Macrophage PET imaging in mouse models of cardiovascular disease and cancer with an apolipoprotein-inspired radiotracer.

Macrophages are key inflammatory mediators in many pathological conditions, including cardiovascular disease (CVD) and cancer, the leading causes of morbidity and mortality worldwide. This makes macrophage burden a valuable diagnostic marker and several strategies to monitor these cells have been reported. However, such strategies are often high-priced, non-specific, invasive, and/or not quantitative. Here, we developed a positron emission tomography (PET) radiotracer based on apolipoprotein A1 (ApoA1), the main protein component of high-density lipoprotein (HDL), which has an inherent affinity for macrophages. We radiolabeled an ApoA1-mimetic peptide (mA1) with zirconium-89 (89Zr) to generate a lipoprotein-avid PET probe (89Zr-mA1). We first characterized 89Zr-mA1's affinity for lipoproteins in vitro by size exclusion chromatography. To study 89Zr-mA1's in vivo behavior and interaction with endogenous lipoproteins, we performed extensive studies in wildtype C57BL/6 and Apoe-/- hypercholesterolemic mice. Subsequently, we used in vivo PET imaging to study macrophages in melanoma and myocardial infarction using mouse models. The tracer's cell specificity was assessed by histology and mass cytometry (CyTOF). Our data show that 89Zr-mA1 associates with lipoproteins in vitro. This is in line with our in vivo experiments, in which we observed longer 89Zr-mA1 circulation times in hypercholesterolemic mice compared to C57BL/6 controls. 89Zr-mA1 displayed a tissue distribution profile similar to ApoA1 and HDL, with high kidney and liver uptake as well as substantial signal in the bone marrow and spleen. The tracer also accumulated in tumors of melanoma-bearing mice and in the ischemic myocardium of infarcted animals. In these sites, CyTOF analyses revealed that natZr-mA1 was predominantly taken up by macrophages. Our results demonstrate that 89Zr-mA1 associates with lipoproteins and hence accumulates in macrophages in vivo. 89Zr-mA1's high uptake in these cells makes it a promising radiotracer for non-invasively and quantitatively studying conditions characterized by marked changes in macrophage burden.

Tea authentication and determination of chemical constituents using digital image-based fingerprint signatures and chemometrics.

Tea (Camellia sinensis) fraud has been frequently identified and involves tampering with the labelling of inferior products or without geographical origin certification and even mixing them with superior quality teas to mask an adulteration. Consequently, economic losses and health damage to consumers are observed. Thus, a Chemometrics-assisted Color Histogram-based Analytical System (CACHAS) was employed a simple, cost-effective, reliable, and green analytical tool to screen the quality of teas. Data-Driven Soft Independent Modeling of Class Analogy was used to authenticate their geographical origin and category simultaneously, recognizing correctly all Argentinean and Sri Lankan black teas and Argentinean green teas. For the determination of moisture, total polyphenols, and caffeine, Partial Least Squares obtained satisfactory predictive abilities, with values of root mean squared error of prediction (RMSEP) of 0.50, 0.788, and 0.25 mg kg-1, rpred of 0.81, 0.902, and 0.81, and relative error of prediction (REP) of 6.38, 9.031, and 14.58%., respectively. CACHAS proved to be a good alternative tool for environmentally-friendly non-destructive chemical analysis.

Development and validation of a prototype multimedia application to enhance health education on the pelvic floor muscles among pregnant and puerperal women in Brazil.

Background: Women are interested in and need to receive more information about pelvic floor muscles (PFMs), its functions, and dysfunctions. The aim of this study is to develop and validate a multimedia application (app) aimed to enhance health education on PFM among pregnant and postpartum women in Brazil. Methods: This is a descriptive, transversal study in the modality of technological production, consisting of three stages, namely, bibliographic review, development of the multimedia app prototype, and validation of the multimedia app by specialists in the fields of health and technology as well as pregnant and postpartum women. The validation specialists answered an instrument that evaluated several skills including functioning, content, language, illustrations, general aspects, innovation and design, and level of satisfaction. The data obtained were tabulated and analyzed using Microsoft Excel for Windows® 2010. Analysis of the validation of the app prototype and its content was performed using the Content Validity Index (CVI) and by calculating the percentage of absolute agreement. Results: The app presented a CVI of 0.89 by experts and 0.93 by the participating pregnant and postpartum women, with a global CVI of 0.91. The level of agreement between professionals and the participating pregnant and postpartum women was 93.7% and 95.8%, respectively, resulting in an overall level of agreement of 94.8%. Conclusions: The educational material in the app format was evaluated based on its functionality, content, language, illustrations, design, and innovation. Furthermore, the content has been validated for pregnant and postpartum women. Thus, this content will contribute to the promotion of health education and dissemination of information regarding PFM, its functions, and dysfunctions.

Stress levels, psychological symptoms, and C-reactive protein levels in COVID-19: A cross-sectional study.

