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INTRODUCTION: Pro-resolving molecules may curb disease caused by viruses without altering the capacity of the host to deal with infection. AP1189 is a melanocortin receptor-biased agonist endowed with pro-resolving and anti-inflammatory activity. We evaluated the preclinical and early clinical effects of treatment with AP1189 in the context of COVID-19. METHODS: C57BL/6j mice were infected intranasally with MHV-A59 or hK18-ACE2 mice with SARS-CoV-2. AP1189 (10 mg·kg-1, BID, s.c.) was given to the animals from day 2 and parameters evaluated at day 5. Human PBMCs from health donors were infected with SARS-CoV-2 in presence or absence of AP1189 and production of cytokines quantified. In the clinical study, 6 patients were initially given AP1189 (100 mg daily for 14 days) and this was followed by a randomized (2:1), placebo-controlled, double-blind trial that enrolled 54 hospitalized COVID-19 patients needing oxygen support. The primary outcome was the time in days until respiratory recovery, defined as a SpO2 ≥ 93% in ambient air. RESULTS: Treatment with AP1189 attenuated pulmonary inflammation in mice infected with MHV-A59 or SARS-CoV-2 and decreased the release of CXCL10, TNF-α and IL-1ß by human PBMCs. Hospitalized COVID-19 patients already taking glucocorticoids took a median time of 6 days until respiratory recovery when given placebo versus 4 days when taking AP1189 (P = 0.017). CONCLUSION: Treatment with AP1189 was associated with less disease caused by beta-coronavirus infection both in mice and in humans. This is the first demonstration of the effects of a pro-resolving molecule in the context of severe infection in humans.

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PURPOSE: We aim to compare interfragmentary compression with the position osteosynthesis in the fixation of different femoral neck fractures (FN) in synthetic bones subjected to vertical load. METHODS: Forty-two synthetic femurs were subjected to neck fractures and separated into 3 groups according to the Pauwels classification: Pauwels I had 6 units (PI); Pauwels II, 24 units, with and without comminution (PII); and Pauwels III, 12 units, with and without comminution (PIII). After, they were fixed with 2 different ways: three 7, 0 mm cannulated lag screws (CSs) versus three 6, 5 mm solid fully threaded screws (SSs). Screws positioning was oriented by the Pauwels classification: inverted triangle or crossed screws. All specimens were submitted to vertical loading until failure. RESULTS: The average force was 79.4 ± 22.6 Kgf. The greatest one was recorded in model 1 (135.6 Kgf), and the lowest in model 41 (39.6 Kgf). CSs and SSs had similar resistance until failure (p = 0.2). PI showed heightened resistance and PIII showed a worse response (p < 0,01). CSs had better performance in PIII (p = 0.048). Comminution and screws orientation caused no difference on peak force (p = 0.918 and p = 0.340, respectively). CONCLUSIONS: In synthetic bones, the resistance of a femoral neck fracture osteosynthesis using a 7, 0 mm cannulated lag screw or 6, 5 mm solid fully threaded screw are similar. There was no loss of efficiency with comminution in the femoral neck. Osteosynthesis resistance decreased with the verticalization of the fracture line and, in the more vertical ones, interfragmentary compression with CSs was more resistant than positional osteosynthesis with SSs.

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Introduction: Solanum chilense is a wild relative of tomato reported to exhibit resistance to biotic and abiotic stresses. There is potential to improve tomato cultivars via breeding with wild relatives, a process greatly accelerated by suitable genomic and genetic resources. Methods: In this study we generated a high-quality, chromosome-level, de novo assembly for the S. chilense accession LA1972 using a hybrid assembly strategy with ~180 Gbp of Illumina short reads and ~50 Gbp long PacBio reads. Further scaffolding was performed using Bionano optical maps and 10x Chromium reads. Results: The resulting sequences were arranged into 12 pseudomolecules using Hi-C sequencing. This resulted in a 901 Mbp assembly, with a completeness of 95%, as determined by Benchmarking with Universal Single-Copy Orthologs (BUSCO). Sequencing of RNA from multiple tissues resulting in ~219 Gbp of reads was used to annotate the genome assembly with an RNA-Seq guided gene prediction, and for a de novo transcriptome assembly. This chromosome-level, high-quality reference genome for S. chilense accession LA1972 will support future breeding efforts for more sustainable tomato production. Discussion: Gene sequences related to drought and salt resistance were compared between S. chilense and S. lycopersicum to identify amino acid variations with high potential for functional impact. These variants were subsequently analysed in 84 resequenced tomato lines across 12 different related species to explore the variant distributions. We identified a set of 7 putative impactful amino acid variants some of which may also impact on fruit development for example the ethylene-responsive transcription factor WIN1 and ethylene-insensitive protein 2. These variants could be tested for their ability to confer functional phenotypes to cultivars that have lost these variants.

