High-risk clones of carbapenem resistant Klebsiella pneumoniae recovered from pediatric patients in Southern Brazil.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) exhibit high mortality rates in pediatric patients and usually belong to international high-risk clones. This study aimed to investigate the molecular epidemiology and carbapenem resistance mechanisms of K. pneumoniae isolates recovered from pediatric patients, and correlate them with phenotypical data. Twenty-five CRKP isolates were identified, and antimicrobial susceptibility was assessed using broth microdilution. Carbapenemase production and ß-lactamase genes were detected by phenotypic and genotypic tests. Multilocus sequence typing was performed to differentiate the strains and whole-genome sequencing was assessed to characterize a new sequence type. Admission to the intensive care unit and the use of catheters were significantly positive correlates of CRKP infection, and the mortality rate was 36%. Almost all isolates showed multidrug-resistant phenotype, and most frequent resistant gene was blaKPC. We observed the dissemination of ST307 and clones belonging to CG258, which are considered high risk. In pediatric patients, these clones present with high genomic plasticity, favoring adaptation of the KPC and NDM enzymes to healthcare environments.

Total Fertilization Failure: A Single Center Analysis.

Our main objective was to identify the male and female parameters associated with total fertilization failure (TFF) in IVF with nonmasculine indications. The present work, IRB equivalent INS 63209, is a case-control study that evaluated all cases with TFF after conventional IVF at the Center for Human Reproduction from January 2010 to December 2019 (n = 154). As a control group, we analyzed all patients who did not experience fertilization failure after conventional IVF in the same period (n = 475). We evaluated various parameters, both male and female, assessed during infertility treatment, and only cases without masculine etiology (normal seminal parameters) were included. Ages (female and male) were not different between the groups. Moreover, AMH (anti-Müllerian hormone), semen volume, preprocessing concentration and preprocessing motility were not significantly different (P > 0.05). However, the number of collected oocytes (study versus control groups, median [25-75 interquartile]: 2 [1-5] and 5 [3-8]); MII (2 [1-4] and 5 [2-7]); and postprocessing motility (85 [70-90] and 90 [80-95]) were significantly different between both groups (P < 0.05). Furthermore, a logistic regression analysis including all significant data demonstrated that the number of collected oocytes was significantly related to IVF failure. Patients with fewer than 5 oocytes had an OR of - 1.37 (- 0.938 to - 1.827) for TFF after conventional IVF. Our results showed that a lower follicular response to controlled ovarian stimulation, evidenced by a decreased number of collected oocytes, was the most important parameter associated with IVF failure in nonmasculine infertility.

Outbreak of vancomycin-resistant Enterococcus faecium ST1133 in paediatric patients with acute lymphoblastic leukaemia from southern Brazil.

OBJECTIVES: We aimed to investigate an outbreak of vancomycin-resistant Enterococcus faecium (VREfm) in paediatric patients from Hospital Pequeno Príncipe. The susceptibility profile was determined, and whole-genome sequencing (WGS) was used to analyse the genetic context of the strains. METHODS: Five VREfm isolates were recovered from sterile sites and surveillance cultures of two paediatric patients with acute lymphoblastic leukaemia. Species identification was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), and the minimum inhibitory concentration (MIC) was assessed according to the European Committee for Antimicrobial Susceptibility Testing (EUCAST). WGS was performed to analyse the genetic context of virulence and resistance genes, and in silico multilocus sequence typing was performed to identify the sequence typing of the strains. RESULTS: High-level vancomycin resistance was observed in all isolates (≥256 mg/L). WGS revealed the presence of mobile genetic elements, such as plasmids (rep2, rep11a, repUS15, rep17, and rep18a), insertion sequences, and phages. Multiple resistance genes (aac(6')-aph(2"), dfrG, ermB, and vanA) and virulence genes (acm and efaAfm) were identified. All the isolates were assigned to ST117 (ST1133 - via a novel MLST), an important epidemic lineage associated with nosocomial infections and outbreaks. CONCLUSION: Our results show that the ST117 (ST1133) VREfm isolates are circulating in paediatric patients, which raises a great concern. The development of new drugs as well as the implementation of an antimicrobial stewardship program are necessary for their correct management, limiting the spread of resistance in oncohematological patients.

