebé saliera. Conclusión: muchas de estas acciones no son entendidas por estas mujeres como violencia obstétrica, ayudando a mantener este tipo de posturas

Sleep in children with microcephaly due to Zika virus infection: a systematic review.

OBJECTIVE: To review the literature on sleep changes and brain function in children with microcephaly due to Zika virus. METHOD: Systematic review conducted in the databases MEDLINE (PubMed), Scopus, Web of Science, CINAHL, EMBASE, LILACS, and SciELO and the grey databases Google Scholar and OpenGrey. RESULTS: Ten Brazilian primary studies with observational research design were included. These were published between 2017 and 2020 with 516 children with microcephaly due to Zika virus infection aged 4 months to 4 years. Out of these, 4 investigated qualitative aspects of sleep using the questionnaires Brief Infant Sleep Questionnaire or Infant Sleep Questionnaire and 6 investigated changes in brain activities during sleep using the Electroencephalogram or Video-Electroencephalogram exams. The children's quality of sleep was not compromised in most studies. Changes in brain activity during sleep were frequent, with epileptogenic activity being a common finding among the studies. CONCLUSION: The quality of sleep of children with microcephaly due to Zika virus has shown to be similar to that of children with typical development and the presented behavioral changes may be related to changes in electric brain activity.

Expanded Protocol of Orofacial Myofunctional Evaluation with Scores for Nursing Infants (6-24 months) (OMES-E Infants). / Protocolo de Avaliação Miofuncional Orofacial com Escores Expandido: AMIOFE-E LACTENTES (6-24 MESES).

PURPOSE: Adapt and validate the content and appearance of the Expanded Protocol of Orofacial Myofunctional Evaluation with Scores (OMES-E) for nursing infants aged 6 to 24 months. METHODS: This is a validation study. The parameters were based on the literature on orofacial motor development, the authors' experience, and on a committee of ten members. Data analysis was performed using descriptive statistics, content validity index, and agreement among experts. RESULTS: The protocol was organized into functional blocks after maintenance, exclusion, modification, and addition of items, and was adapted according to the age group. A high level of agreement between experts was obtained for 90% of the items. The final version of the protocol includes new items such as history of feeding, orofacial parafunctional habits, facial mobility, dentition, oral breathing mode, swallowing of pasty food, and details specific for the age group. An operational manual and a table for recording the scores were also included. CONCLUSIONS: The OMES-E Infants protocol was validated for its content and appearance, and may contribute to orofacial myofunctional diagnosis in the 6 to 24-month age group.

OBJETIVO: Adaptar e validar conteúdo e aparência do Protocolo de Avaliação Miofuncional Orofacial com Escores Expandido (AMIOFE-E) para lactentes de 6 a 24 meses de idade. MÉTODO: Estudo de validação. Os parâmetros foram baseados em literatura sobre desenvolvimento motor orofacial, experiência dos autores e painel de 10 especialistas. Os dados foram analisados por estatística descritiva, Índice de Validade de Conteúdo e concordância entre especialistas. RESULTADOS: O protocolo foi organizado em blocos funcionais após manutenção, exclusão, modificação e acréscimo de itens, adaptando-se à faixa etária. Obteve-se alto nível de concordância em 90% dos itens. Na versão final foram acrescidos: histórico de alimentação e hábitos parafuncionais orofaciais, mobilidade facial, dentição, modo oral de respiração, deglutição de pastoso e detalhamentos específicos para a faixa etária. Acrescentou-se um manual operacional e uma tabela para registro de escores. CONCLUSÃO: O Protocolo AMIOFE-E Lactentes e respectivo manual operacional foram validados quanto ao conteúdo e aparência, e poderá contribuir no diagnóstico miofuncional orofacial na faixa etária de 6 a 24 meses de idade.

New Pd-Fe ferrocenyl antiparasitic compounds with bioactive 8-hydroxyquinoline ligands: a comparative study with their Pt-Fe analogues.