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The Covid-19 pandemic revealed the difficulties of vaccinating a population under the circumstances marked by urgency and limited availability of doses while balancing benefits associated with distinct guidelines satisfying specific ethical criteria. We offer a vaccination strategy that may be useful in this regard. It relies on the mathematical concept of envy-freeness. We consider finding balance by allocating the resource among individuals that seem heterogeneous concerning the direct and indirect benefits of vaccination, depending on age. The proposed strategy adapts a constructive approach in the literature based on Sperner's Lemma to point out an approximate division of doses guaranteeing that both benefits are optimized each time a batch becomes available. Applications using data about population age distributions from diverse countries suggest that, among other features, this strategy maintains the desired balance, throughout the entire vaccination period. We discuss complementary aspects of the method in the context of epidemiological models of age-stratified Susceptible - Infected - Recovered (SIR) type.

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The choice of retaining material that will replace the lost properties of the tooth, in which it is fragile and with loss of dentin structure, is important. The success of the treatment will depend on the qualities presented in it. Therefore, the objective of this work, through a literature review, is to present the advantages and disadvantages observed in the use of fiberglass post intraradicular retainer. This paper reviews the most relevant articles on the specificities presented in the fiberglass post retaining material, published in the period (2003 to 2020). The bibliographic search was performed in PubMed, Lilacs, Scielo, Google Scholar databases. In view of the selected articles on the subject, it is possible to observe the authors' acceptance of the application of the use of retainers, highlighting that in the treatment of cases with extensive coronary destruction, the aim is to have the functional and retentive capacity returned, in addition to the tension resistance. Therefore, theThe use of fiberglass posts in weakened teeth is effective as the material of choice. In cases that require reconstruction and return of tissue integrity, it has sufficient advantages for its selection. Despite the disadvantages it has, these do not outweigh the benefits to the point of making its use unfeasible. However, knowing when, where and how to treat is always important in any procedure for a satisfactory final outcome.

A escolha do material retentor que irá substituir as propriedades perdidas do dente, no qual este se apresenta de forma fragilizada e com perca de estrutura dentinária é importante. O sucesso do tratamento irá depender das qualidades apresentadas no mesmo. Sendo assim, o objetivo deste trabalho por meio de uma revisão de literatura é apresentar as vantagens e desvantagens observadas no uso do retentor intrarradicular de pino de fibra de vidro. Este trabalho revisa os artigos mais relevantes sobre as especificidades apresentadas no material retentor de pino de fibra de vidro, publicadas no período (2003 até 2020). A busca bibliográfica foi realizada nos bancos de dados PubMed, Lilacs, Scielo, Google Scholar. Diante dos artigos selecionados referentes ao tema, pode-se observar a aceitação dos autores sobre a aplicação do uso de retentores, destacando-se que no tratamento de casos com destruição coronária extensa o intuito é dispor da devolução da capacidade funcional, retentiva, além da resistência a tensão. Portanto, a utilização de pinos de fibra de vidro em dentes fragilizados apresenta efetividade como material de escolha. Em casos que necessitam de reconstrução e devolução de sua integridade tecidual, possui consigo vantagens suficientes para sua seleção. Apesar das desvantagens que possui, essas não se sobrepõem aos benefícios a ponto de tornarem inviáveis ao seu uso. Entretanto, saber quando, onde e como tratar é sempre importante em qualquer procedimento para um desfecho final satisfatório.

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BACKGROUND: Working part-time or full-time is a persistent dilemma for women, especially mothers, as they strive to manage their time across various roles. However, the existing literature remains unclear on whether part-time work contributes more to life satisfaction than full-time work. OBJECTIVE: This study aims to describe and compare time-use patterns in different occupational roles and levels of life satisfaction among 795 mothers in Brazil who are employed either part-time or full-time. METHODS: Data was collected through an online survey and the snowball technique. Regression and correlation analyses were performed on the data obtained from the following instruments: the Role Checklist for assessing time-use within occupational roles, the Satisfaction with Life Scale, and demographic information. RESULTS: Our analysis revealed no significant differences in life satisfaction between mothers working full-time and those working part-time (t (793)=1.160, p = 0.24). However, life satisfaction scores were positively correlated with the number of occupational roles performed (r = 0.222, p < 0.01), higher family income (P < 0.001), and engagement in social roles such as Friend (r = 0.106, p = 0.003), Hobbyist/Amateur (r = 0.08, p = 0.018), and Caregiver (r = 0.07, p = 0.026). CONCLUSION: While our society places significant emphasis on time spent at work, our findings highlight that life satisfaction extends far beyond the dichotomy of working part-time or full-time. There are deeper dimensions to consider, including the number of occupational roles, family income, and engagement in social roles, which have a more substantial impact on overall life satisfaction.