BACKGROUND: Although many studies have pointed out a possible relationship between COVID-19 and the presence of psychiatric disorders, the majority of the studies have significant limitations. This study investigates the influence of COVID-19 infection on mental health. METHODS: This cross-sectional study included an age- and sex-matched sample of adult individuals positive (cases) or negative (controls) for COVID-19. We evaluated the presence of psychiatric conditions and C-reactive protein (CRP). RESULTS: Findings showed greater severity of depressive symptoms, higher levels of stress, and greater CRP in cases. The severity of depressive and insomnia symptoms, as well as the CRP were more remarkable in individuals with moderate/severe COVID-19. We found a positive correlation between stress and severity of anxiety, depression, and insomnia in individuals with or without COVID-19. There was a positive correlation between CRP levels and severity of depressive symptoms in cases and controls, and a positive correlation between CRP levels and the severity of anxiety symptoms and stress levels only in individuals with COVID-19. Individuals with COVID-19 and depression had greater CRP than those with COVID-19 without current major depressive disorder. LIMITATIONS: We cannot infer causality because this is a cross-sectional study, and the majority of COVID-19 sample was asymptomatic or had mild symptoms, which may limit the generalizability of our findings for moderate/severe cases. CONCLUSIONS: Individuals with COVID-19 showed greater severity of psychological symptoms, which may impact on the development of psychiatric disorders in the future. CPR seem to be a promising biomarker for earlier detection of post-COVID depression.

Adaptação transcultural e validação da escala "indicadora de trabalho-vida" (work-life indicator) para uso no Brasil: Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) / Transcultural adaptation and validation of the work-life indicator scale for use in Brazil: Longitudinal Study of Adult Health (ELSA-Brasil)

Resumo Objetivo: descrever etapas de adaptação transcultural e validade dimensional para uso, no Brasil, da escala "indicadora de trabalho-vida" (work-life indicator). Métodos: realizaram-se análises das equivalências conceitual, de itens e da semântica, conduzidas por pesquisadores experientes em uso de escalas e/ou saúde ocupacional. A escala foi aplicada a participantes da terceira onda do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Procedeu-se, então, a avaliação da equivalência de mensuração, utilizando-se Análises Fatoriais Exploratória (AFE) e Confirmatória (AFC). Resultados: aplicada a 7.277 participantes (50,3% do sexo masculino), a escala apresentou equivalências conceitual, de itens e semântica pertinentes no contexto brasileiro, bem como adequada correspondência de significado referencial/denotativa de termos e geral/conotativa dos itens. As AFE e AFC corroboraram a estrutura teórica de três dimensões - i) vida pessoal invadindo trabalho, ii) trabalho invadindo vida pessoal e iii) controle de limites percebidos -, com indicadores de ajuste adequados após a exclusão de dois itens da primeira dimensão. Na AFC, obteve-se índice de ajuste comparativo=0,968, índice de Tucker-Lewis=0,957 e raiz do erro quadrático médio de aproximação=0,039 (IC90%: 0,035;0,041). Conclusão: a escala é promissora para avaliar o gerenciamento de limites entre trabalho e vida pessoal no contexto brasileiro, assim como facilitará a realização de estudos sobre a influência desse gerenciamento na saúde e bem-estar dos(as) trabalhadores(as).

Abstract Objective: to describe the stages in the transcultural adaptation and dimensional validation of the "life-work indicator" scale for use in Brazil. Methods: equivalence analyses regarding concept, items, and semantics were conducted by researchers experienced in using scales and/or occupational health. The scale was applied to the third wave of the Longitudinal Study of Adult Health (Estudo Longitudinal de Saúde do Adulto, ELSA-Brasil). Measurement equivalence was then assessed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Results: applied to 7,277 participants (50.3% of them male), the scale displayed equivalences regarding concept, items, and semantics proper to the Brazilian context, as well as appropriate correspondences in referential/denotative meaning of terms and overall/connotative meaning of items. EFA and CFA corroborated its theoretical structure in three dimensions -i) personal life invading work, ii) work invading personal life, and iii) perceived boundary control - returning suitable fit indices after exclusion of two items from the first dimension. CFA returned comparative fit index of 0.968, Tucker-Lewis index of 0.957, and root mean square error of approximation of 0.039 (90%CI: 0.035;0.041). Conclusion: the scale shows to be promising for assessing the management of boundaries between work and personal life in the Brazilian context, and will facilitate studies on the influence of such management on workers' health and wellbeing.

FSH-blocking therapeutic for osteoporosis.