In the search for a more effective chemotherapy for the treatment of Human African Trypanosomiasis, a disease caused by the parasite Trypanosoma brucei, the development of ferrocenyl compounds has arisen as a promising strategy. In this work, five new Pd-Fe heterobimetallic [PdII(L)(dppf)](PF6) compounds, including 8-hydroxyquinolyl derivatives HL1-HL5 as bioactive ligands and dppf = 1,1'-bis(diphenylphosphino)ferrocene as the organometallic co-ligand, were synthesized and fully characterized in the solid state and in solution. Molecular structures of three compounds were solved by single crystal X-ray diffraction methods. The compounds displayed submicromolar or micromolar IC50 values against bloodstream T. brucei (IC50: 0.33-1.2 µM), and good selectivity towards the pathogen (SI: 4-102) with respect to mammalian macrophages (cell line J774). The new Pd complexes proved to be 2-fold to 45-fold more potent than the drug nifurtimox but most of them are less active than their Pt analogues. Potential molecular targets were studied. The complexes interact with DNA but they do not alter the intracellular thiol-redox homeostasis of the parasite. In order to understand and predict the main structural determinants on the anti-T. brucei activity, a search of quantitative structure-activity relationships (QSAR) was performed including all the [M(L)(dppf)](PF6) complexes, where M = Pd(ii) or Pt(ii), currently and previously developed by us. The correlation obtained shows the relevance of the electronic effects, the lipophilicity and the type of metal. According to the QSAR study, compounds with electron-withdrawing ligands, higher lipophilicity and harboring Pt would result in higher T. brucei cytotoxicity. From the whole series of [M(L)(dppf)](PF6) compounds developed, where M = Pt(ii) or Pd(ii) and HL = 8-hydroxyquinolyl derivatives, Pt-dppf-L4 (IC50 = 0.14 µM, SI = 48) was selected to perform an exploratory pre-clinical study in infected mice. This hit compound lacks acute toxicity when applied to animals in the dose/regimen described and exerts an anti-proliferative effect on parasites, which extends animal survival but is not curative.

Factors associated with extubation failure in very low birth weight infants: a cohort study in the northeast Brazil.

OBJECTIVES: Identifying and understanding the main risk factors associated with extubation failure of very low birthweight (VLBW) infants in different populations can subsequently help in establishing better criteria while taking decision of extubation. The aim of the study was to identify factors associated with extubation failure in VLBW infants. METHODS: A cohort study of VLBW infants who underwent their first extubation between April 2018 and December 2019 in a Neonatal Intensive Care Unit, Alagoas, Brazil, were included in this study. Extubation failure was defined as reintubation within seven days of extubation. Relative risks of predictive variables different between the extubation success group (ES) and extubation failure group (EF) were estimated with a robust Poisson regression model. RESULTS: Out of the 112 infants included, 26 (23%) cases exhibited extubation failure. Extremely low birth weight (RR 2.55, 95% CI 1.07, 6.06), mechanical ventilation duration for first extubation greater than seven days (RR 2.66, 95% CI 1.10, 6.45), vaginal delivery (RR 2.07, 95% CI 1.03, 4.18) and maternal chorioamnionitis (RR 4.89, 95% CI 1.26-18.98) remained independently associated with extubation failure. EF had a significant greater need for respiratory support, longer oxygen therapy duration, more bronchopulmonary dysplasia (BPD) and longer length of hospital stay, even when adjusted for confounding variables. CONCLUSIONS: Extremely low birth weight infants needing mechanical ventilation, wherein the duration for first extubation was longer than seven days, with vaginal delivery and maternal chorioamnionitis failed more frequently at the first attempt of extubation. And this failure increased the risk of BPD and the length of hospital stay.

Spontaneous Breathing Trials in Preterm Infants: Systematic Review and Meta-Analysis.

BACKGROUND: Few data are available on the use of spontaneous breathing trials (SBTs) in the neonatal population, despite advocacy of the practice in many neonatal ICUs. In this meta-analysis, we systematically reviewed the literature regarding the accuracy of SBTs as a predictor for extubation failure in premature infants. METHODS: Following the PRISMA recommendations, scientific articles were collected in December 2019 and January 2020 using PubMed, LILACS, Web of Science, Scopus, Google Scholar, OATD, and BDTD databases. The risk of bias in the studies included herein was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The pooled sensitivity and specificity of the studies were estimated using a mixed logistic regression model of 2 levels and a normal bivariate model. RESULTS: Six studies were included for qualitative and quantitative evaluation in this study. All SBTs were performed with endotracheal CPAP, with a total observation time of 3-5 min. The parameters for passing/failing the test were similar in 5 of the 6 studies and included bradycardia or desaturation during the test. The SBT showed a high pooled sensitivity (0.97, 95% CI 0.85-0.99), indicating proper identification of neonates "ready" for successful extubation. However, a low pooled specificity (0.40, 95% CI 0.24-0.58), with many false-positive cases, indicated inaccurate prediction of extubation failure. Heterogeneity of included studies was considerable for sensitivity and substantial for specificity. CONCLUSIONS: The SBT in premature infants can accurately predict extubation success but not extubation failure. Therefore, even though it is an attractive, practical, and easy-to-perform bedside assessment tool, there is a lack of evidence to support its use as an independent predictor of extubation failure in premature infants. Its routine use should be evaluated and monitored carefully.