Sustainable Polypropylene-Based Composites with Agro-Waste Fillers: Thermal, Morphological, Mechanical Properties and Dimensional Stability.

Natural fiber composites (NFC) are eco-friendly alternatives to synthetic polymers. However, some intrinsic natural fillers' properties hinder their widespread implementation as reinforcement in polymeric matrices and require further investigation. In the scope of this study, the thermal, rheologic, mechanical (tension and flexural modes), and morphological properties, as well as the water absorption and dimensional stability of the NF polypropylene (PP)-based injection molded composites reinforced with rice husk (rh) and olive pits (op) of 20 wt.% and 30% wt.%, respectively, were investigated. The results suggest that the higher content of the rice husk and olive pits led to a similar reduction in the melt flow index (MFI), independent of the additive type compared to virgin polypropylene (PPv). The melting and crystallization temperatures of the PPrh and PPop composites did not change with statistical significance. The composites are stiffer than the PP matrix by up to 49% and possess higher mechanical strength in the tension mode at the expense of decreased ductility. PPrh and PPop have a superior flexural modulus in the bending mode, while the flexural strength improvement was accomplished for the PP30%rh. The influence of the fibers' distribution in the bulk of the parts on their mechanical performance was confirmed based on a non-localized morphology evaluation, which constitutes a novelty of the presented research. The dimensional stability of the composites was improved as the linear shrinkage in the flow direction was decreased by 49% for PPrh and 30% for PPop, positively correlating with an increase in the filler content and stiffness. PPop was less susceptible to water sorption than PPrh due to fibers' composition and larger surface-to-area volume ratios.

Iron overload induces dysplastic erythropoiesis and features of myelodysplasia in Nrf2-deficient mice.

Iron overload (IOL) is hypothesized to contribute to dysplastic erythropoiesis. Several conditions, including myelodysplastic syndrome, thalassemia and sickle cell anemia, are characterized by ineffective erythropoiesis and IOL. Iron is pro-oxidant and may participate in the pathophysiology of these conditions by increasing genomic instability and altering the microenvironment. There is, however, lack of in vivo evidence demonstrating a role of IOL and oxidative damage in dysplastic erythropoiesis. NRF2 transcription factor is the master regulator of antioxidant defenses, playing a crucial role in the cellular response to IOL in the liver. Here, we crossed Nrf2-/- with hemochromatosis (Hfe-/-) or hepcidin-null (Hamp1-/-) mice. Double-knockout mice developed features of ineffective erythropoiesis and myelodysplasia including macrocytic anemia, splenomegaly, and accumulation of immature dysplastic bone marrow (BM) cells. BM cells from Nrf2/Hamp1-/- mice showed increased in vitro clonogenic potential and, upon serial transplantation, recipients disclosed cytopenias, despite normal engraftment, suggesting defective differentiation. Unstimulated karyotype analysis showed increased chromosome instability and aneuploidy in Nrf2/Hamp1-/- BM cells. In HFE-related hemochromatosis patients, NRF2 promoter SNP rs35652124 genotype TT (predicted to decrease NRF2 expression) associated with increased MCV, consistent with erythroid dysplasia. Our results suggest that IOL induces ineffective erythropoiesis and dysplastic hematologic features through oxidative damage in Nrf2-deficient cells.

Advancing hospital-based health technology assessment: evaluating genomic panel contracting strategies for blood tumors through a multimethodology.

INTRODUCTION: The adoption of genomic technologies in the context of hospital-based health technology assessment presents multiple practical and organizational challenges. OBJECTIVE: This study aimed to assist the Instituto Português de Oncologia de Lisboa Francisco Gentil (IPO Lisboa) decision makers in analyzing which acute myeloid leukemia (AML) genomic panel contracting strategies had the highest value-for-money. METHODS: A tailored, three-step approach was developed, which included: mapping clinical pathways of AML patients, building a multicriteria value model using the MACBETH approach to evaluate each genomic testing contracting strategy, and estimating the cost of each strategy through Monte Carlo simulation modeling. The value-for-money of three contracting strategies - "Standard of care (S1)," "FoundationOne Heme test (S2)," and "New diagnostic test infrastructure (S3)" - was then analyzed through strategy landscape and value-for-money graphs. RESULTS: Implementing a larger gene panel (S2) and investing in a new diagnostic test infrastructure (S3) were shown to generate extra value, but also to entail extra costs in comparison with the standard of care, with the extra value being explained by making available additional genetic information that enables more personalized treatment and patient monitoring (S2 and S3), access to a broader range of clinical trials (S2), and more complete databases to potentiate research (S3). CONCLUSION: The proposed multimethodology provided IPO Lisboa decision makers with comprehensive and insightful information regarding each strategy's value-for-money, enabling an informed discussion on whether to move from the current Strategy S1 to other competing strategies.

Evaluation of acute toxicity and in vitro antitumor activity of a novel doxorubicin-loaded folate-coated pH-sensitive liposome.