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INTRODUCTION: it is estimated that approximately 20 million people undergo inguinal hernia surgery annually in the world, with the Lichtenstein technique being the most performed surgical procedure. The objective of this study is to analyze the knowledge of the technical principles used in the Lichtenstein technique. METHOD: Survey-type intersectional study approved by the research ethics committee of São Camilo University Center (CAAE: 70036523.1.0000.0062). During the research period, 11,622 e-mails were sent to members of the main national surgical societies with research on the technical principles of Lichtenstein surgery. The survey was carried out using an electronic form with 10 multiple-choice questions. The form was answered anonymously on the SurveyMonkey and Google Forms platforms. RESULT: 744 responses were received to the electronic form. Based on this number of respondents, our survey has a confidence level of 95% with a margin of error of 3.5%. It was observed that there is no standardization of the technique among the majority of responders (53.4%). Many surgeons still perform digital dissection of the spermatic cord (47%). A small number of interviewees (15.2%) performed sutures with absorbable thread in the region of the internal oblique aponeurosis, while more than half (55.2%) continued to perform sutures with non-absorbable thread. Most surgeons use a small overlap or fix the mesh juxtaposed to the pubic symphysis (51%). CONCLUSION: Our research identified that a small percentage of respondents adequately know the technical principles of Lichtenstein surgery. The result brings us new insights into the need to review Lichtenstein technique.

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Heliotropium elongatum is used to treat inflammation, cough, and flu. This study aimed to characterize the phytochemical profile and determine the total phenolic content (TPC), antioxidant and cytogenotoxic activity of the ethanolic extract (EE), and fractions of H. elongatum leaves. In the phytochemical profile analysis, organic acids, reducing sugars, flavonoids, saponins, anthraquinones, steroids/triterpenes, and depsides/depsidones were detected in the EE and/or fractions (hexanic/FH, chloroformic/FC, ethyl acetate/FAE, and hydromethanolic/FHM). The highest TPC and highest antioxidant activity (DPPH and ABTS) was detected in FHM. In FH, 16 compounds were identified by GC-MS, and ursolic acid was isolated by 1H NMR and 13C NMR. HPLC-DAD from EE, FAE, and FHM demonstrated characteristic wavelengths for flavonoids, flavonols, flavones, and anthraquinones. ESI-IT/MSn analysis of EE, FC, FAE, and FHM revealed alkaloids, steroids, terpenoids, flavonoids, and phenolic acids. In Allium cepa assay there was no significant cytotoxic effect initiated by EE (62.5 to 1,000 µg/ml), FHM (1,000 µg/ml), and FAE (62.5 µg/ml). Genotoxicity was evidenced only with EE at 500 and 1,000 µg/ml, and FHM (62.5 to 1,000 µg/ml) as evidenced by presence of micronuclei (MN) and nuclear buds (NB). Our results identified compounds of medicinal interest with antioxidant activity; however observed cytogenotoxic changes indicated the need for caution when using these compounds for therapeutic purposes.

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INTRODUCTION: cutaneous melanoma (MC) is a malignant neoplasm derived from melanocytic cells with an aggressive behavior. It is usually associated with the multifactorial interaction of genetic susceptibility and environmental exposure, usually ultraviolet radiation. Despite advances in treatment, the disease remains relentless with poor prognosis. Sentinel lymph node (SLN) biopsy is a technique used to screen patients in need of lymph node dissection. OBJECTIVES: to correlate the tumor burden in the SLN with the mortality of patients undergoing SLN biopsy. METHODOLOGY: the medical records and histological slides of patients with MC who underwent SLN biopsy treated at HC-Unicamp from 2001 to 2021 were retrospectively analyzed. The positive SLN were measured according to the size of the tumor infiltration area, for analysis of the depth of invasion (DI), closest proximity to the capsule (CPC) and tumor burden (TB). For statistical analysis, associations between variables were analyzed using Fishers exact test, with post Bonferroni test and Wilcoxon test. RESULTS: 105 records of patients who underwent SLN biopsy of MC were identified. Of these, nine (8.6%) had positive SLN and 81 (77.1%) had negative SLN. The performed lymphadenectomies resulted in 55.6% (n=5) affected, 22.2% (n=2) without disease and 22.2% (n=2) were not performed. Mean CPC, TB, and DI were 0.14mm, 32.10mm and 2.33mm, respectively. Patients with T2 and T3 tumors were more likely to show the SLN affected (p=0.022). No patient with positive SLN died during follow-up. CONCLUSION: patients who presented T3 staging are the ones who most presented positive SLN.

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OBJECTIVES: This study aimed to analyze cognitive impairment associated with long-term coronavirus disease 2019 (COVID-19) syndrome and its correlation with anxiety, depression, and fatigue in patients infected with severe acute respiratory syndrome coronavirus. METHODS: This was a cross-sectional study of 127 patients with COVID-19. Tests to screen for neuropsychiatric symptoms included the Fatigue Severity Scale, Mini-Mental State Exam 2 (MMSE-2), Symbol Digit Modalities Test (SDMT), and Hospital Anxiety and Depression Scale. RESULTS: In cognitive tests, SDMT was abnormal in 22%, being more sensitive than MMSE-2 to detect cognitive changes. Furthermore, although manifestations such as fatigue, depression, and anxiety were frequent in the post-COVID-19 phase, these 3 conditions, known to contribute to cognitive impairment, were slightly correlated with worse performance on the rapid screening tests. CONCLUSIONS: In patients with mild COVID-19 and cognitive complaints, SDMT helped to confirm disturbances in the attention domain and processing speed.