Genotypic Diversity of Candida parapsilosis Complex in Invasive Candidiasis at a Pediatric Tertiary Hospital: A 5-Year Retrospective Study.

Invasive candidiasis (IC) contributes to the morbidity and mortality of hospitalized patients and represents a significant burden to the healthcare system. Previous Brazilian studies have reported the presence of endemic Candida parapsilosis sensu stricto genotypes causing candidemia and clonal transmission involving fluconazole-resistant isolates. We performed a 5-year retrospective analysis of IC cases in a Brazilian tertiary pediatric hospital and conducted a molecular investigation of C. parapsilosis sensu stricto. Non-duplicate C. parapsilosis sensu stricto genotyping was performed by microsatellite analysis. Antifungal susceptibility and biofilm formation were also evaluated. A total of 123 IC episodes were identified, with an IC incidence of 1.24 cases per 1000 hospital admissions and an overall mortality of 34%. The main species were the C. parapsilosis complex (35.8%), Candida albicans (29.2%), and Candida tropicalis (21.9%). All C. parapsilosis sensu stricto were recovered from blood cultures, and 97.5% were biofilm producers. Microsatellite typing identified high genotypic diversity among the isolates. We observed that all isolates were sensitive to amphotericin B, and although one isolate was non-sensitive to fluconazole, only a silent mutation on ERG11 gene was identified. No clear evidence of clonal outbreak or emergence of fluconazole-resistant isolates was found, suggesting that multiple sources may be involved in the epidemiology of IC in children.

Lower airway microbiota and decreasing lung function in young Brazilian cystic fibrosis patients with pulmonary Staphylococcus and Pseudomonas infection.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene that leads to respiratory complications and mortality. Studies have shown shifts in the respiratory microbiota during disease progression in individuals with CF. In addition, CF patients experience short cycles of acute intermittent aggravations of symptoms called pulmonary exacerbations, which may be characterized by a decrease in lung function and weight loss. The resident microbiota become imbalanced, promoting biofilm formation, and reducing the effectiveness of therapy. The aim of this study was to monitor patients aged 8-23 years with CF to evaluate their lower respiratory microbiota using 16S rRNA sequencing. The most predominant pathogens observed in microbiota, Staphylococcus (Staph) and Pseudomonas (Pseud) were correlated with clinical variables, and the in vitro capacity of biofilm formation for these pathogens was tested. A group of 34 patients was followed up for 84 days, and 306 sputum samples were collected and sequenced. Clustering of microbiota by predominant pathogen showed that children with more Staph had reduced forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) compared to children with Pseud. Furthermore, the patients' clinical condition was consistent with the results of pulmonary function. More patients with pulmonary exacerbation were observed in the Staph group than in the Pseud group, as confirmed by lower body mass index and pulmonary function. Additionally, prediction of bacterial functional profiles identified genes encoding key enzymes involved in virulence pathways in the Pseud group. Importantly, this study is the first Brazilian study to assess the lower respiratory microbiota in a significant group of young CF patients. In this sense, the data collected for this study on the microbiota of children in Brazil with CF provide a valuable contribution to the knowledge in the field.

In Situ Gene Therapy.

Gene therapy is a technique that aims at the delivery of nucleic acids to cells, to obtain a therapeutic effect. In situ gene therapy consists of the administration of the gene product to a specific site. It possesses several advantages, such as the reduction in potential side effects, the need for a lower vector dose, and, as a consequence, reduced costs, compared to intravenous administration. Different vectors, administration routes and doses involving in situ gene transfer have been tested both in animal models and humans, with in situ gene therapy drugs already approved in the market. In this review, we present applications of in situ gene therapy for different diseases, ranging from monogenic to multifactorial diseases, focusing mainly on therapies designed for the intra-articular and intraocular compartments, as well as gene therapies for the central nervous system (CNS) and for tumors. Gene therapy finally seems to blossom as a viable therapeutic approach. The growth in the number of clinical protocols shown here is evident, and the positive outcomes observed in several clinical trials indicate that more products based on in situ gene therapy should reach the market in the next years.

Penicillium genus as a source for anti-leukemia compounds: an overview from 1984 to 2020.