Doxorubicin (DOX) loaded liposomes have been used and studied in the last decades due to the significant decrease in DOX induced cardiac and systemic toxicity relative to administration of free drug. Therefore, new strategies are sought to improve DOX delivery and antitumor activity, while avoiding side effects. Recently, folate-coated pH-sensitive liposomes (SpHL-Fol) have been studied as a tool to enhance cellular uptake and antitumor activity of paclitaxel and DOX in breast cancer cells expressing folate receptor (FR+). However, the elucidation of folate functionalization relevance in DOX-loaded SpHL (SpHL-DOX-Fol) in different cell types (MDA-MB-231, MCF-7, and A549), as well as, the complete safety evaluation, is necessary. To achieve these objectives, SpHL-DOX-Fol was prepared and characterized as previously described. Antitumor activity and acute toxicity were evaluated in vivo through direct comparison of free DOX verses SpHL-DOX, a well-known formulation to reduce DOX cardiotoxicity. The obtained data are crucial to support future translational research. Liposomes showed long-term stability, suitable for biological use. Cellular uptake, cytotoxicity, and percentage of migration inhibition were significantly higher for MDA-MB-231 (FR+) treated with SpHL-DOX-Fol. In addition, SpHL-DOX-Fol demonstrated a decrease in the systemic toxic effects of DOX, mainly in renal and cardiac parameters evaluation, even using a higher dose (20 mg/kg). Collectively these data build the foundation of support demonstrating that SpHL-DOX-Fol could be considered a promising drug delivery strategy for the treatment of FR+ breast tumors.

Assessment of the Impact of Superficial Contamination and Thermo-Oxidative Degradation on the Properties of Post-Consumer Recycled Polypropylene.

Single-use plastics are a matter of convenience in everyday life, with the majority allocated to packaging production. However, it comes with a high environmental price as its mass recycling is challenging due to the heterogeneity of composition, contaminations of different kinds, and degradation caused by service and processing. This study aims to ascertain the impact of removing contaminants from post-consumer recycled polypropylene (rPP) on its degradation and properties by implementing a systematic approach for decontamination by washing. Four lots of recycled plastics with different degrees of contamination were evaluated via Fourier transform infrared, melt flow indexer, and differential scanning calorimetry and tested for tensile strength. Degradation of the rPP was manifested by the deterioration in ductility, resulting in 14.58% elongation at break (unwashed rPP) compared with 191.41% (virgin PP)) and a significant reduction in oxidation induction time. In the unwashed rPP sample, a wave intensity peak at 1730 cm-1, assigned to the saturated C = 0 stretch of the carbonyl functional group, was detected. This peak was gradually disappearing with an increase in the cleaning efficiency of rPP, highlighting the role of contaminants as degradation catalysts. The cold-washing method showed similar processing and mechanical performance improvement results compared with the other washing methods, while being more environmentally friendly and energy efficient.

Resultados terapêuticos da homeopatia em pacientes suspeitos ou confirmados de COVID-19: um estudo longitudinal prospectivo / Therapeutic results of homeopathy in suspected or confirmed COVID-19 patients: a longitudinal study

A infecção humana causada pelo vírus SARS-CoV-2 (COVID-19), diagnosticada como pneumonia de causa desconhecida originalmente na cidade de Wuhan (China), foi considerada como pandemia pela Organização Mundial da Saúde. Com a inexistência inicial de uma vacina para proteção dos sadios, foi adotada a estratégia de isolamento social e tratamento com medidas de suporte geral e/ou avançado. Neste contexto, coube investigar a contribuição da terapêutica homeopática no enfrentamento da doença, notadamente no alívio dos sintomas desconfortáveis por ela provocados em sua fase inicial, com acompanhamento e registro dos resultados obtidos pelos médicos homeopatas. MÉTODO: Este estudo coletou, durante o período de maio a setembro de 2020 (após aprovação pelo CEP), informações de pacientes diagnosticados com a doença, tratados por médicos homeopatas com medicamentos homeopáticos escolhidos de acordo com a sintomatologia apresentada pelo paciente. Foram avaliados os efeitos no estado de saúde do paciente, por meio de escores e escalas clínicas, bem como aspectos relacionados à segurança do medicamento, variação na duração da doença e medicamentos mais associados a eventuais sucessos terapêuticos. Questionário padronizado e específico para a COVID-19 foi elaborado e e aplicado para preenchimento dos médicos colaboradores do estudo durante o acompanhamento dos pacientes. Os dados foram armazenados em planilhas eletrônicas e analisados com técnicas estatísticas descritivas e inferenciais. Os pacientes selecionados eram colaboradores do Hospital Santo Antônio - Obras Sociais Irmã Dulce (OSID) e foram submetidos a uma avaliação preliminar presencial no ambulatório de Otorrinolaringologia deste hospital. As consultas homeopáticas foram realizadas por plataforma de Telemedicina para seguimento e acompanhamento do caso. Foram avaliados 116 colaboradores, com faixa etária que variou entre 21 e 66 anos, sendo a média de idade 38 anos; destes, 84 (72%) eram do gênero feminino e 32 (16%) gênero masculino; 53 pacientes (70% dos colaboradores atendidos) eram profissionais da saúde (médicos, enfermeiros e técnicos de enfermagem); 63 (30%) eram colaboradores de áreas administrativas ou técnicas; 50 pacientes tinham critérios para inclusão no grupo de risco (43%). Quanto ao resultado do RT-PCR: 58 pacientes (50%) tiveram RT-PCR detectado (confirmados); 58 pacientes (50%) tiveram RT-PCR não-detectado - destes, 18 pacientes (31%) apresentaram anosmia em sua evolução. Dos 116 pacientes do critério de inclusão, 77 estavam incluídos na síndrome clássica da COVID19. Destes 77 colaboradores, 3 não usaram o medicamento homeopático (N=74). Os medicamentos homeopáticos mais indicados foram: Arsenicum album (42%); Bryonia (24%), Phosphorus (15%); Gelsemium (15%); Pulsatilla (2%); outros (4%). O Score médio de sintomas antes do tratamento foi 12,27 e após o tratamento foi 0,52 (p < xxxxx). Dos 57 pacientes que tiveram anosmia, houve recuperação total em 43 (75%) dos casos no momento da reavaliação. O tempo médio decorrido entre o uso da medicação homeopática e a recuperação dos sintomas foi de 9 dias. Apenas 3 pacientes (3,9%) necessitaram de internamento hospitalar sem necessidade de intubação, sendo 2 deles pertencentes ao grupo de risco. apesar destes resultados serem parciais (pois ainda existem sujeitos da pesquisa ainda em fase de avaliação), os resultados sugerem que o tratamento homeopático promoveu o restabelecimento do quadro infeccioso sem necessidade de internamento em 97% dos pacientes. A anosmia teve recuperação completa em 75% dos pacientes. Arsenicum album, Bryonia e Phosphorus foram os medicamentos predominantemente eleitos para o tratamento, o que corrobora com outros estudos homeopáticos.