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Amburana cearensis leaves have been used in folk medicine to treat respiratory diseases and inflammations. This study aimed to evaluate the biological potential of A. cearensis leaves by antioxidant and in vitro cytogenotoxic analyses of ethanolic crude extract (EE) and its fractions in healthy human cells. The EE was obtained by percolation, followed by fractionation using dichloromethane, cyclohexane, ethyl acetate (EtOAc), and methanol (MeOH) as organic solvents. Extract and all fractions were evaluated for their antioxidant potential by DPPH and reducing power tests. In vitro cytotoxic activity was determined in human peripheral blood mononuclear cells by MTT assay for the extract, EtOAc and MeOH fractions. In turn, the genotoxic activity was determined in human lymphocytes by the Cytokinesis Block Micronucleus assay only for the EtOAc fraction. Only EtOAc fraction was analyzed via gas chromatography coupled to mass spectrometry due to its higher biological activity. Considering the antioxidant potential, the EtOAc fraction was most effective in DPPH (EC50 43.37 µg/mL) and reducing power (EC50 89.80 µg/mL) assays. GC-MS analysis of the EtOAc fraction led to the identification of guaiacol, 2,3-dihydro-benzofuran, 2-methoxy-4-vinylphenol, isovanillic acid methyl ester, 4-hydroxybenzaldehyde, and 4-(ethoxymethyl)-phenol. The EE (400-1000 µg/mL), EtOAc (≤150 µg/mL) and MeOH (50 and 150-600 µg/mL) fractions were not cytotoxic by MTT test. Additionally, the EtOAc fraction (100-400 µg/mL) did not induce significant genotoxic damage. Concentrations of the EtOAc fraction with antioxidant activity showed no cytotoxicity, nor genotoxicity potential, indicating them as a nontoxic natural antioxidant source.

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The collapse of the Fundão tailings dam (Minas Gerais, Brazil) was the largest environmental disaster in Brazil's history and in the world mining industry. This disaster carried approximately 55 million m3 of iron ore tailings along the rivers and the lagoons of the Doce river basin. Although multiple studies assessed the impact on microbial communities in those rivers and lagoons right after the dam rupture, it is not known whether the microbiome in those environments remains impacted years after the disaster. Assessing the microbiome is very important to evaluate impacts and evaluate the health of the environment, due to the several ecological roles played by microorganisms. Here, we evaluated the impact of the dam failure on water and sediment bacteriome and archaeome by high-throughput next-generation sequencing. Samples were taken from two rivers and six lagoons during the dry and rainy seasons approximately three years post disturbance. The results showed a large number and abundance of microbial groups associated with the presence of heavy metals and mine tailings sediments. Some of these microorganisms were also reported in large abundance in the impacted rivers shortly after the Fundão dam rupture. Among the most abundant microorganisms in the Doce River, we can highlight the bacteria hgcI clade and the archaea Nitrososphera sp. in the water, and the bacteria Anaerolineaceae sp. in the sediment. These results suggest that the microbiome of the rivers and the lagoons in the Doce river basin remains severely impacted by the Fundão tailings dam failure even three years after the disaster. The presence of those microorganisms can also help to assess the occurrence of the Fundão dam sediment in other environments.

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ABSTRACT Introduction: it is estimated that approximately 20 million people undergo inguinal hernia surgery annually in the world, with the Lichtenstein technique being the most performed surgical procedure. The objective of this study is to analyze the knowledge of the technical principles used in the Lichtenstein technique. Method: Survey-type intersectional study approved by the research ethics committee of São Camilo University Center (CAAE: 70036523.1.0000.0062). During the research period, 11,622 e-mails were sent to members of the main national surgical societies with research on the technical principles of Lichtenstein surgery. The survey was carried out using an electronic form with 10 multiple-choice questions. The form was answered anonymously on the SurveyMonkey and Google Forms platforms. Result: 744 responses were received to the electronic form. Based on this number of respondents, our survey has a confidence level of 95% with a margin of error of 3.5%. It was observed that there is no standardization of the technique among the majority of responders (53.4%). Many surgeons still perform digital dissection of the spermatic cord (47%). A small number of interviewees (15.2%) performed sutures with absorbable thread in the region of the internal oblique aponeurosis, while more than half (55.2%) continued to perform sutures with non-absorbable thread. Most surgeons use a small overlap or fix the mesh juxtaposed to the pubic symphysis (51%). Conclusion: Our research identified that a small percentage of respondents adequately know the technical principles of Lichtenstein surgery. The result brings us new insights into the need to review Lichtenstein technique.