Penicillium is a widely explored genus due to its chemical diversity and associated biological properties; in addition, it represents an important source for cytotoxic compounds with good application perspectives. Based on these aspects, in this review, Penicillium compounds that presented activity against human leukemia cell lines are being listed and discussed. For this, a careful bibliographic survey was carried out in the main electronic databases, i.e. Scopus, SciFinder, Web of Science and Pubmed. Between 1984 and 2020, thirty seven original papers were selected, when using the search terms Penicillium and leukemia. The occurrence of l-asparaginase produced by some Penicillium spp. was also highlighted since this enzyme is being employed for acute lymphoblastic leukemia and lymphosarcoma therapies. Therefore, this overview aims to demonstrate the potential of metabolites biosynthesized by Penicillium fungi which can be applied in human leukemia therapies and opportunities for designing new lead compounds.

O cotidiano da pessoa em terapia renal substitutiva antes do transplante renal / The daily life of the person in renal replacement therapy before renal transplantation

Objetivo: Descrever o cotidiano da pessoa em terapia renal substitutiva (hemodiálise ou diálise peritoneal) antes do transplante renal. Métodos: Este é recorte de uma pesquisa qualitativa e descritiva, realizada com 20 pessoas com o transplante renal. Os dados foram coletados por meio de dois roteiros, um para identificar o perfil socioeconômico dos entrevistados e outro com perguntas semiestruturadas. Os dados foram analisados de acordo com a proposta operativa de Minayo. Resultados: Apresentam-se quatro temáticas: O cotidiano vivenciado no período do tratamento dialítico; A presença de efeito colateral da diálise; O autocuidado com a saúde; Repercussões psíquicas na vida das pessoas em diálise. Conclusões: Cada indivíduo apresenta uma resposta ao tratamento dialítico, de acordo com suas vivências e redes de apoio, e essas singularidades devem ser consideradas pelos profissionais de saúde.

Autonomia de mulheres com doença renal para a diálise peritoneal no domicílio

Introdução: A doença renal crônica se caracteriza pela disfunção dos rins na eliminação de toxinas. Uma das alternativas de terapia é a diálise peritoneal, na qual o indivíduo encontra diversos desafios, visto que, além das mudanças no estilo de vida devido à doença, o tratamento exige certa adaptação e disciplina, tanto da pessoa, quanto da família. Objetivo: Analisar a construção da autonomia de mulheres com doença renal crônica para realizar a diálise peritoneal no domicílio. Método: Estudo de abordagem qualitativa, sustentado teoricamente pelo conceito de autonomia proposto pelo educador brasileiro Paulo Freire. Os dados foram produzidos entre abril de 2013 e junho de 2014, por meio de entrevista semiestruturada e aberta, organizados no programa Ethnograph v6, tendo sido submetidos à análise de conteúdo proposta por Laurence Bardin. Resultados: Foram construídas quatros categorias que descreveram a construção da autonomia das mulheres, sendo elas: Surgimento da doença: busca por cuidados e diagnóstico; Necessidade de realizar a diálise peritoneal no hospital; Transição do cuidado: apoio e assistência para o retorno ao domicílio, e Gerenciando a diálise peritoneal no domicílio. Conclusão: A construção da autonomia das mulheres ocorreu no decorrer do processo de adoecimento e seguiu-se no retorno ao domicílio com o auto manejo da diálise. Ainda, evidenciou-se que o (re)conhecimento do próprio corpo e avaliação constante da diálise foram indispensáveis para empoderá-las e decidir sobre o tratamento.

Introducción: La enfermedad renal crónica se caracteriza por una disfunción renal en la eliminación de toxinas. Una de las alternativas terapéuticas es la diálisis peritoneal, en la que el individuo se enfrenta a varios retos, ya que, además de los cambios en el estilo de vida debido a la enfermedad, el tratamiento requiere cierta adaptación y disciplina, tanto de la persona como de la familia. Objetivo: Analizar la construcción de la autonomía de las mujeres con enfermedad renal crónica para realizar diálisis peritoneal en el domicilio. Método: Estudio cualitativo, teóricamente apoyado en el concepto de autonomía propuesto por el educador brasileño Paulo Freire. Los datos fueron producidos entre abril de 2013 y junio de 2014, mediante entrevistas semiestructuradas y abiertas, organizadas en el programa Ethnograph v6, habiendo sido sometidos al análisis de contenido propuesto por Laurence Bardin. Resultados: Se construyeron cuatro categorías que describieron la construcción de la autonomía de las mujeres, a saber: Aparición de la enfermedad: búsqueda de atención y diagnóstico; Necesidad de realizar diálisis peritoneal en el hospital; Transición de la atención: apoyo y asistencia para el regreso a casa y Manejo de la diálisis peritoneal en casa. Conclusión: La construcción de la autonomía de la mujer ocurrió en el transcurso del proceso de la enfermedad y siguió en el regreso a casa con el autocontrol de la diálisis. Aun así, se evidenció que el (re)conocimiento del propio cuerpo y la evaluación constante de la diálisis eran indispensables para empoderarlas y decidir el tratamiento.