Pharmacological and genetic studies over the past decade have established the follicle-stimulating hormone (FSH) as an actionable target for diseases affecting millions, namely osteoporosis, obesity, and Alzheimer's disease. Blocking FSH action prevents bone loss, fat gain, and neurodegeneration in mice. We recently developed a first-in-class, humanized, epitope-specific FSH-blocking antibody, MS-Hu6, with a KD of 7.52 nM. Using a Good Laboratory Practice (GLP)-compliant platform, we now report the efficacy of MS-Hu6 in preventing and treating osteoporosis in mice and parameters of acute safety in monkeys. Biodistribution studies using 89Zr-labeled, biotinylated or unconjugated MS-Hu6 in mice and monkeys showed localization to bone and bone marrow. The MS-Hu6 displayed a ß phase t½ of 7.5 days (180 hr) in humanized Tg32 mice. We tested 217 variations of excipients using the protein thermal shift assay to generate a final formulation that rendered MS-Hu6 stable in solution upon freeze-thaw and at different temperatures, with minimal aggregation, and without self-, cross-, or hydrophobic interactions or appreciable binding to relevant human antigens. The MS-Hu6 showed the same level of "humanness" as human IgG1 in silico and was non-immunogenic in ELISpot assays for IL-2 and IFN-γ in human peripheral blood mononuclear cell cultures. We conclude that MS-Hu6 is efficacious, durable, and manufacturable, and is therefore poised for future human testing.

Reliability of the PERFECT scheme assessed by unidigital and bidigital vaginal palpation.

INTRODUCTION AND HYPOTHESIS: The aim of the present study was to evaluate the inter- and intra-rater reliability of the PERFECT scheme assessed by uni- and bidigital vaginal palpation in young nulligravid women. METHODS: Forty healthy women [median age 22 (19-34) years] were evaluated by unidigital vaginal palpation by both Examiners A and C, while the other 40 participants [median age 23.5 (19-35) years] were assessed by Examiners B and C by bidigital vaginal palpation. Inter- and intra-rater reliability of all items of the PERFECT scheme were evaluated: P = power (Modified Oxford Scale); E = endurance; R = repetitions; F = fast contractions. Cohen's linear weighted kappa (κw) was used to assess the reliability of the power, while the intraclass correlation coefficient (ICC) was applied for the other items. A priori sample size calculation found that 40 participants would be adequate. RESULTS: Inter-rater reliability of unidigital palpation was considered fair for power (κw = 0.34) and poor for other items (ICC < 0.50); bidigital inter-rater reliability was considered moderate (power: κw = 0.57; endurance: ICC = 0.53; fast contractions: ICC = 0.65, respectively) and low (repetitions: ICC = 0.27). Intra-rater reliability was substantial for power (κw = 0.73 and 0.62), moderate for fast contractions (ICC = 0.63 and 0.51) and poor for repetitions (ICC < 0.50), respectively, for uni- and bidigital palpation. Endurance showed poor (ICC < 0.50) and moderate (ICC = 0.61) reliability for uni- and bidigital palpation. CONCLUSIONS: The PERFECT scheme carried out by bidigital vaginal palpation presents higher reliability when two examiners carry out the physical examination. When one examiner is responsible for PFM assessment, both types of palpation are recommended for evaluation of power and fast contraction; endurance should be evaluated using bidigital palpation. Examiners should be careful during the assessment of repetition of sustained contractions because inter- and intra-reliabilities for both types of palpation were classified as poor.

Heparin Administered to Anopheles in Membrane Feeding Assays Blocks Plasmodium Development in the Mosquito.

Innovative antimalarial strategies are urgently needed given the alarming evolution of resistance to every single drug developed against Plasmodium parasites. The sulfated glycosaminoglycan heparin has been delivered in membrane feeding assays together with Plasmodium berghei-infected blood to Anopheles stephensi mosquitoes. The transition between ookinete and oocyst pathogen stages in the mosquito has been studied in vivo through oocyst counting in dissected insect midguts, whereas ookinete interactions with heparin have been followed ex vivo by flow cytometry. Heparin interferes with the parasite's ookinete-oocyst transition by binding ookinetes, but it does not affect fertilization. Hypersulfated heparin is a more efficient blocker of ookinete development than native heparin, significantly reducing the number of oocysts per midgut when offered to mosquitoes at 5 µg/mL in membrane feeding assays. Direct delivery of heparin to mosquitoes might represent a new antimalarial strategy of rapid implementation, since it would not require clinical trials for its immediate deployment.

Microbiologic characteristics and antibiotic resistance rates of diabetic foot infections.

PURPOSE: the purpose of this research was to identify the sociodemographic and microbiological characteristics and antibiotic resistance rates of patients with diabetic foot infections, hospitalized in an emergency reference center. METHODS: it was an observational and transversal study. The sociodemographic data were collected by direct interview with the patients. During the surgical procedures, specimens of tissue of the infected foot lesions were biopsied to be cultured, and for bacterial resistance analysis. RESULTS: the sample consisted of 105 patients. The majority of patierns were men, over 50 years of age, married and with low educational level. There was bacterial growth in 95 of the 105 tissue cultures. In each positive culture only one germ was isolated. There was a high prevalence of germs of the Enterobacteriaceae family (51,5%). Gram-negative germs were isolated in 60% of cultures and the most individually isolated germs were the Gram-positive cocci, Staphylococcus aureus (20%) and Enterococcus faecalis (17,9%). Regarding antibiotic resistance rates, a high frequency of Staphylococcus aureus resistant to methicillin (63,0%) and to ciprofloxacin (55,5%) was found; additionally, 43,5% of the Gram-negative isolated germs were resistant to ciprofloxacin. CONCLUSIONS: the majority of patients were men, over 50 years of age, married and with low educational level. The most prevalent isolated germs from the infected foot lesions were Gram-negative bacteria, resistant to ciprofloxacin, and the individually most isolated germ was the methicillin resistant Staphylococcus aureus.