RESUMO Introdução: estima-se que aproximadamente 20 milhões de pessoas sejam submetidas a cirurgia de hérnia inguinal anualmente no mundo, sendo a técnica de Lichtenstein o procedimento cirúrgico mais realizado. O objetivo desse estudo é analisar o conhecimento dos principios técnicos empregados na técnica de Lichtenstein. Método: estudo tipo levantamento interseccional aprovado pelo comitê de ética em pesquisa do Centro Universitário São Camilo (CAAE: 70036523.1.0000.0062). Durante o período da pesquisa foram encaminhados 11.622 e-mails aos membros das principais sociedades cirúrgicas nacionais com uma pesquisa sobre os princípios técnicos da cirurgia de Lichtenstein. A pesquisa foi realizada por formulário eletrônico com 10 questões de múltipla escolha. O formulário foi respondido de forma anônima nas plataformas SurveyMonkey e Google Forms. Resultado: foram recebidos 744 respostas ao formulário eletrônico. Com base nesse número de respondedores, nossa pesquisa apresenta grau de confiança de 95% com margem de erro de 3,5%. Foi observado que não há padronização da técnica entre a maioria dos respondedores (53.4%). Muitos cirurgiões ainda fazem dissecção digital do funículo espermático (47%). Um pequeno número de entrevistados (15,2%) realizam sutura com fio absorvível na região da aponeurose do obliquo interno, enquanto, mais da metade (55,2%) continua fazendo sutura com fio inabsorvível. A maior parte dos cirurgiões utilizam overlap pequeno ou fixam a tela justaposta a sínfise púbica (51%). Conclusão: nossa pesquisa identificou que uma porcentagem pequena dos entrevistados conhecem adequadamente os princípios técnicos da cirurgia de Lichtenstein. O resultado nos traz novas percepções sob a necessidade de revistar a consagrada técnica de Lichtenstein.

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Aim: Report a clinical case of endodontic retreatment using a hybrid instrumentation technique, L&C paste associated with glycerin as intracanal medication and bioceramic cement.Methods: A 42-year-old male, melanoderma patient, attended the Nilton Lins University Dentistry clinic complaining of tooth fracture and sensitivity in the upper frontal region and pain on chewing. The image exams, showed a bone radiolucense on the root tip, suggestive of a periapical lesion. Clinicaly, pain on vertical percussion was observed. The findings indicated an unsatisfactory primary endodontic treatment. Given the characteristics presented, endodontic reintervention in two sessions was chosen.Results: After the endodontic obturation, the patient was followed through a year. During the months of follow-up, it was observed decrease of the radiolucense on the root tip, as well as the appearance of radiopaque areas, suggestive of bone formation, indicating the effectiveness of the proposed treatment.Conclusion: Therefore, the endodontic reintervention using hybrid instrumentation technique, L&C paste associated with glycerin as intracanal medication and bioceramic cement, showed a satisfactory result in the controlling of the infection. After 1 year, signs of bone remodeling can be seen, meeting the heal expectations predicted in the case planning, leaving the tooth suitable for prosthetic rehabilitation and return to its function.

Objetivo: Relatar um caso clínico de retratamento endodôntico utilizando uma técnica de instrumentação híbrida, pasta L&C associada à glicerina como medicação intracanal e cimento biocerâmico.Métodos: Paciente gênero masculino, 42 anos, melanoderma, compareceu ao clínica de Odontologia da Universidade Nilton Lins com queixa de fratura dentaria, sensibilidade na região anterosuperior e dor a mastigação. Os exames de imagem mostraram radiolucidez óssea no ápice radicular, sugestiva de lesão periapical. Clinicamente, foi observada dor à percussão vertical. Os achados indicaram um tratamento endodôntico primário insatisfatório. Dadas as características apresentadas optou-se pela reintervenção endodôntica em duas sessões. Resultados: Após à obturação endodôntica, o paciente foi acompanhado por um ano. Durante os meses de acompanhamento, observou-se diminuição da radiolucência no ápice da raiz, bem como o aparecimento de áreas radiopacas, sugestivas de formação óssea, indicando à eficácia do tratamento proposto.Conclusão: Portanto, a reintervenção endodôntica utilizando a técnica de instrumentação híbrida, pasta L&C associada à glicerina como medicação intracanal e cimento biocerâmico, apresentou um resultado satisfatório no controle da infecção. Após 1 ano, é possível observar sinais de remodelação óssea, atendendo às expectativas de cura previstas no planejamento do caso, deixando o dente apto para reabilitação protética e retorno à sua função.