Introduction: Peritoneal dialysis is a complex treatment because it requires both a strict therapeutic regimen and a greater development of autonomy to manage it. Objective: To analyze the construction of the autonomy in women with chronic kidney disease to perform peritoneal dialysis at home. Material and Method: This is a qualitative study, theoretically supported by Paulo Freire's concept of autonomy. Fourteen women on peritoneal dialysis participated in the study. The data were produced in a nephrology service in the Southern Region of Brazil, from April 2013 to June 2014, through semi-structured and open interviews, organized in the Ethnograph v6 program and submitted to content analysis. Results: Four categories were identified that describe the construction of women's autonomy, which are: Emergence of the disease: search for care and diagnosis, need to perform peritoneal dialysis in the hospital; Care transition: support and assistance for returning home, and managing peritoneal dialysis at home. Conclusion: The construction of women's autonomy occurred during the illness process and continued when they returned home with self-management of dialysis. Still, it was evidenced that the recognition of the own body and constant evaluation of the dialysis had a key role in the empowerment of such women and help them to decide on the treatment.

Planned Yellow Fever Primary Vaccination Is Safe and Immunogenic in Patients With Autoimmune Diseases: A Prospective Non-interventional Study.

Yellow Fever (YF) vaccination is suggested to induce a large number of adverse events (AE) and suboptimal responses in patients with autoimmune diseases (AID); however, there have been no studies on 17DD-YF primary vaccination performance in patients with AID. This prospective non-interventional study conducted between March and July, 2017 assessed the safety and immunogenicity of planned 17DD-YF primary vaccination in patients with AID. Adult patients with AID (both sexes) were enrolled, along with healthy controls, at a single hospital (Vitória, Brazil). Included patients were referred for planned vaccination by a rheumatologist; in remission, or with low disease activity; and had low level immunosuppression or the attending physician advised interruption of immunosuppression for safety reasons. The occurrence of AE, neutralizing antibody kinetics, seropositivity rates, and 17DD-YF viremia were evaluated at various time points (day 0 (D0), D3, D4, D5, D6, D14, and D28). Individuals evaluated (n = 278), including patients with rheumatoid arthritis (RA; 79), spondyloarthritis (SpA; 59), systemic sclerosis (8), systemic lupus erythematosus (SLE; 27), primary Sjögren's syndrome (SS; 54), and healthy controls (HC; 51). Only mild AE were reported. The frequency of local and systemic AE in patients with AID and HC did not differ significantly (8 vs. 10% and 21 vs. 32%; p = 1.00 and 0.18, respectively). Patients with AID presented late seroconversion profiles according to kinetic timelines of the plaque reduction neutralization test (PRNT). PRNT-determined virus titers (copies/mL) [181 (95% confidence interval (CI), 144-228) vs. 440 (95% CI, 291-665), p = 0.004] and seropositivity rate (78 vs. 96%, p = 0.01) were lower in patients with AID after 28 days, particularly those with SpA (73%) and SLE (73%), relative to HC. The YF viremia peak (RNAnemia) was 5-6 days after vaccination in all groups. In conclusion, consistent seroconversion rates were observed in patients with AID and our findings support that planned 17DD-YF primary vaccination is safe and immunogenic in patients with AID.

First Genome Sequences of Two Multidrug-Resistant Candida haemulonii var. vulnera Isolates From Pediatric Patients With Candidemia.