A Dança Sênior® como recurso do terapeuta ocupacional com idosos: contribuições na qualidade de vida / Senior dance as a resource of the occupational therapist with older adults: contributions in the quality of life

Resumo Objetivou-se analisar e identificar possíveis contribuições na qualidade de vida de idosos participantes de oficinas de Dança Sênior® aplicadas como recurso do terapeuta ocupacional. Trata-se de um estudo exploratório, descritivo, intervencional, longitudinal prospectivo, com abordagem qualitativa e quantitativa. Para a seleção da amostra, os idosos foram submetidos a um rastreamento cognitivo por meio do Mini Exame do Estado Mental (MEEM), e para a análise da qualidade de vida foi aplicada a avaliação Short Form Health Survey 36 (SF-36) antes e após a oficina. Para coleta de dados qualitativos, os idosos participaram de dois grupos focais, antes e após a oficina. Os dados foram analisados por estatística descritiva, Teste t e análise de conteúdo. A oficina foi desenvolvida ao longo de 12 encontros semanais, com duração de 90 minutos cada. Observou-se, após o término da oficina, melhora na qualidade de vida, com destaque para as médias individuais dos domínios aspectos físicos (pré-oficina: 69,4; pós-oficina: 83,3) e aspectos emocionais (pré-oficina: 74,1; pós-oficina: 96,3). Quando comparadas às médias do grupo como um todo, antes e após a oficina, foi possível notar que os domínios "capacidade funcional" (p=0,01), "aspectos sociais" (p=0,04) e "saúde mental" (p=0,02) apresentaram melhora significativa. Portanto, o presente estudo apontou os benefícios de uma oficina de Dança Sênior® sendo utilizada como recurso do terapeuta ocupacional com idosos, e os resultados obtidos possibilitam chegar à conclusão que a oficina de dança contribuiu para melhoria na qualidade de vida dos idosos que dela participaram.

Abstract This study aimed to analyze and identify possible contributions in the quality of life of older adult participants of senior dance workshops applied as a resource of the occupational therapist. It is an exploratory, descriptive, interventional, longitudinal prospective study with a qualitative and quantitative approach. For the selection of the sample, the elderly were submitted to a cognitive screening through the Mini-Mental State Examination (MMSE), for the analysis of the quality of life, the 36-Item Short-Form Health Survey (SF-36) was applied before and after the workshop. To collect qualitative data, the older adults participated in two focus groups, before and after the workshop. The data were analyzed by descriptive statistics, paired T-test of the difference between two means and content analysis. The workshop was developed over 12 weekly meetings, lasting 90 minutes each. After finishing the workshop, it was observed improvement in the quality of life, with emphasis on the individual averages of the physical aspects (pre-workshop: 69.4, post-workshop: 83.3) and emotional aspects (pre-workshop: 74.1; post-workshop: 96.3). When the Student's T-test was used to compare the means of the group as a whole before and after the workshop, it was possible to note that the domains "functional capacity" (p=0.01), "social aspects" (p=0.04) and "mental health" (p=0.02) presented significant improvement. Therefore, the present study pointed out the benefits of a senior dance workshop being used as a resource for the occupational therapist with the elderly, and the results obtained lead to the conclusion that the dance workshop contributed to an improvement in the quality of life of elderly people who participated in it.

Microbiologic characteristics and antibiotic resistance rates of diabetic foot infections / Perfil microbiológico e de resistência bacteriana no pé diabético infectado

ABSTRACT Purpose: the purpose of this research was to identify the sociodemographic and microbiological characteristics and antibiotic resistance rates of patients with diabetic foot infections, hospitalized in an emergency reference center. Methods: it was an observational and transversal study. The sociodemographic data were collected by direct interview with the patients. During the surgical procedures, specimens of tissue of the infected foot lesions were biopsied to be cultured, and for bacterial resistance analysis. Results: the sample consisted of 105 patients. The majority of patierns were men, over 50 years of age, married and with low educational level. There was bacterial growth in 95 of the 105 tissue cultures. In each positive culture only one germ was isolated. There was a high prevalence of germs of the Enterobacteriaceae family (51,5%). Gram-negative germs were isolated in 60% of cultures and the most individually isolated germs were the Gram-positive cocci, Staphylococcus aureus (20%) and Enterococcus faecalis (17,9%). Regarding antibiotic resistance rates, a high frequency of Staphylococcus aureus resistant to methicillin (63,0%) and to ciprofloxacin (55,5%) was found; additionally, 43,5% of the Gram-negative isolated germs were resistant to ciprofloxacin. Conclusions: the majority of patients were men, over 50 years of age, married and with low educational level. The most prevalent isolated germs from the infected foot lesions were Gram-negative bacteria, resistant to ciprofloxacin, and the individually most isolated germ was the methicillin resistant Staphylococcus aureus.