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Introdução A COVID-19 é caracterizada por uma fase viral inicial seguida por uma fase inflamatória. AP1189 é um agonista enviesado da melanocortina com importante ação anti-inflamatória e pró-resolutiva. Nesta dissertação investigamos a segurança e eficácia de AP1189 no tratamento de pacientes com COVID-19 grave. Métodos O ensaio foi composto de duas partes. A primeira parte foi uma fase de braço único de 6 pacientes para avaliar a segurança da administração de AP1189 a pacientes COVID-19. Na segunda parte, 54 pacientes foram randomizados 2:1 para receber tratamento padrão mais AP1189 ou placebo de forma duplo-cega. AP1189 ou placebo pareado foi administrado como uma suspensão oral uma vez ao dia por até 2 semanas a partir do início da oxigenoterapia suplementar. O desfecho primário de eficácia foi o número de dias necessários para que os pacientes alcançassem a recuperação respiratória, definido como um valor de saturação periférica de oxigênio (SpO2) ≥ 93% por 30 min em ar ambiente. Resultados No total, 42 pacientes foram designados no grupo AP1189, enquanto 18 receberam placebo. Todos os pacientes receberam dexametasona como tratamento padrão. O grupo AP1189 levou uma mediana (IQR) de 4 (3,7) dias vs. 6 (4,12) dias com placebo para alcançar a recuperação respiratória (p<0.0001). Os pacientes tratados com AP1189 tiveram menor tempo de internação hospitalar, mediana de 6 dias (4,8), quando comparados ao placebo, 7 dias (5,14) (p<0.0001). O perfil de segurança foi semelhante para AP1189 e placebo. Conclusão O tratamento com AP1189 foi seguro em pacientes COVID-19 graves que já tomavam glicocorticoides e foi eficaz em diminuir o tempo de recuperação respiratória e o tempo de internação hospitalar.

Introduction COVID-19 is characterized by an initial viral phase followed by an inflammatory phase. AP1189 is a biased melanocortin agonist with important anti-inflammatory and pro-resolving action. In this dissertation, we investigated the safety and efficacy of AP1189 in the treatment of patients with severe COVID-19. Methods The trial was composed of two parts. The first part was a 6-patient single-arm phase to evaluate the safety of administering AP1189 to COVID-19 patients. In the second part, 54 patients were randomized 2:1 to receive standard treatment plus AP1189 or placebo in a double-blind fashion. AP1189 or matched placebo was administered as an oral suspension once daily for up to 2 weeks from the start of supplemental oxygen therapy. The primary efficacy endpoint was the number of days required for patients to achieve respiratory recovery, defined as a peripheral oxygen saturation (SpO2) value ≥ 93% for 30 min on room air. Results In total, 42 patients were assigned to the AP1189 group, while 18 received placebo. All patients received dexamethasone as standard treatment. The AP1189 group took a median (IQR) of 4 (3.7) days vs. 6 (4.12) days with placebo to achieve respiratory recovery (p<0.0001). Patients treated with AP1189 had a shorter hospital stay, a median of 6 days (4.8), when compared to placebo, 7 days (5.14) (p<0.0001). The safety profile was similar for AP1189 and placebo. Conclusion Treatment with AP1189 was safe in severe COVID-19 patients who were already taking glucocorticoids and was effective in reducing respiratory recovery time and hospital stay.

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ABSTRACT Permanent canines are essential for the preservation of the stomatognathic system, as they are part of the occlusal and aesthetic function and balance. During the normal development of occlusion, canines follow a long and complex trajectory until their eruption, that is, they are more likely to suffer disturbances during this process. Removal of the permanent canine should only be considered in extreme cases, where the canine itself is not susceptible to orthodontic traction. Orthodontic traction is the most indicated treatment due to the high morphofunctional and aesthetic value of the permanent canine. The aim of this study is to report a clinical case of traction surgery of the superior permanent canine included in the maxilla. A 13-year-old female patient attended the dental clinic at the Nilton Lins University accompanied by her guardian, referred by an orthodontistfor canine traction surgery. during the examIn the clinical analysis, tooth 13 was absent from the dental arch. The patient had a computed tomography scan, where it was possible to verify the actual position of the toothimpacted with the partially erupted crown on the alveolar ridge. After planning, surgery was performed to install an orthodontic button and adapt the ligature with a 0.30 mm wire. After the 10-month follow-up period, the presence of the tooth in arch, completely erupted, was observed, showing effectiveness in the proposed treatment. Therefore, the procedure for bonding the orthodontic device was performed satisfactorily without complications or intercurrences, making it possible to continue the orthodontic treatment. The patient remains under follow-up.