The human infection caused by the SARS-CoV-2 virus (COVID-19), originally diagnosed as pneumonia of unknown cause in the city of Wuhan (China), was considered a pandemic by the World Health Organization. With the initial lack of a vaccine to protect healthy people, the strategy relating to social isolation and treatment with general and/or advanced support measures was adopted. In this context, it was necessary to investigate the contribution of homeopathic therapy in coping with the disease, particularly in terms of relieving the uncomfortable symptoms caused by it in its initial phase, with monitoring and recording of the results obtained by homeopathic physicians. METHOD: This study collected information from patients diagnosed with the disease, treated by homeopathic physicians with homeopathic medications chosen according to the symptoms manifested by the patient, from May to September 2020 (after approval by the REC). The effects on the health conditions of patients were assessed using clinical scores and scales, as well as aspects related to the safety of the medication, variations in the duration of the disease and the medications most associated with any therapeutic successes. A standardized questionnaire specific to COVID-19 was drawn up and filled in by the physicians who collaborated in the study during patient monitoring. The data was stored in electronic spreadsheets and analyzed using descriptive and inferential statistical techniques. The selected patients were employees of Hospital Santo Antônio - Obras Sociais Irmã Dulce (OSID) and underwent a preliminary in-person assessment at the otolaryngology outpatient clinic of this hospital. The homeopathic consultations were carried out via a telemedicine platform to follow-up and monitor the case. A total of 116 employees were assessed, ranging in age from 21 to 66, with the average age being 38; of these, 84 (72%) were females and 32 (16%) males; 53 patients (70% of the employees cared for) were health care professionals (physicians, nurses and nursing technicians); 63 (30%) were employees from administrative or technical areas; 50 patients met the criteria for inclusion in the risk group (43%). As for the RT-PCR result: 58 patients (50%) had RT-PCR detected (confirmed); 58 patients (50%) had RT-PCR not detected - of these, 18 patients (31%) had anosmia during their evolution. Of the 116 patients who met the inclusion criteria, 77 were included in the classic COVID-19 syndrome. Of these 77 collaborators, 3 did not use homeopathic medication (N=74). The most indicated homeopathic medications were: Arsenicum album (42%); Bryonia (24%), Phosphorus (15%); Gelsemium (15%); Pulsatilla (2%); others (4%). The average symptom score before treatment was 12.27 and after treatment was 0.52 (p < xxxxx). Of the 57 patients who had anosmia, there was full recovery in 43 (75%) of the cases at the time of reassessment. The average time elapsed between the use of homeopathic medication and the recovery of symptoms was 9 days. Only 3 patients (3.9%) required hospitalization without the need for intubation, 2 of whom belonged to the risk group. Although these results are partial (as there are still research subjects in the evaluation phase), the results suggest that homeopathic treatment promoted the re-establishment of the infectious condition without the need for hospitalization in 97% of the patients. Anosmia recovered completely in 75% of the patients. Arsenicum album, Bryonia and Phosphorus were the drugs predominantly chosen for treatment, which corroborates other homeopathic studies.

Investigation of the Antitumor Activity and Toxicity of Tumor-Derived Exosomes Fused with Long-Circulating and pH-Sensitive Liposomes Containing Doxorubicin.

Exosome-liposome hybrid nanocarriers containing chemotherapeutic agents have been developed to enhance drug delivery, improve the efficacy of the treatment of metastatic cancer, and overcome chemoresistance in cancer therapy. Thus, the objectives of this study were to investigate the toxicological profiles of exosomes fused with long-circulating and pH-sensitive liposomes containing doxorubicin (ExoSpHL-DOX) in healthy mice and the antitumor activity of ExoSpHL-DOX in Balb/c female mice bearing 4T1 breast tumors. The acute toxicity was determined by evaluating the mortality and morbidity of the animals and conducting hematological, biochemical, and histopathological analyses after a single intravenous administration of ExoSpHL-DOX. The results of the study indicated that the ExoSpHL-DOX treatment is less toxic than the free doxorubicin (DOX) treatment. ExoSpHL-DOX showed no signs of nephrotoxicity, even at the highest dose of DOX, indicating that the hybrid nanosystem may alter the distribution of DOX and reduce the kidney damage. Regarding the antitumor activity, ExoSpHL-DOX showed an antitumor effect compared to the control group. Furthermore, the hybrid nanocarrier of tumor-derived exosomes fused with long-circulating and pH-sensitive liposomes reduced the number of metastatic foci in the lungs. These results indicate that ExoSpHL-DOX may be a promising nanocarrier for the treatment of breast cancer, reducing toxicity and inhibiting metastasis, mainly in the lungs.