RESUMO Objetivo: identificar o perfil sociodemográfico, microbiológico e de resistência bacteriana em pacientes com pé diabético infectado. Métodos: tratou-se de estudo observacional, transversal que avaliou os perfis sóciodemográfico e microbiológico de pacientes portadores de pé diabético infectado internados em Pronto Socorro de referência. Os dados sociodemográficos foram coletados por meio de entrevista. Foram colhidos, durante os procedimentos cirúrgicos, fragmentos de tecidos das lesões podais infectadas para realização de cultura/antibiograma. Resultados: a amostra foi composta por 105 pacientes. O perfil sociodemográfico mais prevalente foi o de pacientes do sexo masculino, acima dos 50 anos, casados e com baixa escolaridade. Das 105 amostras de fragmentos de tecidos colhidos para realização de cultura e antibiograma, 95 foram positivas, com crescimento de um único germe em cada um dos exames. Houve predomínio de germes da família Enterobacteriaceae (51,5%). Germes Gram-negativos foram isolados em 60,0% das culturas e os espécimes mais isolados individualmente foram os cocos Gram-positivos, Staphylococcus aureus (20,0%) e Enterococcus faecalis (17,9%). Considerando-se os perfis de resistência bacteriana, verificou-se alta taxa de Staphylococcus aureus resistente à meticilina (63,0%) e à ciprofloxacino (55,5%); verificou-se, também, que 43,5% dos germes Gram-negativos eram resistentes à ciprofloxacino. Conclusões: o perfil sociodemográfico majoritário, foi o de homens, com mais de 50 anos e com baixa escolaridade. Concluímos que os germes mais prevalentes nas lesões podais dos pacientes diabéticos foram os Gram-negativos, resistentes ao ciprofloxacino e que o germe mais isolado individualmente foi o Staphylococcus aureus resistente à meticilina.

A influência da prática do teatro no desenvolvimento da espontaneidade: uma pesquisa com alunos de uma escola de teatro / The influence of theater practice on the development of spontaneity: a research with students of a theater school / La influencia de la práctica del teatro en el desarrollo de la espontaneidad: una investigación con alumnos de una escuela de teatro

Este artigo teve por objetivo compreender as possíveis influências de aulas de teatro no desenvolvimento da espontaneidade dos alunos. A pesquisa ocorreu com oito alunos, cinco do nível básico do curso de teatro e três do nível avançado. Os dados da entrevista foram analisados mediante a Classificação Hierárquica Descendente, com auxílio do software Iramuteq; e os dados da escala de espontaneidade foram analisados pela estatística descritiva. Identificou-se uma maior média de espontaneidade em alunos que frequentavam as aulas há mais tempo. O desenvolvimento dessa característica ficou evidenciado por falas que reforçaram mudanças nas relações sociais, na forma como percebem a si, ao mundo e encaram as opiniões alheias, resultando em maior liberdade para expressar sentimentos e pensamentos diante do outro.

The objective of this article was to understand the possible influences of theater classes in the development of students' spontaneity. The research was conducted with eight students, five from the basic level of the theater course and three from the advanced level. The interview data were analyzed through the Descending Hierarchical Classification, using the Iramuteq software; and the spontaneity scale data were analyzed through descriptive statistics. A greater average of spontaneity was identified in students who attended classes longer. The development of this characteristic was evidenced by the words that reinforced changes in social relationships, in the way they perceive themselves, the world, and face the opinions of others, resulting in greater freedom to express feelings and thoughts before the other.

Este artículo tuvo por objetivo comprender las posibles influencias de clases de teatro en el desarrollo de la espontaneidad de los alumnos. La investigación tuvo lugar con ocho alumnos, cinco del nivel básico del curso de teatro y tres del nivel avanzado. Los datos de la entrevista fueron analizados mediante la Clasificación Jerárquica Descendente, con ayuda del software Iramuteq; y los datos de la escala de espontaneidad fueron analizados a través de la estadística descriptiva. Se identificó una mayor media de espontaneidad en alumnos que frecuentaban las clases hace más tiempo. El desarrollo de esta característica quedó evidenciado por las palabras que reforzaron cambios en las relaciones sociales, en la forma en que se perciben a sí, al mundo y encaran las opiniones ajenas, resultando en mayor libertad para expresar sentimientos y pensamientos ante el otro.

Amino acid conjugated chitosan nanoparticles for the brain targeting of a model dipeptidyl peptidase-4 inhibitor.