RESUMO Os caninos permanentes são essenciais para a preservação do sistema estomatognático, visto que, fazem parte da função e equilíbrio oclusal e estético. Durante o desenvolvimento normal da oclusão, os caninos seguem uma longa e complexa trajetória até seu irrompimento, ou seja, estão mais propensos a sofrerem distúrbios no decorrer desse processo. A extração do canino permanente só deve ser considerada em casos extremos, onde o próprio não se encontra suscetível à tração ortodôntica. O tracionamento ortodôntico é o tratamento mais indicado devido ao alto valor morfofuncional e estético do canino permanente. Sendo assim, o objetivo deste estudo é relatar um caso clínico de cirurgia de tracionamento de canino permanente superior incluso em maxila. Paciente de 13 anos, gênero feminino, compareceu a clínica odontológica da Universidade Nilton Lins acompanhado de seu responsável, encaminhada por um ortodontista para cirurgia de tracionamento de canino. Durante o exame clínico observou-se ausência do dente 13 na arcada dentária. A paciente apresentou a tomografia computadorizada, onde foi possível verificar o real posicionamento do dente impactado com a coroa parcialmente irrompida no rebordo alveolar. Após o planejamento, realizou-se a cirurgia destinada a instalação de botão ortodôntico e adaptação da amarrilha com fio 0,30 mm. Posteriormente ao período de acompanhamento de 10 meses, observou-se a presença do dente em arco, totalmente erupcionado, mostrando efetividade no tratamento proposto. Portando, o procedimento de colagem de dispositivo ortodôntico ocorreu de forma satisfatória sem complicações ou intercorrências, tornando possível a continuidade do tratamento ortodôntico. A paciente permanece em acompanhamento.

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ABSTRACT Introduction: cutaneous melanoma (MC) is a malignant neoplasm derived from melanocytic cells with an aggressive behavior. It is usually associated with the multifactorial interaction of genetic susceptibility and environmental exposure, usually ultraviolet radiation. Despite advances in treatment, the disease remains relentless with poor prognosis. Sentinel lymph node (SLN) biopsy is a technique used to screen patients in need of lymph node dissection. Objectives: to correlate the tumor burden in the SLN with the mortality of patients undergoing SLN biopsy. Methodology: the medical records and histological slides of patients with MC who underwent SLN biopsy treated at HC-Unicamp from 2001 to 2021 were retrospectively analyzed. The positive SLN were measured according to the size of the tumor infiltration area, for analysis of the depth of invasion (DI), closest proximity to the capsule (CPC) and tumor burden (TB). For statistical analysis, associations between variables were analyzed using Fishers exact test, with post Bonferroni test and Wilcoxon test. Results: 105 records of patients who underwent SLN biopsy of MC were identified. Of these, nine (8.6%) had positive SLN and 81 (77.1%) had negative SLN. The performed lymphadenectomies resulted in 55.6% (n=5) affected, 22.2% (n=2) without disease and 22.2% (n=2) were not performed. Mean CPC, TB, and DI were 0.14mm, 32.10mm and 2.33mm, respectively. Patients with T2 and T3 tumors were more likely to show the SLN affected (p=0.022). No patient with positive SLN died during follow-up. Conclusion: patients who presented T3 staging are the ones who most presented positive SLN.

RESUMO Introdução: o melanoma cutâneo (MC) é uma neoplasia maligna de comportamento agressivo, derivada das células melanocíticas, geralmente causado pela associação de interação da suscetibilidade genética e a exposição ambiental. A biópsia do linfonodo sentinela (LNS) é um procedimento utilizado para rastreamento de doentes com necessidade ou não de linfadenectomia, diminuindo a exposição do paciente a cirurgias maiores. Objetivos: correlacionar a carga do tumor no LNS com a mortalidade de pacientes com MC. Métodos: foram examinados retrospectivamente prontuários e lâminas histológicas de doentes com MC submetidos a biópsia de LNS atendidos no HC-Unicamp entre o período compreendido de 2001 a 2021. Os LNS positivos foram mensurados quanto ao tamanho da área de infiltração do tumor, para análise da profundidade de invasão (PI), menor proximidade com a cápsula (MPC) e carga do tumor (CT). As associações entre as variáveis foram analisadas pelo teste Exato de Fisher, com pós teste de Bonferroni e Wilcoxon. Resultados: foram identificados 105 pacientes com biópsia de LNS, sendo nove (8,6%) casos com LNS positivo. A média de MDC, CT e PI foram 0,14 mm, 32,10 mm, e 2,33 mm, respectivamente. Doentes com tumores T2 e T3 apresentaram maior chance de acometimento do LNS (p=0,022). Nenhum paciente com LNS positivo foi a óbito durante o acompanhamento. Conclusão: doentes que apresentaram tumores maiores (T2 e T3) apresentaram maior chance de linfonodos sentinelas positivos. Além do tamanho do tumor, a presença de maior carga do tumor demonstrou que os mesmos podem ser beneficiados pela biópsia de LNS.