TIDE: evidências de validade baseadas em critérios externos / TIDE: evidence of validity based on external criteria / TIDE: evidencia de validez basada en criterios externos

Objetivou-se buscar evidências de validade baseadas em critérios externos do Teste Informatizado e Dinâmico de Escrita - TIDE, em relação à ortografia e cognição. Participaram 304 alunos, entre 10 e 17 anos. Foram utilizados o TIDE, o instrumento Ditado Balanceado de Moojen e os subtestes: "Dígitos, Informação, Compreensão e Vocabulário" do WISC III. Em relação ao critério ortográfico, o módulo pré-teste esteve negativamente associado aos erros do Ditado, com exceção dos erros relacionados a irregularidades da língua. O módulo instrucional correlacionou-se de forma significativa negativa com os três tipos de erro do ditado. Em relação aos aspectos cognitivos, o módulo pré-teste não esteve associado. O módulo instrucional correlacionou-se com os quatro subtestes do WISC-III, demonstrando relação com aspectos cognitivos, memória, atenção, julgamento e o conhecimento lexical dos sujeitos. (AU)

The aim of this study was to investigate evidence of validity based on external criteria for the Computerized and Dynamic Writing Test - TIDE, in relation to spelling and cognition. Participants were 304 students, aged between 10 and 17 years. The TIDE, the Moojen Balanced Dictation instrument and the "Digits, Information, Understanding and Vocabulary" subtests of the WISC III were used. Regarding the orthographic criterion, the TIDE pre-test module was negatively associated with Dictation errors, with the exception of errors related to language irregularities. The instructional module presented significant negative correlations with the three types of dictation error. The pre-test module was not associated with the cognitive aspects. The instructional module correlated with the four WISC-III subtests, demonstrating a relation with cognitive aspects, memory, attention, judgment and the lexical knowledge of the subjects. (AU)

Se objetivó buscar evidencias de validez basadas en criterios externos del Test de Escritura Computarizada y Dinámica - TIDE, con relación a la ortografía y la cognición. Participaron 304 estudiantes, entre 10 y 17 años. Se utilizaron TIDE, el instrumento de Dictado Equilibrado de Moojen y las subpruebas "Dígitos, Información, Comprensión y Vocabulario" de WISC III. En cuanto a los criterios ortográficos, el módulo de prueba previa se asoció negativamente con los errores del Dictado, a excepción de los errores relacionados con las irregularidades del idioma. El módulo de instrucción se correlacionó significativamente de manera negativa con los tres tipos de errores del dictado. Con respecto a los aspectos cognitivos, el módulo de prueba previa no se ha asociado. El módulo de instrucción se correlacionó con las cuatro subpruebas de WISC-III, demostrando una relación con los aspectos cognitivos, la memoria, la atención, el juicio y el conocimiento léxico de los sujetos. (AU)

PEGylated versus Non-PEGylated pH-Sensitive Liposomes: New Insights from a Comparative Antitumor Activity Study.

PEGylated liposomes are largely studied as long-circulating drug delivery systems. Nevertheless, the addition of PEG can result in reduced interactions between liposomes and cells, hindering liposomal internalization into target cells. The presence of PEG on the surface of pH-sensitive liposomes is not advantageous in terms of biodistribution and tumor uptake, raising the question of whether the indiscriminate use of PEG benefits the formulation. In this study, two doxorubicin-loaded pH-sensitive liposomal formulations, PEGylated (Lip2000-DOX) or non-PEGylated (Lip-DOX), were prepared and characterized. Overall, the PEGylated and non-PEGylated liposomes showed no differences in size or morphology in Cryo-TEM image analysis. Specifically, DLS analysis showed a mean diameter of 140 nm, PDI lower than 0.2, and zeta potential close to neutrality. Both formulations showed an EP higher than 90%. With respect to drug delivery, Lip-DOX had better cellular uptake than Lip2000-DOX, suggesting that the presence of PEG reduced the amount of intracellular DOX accumulation. The antitumor activities of free-DOX and both liposomal formulations were evaluated in 4T1 breast tumor-bearing BALB/c mice. The results showed that Lip-DOX was more effective in controlling tumor growth than other groups, inhibiting tumor growth by 60.4%. Histological lung analysis confirmed that none of the animals in the Lip-DOX group had metastatic foci. These results support that pH-sensitive liposomes have interesting antitumor properties and may produce important outcomes without PEG.

The effect of free and encapsulated cisplatin into long-circulating and pH-sensitive liposomes on IEC-6 cells during wound healing in the presence of host-microbiota.

