New Oncologic Drugs from 2008 to 2023-Differences in Approval and Access between the United States, Europe and Brazil.

INTRODUCTION: Advancements in oncology have revolutionized cancer treatment, with new drugs being approved at different rates worldwide. Our objective was to evaluate the approval of new oncological drugs for solid tumors by the Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Brazilian Health Regulatory Agency (ANVISA) since 2008. METHODS: Data were collected from public and online databases by searching for the date of submission, the date of the procedure, the date of approval, clinical indication, and drug characteristics. The distribution was tested using the Shapiro-Wilk, test and comparisons were made using the Mann-Whitney U test; the data are reported using median days and interquartile range (IQR1-IQR3). RESULTS: In total, 104 new oncologic drugs for the treatment of solid tumors were approved by the three agencies: 98 by the FDA, 90 by the EMA, and 68 by ANVISA. The cancer types with the highest number of first indications were lung cancer (n = 24), breast cancer (n = 15), and melanoma (n = 15). Most approvals were for oral medications (n = 63) and tyrosine-kinase inhibitors or other small-molecule inhibitors (n = 54). Time to approval after submission was as follows: the FDA-224 days (167-285); the EMA-364 days (330-418); and ANVISA-403 days (276-636) (p < 0.00001 for the FDA to the EMA and the FDA to ANVISA). The difference between submission dates among the agencies was as follows: EMA-FDA: 24 days (0-85); ANVISA-FDA: 255 (114-632); and ANVISA-EMA: 260 (109-645). The difference in approval dates between the agencies was as follows: EMA-FDA: 185 days (59-319); ANVISA-FDA: 558 (278-957); and ANVISA-EMA: 435 days (158-918). CONCLUSIONS: New oncologic drugs are submitted to the FDA and EMA for approval on similar dates; however, the longer appraisal period by the EMA pushes the approval date for Europe to approximately 6 months later. The same steps at ANVISA delay the approval by 1.5 years. Such procedures cause a significant difference in available medications between these regions.

Biosimilars in the Era of Artificial Intelligence-International Regulations and the Use in Oncological Treatments.

This research is based on three fundamental aspects of successful biosimilar development in the challenging biopharmaceutical market. First, biosimilar regulations in eight selected countries: Japan, South Korea, the United States, Canada, Brazil, Argentina, Australia, and South Africa, represent the four continents. The regulatory aspects of the countries studied are analyzed, highlighting the challenges facing biosimilars, including their complex approval processes and the need for standardized regulatory guidelines. There is an inconsistency depending on whether the biosimilar is used in a developed or developing country. In the countries observed, biosimilars are considered excellent alternatives to patent-protected biological products for the treatment of chronic diseases. In the second aspect addressed, various analytical AI modeling methods (such as machine learning tools, reinforcement learning, supervised, unsupervised, and deep learning tools) were analyzed to observe patterns that lead to the prevalence of biosimilars used in cancer to model the behaviors of the most prominent active compounds with spectroscopy. Finally, an analysis of the use of active compounds of biosimilars used in cancer and approved by the FDA and EMA was proposed.

Determination of Mandibular Position and Mouth Opening in Healthy Patients and Patients with Articular and/or Muscular Pathology: A Pilot Study with 3D Electromagnetic Articulography and Surface Electromyography.

Temporomandibular disorders (TMDs) are a group of pathologies that affect the temporomandibular joint and its related structures, producing intracapsular and muscular pathologies. The aim of this study is to describe, by electromagnetic articulography (EMA) and simultaneous electromyography (sEMG), the mandibular postural position and mouth opening in healthy patients and with articular and/or muscular pathology. MATERIALS AND METHODS: A pilot study was conducted with a sample of sixteen participants aged 18 years or older who attended the TMDs and Orofacial Pain Polyclinic of the University of La Frontera due to TMDs. The physiological inoculation space was evaluated from the mandibular postural position (MPP) with swallowing command and without command, in both healthy patients and patients with articular, muscular, and mixed TMDs, measured simultaneously with EMA and sEMG. An angular measurement of the oral opening was also performed with the data obtained. RESULTS: The physiological inoculation space was obtained from the determination of the MPP through the procedures with swallowing command and without command, and different mouth opening degrees were evaluated. CONCLUSIONS: Simultaneous position and sEMG records can be produced from EMA, and different characterization variables such as the vertical distance, Euclidean distance, and angle can be obtained.