Saxagliptin (SAX) is a dipeptidyl peptidase-4 enzyme inhibitor molecule now explored for its activity in the therapy of Alzheimer's disease. Being extremely hydrophilic, it is unable to permeate the blood-brain barrier by the conventional therapy modalities. Further repurposing the drug, SAX is associated with a reduction in the blood sugar level in the periphery. In the present study, the chitosan-l-valine conjugate was synthesized by carbodiimide chemistry. The conjugate was then used to prepare nanoparticles encapsulating SAX. The nanoparticles were characterized by particle size, surface morphology, and entrapment efficiency. The stability of the formulations was determined by incubation with rat plasma and brain homogenate. The blood brain barrier permeability of the nanoparticles was successfully demonstrated by the incorporation of fluorescent dye, Rhodamine B in the nanoparticles. In vivo studies were conducted in rats and the results showed that the nanoparticles were highly stable in the plasma releasing only a minute amount of SAX (2.5 ng/mL) which was less than the Cmax of the pure SAX (51 ng/mL). The brain uptake studies showed an accumulation of 53 ng/mL SAX from the nanoparticles whereas the pure SAX showed no detectable amount of the drug after 24 h. The pharmacokinetic studies demonstrated that nanoparticles had an (AUC0-t) of 3.42 times lower than the pure SAX, indicating the stability of the prepared formulation in the plasma.

Supervised deep learning embeddings for the prediction of cervical cancer diagnosis.

Cervical cancer remains a significant cause of mortality all around the world, even if it can be prevented and cured by removing affected tissues in early stages. Providing universal and efficient access to cervical screening programs is a challenge that requires identifying vulnerable individuals in the population, among other steps. In this work, we present a computationally automated strategy for predicting the outcome of the patient biopsy, given risk patterns from individual medical records. We propose a machine learning technique that allows a joint and fully supervised optimization of dimensionality reduction and classification models. We also build a model able to highlight relevant properties in the low dimensional space, to ease the classification of patients. We instantiated the proposed approach with deep learning architectures, and achieved accurate prediction results (top area under the curve AUC = 0.6875) which outperform previously developed methods, such as denoising autoencoders. Additionally, we explored some clinical findings from the embedding spaces, and we validated them through the medical literature, making them reliable for physicians and biomedical researchers.

Knockout of the gamma subunit of the AP-1 adaptor complex in the human parasite Trypanosoma cruzi impairs infectivity and differentiation and prevents the maturation and targeting of the major protease cruzipain.

The AP-1 Adaptor Complex assists clathrin-coated vesicle assembly in the trans-Golgi network (TGN) of eukaryotic cells. However, the role of AP-1 in the protozoan Trypanosoma cruzi-the Chagas disease parasite-has not been addressed. Here, we studied the function and localization of AP-1 in different T. cruzi life cycle forms, by generating a gene knockout of the large AP-1 subunit gamma adaptin (TcAP1-γ), and raising a monoclonal antibody against TcAP1-γ. Co-localization with a Golgi marker and with the clathrin light chain showed that TcAP1-γ is located in the Golgi, and it may interact with clathrin in vivo, at the TGN. Epimastigote (insect form) parasites lacking TcAP1-γ (TcγKO) have reduced proliferation and differentiation into infective metacyclic trypomastigotes (compared with wild-type parasites). TcγKO parasites have also displayed significantly reduced infectivity towards mammalian cells. Importantly, TcAP1-γ knockout impaired maturation and transport to lysosome-related organelles (reservosomes) of a key cargo-the major cysteine protease cruzipain, which is important for parasite nutrition, differentiation and infection. In conclusion, the defective processing and transport of cruzipain upon AP-1 ablation may underlie the phenotype of TcγKO parasites.

Inducción de ovulación en pacientes bajas respondedoras en fecundación in vitro: microdosis de acetato de leuprolide vs priming de estradiol

Objetivo: Comparar los protocolos de microdosis de acetato de leuprolide y priming de estradiol. Métodos: Estudio retrospectivo de 115 pacientes bajas respondedoras (según criterios de Bologna), evaluadas en UNIFERTES desde enero 2010 a diciembre 2012, sometidas a hiperestimulación ovárica controlada según protocolo. La inducción ovárica constó de pauta fija con gonadotropinas (hormona folículo estimulante recombinante 450 UI/día + Gonadotropina menopaúsica humana 150 UI/día); realizando disparo de ovulación con 10.000 UI gonadotropina coriónica humana urinaria al obtener 2 o 3 folículos entre 17-18 mm de diámetro. Se realizó aspiración folicular con aguja bilumen a las 35 horas del disparo, fecundación in vitro en medios secuenciales y transferencia embrionaria al día 3. El soporte de fase lútea constó de progesterona natural micronizada 600 mg/día y valerato de estradiol 4 mg/día. Se realizó prueba de embarazo cuantitativa a los quince días y verificación de embriocardia al mes. Se compara: tasa de cancelación, días de estimulación, número de ovocitos aspirados, tasa de embarazo clínico por transferencia y tasa de aborto. Resultados: Se incluyeron 115 pacientes: 69 al protocolo de microdosis y 46 al de priming de estradiol. No hubo diferencias estadísticas entre ambos protocolos en cuanto a: número de ovocitos aspirados, tasa de embarazo clínico y aborto. Los días de estimulación y la dosis total de gonadotropinas fue mayor con microdosis. Conclusiones: Aunque no hubo diferencias estadísticamente significativas entre ambos protocolos, el de priming de estradiol por tener menos días de estimulación y dosis totales de gonadotropinas menores, implica mayor bienestar de la paciente.