Candida haemulonii is a complex formed by C. haemulonii sensu stricto, C. haemulonii var. vulnera, and C. duobushaemulonii. Members of this complex are opportunistic pathogens closely related to C. pseudohaemulonii, C. lusitaniae, and C. auris, all members of a multidrug-resistant clade. Complete genome sequences for all members of this group are available in the GenBank database, except for C. haemulonii var. vulnera. Here, we report the first draft genomes of two C. haemulonii var. vulnera (isolates K1 and K2) and comparative genome analysis of closely related fungal species. The isolates were biofilm producers and non-susceptible to amphotericin B and fluconazole. The draft genomes comprised 350 and 387 contigs and total genome sizes of 13.21 and 13.26 Mb, with 5,479 and 5,507 protein-coding genes, respectively, allowing the identification of virulence and resistance genes. Comparative analyses of orthologous genes within the multidrug-resistant clade showed a total of 4,015 core clusters, supporting the conservation of 24,654 proteins and 3,849 single-copy gene clusters. Candida haemulonii var. vulnera shared a larger number of clusters with C. haemulonii and C. auris; however, more singletons were identified in C. lusitaniae and C. auris. Additionally, a multiple sequence alignment of Erg11p proteins revealed variants likely involved in reduced susceptibility to azole and polyene antifungal agents. The data presented in this work will, therefore, be of utmost importance for researchers studying the biology of the C. haemulonii complex and related species.

Free carnitine and branched chain amino acids are not good biomarkers in Huntington's disease.

BACKGROUND: Huntington's disease (HD), caused by an expanded CAG repeat at HTT, has no treatment, and biomarkers are needed for future clinical trials. OBJECTIVE: The objective of this study was to verify if free carnitine and branched chain amino acids levels behave as potential biomarkers in HD. METHODS: Symptomatic and asymptomatic HD carriers and controls were recruited. Age, sex, body mass index (BMI), age of onset, disease duration, UHDRS scores, and expanded CAG tract were obtained; valine, leucine, isoleucine, and free carnitine were measured. Baseline and longitudinal analysis were performed. RESULTS: Seventy-four symptomatic carriers, 20 asymptomatic carriers, and 22 non-carriers were included. At baseline, valine levels were reduced in symptomatic and asymptomatic HD carriers when compared to non-carriers. No difference in free carnitine or isoleucine+leucine levels were observed between groups. BMI of symptomatic individuals was lower than those of non-carriers. Valine levels correlated with BMI. Follow-up evaluation was performed in 43 symptomatic individuals. UHDRS total motor score increased 4.8 points/year on average. No significant reductions in BMI or valine were observed, whereas free carnitine and isoleucine+leucine levels increased. CONCLUSIONS: Although valine levels were lower in HD carriers and were related to BMI losses observed in pre-symptomatic individuals, none of these metabolites seem to be biomarkers for HD.

Free carnitine and branched chain amino acids are not good biomarkers in Huntington's disease / Carnitina livre e aminoácidos de cadeia ramificada não são bons biomarcadores na doença de Huntington

ABSTRACT Background: Huntington's disease (HD), caused by an expanded CAG repeat at HTT, has no treatment, and biomarkers are needed for future clinical trials. Objective: The objective of this study was to verify if free carnitine and branched chain amino acids levels behave as potential biomarkers in HD. Methods: Symptomatic and asymptomatic HD carriers and controls were recruited. Age, sex, body mass index (BMI), age of onset, disease duration, UHDRS scores, and expanded CAG tract were obtained; valine, leucine, isoleucine, and free carnitine were measured. Baseline and longitudinal analysis were performed. Results: Seventy-four symptomatic carriers, 20 asymptomatic carriers, and 22 non-carriers were included. At baseline, valine levels were reduced in symptomatic and asymptomatic HD carriers when compared to non-carriers. No difference in free carnitine or isoleucine+leucine levels were observed between groups. BMI of symptomatic individuals was lower than those of non-carriers. Valine levels correlated with BMI. Follow-up evaluation was performed in 43 symptomatic individuals. UHDRS total motor score increased 4.8 points/year on average. No significant reductions in BMI or valine were observed, whereas free carnitine and isoleucine+leucine levels increased. Conclusions: Although valine levels were lower in HD carriers and were related to BMI losses observed in pre-symptomatic individuals, none of these metabolites seem to be biomarkers for HD.