OBJECTIVES: To circumvent cisplatin (CDDP) toxic effects and improve the antitumoural effect, our research group developed long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP). This study aimed to evaluate whether SpHL-CDDP is associated with intestinal protection under in-vitro conditions in the presence of host-microbiota, compared with free CDDP. METHODS: The cytotoxicity of CDDP and SpHL-CDDP were evaluated by colorimetric MTT and sulforhodamine B (SRB) assays. Epithelial proliferation was assessed by using an in-vitro wounding model in the presence of host-microbiota with intestinal epithelial cell line 6 (IEC-6) monolayers. Cytokines were determined by ELISA. KEY FINDINGS: Reduced cytotoxicity of SpHL-CDDP in IEC-6 cells (minimum of 1.3-fold according to the IC50 values) was observed when compared with CDDP. The presence of microbiota or CDDP reduced the wound healing. The association of microbiota and SpHL-CDDP improved the wound healing and cell number in IEC-6 cells when compared with control. These beneficial results can be associated with increased IL-6 and IL-10 levels induced by SpHL-CDDP which were affected by the presence of microbiota. CONCLUSIONS: These results indicate that the presence of microbiota associated with SpHL-CDDP provided less intestinal cellular damages compared with CDDP and constitutes a promising candidate for clinical use.

Long-Circulating and Fusogenic Liposomes Loaded with Paclitaxel and Doxorubicin: Effect of Excipient, Freezing, and Freeze-Drying on Quality Attributes.

Liposomes can increase plasma half-life, enhance targeting, and diminish the side-effects of loaded drugs. On the downside, physical and chemical instabilities of dispersions often result in a reduced lifespan, which limits their availability on the market. Solid formulations obtained by freeze-drying can immobilize vesicles and provide extended shelf life. For both processes, the choice of excipients and process parameters are crucial to protect the carrier layers against tension caused by freezing and/or dehydration. The aim of this work is to evaluate the influence of freezing and drying parameters, besides excipient choice, to obtain solid long-circulating and fusogenic liposomes (LCFL-PTX/DXR) co-encapsulating paclitaxel (PTX) and doxorubicin (DXR) at a synergistic ratio (1:10). METHODS: LCFL-PTX/DXR was evaluated by freeze-drying microscopy (glass transition, Tg'), differential scanning calorimetry (collapse temperature, Tc), freeze-thawing and freeze-drying processes. Freeze-dried samples were evaluated by thermogravimetry (residual moisture) and the resuspended liposomes were characterized in terms of size, polydispersity index (PI), zeta potential (ZP), and drug content. Liposomes morphology was evaluated by cryomicroscopy. RESULTS: Trehalose protected PTX cargo upon freeze-thawing and more than 80% of the original DXR retention. The formulations with trehalose resulted in a cake with 5-7% of moisture content (200-240 nm); 44-60% of PTX retention, and 25-35% of DXR retention, with the variations caused by cryoprotector concentration and process changes. CONCLUSIONS: Trehalose protected liposome integrity, maintaining PTX retention and most of DXR upon freeze-thawing. Freeze-drying reduced the retention of both drugs inside all liposomes, whereas formulation with trehalose presented minor losses. Therefore, this frozen formulation is an alternative product option, with no need for manipulation before use.

Official Position of the Brazilian Association of Bone Assessment and Metabolism (ABRASSO) on the evaluation of body composition by densitometry—part II (clinical aspects): interpretation, reporting, and special situations

Abstract Objective: To present an updated and evidence-based guideline for the use of dual-energy x-ray absorptiometry (DXA) to assess body composition in clinical practice. Materials and methods: This Official Position was developed by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism ( Associação Brasileira de Avaliação Óssea e Osteometabolismo , ABRASSO) and experts in the field who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications in the area of body composition assessment. In this second part of the Official Position, the authors discuss the interpretation and reporting of body composition parameters assessed by DXA and the use of DXA for body composition evaluation in special situations, including evaluation of children, persons with HIV, and animals. Conclusion: This document offers recommendations for the use of DXA in body composition evaluation, including indications, interpretation, and applications, to serve as a guiding tool in clinical practice and research for health care professionals in Brazil.

Consenso Abem para o ensino de comunicação nas escolas médicas brasileiras / ABEM consensus for the brazilian medical schools' communication curriculum

Resumo: Introdução: A comunicação é uma competência essencial para o(a) médico(a) e outras categorias profissionais, e deve ser desenvolvida durante sua formação profissional. A elaboração de um projeto de comunicação, incluindo um consenso brasileiro, visou subsidiar as escolas médicas a preparar os estudantes de Medicina para se comunicarem efetivamente com os(as) cidadãos/cidadãs brasileiros(as), de características plurais intra e inter-regionais, pautando-se no profissionalismo e nos princípios do Sistema Único de Saúde (SUS). Objetivo: Este manuscrito apresenta o consenso para o ensino de comunicação nas escolas médicas brasileiras. Método: O consenso foi construído colaborativamente com 276 participantes, experts em comunicação, docentes, profissionais de saúde e discentes, de 126 escolas médicas e cinco instituições de saúde, ao longo de nove encontros presenciais em congressos e de encontros virtuais quinzenais ou mensais. Nos encontros, compartilharam-se as experiências dos participantes e o material bibliográfico, incluindo os consensos internacionais, e apresentou-se o consenso em construção, com discussão em grupos para elencar novos componentes para o consenso brasileiro, seguida por debate com todos para pactuá-los. A versão final foi aprovada em reunião virtual, com convite a todos(as) os(as) participantes em julho de 2021. Após submissão, diversas alterações foram requeridas, o que demandou novos encontros para revisão da versão final do consenso. Resultado: O consenso tem como pressupostos que a comunicação deve ser centrada nas relações, pautada nos princípios do SUS, na participação social e no profissionalismo, e embasada nas Diretrizes Curriculares Nacionais do curso de graduação em Medicina, em referenciais teóricos e nas evidências científicas. São descritos objetivos específicos para desenvolver a competência em comunicação nos estudantes, abrangendo: fundamentos teóricos; busca e avaliação crítica da literatura; elaboração e redação de documentos; comunicação intrapessoal e interpessoal no ambiente acadêmico-científico, na atenção à saúde em diversos contextos clínicos e na gestão em saúde. Recomenda-se a inserção curricular da comunicação do início ao final do curso, integrada a outros conteúdos e áreas de saber. Conclusão: Espera-se que esse consenso contribua para a revisão ou implementação da comunicação nos currículos das escolas médicas brasileiras.