Objective: To compare microdose leuprolide acetate protocols and Estradiol Priming. Methods: Retrospective study of 115 low-responding patients (according to Bologna Criteria), evaluated at UNIFERTES from January 2010 to December 2012, who underwent controlled ovarian hyperstimulation as per Microdose leuprolide acetate protocol or Estradiol Priming Protocols. Ovarian induction consisted of a set standard with gonadotropins, 450UI/day recombinant follicle-stimulating hormone + 150UI/day Human Menopausal Gonadotropin; performing an ovulation trigger shot with 10,000UI urinary human chorionic gonadotropin when obtaining 2 to 3 follicles of 17-18mm diameter. Follicular aspiration is performed with double lumen needle, 35 hours from trigger shot with in vitro fertilization in sequential media, and embryo transfer on day 3. Luteal phase support consisted of 600mg/day micronized natural progesterone and 4mg/day of estradiol valerate. Quantitative pregnancy test was carried out at fifteen days and embryo cardiac activity validation at one month. The following are compared: cancellation rate, stimulation days, number of aspirated oocytes, rate of clinical pregnancy by transfer and abortion rate. Results: 115 patients were included: 69 underwent microdose leuprolide acetate protocol flare and 46 underwent estradiol priming. There were no statistical differences between both protocols with regards to: number of aspirated oocytes, rate of clinical pregnancy by transfer and abortion rate. Stimulation days and therefore, gonadotropins total dosage was greater with microdose leuprolide acetate protocol. Conclusions: Even though there were no significant statistical differences between both protocols, estradiol priming entails greater patient’s wellbeing, since it requires less stimulation days and less gonadotropin total dosages.

Lazer e espaços públicos: o circo como opção / Leisure and public spaces: the circus as option

Dentre as diversas atividades de lazer que se podem vivenciar nos espaços públicos, encontra-se o circo. Nesse contexto, um conjunto de encontros circenses vem se consolidando em diversas cidades brasileiras. Estudamos dois deles, realizados no estado de São Paulo, com o objetivo de conhecer suas formas de organização e as motivações que configuram a participação de jovens e adultos nesses encontros. Para tal, realizamos uma pesquisa de campo que incluiu a observação-participante e a aplicação de questionários a participantes e organizadores. Os resultados indicaram que os encontros representam uma forma de lazer e de difusão do circo e contribuem para o desenvolvimento técnico e artístico do circo, assim como para uma maior integração social e novos usos dos espaços públicos. Em ambos, as redes sociais são sua plataforma de divulgação e comunicação, e as adversidades climáticas, o maior desafio para sua manutenção.

Among the many leisure activities that one can experience in public areas, is the circus. In this context, a set of circus meetings has been consolidated in several Brazilian cities. We studied two of them, conducted in the state of São Paulo, in order to meet their forms of organization and the motivations that shape the participation of young people and adults in these meetings. To this end, we conducted a field survey that included participant observation and questionnaires to participants and organizers. The results indicated that the meetings represent a form of leisure and circus dissemination and contribute to the technical and artistic development of the circus, as well as to greater social integration and new uses of public spaces. In both social networks are its dissemination and communication platform, and climatic adversities, the biggest challenge for its maintenance.

Trastornos de diferenciación sexual

Objetivo: Presentar la clínica, citogenética y hallazgos histopatológicos en pacientes adultas, que consultaron a la Unidad de Endocrinología Ginecológica del Hospital Universitario de Caracas con trastornos de la diferenciación sexual. Se reportan cuatro casos clínicos: dos casos con trastorno de la diferenciación sexual 46, XY por alteración en la acción de los andrógenos anteriormente denominado insensibilidad androgénica parcial, una paciente con trastorno de la diferenciación sexual 46, XX y otra con trastorno de la diferenciación sexual 46, XY ovotesticular sin gonadoblastoma por síndrome de Frasier. Es importante realizar un diagnóstico temprano para su tratamiento precoz, por la trascendencia que la definición del sexo tiene para el futuro del individuo. Conclusiones: A pesar de los avances alcanzados a lo largo de los últimos 20 años, algunos casos quedan aún sin diagnóstico etiológico definido, sea por falta de estudio molecular o genes aún no conocidos. Su abordaje diagnóstico y terapéutico es complejo, requiere de un equipo multidiscplinario integrado por ginecólogos, endocrinólogos, psiquiatras, urólogos, cirujanos plásticos.

The aim of this paper is to present the clinical, cytogenetic and histopathological findings in adult patients who consulted the Gynecological Endocrinology Unit of the University Hospital of Caracas with Disorders of sexual development. Four clinical cases reported: Two with Disorder of sexual development 46, XY due defect in androgen action previously called partial androgen insensitivity, one patient with disorders of sexual development 46, XX and another with disorder of sexual development 46, XY ovotesticular without gonadoblastoma by Frasier syndrome. It is important an early diagnosis and treatment to define the sex for the individual’s future. Conclusion: Despite the progress made over the last 20 years, some cases are still without etiologic diagnosis, either through lack of molecular study or yet unknown genes. Its diagnostic and therapeutic approach is complex, requiring a team of gynecologists, endocrinologists, psychiatrists, urologists, plastic surgeons.