RESUMO Introdução: A doença de Huntington (DH), causada por uma repetição CAG expandida no HTT, não possui tratamento e biomarcadores são necessários para futuros ensaios clínicos. Objetivo: Nosso objetivo foi verificar se os níveis de carnitina livre e aminoácidos de cadeia ramificada se comportam como potenciais biomarcadores na DH. Métodos: Portadores sintomáticos e assintomáticos e controles foram recrutados. Idade, sexo, índice de massa corporal (IMC), idade de início, duração da doença, escores UHDRS e trato CAG expandido foram obtidos; valina, leucina, isoleucina e carnitina livre foram medidas. Foram realizadas análises basal e longitudinal. Resultados: Setenta e quatro portadores sintomáticos, 20 portadores assintomáticos e 22 não portadores foram incluídos. No início do estudo, os níveis de valina estavam reduzidos em portadores de DH sintomáticos e assintomáticos quando comparados aos não portadores. Não foram observadas diferenças nos níveis de carnitina livre ou isoleucina + leucina entre os grupos. O IMC dos indivíduos sintomáticos foi menor que o dos não portadores. Níveis de valina correlacionaram-se com o IMC. Avaliação de acompanhamento foi realizada em 43 indivíduos sintomáticos. A pontuação do escore motor total da UHDRS aumentou 4,8 pontos/ano em média. Não foram observadas reduções significativas no IMC ou na valina, enquanto os níveis de carnitina livre e isoleucina+leucina aumentaram. Conclusões: Embora os níveis de valina tenham sido menores nos portadores de DH e estivessem relacionados às perdas de IMC observadas em indivíduos pré-sintomáticos, nenhum desses metabólitos parece ser biomarcador para a DH.

U.S. Food and Drug Administration anticancer drug approval trends from 2016 to 2018 for lung, colorectal, breast, and prostate cancer.

OBJECTIVE: This paper aims to describe the clinical and regulatory aspects of new drugs and indications that were approved for lung, breast, prostate, and colorectal cancer, from 2016 to 2018, in order to provide health technology assessment trends in oncology. METHODS: Data were collected from the US Food and Drug Administration (FDA) online database for new medications and indications approved for the above-mentioned types of cancer. Data regarding clinical study characteristics and regulatory information were collected. RESULTS: From 2016 to 2018, 53 percent of the FDA approvals of new drugs and indications for the most incident cancers were for oral protein kinase inhibitor monotherapy for advanced lung cancer. Since 2018, four drugs were approved as tumor-agnostic therapies. A biomarker was included in 72 percent of indications, and 58 percent of approvals were for targeted therapies, potentially heralding an end to research into conventional cytotoxic agents. A special designation for faster approval was granted in 78 percent of new approvals. The majority of the studies were open label randomized controlled trials (RCTs) (44 percent), followed by blind RCTs, single-arm clinical trials, and cohort studies. Only 14 percent of studies used overall survival as the primary end point; the vast majority used surrogate end points, and did not use patient-important outcomes. Three biosimilars were approved in the period. CONCLUSION: Advanced lung cancer therapy, mainly targeted drugs, accounted for 53 percent of approvals. Special designations for faster approval were used in 78 percent of FDA approvals, and four drugs were approved for tumor-agnostic treatment-a new form of approval.

A Model to Predict Significant Macrosteatosis in Hepatic Grafts.

BACKGROUND AND AIMS: Assessing the risk of significant macrosteatosis in donors is crucial before considering hepatic graft procurement. We aimed to build a model to predict significant macrosteatosis based on noninvasive methods. METHODS: From January 2012 to December 2018, liver attenuation indices and liver-to-spleen (L/S) ratio were measured in 639 brain-dead donors by local radiologists. Quantity and quality of steatosis were evaluated by an expert pathologist, blinded for attenuation indices measurement. RESULTS: Macrosteatosis ≥ 30% was found in 33 donors (5.2%). Body weight, body mass index (BMI), abdominal perimeters, history of alcohol abuse, L/S ratio, and liver parenchyma attenuation were associated with macrosteatosis ≥ 30%. The L/S ratio, BMI, and a history of alcohol abuse remained independent predictors in multivariate analysis and were used to build a predictive model (C-index: 0.77). The optimal cutoff to predict macrosteatosis ≥ 60% was 0.85. CONCLUSION: Our model, including L/S ratio, BMI, and history of alcohol, might be helpful to refine indication for liver biopsy before donation after brain death. External validation is required.