Nasal Cerebrospinal Leaks in the Milieu of COVID-19 Pandemic / Vazamentos nasais cerebroespinhais no meio da pandemia de COVID-19

Background The unintentional ingestion of oropharyngeal or gastric contents into the respiratory tract is known as aspiration. Rhinorrhea can cause aspiration pneumonia (cerebrospinal fluid leakage). Objective There are only a few reports in the literature about pneumonia as a complication of rhinorrhea. There are no reports on how to handle such cases if they present to the clinic at the peak of COVID-19 disease and distinguish between these two conditions. Methods We reviewed the literature and retrospectively analyzed the clinical information and treatment protocols used to treat the two clinical cases. Results By screening the COVID-19 PCR and antibodies more than twice, surgery was postponed for 10­14 days in both cases to rule out COVID-19-induced pneumonia. Chest CT scans still revealed ground glass opacities. In both cases, the skull base defect was repaired. In both cases, radiological signs of rhinorrhea-induced pneumonia had completely resolved at the 24- and 30-day follow-ups. Conclusion CSF aspiration causes radiological changes in the lungs in rhinnorhea. This is a short-term local decrease in lung tissue airness (partial filling of alveoli with fluids), which is visible radiographically (ground-glass opacities). To rule out COVID-19 infection, surgery should be postponed for 10­14 days, and PCR and antibodies (IgG, IgM) should be performed at least twice. If the COVID-19 screening test is negative, repair surgery can be scheduled.

Introdução A ingestão não intencional de conteúdo orofaríngeo ou gástrico no trato respiratório é conhecida como aspiração. A rinorréia pode causar pneumonia por aspiração (vazamento de líquido cefalorraquidiano). Objetivo Existem poucos relatos na literatura sobre pneumonia como complicação da rinorréia. Não há relatos sobre como lidar com esses casos se eles se apresentarem à clínica no pico da doença COVID-19 e distinguirem entre essas duas condições. Métodos Revisamos a literatura e analisamos retrospectivamente as informações clínicas e os protocolos de tratamento utilizados para tratar os dois casos clínicos. Resultados Ao rastrear a PCR e os anticorpos da COVID-19 mais de duas vezes, a cirurgia foi adiada por 10 a 14 dias em ambos os casos para descartar pneumonia induzida pela COVID-19. A tomografia computadorizada de tórax ainda revelou opacidades em vidro fosco. Em ambos os casos, o defeito na base do crânio foi reparado. Em ambos os casos, os sinais radiológicos de pneumonia induzida por rinorréia foram completamente resolvidos nos acompanhamentos de 24 e 30 dias. Conclusão A aspiração do LCR causa alterações radiológicas nos pulmões na rinorreia. Esta é uma diminuição local de curto prazo na leveza do tecido pulmonar (preenchimento parcial dos alvéolos com fluidos), que é visível radiograficamente (opacidades em vidro fosco). Para descartar infecção por COVID-19, a cirurgia deve ser adiada por 10 a 14 dias e a PCR e anticorpos (IgG, IgM) devem ser realizados pelo menos duas vezes. Se o teste de rastreio da COVID-19 for negativo, pode ser agendada uma cirurgia reparadora.

Laboratory Indices in Patients with Positive and Borderline Flow Cytometry Eosin-5-Maleimide-Screening Test Results for Hereditary Spherocytosis.

OBJECTIVE: To evaluate laboratory indices in patients with hereditary spherocytosis, with positive and borderline flow cytometry eosin-5-melamide (EMA)-bound red blood cells screening test. STUDY DESIGN: We compared laboratory indices of 151 samples obtained from 139 different individual patients with negative, borderline, or positive EMA-test results. We also compared the clinical data of the patients in each EMA test results group. RESULTS: Borderline EMA-test results were obtained for 13 patients and were associated with more severe anemia, and lower reticulocyte count and reticulocyte production index compared with samples with positive EMA-test results. A receiving operator characteristic analysis identified mean corpuscular hemoglobin concentration of <32.5 g/dL as a cut-off, between positive/borderline and negative test results with 100% sensitivity. A higher prevalence of clinical markers typical of hereditary spherocytosis was found in patients with borderline or positive compared with negative EMA test samples. CONCLUSIONS: Based on laboratory data, borderline EMA-test results may be an indication of a more severe form of hereditary spherocytosis. Using mean corpuscular hemoglobin concentration as a cut-off may help predict and reduce negative EMA tests without compromising sensitivity. This finding needs to be further validated in other flow cytometry laboratories with a large EMA test sample pool.