Abstract: Introduction: Communication is an essential competence for the physician and other professional categories, and must be developed their professional training. The creation of a communication project including a Brazilian consensus aimed to subsidize medical schools in preparing medical students to communicate effectively with Brazilian citizens, with plural intra and inter-regional characteristics, based on the professionalism and the Brazilian Unified System (SUS) principles. Objective: The objective of this manuscript is to present the consensus for the teaching of communication in Brazilian medical schools. Method: The consensus was built collaboratively with 276 participants, experts in communication, faculty, health professionals and students from 126 medical schools and five health institutions in face-to-face conference meetings and biweekly or monthly virtual meetings. In the meetings, the participants' experiences and bibliographic material were shared, including international consensuses, and the consensus under construction was presented, with group discussion to list new components for the Brazilian consensus, followed by debate with everyone, to agree on them. The final version was approved in a virtual meeting with invitation to all participants in July 2021. After the submission, several changes were required, which demanded new meetings to review the consensus final version. Result: The consensus is based on assumptions that communication should be relationship-centered, embedded on professionalism, grounded on the SUS principles and social participation, and based on the National Guidelines for the undergraduate medical course, theoretical references and scientific evidence. Specific objectives to develop communication competence in the students are described, covering: theoretical foundations; literature search and its critical evaluation; documents drafting and editing; intrapersonal and interpersonal communication in the academicscientific environment, in health care and in health management; and, communication in diverse clinical contexts. The inclusion of communication in the curriculum is recommended from the beginning to the end of the course, integrated with other contents and areas of knowledge. Conclusion: It is expected that this consensus contributes the review or implementation of communication in Brazilian medical schools' curricula.

Percepção da sensação subjetiva de bem-estar geral em sujeitos tratados com homeopatia: uma abordagem qualitativa / Perception of the subjective sensation of general well-being in subjects treated with homeopathy: a qualitative approach

Durante o tratamento homeopático a melhora costuma ser identificada a partir de uma sensação inespecífica de bem-estar, denominada Sensação Subjetiva de Bem-Estar Geral (SSBEG). Este estudo qualitativo buscou compreender como sujeitos tratados com homeopatia percebem a SSBEG a partir de uma compreensão hermenêutica associada à visão da Medicina Centrada na Pessoa. Foram entrevistados sujeitos que faziam acompanhamento no ambulatório de Homeopatia de uma faculdade particular em Salvador-Bahia e utilizada a análise de conteúdo para avaliação dos resultados. A SSBEG apresentou-se como um estado de equilíbrio dinâmico no qual sujeito é capaz de gerir a sua vida, lidar com seus sofrimentos, buscando novas formas de sentir-se bem. Implica um estado de satisfação, de harmonia, de equilíbrio interno, não apenas uma ausência de sofrimento, mas uma sensação de estar vivendo inteiramente.

To evalu ate response to homeopathic treatment, improvement can be referred to as an unspecific sense of well-being. This sensation is named in homeopathic literature as Subjective Sensation of General Well-Being (SSGWB). This study so ught to qualitatively analyze how subjects treated with homeopathy perceive SSGWB after at least 6 months of treatment, based on a hermeneutic approach along with a Person-Centered Medicine perspective. Semi-structured interviews were conducted with subjectswho were being followed up at the homeopathic outpatient clinic of the medical center of a private college in Salvador-Bahia and used content analysis to evaluate results. The SSGWB presented itself as a state of dynamic equilibrium in which the subject can manage his life, deal with his sufferings, looking for new ways to feel good. It implies a state of satisfaction, harmony, internal balance, not just an absence of suffering but a feeling of being fully alive.

Durante el tratamiento homeopático, la mejora generalmente se identifica a partir de una sensación de bienestar no específica llamada sensación subjetiva de bienestar general (SSBEG). Este estudio buscó comprender cómo los sujetos tratados con homeopatía perciben SSBEG, basado en una comprensión hermenéutica asociada con la visión de la Medicina Centrada en la Persona. Se entrevistó a sujetos que fueron monitoreados en la clínica ambulatorial de homeopatía de una universidad privada en Salvador-Bahía y se utilizó el análisis de contenido para evaluar los resultados. El SSBEG se presentó como un estado de equilibrio dinámico, en el que el sujeto es capaz de gestionar su vida, afrontar sus sufrimientos, buscar nuevas formas de sentirse bien. Implica un estado de satisfacción, armonía, equilibrio interior, no solo una ausencia de sufrimiento, sino una sensación de estar viviendo con plenitud.