NOx-, IL-1ß-, TNF-α-, and IL-6-Inhibiting Effects and Trypanocidal Activity of Banana (Musa acuminata) Bracts and Flowers: UPLC-HRESI-MS Detection of Phenylpropanoid Sucrose Esters.

Banana inflorescences are a byproduct of banana cultivation consumed in various regions of Brazil as a non-conventional food. This byproduct represents an alternative food supply that can contribute to the resolution of nutritional problems and hunger. This product is also used in Asia as a traditional remedy for the treatment of various illnesses such as bronchitis and dysentery. However, there is a lack of chemical and pharmacological data to support its consumption as a functional food. Therefore, this work aimed to study the anti-inflammatory action of Musa acuminata blossom by quantifying the cytokine levels (NOx, IL-1ß, TNF-α, and IL-6) in peritoneal neutrophils, and to study its antiparasitic activities using the intracellular forms of T. cruzi, L. amazonensis, and L. infantum. This work also aimed to establish the chemical profile of the inflorescence using UPLC-ESI-MS analysis. Flowers and the crude bract extracts were partitioned in dichloromethane and n-butanol to afford four fractions (FDCM, FNBU, BDCM, and BNBU). FDCM showed moderate trypanocidal activity and promising anti-inflammatory properties by inhibiting IL-1ß, TNF-α, and IL-6. BDCM significantly inhibited the secretion of TNF-α, while BNBU was active against IL-6 and NOx. LCMS data of these fractions revealed an unprecedented presence of arylpropanoid sucroses alongside flavonoids, triterpenes, benzofurans, stilbenes, and iridoids. The obtained results revealed that banana inflorescences could be used as an anti-inflammatory food ingredient to control inflammatory diseases.

Repercussões de desencontros e ambiente familiar na relação mãe-bebê: experienciando o método Bick de observação / Repercussions of mismatches and family environment in the mother-baby relationship: experiencing the Bick observation method / Repercusiones de desencuentros y ambiente familiar en la relación madre-bebé: experimentando el método Bick de observación

A observação da relação mãe-bebê possibilita ao terapeuta em formação o desenvolvimento de habilidades importantes para sua prática. Desenvolvido por Esther Bick, o método Bick de observação de bebês abarca os principais conceitos da psicanálise, como o inconsciente, a transferência, a contratransferência e a atenção flutuante. O estudo tencionou compreender os desencontros ocorridos entre mãe e bebê e a importância do ambiente familiar, a partir de um relato de experiência de uma observação da relação mãe-bebê e das formulações teóricas de Winnicott. A observação foi realizada por meio de uma adaptação do método Bick de observação de bebês. Ao longo das observações, foram identificadas dificuldades iniciais na interação decorrentes dos desencontros na relação da díade mãe-bebê. O ambiente familiar e, em especial, o auxílio da avó materna foram importantes enquanto fontes de afeto e empatia para com a díade, promovendo uma nova possibilidade de interação para o bebê. Concluiu-se que o ambiente familiar se mostrou fundamental, tanto para o desenvolvimento da criança quanto para um cuidado materno mais empático.

The observation of the mother-baby relationship allows the therapist in training to develop important skills for his practice. Developed by Esther Bick, the Bick method of infant observation covers the main concepts of psychoanalysis, such as the unconscious, transference, countertransference, and free-floating attention. The study aimed to understand mismatches between mother and baby and the importance of the familiar environment, from an experience report of an observation of a mother-baby relationship and Winnicott's theoretical formulations. The format of the activity was adapted from the Bick method of infant observation. Throughout the observations, it was possible to identify initial difficulties in the interaction due to mismatches in the mother-baby relationship. The family environment and, in particular, the maternal grandmother's help were important as sources of affection and empathy for the dyad, promoting a new possibility of interaction for the baby. It was concluded that the family environment was fundamental, both for the development of the infant and for a maternal care with more empathy.

La observación de la relación madre-bebé posibilita al terapeuta en formación el desarrollo de habilidades importantes para su práctica. Desarrollado por Esther Bick, el método Bick de observación de bebés abarca los principales conceptos del psicoanálisis, como el inconsciente, la transferencia, la contratransferencia y la atención flotante. El estudio pretendió comprender los desencuentros ocurridos entre madre y bebé y la importancia del ambiente familiar, a partir de un relato de experiencia de una observación de la relación madre-bebé y de las formulaciones teóricas de Winnicott. La observación fue realizada por medio de una adaptación del método Bick de observación de bebés. A lo largo de las observaciones, se identificaron dificultades iniciales en la interacción derivadas de los desencuentros en la relación madre-bebé. El ambiente familiar y, en especial, la ayuda de la abuela materna fueron importantes como fuentes de afecto y empatía para la díada, promoviendo una nueva posibilidad de interacción para el bebé. Se concluyó que el ambiente familiar se mostró fundamental para el desarrollo del bebé y para un cuidado materno más empático.