Uterine rescue in high-risk gestational trophoblastic neoplasia treated with ema-co by uterine arteries embolization due to arteriovenous malformations / Resgate uterino em neoplasia trofoblástica gestacional de alto risco tratada com EMA-CO por embolização de artérias uterinas devido a malformações arteriovenosas

Abstract Complete hydatidiform mole (CHM) is a rare type of pregnancy, in which 15 to 20% of the cases may develop into gestational trophoblastic neoplasia (GTN). The diagnostic of GTN must be done as early as possible through weekly surveillance of serum hCG after uterine evacuation.We report the case of 23-year-old primigravida, with CHM but without surveillance of hCG after uterine evacuation. Two months later, the patient presented to the emergency with vaginal bleeding and was referred to the Centro de Doenças Trofoblásticas do Hospital São Paulo. She was diagnosed with high risk GTN stage/score III:7 as per The International Federation of Gynecology and Obstetrics/World Health Organization (FIGO/WHO). The sonographic examination revealed enlarged uterus with a heterogeneous mass constituted of multiple large vessels invading and causing disarrangement of the myometrium. The patient evolved with progressive worsening of vaginal bleeding after chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) regimen. She underwent blood transfusion and embolization of uterine arteries due to severe vaginal hemorrhage episodes, with complete control of bleeding. The hCG reached a negative value after the third cycle, and there was a complete regression of the anomalous vascularization of the uterus as well as full recovery of the uterine anatomy. The treatment in a reference center was essential for the appropriate management, especially regarding the uterine arteries embolization trough percutaneous femoral

Resumo Mola hidatiforme completa (MHC) é um tipo raro de gravidez, na qual 15 a 20% dos casos podem desenvolver neoplasia trofoblástica gestacional (NTG). O diagnóstico de NTG deve ser feito o mais cedo possível, pelo monitoramento semanal do hCG sérico após esvaziamento uterino. Relatamos o caso de uma paciente primigesta, de 23 anos de idade, com MHC, sem vigilância de hCG após esvaziamento uterino. Dois meses depois, a paciente compareceu na emergência com sangramento vaginal, sendo encaminhada ao Centro de Doenças Trofoblásticas do Hospital São Paulo, onde foi diagnosticada com NTG de alto risco, estádio e score de risco III:7 de acordo com a The International Federation of Gynecology and Obstetrics/Organização Mundial de Saúde (FIGO/OMS). O exame ultrassonográfico revelou útero aumentado com uma massa heterogênea constituída pormúltiplos vasos volumosos invadindo e desestruturando o miométrio. A paciente evoluiu com piora progressiva do sangramento vaginal após quimioterapia com o regime etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO). Ela foi submetida a transfusão de sangue e embolização das artérias uterinas devido aos episódios graves de hemorragia vaginal, com completo controle do sangramento. O hCG atingiu valor negativo após o terceiro ciclo, havendo regressão completa da vascularização uterina anômala, assim como recuperação da anatomia uterina. O tratamento em um centro de referência permitiu o manejo adequado, principalmente no que se refere à embolização das artérias uterinas através da punção percutânea da artéria femoral, que foi crucial para evitar a histerectomia, permitindo a cura da NTG e a manutenção da vida reprodutiva.

Mandibular border movements: The two envelopes of motion.

BACKGROUND: The envelope of motion is a diagrammatic representation of the mandibular border movements. Classically, those movements are carried out eccentrically; starting from the position of maximal intercuspation, the mandible describes an excursion movement until reaching maximal mouth opening. Reverse movements would describe a different path, but up to now concentric development of mandibular border movements has not been considered. Literature states that beyond mandibular border movements limits, no movement is possible. Therefore, it is of great interest to compare both paths-both envelopes of motion-and define the actual limits of mandibular movement. OBJECTIVE: The aim of this study was to compare the geometric characteristics of mandibular border movements carried out eccentrically and concentrically by healthy subjects. METHODS: Sixteen individuals aged between 18 and 27 years, molar class I and with no temporomandibular disorders, participated in the study. Eccentric and concentric mandibular movements were recorded using a 3D electromagnetic articulograph. Data were processed with computational scripts developed in MATLAB. Maximum mouth opening, trajectories, displacement ranges, polygon areas and chewing cycle area/ mandibular border movements area ratio were analysed. RESULTS: The frontal plane showed significant differences in all the parameters evaluated. Higher values were registered in the concentric area of the border movement envelope (P = .008) and in the trajectories on both sides. Statistical differences were observed in polygon areas (P = .006) in the sagittal plane and right ranges (P = .046) in the horizontal plane. CONCLUSION: Concentric mandibular movements revealed significant differences in three-dimensional trajectories in the frontal plane.