A assistência ao parto normal e a satisfação das puérperas / Asistencia al parto normal y satisfacción de las puérperas / Assistance to normal childbirth and the satisfaction of the puerperal women

Objetivo: Averiguar o que diz a literatura quanto à satisfação das puérperas em relação à assistência recebida no trabalho de parto e parto nos serviços de saúde. Método: Estudo qualitativo do tipo revisão integrativa, nas Bases de Dados: MEDLINE/BVS, SciELO, BDENF, PubMed, e DOAJ, no período de 15 de janeiro a 20 de fevereiro de 2021. Foi realizada leitura analítica dos estudos identificando os pontos chave para hierarquização e síntese das ideias. Resultados: Foram selecionados 14 estudos. Os dados obtidos com a pesquisa apontam para a inexistência de unanimidade quanto à percepção e satisfação das mulheres em relação à assistência ao trabalho de parto e parto. Conclusão: Portanto, atenção, acolhimento, cuidado e vínculo são elementos fundamentais para uma melhor assistência e, consequentemente, para o alcance da satisfação destas mulheres em relação à assistência recebida(AU)

Objective: To investigate what the literature says about the satisfaction of postpartum women in relation to the assistance received in labor and delivery in health services. Method: Qualitative study of the integrative review type, in Databases: MEDLINE/BVS, SciELO, BDENF, PubMed, and DOAJ, from January 15th to February 20th of 2021. An analytical reading of the studies was carried out, identifying the key points for the hierarchy and synthesis of ideas. Results: 14 studies were selected. The data obtained from the survey point to the lack of unanimity regarding the perception and satisfaction of women in relation to care during labor and delivery. Conclusion: Therefore, attention, reception, care and bonding are fundamental elements for better care and, consequently, for achieving these women's satisfaction in relation to the care received.(AU)

Objetivo: Investigar lo que dice la literatura sobre la satisfacción de las mujeres posparto en relación a la asistencia recibida en el trabajo de parto y parto en los servicios de salud. Método: Estudio cualitativo del tipo revisión integrativa, en Bases de datos: MEDLINE / BVS, SciELO, BDENF, PubMed, y DOAJ, del 15 de enero al 20 de febrero de 2021. Análisis analítico Se realizó la lectura de los estudios, identificando los puntos clave para la jerarquía y síntesis de las ideas. Resultados: Se seleccionaron 14 estudios. Los datos obtenidos de la encuesta apuntan a la falta de unanimidad en cuanto a la percepción y satisfacción de las mujeres en relación al cuidado durante el trabajo de parto y parto. Conclusión: Por lo tanto, la atención, la recepción, el cuidado y la vinculación son elementos fundamentales para un mejor cuidado y, en consecuencia, para lograr la satisfacción de estas mujeres en relación con el cuidado recibido(AU)

Polysonographic changes in obese patients with indication of bariatric surgery.

INTRODUCTION: obstructive Sleep Apnea Syndrome (OSAS) is a serious confition that compromises the quality of life and survival of patients. Its main risk fator in adults is obesity and the gold standard test for diagnosis is polysomnography (PSG), mainly through the apneia-hypopnea index (AHI). Objective: to analyze the sleep pattern of obese patients with indication for bariatric surgery, determining the main polisomnographic parameters compromised by obesity. METHODS: This work is a cross-sectional study with analysis of polysomnography perfomed in patients with obesity in the peroperative period of bariatric surgery at a clinic in Vitória da Conquista/BA during 2017. The Epi Info 7 platform was used for analysis of the data. RESULTS: 58 polysomnographic reports were analyzed, with 56,9% morbdly obese and 43,1% non-morbid. The prevalence of OSAS was 70,68% and de AHI ranged from zero to 84,6 with a mean of 19,47±22,89 e/h. morbidly obese, compared to "non-morbid", had a longer saturation time below 80% and 90% (0,4±0,93 vs. 0,12±0,45 e 4,87±7,38 vs. 1,36±2,87 respectively; p-value=0,02 in both), worse index respiratory disorders ((29,24±25,36 vs. 16,88±16,21; p-value=0,02), higher AHI (24,71±25,68 vs. 12,56±16,67; p-value=0,02), higher hypopnea index values (16,41±17,10 vs. 6,99±8,52; p-value=0,006) and lower minimum saturation (78,24±9,80 vs. 85,24±6,33; p-value=0,004). CONCLUSIONS: the high prevalence of OSAS found confirms its indication in the preoperative period of bariatric surgery. The main respiratory event involved in most individuals with OSAS was the hypopnea index.

Preclinical toxicological study of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in synergic ratio.