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Croton heliotropiifolius Kunth, popularly known as "quince" and "velame," contains a high concentration of volatile oils in the leaves, and widely used in folk medicine as an antiseptic, analgesic, sedative, anti-inflammatory, spasmolytic and local anesthetic. The objectives of this investigation were to (1) identify the phytochemical compounds and (2) assess the cytogenotoxicity of the essential oil extracted from the leaves of C. heliotropiifolius Kunth. The oil was extracted utilizing hydrodistillation and phytochemical profile determined using gas chromatography and mass spectrometry (GCMS). In the toxicogenetics analysis, Allium cepa roots were exposed to 1% dimethylsulfoxide or methylmethanesulfonate (MMS, 10 µg/ml) negative and positive controls, respectively, and to C. heliotropiifolius oil at 6 concentrations (0.32; 1.6; 8; 40; 200 or 1000 µg/ml). The phytochemical profile exhibited 40 chromatographic bands, and 33 compounds identified. α-pinene (16.7%) and 1,8-cineole (13.81%) were identified as the major compounds. Some of these identified secondary metabolites displayed biological and pharmacological activities previously reported including antiseptic, analgesic, sedative, anti-inflammatory as well insecticidal, antiviral, anti-fungal actions. In the A. cepa test, C. heliotropiifolius leaves oil induced cytotoxicity at concentrations of 0.32, 1.6 or 200 µg/ml and genotoxicity at 200 or 1000 µg/ml as evidenced by increased presence of micronuclei and significant chromosomal losses. Based upon our observations data demonstrated that the essential oil of C. heliotropiifolius leaves contain monoterpene hydrocarbons, and oxygenated monoterpenes, sesquiterpenes, and oxygenated sesquiterpenes which are associated with cytotoxic and genotoxic responses noted in on A. cepa cells.

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A Política Nacional de Atenção às Urgências (PNAU) estimula, desde 2003, a expansão de serviços de atendimento pré-hospitalar de urgência (APH), unidades capazes de prestar, por períodos superiores a 24 horas, assistência semelhante à das internações hospitalares, o que pode interferir no índice de Internação por Condições Sensíveis à Atenção Primária (ICSAP). Este trabalho objetiva analisar, por meio de revisão integrativa, a produção científica acerca da relação entre estes "internamentos" e o índice ICSAP, buscando nas bases de dados eletrônicas (Scopus, Scielo e PubMed), produções relacionadas ao tema, utilizando-se dos descritores (condições sensíveis) AND (atenção primária OR atenção básica) AND (hospitalização OR internamento OR atendimento) AND (pronto atendimento). A busca resultou em 2.153 artigos, dos quais 92 (4,27%) foram selecionados para a coleta de dados após a aplicação dos critérios de inclusão e de exclusão. A análise das publicações resultou em quatro (4) estudos que problematizaram a relação dos atendimentos por CSAP nas emergências e o índice de ICSAP, dos quais apenas um (1) sob a ótica do serviço pré-hospitalar, com nenhum deles, porém, tendo avaliado essa hipótese. Conclui-se que as publicações sobre as ICSAP ainda são escassas e poucodiversificadas, não avançando sobre questões mais profundas pertinentes ao tema

The Brazilian National Policy on Emergency Care has encouraged the expansion of pre-hospital emergency care services in the past few years. These units can provide health care for periods longer than 24 hours, such as a hospital stay, which may interfere with the rate of hospitalization due to Primary Care Sensitive Conditions (PCSC). This paper aims to analyze, through an integrative review, the scientific production about the interference of "hospitalization-like" stays in non-hospital emergency rooms by PCSC. This review was conducted by searching electronic databases (Scopus, Scielo, and PubMed) for relevant productions, using as descriptors sensitive conditions AND (primary care OR basic care OR ambulatory care) AND (hospitalization OR internship OR care) AND emergency care, yielding 2153 articles, of which 92 (4.27%) were chosen for data collection after applying the inclusion and exclusion criteria. The collected data analysis has left four studies that problematized the relationship between ACSC care in emergencies and the PCSC index, of which only one from the perspective of the pre-hospital service, although none of them evaluated this hypothesis. It has been concluded that publications on PCSC are still scarce and little diversified, not advancing on the deeper issues related to the theme.

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Kavain is one of the main kavalactones of Piper methysticum (Piperaceae) with anxiolytic, analgesic, and antioxidant activities. Therefore, the aim of the study was to evaluate the cytotoxic, mutagenic, and antimutagenic potential of kavain in Allium cepa cells. Roots of A. cepa were transferred to the negative (2% acetone) and positive (10 µg/mL of Methylmethanesulfonate, MMS) controls and to the concentrations of kavain (32, 64 and 128 µg/mL) for 48 h. A total of 5,000 meristematic cells were analyzed under an optical microscope to determine the mitotic index, mean number of chromosomal alterations and percentage of damage reduction. Data were analyzed by Kruskal-Wallis test (p <0.05). All concentrations of kavain were not cytotoxic and did not show significant chromosomal changes when compared to 2% acetone. Kavain showed a cytoprotective effect in the pre (128 µg/mL) and in the post-treatment (32 and 64 µg/mL) and reduced damage against the mutagenic action of MMS in all concentrations of the pre and simultaneous and at the highest of post (128 µg/mL). Kavain promoted a significant reduction in micronuclei, nuclear buds and chromosomal losses in relation to MMS. The observed data indicate the importance of kavain for the inhibition of damage and chemoprevention.

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