Unmet needs in PKU and the disease impact on the day-to-day lives in Brazil: Results from a survey with 228 patients and their caregivers.

BACKGROUND: Accumulation of phenylalanine (Phe) due to deficiency in the enzyme phenylalanine hydroxylase (PAH), responsible for the conversion of Phe into tyrosine leads to Phenylketonuria (PKU), a rare autosomal recessive inborn error of metabolism with a mean prevalence of approximately 1:10,000 to 1:15,000 newborns. Physical, neurocognitive and psychiatric symptoms include neurodevelopmental disorder as intellectual disability and autism spectrum disorder. The most common treatments such as low-Phe diet and supplements may decrease blood Phe concentrations, but neuropsychological, behavioral and social issues still occur in some patients. This study aimed to better understand (i) the Brazilian population's knowledge about newborn screening (NBS), the main diagnostic method for PKU, as well as (ii) the impacts of phenylketonuria in the daily lives of patients and parents. METHODS: Two surveys in Real World Data format gathering of Brazilian residents by online questionnaires with (i) 1000 parents of children up to 5 years old between March and April 2019; (ii) 228 PKU patients and caregivers in March 2019. The survey was conducted in partnership with Abril Publisher and two Brazilian patient associations: Metabolic Mothers and SAFE Brasil, for families with rare diseases and PKU patients, respectively. RESULTS: The first questionnaire shows that 93% of parents recognize the importance of NBS and 92% report that their children have undergone the test. Still, two out of ten participants did not know what the exam is or what it is for. From the second questionnaire nine out of ten patients had their PKU diagnosis by NBS. Although strict dietary controls for PKU were claimed by 44% of respondents from second questionnaire, 55% assume not following all nutritionist recommendations and 52% did not maintain routinely Phe control levels. In addition, 53% said they had high spending on medical appointments, therapies and purchase of special foods. CONCLUSIONS: Despite the lack of understanding, the awareness of NBS importance is present in the studied population. The early diagnosis of most PKU patients in the study corroborates with neonatal screening central role of PKU early detection. The difficulty in adhering to dietary adjustments and the possibility that current and new therapeutic strategies other than diet could be determinant to achieve the recommended Phe levels.

mHealth technology for ecological momentary assessment in physical activity research: a systematic review.

OBJECTIVE: To systematically review the publications on ecological momentary assessment (EMA) relating to physical activity (PA) behavior in order to classify the methodologies, and to identify the main mHealth technology-based tools and procedures that have been applied during the first 10 years since the emergence of smartphones. As a result of this review, we want to ask if there is enough evidence to propose the use of the term "mEMA" (mobile-based EMA). DESIGN: A systematic review according to PRISMA Statement (PROSPERO registration: CRD42018088136). METHOD: Four databases (PsycINFO, CINALH, Medline and Web of Science Core Collection) were searched electronically from 2008 to February 2018. RESULTS: A total of 76 studies from 297 potential articles on the use of EMA and PA were included in this review. It was found that 71% of studies specifically used "EMA" for assessing PA behaviors but the rest used other terminology that also adjusted to the inclusion criteria. Just over half (51.3%) of studies (39) used mHealth technology, mainly smartphones, for collecting EMA data. The majority (79.5%) of these studies (31 out of 39) were published during the last 4 years. On the other hand, 58.8% of studies that only used paper-and-pencil were published during the first 3 years of the 10-year period analyzed. An accelerometer was the main built-in sensor used for collecting PA behavior by means of mHealth (69%). Most of the studies were carried out on young-adult samples, with only three studies in older adults. Women were included in 60% of studies, and healthy people in 82%. The studies lasted between 1 and 7 days in 57.9%, and between three and seven assessments per day were carried out in 37%. The most popular topics evaluated together with PA were psychological state and social and environmental context. CONCLUSIONS: We have classified the EMA methodologies used for assessing PA behaviors. A total of 71% of studies used the term "EMA" and 51.3% used mHealth technology. Accelerometers have been the main built-in sensor used for collecting PA. The change of trend in the use of tools for EMA in PA coincides with the technological advances of the last decade due to the emergence of smartphones and mHealth technology. There is enough evidence to use the term mEMA when mHealth technology is being used for monitoring real-time lifestyle behaviors in natural situations. We define mEMA as the use of mobile computing and communication technologies for the EMA of health and lifestyle behaviors. It is clear that the use of mHealth is increasing, but there is still a lot to be gained from taking advantage of all the capabilities of this technology in order to apply EMA to PA behavior. Thus, mEMA methodology can help in the monitoring of healthy lifestyles under both subjective and objective perspectives. The tendency for future research should be the automatic recognition of the PA of the user without interrupting their behavior. The ecological information could be completed with voice messages, image captures or brief text selections on the touch screen made in real time, all managed through smartphone apps. This methodology could be extended when EMA combined with mHealth are used to evaluate other lifestyle behaviors.