Combination therapy between paclitaxel (PTX) and doxorubicin (DXR) is applied as the first-line treatment of breast cancer. Co-administration of drugs at synergistic ratio for treatment is facilitated with the use of nanocarriers, such as liposomes. However, despite the high response rate of solid tumors to this combination, a synergism of cardiotoxicity may limit the use. Thus, the objective of this work was to investigate the toxicity of long-circulating and fusogenic liposomes co-encapsulating PTX and DXR at the synergistic molar ratio (1:10) (LCFL-PTX/DXR). For this, clinical chemistry, histopathological analysis and electrocardiographic exams were performed on female Balb/c mice that received a single intravenous dose of LCFL-PTX/DXR. The results of the study indicated that the LD50 dose range (lethal dose for 50% of animals) of the LCFL-PTX/DXR treatment (28.9-34.7 mg/kg) is much higher than that found for free PTX/DXR treatment (20.8-23.1 mg/kg). In addition, liposomes promoted cardiac protection by not raising CK-MB levels in animals, keeping cardiomyocytes without injury or electrocardiographic changes. After 14 days of treatment, free PTX/DXR caused prolongation of the QRS interval when compared to LCFL-PTX/DXR treatment at the same dose (37.0 ± 5.01 ms and 30.83 ± 2.62 ms, respectively, with p = 0.017). The survival rate of animals treated with LCFL-PTX/DXR was three times higher than that of those treated with free drugs. Thus, it was established that the toxicity of LCFL-PTX/DXR is reduced compared to the combination of free PTX/DXR and this platform has advantages for the clinical treatment of breast cancer.

pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment.

Irinotecan (IRN) is a semisynthetic derivative of camptothecin that acts as a topoisomerase I inhibitor. IRN is used worldwide for the treatment of several types of cancer, including colorectal cancer, however its use can lead to serious adverse effects, as diarrhea and myelosuppression. Liposomes are widely used as drug delivery systems that can improve chemotherapeutic activity and decrease side effects. Liposomes can also be pH-sensitive to release its content preferentially in acidic environments, like tumors, and be surface-functionalized for targeting purposes. Herein, we developed a folate-coated pH-sensitive liposome as a drug delivery system for IRN to reach improved tumor therapy without potential adverse events. Liposomes were prepared containing IRN and characterized for particle size, polydispersity index, zeta potential, concentration, encapsulation, cellular uptake, and release profile. Antitumor activity was investigated in a murine model of colorectal cancer, and its toxicity was evaluated by hematological/biochemical tests and histological analysis of main organs. The results showed vesicles smaller than 200 nm with little dispersion, a surface charge close to neutral, and high encapsulation rate of over 90%. The system demonstrated prolonged and sustained release in pH-dependent manner with high intracellular drug delivery capacity. Importantly, the folate-coated pH-sensitive formulation had significantly better antitumor activity than the pH-dependent system only or the free drug. Tumor tissue of IRN-containing groups presented large areas of necrosis. Furthermore, no evidence of systemic toxicity was found for the groups investigated. Thus, our developed nanodrug IRN delivery system can potentially be an alternative to conventional colorectal cancer treatment.

Loss of erythroblasts in acute myeloid leukemia causes iron redistribution with clinical implications.

Acute myeloid leukemia (AML) is a heterogeneous disease with poor prognosis and limited treatment strategies. Determining the role of cell-extrinsic regulators of leukemic cells is vital to gain clinical insights into the biology of AML. Iron is a key extrinsic regulator of cancer, but its systemic regulation remains poorly explored in AML. To address this question, we studied iron metabolism in patients with AML at diagnosis and explored the mechanisms involved using the syngeneic MLL-AF9-induced AML mouse model. We found that AML is a disorder with a unique iron profile, not associated with inflammation or transfusion, characterized by high ferritin, low transferrin, high transferrin saturation (TSAT), and high hepcidin. The increased TSAT in particular, contrasts with observations in other cancer types and in anemia of inflammation. Using the MLL-AF9 mouse model of AML, we demonstrated that the AML-induced loss of erythroblasts is responsible for iron redistribution and increased TSAT. We also show that AML progression is delayed in mouse models of systemic iron overload and that elevated TSAT at diagnosis is independently associated with increased overall survival in AML. We suggest that TSAT may be a relevant prognostic marker in AML.

Liposomal paclitaxel induces apoptosis, cell death, inhibition of migration capacity and antitumoral activity in ovarian cancer.

The main goal of this study is to evaluate the efficacy of the paclitaxel (PTX) drug formulated with a liposomal nanosystem (L-PTX) in a peritoneal carcinomatosis derived from ovarian cancer. In vitro cell viability studies with the human ovarian cancer line A2780 showed a 50% decrease in the inhibitory concentration for L-PTX compared to free PTX. A2780 cells treated with the L-PTX formulation demonstrated a reduced capacity to form colonies in comparison to those treated with PTX. Cell death following L-PTX administration hinted at apoptosis, with most cells undergoing initial apoptosis. A2780 cells exhibited an inhibitory migration profile when analyzed by Wound Healing and real-time cell analysis (xCELLigence) methods after L-PTX administration. This inhibition was related to decreased expression of the zinc finger E-box-binding homeobox 1 (ZEB1) and transforming growth factor 2 (TGF-ß2) genes. In vivoL-PTX administration strongly inhibited tumor cell proliferation in ovarian peritoneal carcinomatosis derived from ovarian cancer, indicating higher antitumor activity than PTX. L-PTX formulation did not show toxicity in the mice model. This study demonstrated that liposomal paclitaxel formulations are less toxic to normal tissues than free paclitaxel and are more effective in inhibiting tumor cell proliferation/migration and inducing ZEB1/TGF-ß2 gene expression.