Minimal prevalence of Huntington's disease in the South of Brazil and instability of the expanded CAG tract during intergenerational transmissions.

Huntington's disease (HD) is due to dominant expansions of the CAG repeat of the HTT gene. Meiotic instability of the (CAG)n might impact the disorder frequency. We report on HD minimal prevalence in Rio Grande do Sul (RS) state, Brazil, and on intergenerational instability of the (CAG)n in HD families. Symptomatic and at-risk subjects from 179 HD families were ascertained between 2013 and 2016. Clinical, molecular and family history data were obtained. Expanded (CAG)n length differences between parent and child (delta-expanded-(CAG)n) were calculated. Effect of parental age on the (CAG)n instability upon transmission was inferred by correlating delta-expanded-(CAG)n between siblings to their age differences. HD minimal prevalence in RS state was estimated as 1.85:100,000 inhabitants. Alleles with (CAG)27-35 were found on 21/384 non-disease associated chromosomes (5.5%); among 253 expanded alleles, four (1.6%) were within reduced penetrance range with (CAG)36-39. In 32 direct transmissions, mean instability was larger among paternal than maternal transmissions. In direct transmissions and in 51 sibling pairs, parental age at the time of child birth were not correlated with delta-expanded-(CAG)n. Briefly, HD prevalence in RS state was lower than those reported for European populations. Expanded (CAG)n transmissions were unstable and not associated to parental age.

Invasive candidiasis: Risk factor for mortality in a pediatric tertiary care hospital in south of Brazil.

BACKGROUND: Invasive candidiasis (IC) is a major cause of morbimortality in children. Previous studies described the clinical characteristics and risk factors for this infection; however, limited data are available on the predictors of mortality in these patients. In this context, we evaluated the risk factors associated with death due to IC in a pediatric tertiary care hospital in South of Brazil. METHODS: This is a retrospective, cross-sectional, observational, and analytical study of a series of pediatric patients with clinical and laboratory diagnosis of IC from March 2014 to September 2017. Univariate and multivariate analysis were performed to estimate the association between the characteristics of the patients and death. RESULTS: A total of 94 cases of IC were included. The incidence was 1.13 cases per 1000 patients/d, with a mortality rate of 14%. There was a predominance of non-albicans Candida (71.3%) in IC cases and, although there is no species difference in mortality rates, biofilm formation was associated with increased mortality. Clinical characteristics such as male sex, stay in the intensive care unit, and thrombocytopenia; comorbidities such as cardiological disease and renal insufficiency; and risks such as mechanical ventilation and dialysis were associated with increased mortality. CONCLUSION: Data from this study suggest that biofilm formation by Candida sp. is associated with increased mortality, and this is the first study to correlate the male sex and cardiological disease as risk factors for death in pediatric IC patients.

Integrated Analytical Tools for Accessing Acridones and Unrelated Phenylacrylamides from Swinglea glutinosa.

In natural product studies, the purification of metabolites is an important challenge. To accelerate this step, alternatives such as integrated analytical tools should be employed. Based on this, the chemical study of Swinglea glutinosa (Rutaceae) was performed using two rapid dereplication strategies: Target Analysis (Bruker Daltonics®, Bremen, Germany) MS data analysis combined with MS/MS data obtained from the GNPS platform. Through UHPLC-HRMS data, the first approach allowed, from crude fractions, a quick and visual identification of compounds already reported in the Swinglea genus. Aside from this, by grouping compounds according to their fragmentation patterns, the second approach enabled the detection of eight molecular families, which presented matches for acridonic alkaloids, phenylacrylamides, and flavonoids. Unrelated compounds for S. glutinosa have been isolated and characterized by NMR experiments, Lansamide I, Lansiumamide B, Lansiumamide C, and N-(2-phenylethyl)cinnamamide.