El apoyo a la innovación desde las agencias regulatorias. Experiencia internacional y nacional: el equipo multidisciplinario de apoyo a la innovación de la ANMAT / Innovation support from Regulatory Agencies. National and international experiences: The case of the multidisciplinary innovation support team of the ANMAT

En la actualidad existe un notable desarrollo de productos innovadores orientados a dar nuevas soluciones en materia de salud. En este marco, caracterizado por un escenario de conocimientos nuevos, multidisciplinario y, a su vez con pocos antecedentes a nivel regulatorio, las agencias sanitarias tienen el gran desafío de establecer el marco normativo para asegurar la seguridad y eficacia de estos productos. Por otro lado, dichos organismos se imponen el deber de propiciar el desarrollo de nuevas tecnologías de manera de impulsar, lo más pronto posible, su llegada a las personas que lo necesiten. Esta breve revisión se enfoca en analizar algunas de las iniciativas llevadas a cabo por algunas de las más importantes agencias regulatorias internacionales (EMA, FDA, Health Canada), organismos de referencia en salud (OMS, OPS) y espacios de convergencia regulatoria (IMDRF) en la evaluación e impulso a la innovación y, en particular, se hace hincapié en describir el trabajo del Equipo Multidisciplinario de Apoyo a la Innovación (EMAI) de la Administración Nacional de Medicamentos, Alimentos y Tecnología Médica, orientado a brindar asistencia a proyectos y productos que revistan carácter de innovadores y resulten de interés para la salud pública.

Currently, there is a remarkable development of innovative products aimed at offering new solutions in matters of health. In this scenario, characterized by new multidisciplinary knowledge and little regulatory background, sanitary agencies address the great challenge of establishing the regulatory framework to ensure the safety and efficacy of these products. On the other hand, these organizations have the duty to encourage the development of innovative technologies in order to promote, as soon as possible, the arrival to people who need them. This brief review focuses on analyzing some of the initiatives carried out by some of the most important international regulatory agencies (EMA, FDA, Health Canada), health reference organizations (WHO, PAHO) and regulatory convergence spaces (IMDRF) on the evaluation and promotion of innovation and, in particular, it emphasizes describing the work of the Multidisciplinary Innovation Support Team of ANMAT (Argentinian regulatory agency), aimed at providing assistance to projects and products that are innovative and of interest to public health.

Morphogenesis of the rhea (Rhea americana) respiratory system in different embryonic and foetal stages / Morfogênese do sistema respiratório da ema (Rhea americana) em diferentes estágios embrionários e fetais