Amenorrea primaria: experiencia de la Unidad de Endocrinología Ginecológica del Hospital Universitario de Caracas (Revisión de la literatura)

Objetivo: Establecer la prevalencia de amenorrea primaria en la consulta de Endocrinología Ginecológica del Hospital Universitario de Caracas y las entidades nosológicas involucradas. Métodos: Estudio retrospectivo y descriptivo de las historias clínicas de las pacientes que consultaron por amenorrea primaria durante el período 2013 a 2015, quienes fueron categorizadas retrospectivamente en 4 grupos según el algoritmo diagnóstico de Mashchak. Resultados: El 6,48 % (46 / 710 pacientes) fueron casos de amenorrea primaria. La etiología comprendió: hipogonadismo-hipergonadotrópico (46,47 % / 7 casos), hipogonadismo-hipogonadotrópico (33,34% / 5 casos), síndrome de Rokitansky (6,67 % / 1 caso), defecto de acción de andrógeno (6, 67 % / 1 caso) y trastorno 46, XY ovotesticular (6,67 % / 1 caso). Conclusiones: La amenorrea primaria representa un motivo de consulta poco frecuente, pero la diversidad y complejidad de las patologías que la producen, ameritan el uso de esquemas que permitan un diagnóstico sencillo, el uso del algoritmo propuesto por Mashchak nos permitió un diagnóstico eficiente de los casos. La diversidad de estas patologías amerita un equipo multidisciplinario para un manejo adecuado.

Objectives: To establish the prevalence of primary amenorrhea in Gynecological Endocrinologic Unit of Hospital Universitario de Caracas; and the etiology involved. Method: Retrospective and descriptive study of medical records of patients who consulted for primary amenorrhea, during the period 2013-2015. Were retrospectively categorized into 4 groups according Mashchak algoritm. Results: 6.48 % (46/710 patients) were cases of primary amenorrhea. The etiology includeded: hypogonadism hypergonadotropic (46.47 %/7 cases), hypogonadotropic hypogonadism (33.34 % / 5 cases), Rokitansky syndrome (6,67 % / 1 case), defect in androgen action (6. 67 % / 1 case), disorder 46, XY ovotesticular (6.67 % / 1 case). Conclusions: With a wide diversity and complexity of pathologies that produce primary amenorrhea, it requires the use of diagnostic categories based on physical examination and a minimal laboratory investigation that allow a simple diagnosis. In this sense, using the algoritm proposed by Mashchak allowed us to efficiently diagnose the aforementioned cases. The diversity of these diseases requires the inclusion of a multidisciplinary team in orden to achieve a proper management.

Avaliação antropométrica e consumo alimentar de pré-escolares em creches de Umuarama, Paraná / Anthropometric and food intake assessment of preschoolers in day-care centers in Umuarama, Paraná

Na atualidade, as creches representam um grande avanço social, permitindo que as mães possam permanecer no mercado de trabalho, principalmente das médias e grandes cidades. Desta forma, as mães não acompanham de perto a alimentação de seus filhos, sendo que, na faixa etária de pré-escolares, uma boa alimentação é importante para a manutenção da saúde e criação de bons hábitos alimentares. Tendo isso em vista, este trabalho teve como objetivo realizar uma avaliação antropométrica e do consumo alimentar de crianças em creches da cidade de Umuarama, estado do Paraná. A avaliação antropométrica foi realizada com cálculo do IMC e dos escores z para peso/idade, peso/estatura e estatura/idade. A avaliação do consumo alimentar foi realizada pelo método de pesagem direta dos alimentos oferecidos. Os resultados indicaram que os pré-escolares apresentavam uma tendência ao aumento de peso e de estatura e, quanto à oferta de nutrientes nas creches, proteínas e sódio estavam acima das recomendações, enquanto os demais nutrientes e energia encontravam-se abaixo do recomendado. Esses resultados indicam ser necessária uma maior vigilância quanto à oferta de nutrientes oferecidos aos pré-escolares que freqüentam creches.

Day-care centers are social advancement allowing the mothers to stay in the labor market mainly from medium and large cities. Therefore, mothers do not follow their childrens feeding closely, whereas in the age group of preschoolers a balanced diet is important for maintaining health and developing good eating habits. Then, this study carries out an anthropometric and dietary intake assessment on children in day-care centers in Umuarama - PR. The anthropometric assessment was performed by calculating the BMI and the z-scores for weight/age, weight/height, and height/age. Food intake was assessed by direct weighing. Results showed that preschoolers showed a tendency to weight gain and increase in height. Protein and sodium were above the recommended while the supply of other nutrients was below. These results show the need for vigilance on nutrient supply for preschoolers attending day-care centers.