The rhea (Rhea americana) is an important wild species that has been highlighted in national and international livestock. This research aims to analyse embryo-foetal development in different phases of the respiratory system of rheas. Twenty-three embryos and foetuses were euthanized, fixed and dissected. Fragments of the respiratory system, including the nasal cavity, larynx, trachea, syrinx, bronchi and lungs, were collected and processed for studies using light and scanning electron microscopy. The nasal cavity presented cubic epithelium in the early stages of development. The larynx exhibited typical respiratory epithelium between 27 and 31 days. The trachea showed early formation of hyaline cartilage after 15 days. Syrinx in the mucous membrane of 18-day foetuses consisted of ciliated epithelium in the bronchial region. The main bronchi had ciliated epithelium with goblet cells in the syringeal region. In the lung, the parabronchial stage presented numerous parabronchi between 15 and 21 days. This study allowed the identification of normal events that occur during the development of the rhea respiratory system, an important model that has not previously been described. The information generated here will be useful for the diagnosis of pathologies that affect this organic system, aimed at improving captive production systems.(AU)

A ema (Rhea americana) representa importante espécie silvestre que vem se destacando na pecuaria nacional e internacional. Esta pesquisa objetiva analisar o desenvolvimento embrionário-fetal, em diferentes fases, do sistema respiratório de emas. Vinte e três embriões e fetos foram eutanasiados, fixados e dissecados. Fragmentos do sistema respiratório: cavidade nasal, laringe, traqueia, siringe, brônquios e pulmões, foram coletados e processados para estudos por meio de microscopia de luz e microscopia eletrônica de varredura. A cavidade nasal apresentou, nas primeiras fases de desenvolvimento, epitélio estratificado cúbico. A laringe exibiu epitélio respiratório típico entre 27 e 31 dias. A traqueia aos 15 dias apresentou início de formação da cartilagem hialina. Na siringe a túnica mucosa de fetos de 18 dias e formada por epitélio estratificado ciliado na região bronquial. Os brônquios principais apresentavam epitélio estratificado ciliado com células caliciformes na região siringeal. No pulmão, o estágio parabronquial apresentou numerosos parabrônquios entre 15 a 21 dias. Este estudo permitiu a identificação de eventos normais que ocorrem durante o desenvolvimento do sistema respiratório de emas, importante modelo ainda não descrito. As informações geradas serão úteis para o diagnóstico de patologias que acometem este sistema orgânico, visando a melhoria dos sistemas de produção em cativeiro.(AU)

Morphogenesis of the rhea (Rhea americana) respiratory system in different embryonic and foetal stages / Morfogênese do sistema respiratório da ema (Rhea americana) em diferentes estágios embrionários e fetais

The rhea (Rhea americana) is an important wild species that has been highlighted in national and international livestock. This research aims to analyse embryo-foetal development in different phases of the respiratory system of rheas. Twenty-three embryos and foetuses were euthanized, fixed and dissected. Fragments of the respiratory system, including the nasal cavity, larynx, trachea, syrinx, bronchi and lungs, were collected and processed for studies using light and scanning electron microscopy. The nasal cavity presented cubic epithelium in the early stages of development. The larynx exhibited typical respiratory epithelium between 27 and 31 days. The trachea showed early formation of hyaline cartilage after 15 days. Syrinx in the mucous membrane of 18-day foetuses consisted of ciliated epithelium in the bronchial region. The main bronchi had ciliated epithelium with goblet cells in the syringeal region. In the lung, the parabronchial stage presented numerous parabronchi between 15 and 21 days. This study allowed the identification of normal events that occur during the development of the rhea respiratory system, an important model that has not previously been described. The information generated here will be useful for the diagnosis of pathologies that affect this organic system, aimed at improving captive production systems.(AU)

A ema (Rhea americana) representa importante espécie silvestre que vem se destacando na pecuaria nacional e internacional. Esta pesquisa objetiva analisar o desenvolvimento embrionário-fetal, em diferentes fases, do sistema respiratório de emas. Vinte e três embriões e fetos foram eutanasiados, fixados e dissecados. Fragmentos do sistema respiratório: cavidade nasal, laringe, traqueia, siringe, brônquios e pulmões, foram coletados e processados para estudos por meio de microscopia de luz e microscopia eletrônica de varredura. A cavidade nasal apresentou, nas primeiras fases de desenvolvimento, epitélio estratificado cúbico. A laringe exibiu epitélio respiratório típico entre 27 e 31 dias. A traqueia aos 15 dias apresentou início de formação da cartilagem hialina. Na siringe a túnica mucosa de fetos de 18 dias e formada por epitélio estratificado ciliado na região bronquial. Os brônquios principais apresentavam epitélio estratificado ciliado com células caliciformes na região siringeal. No pulmão, o estágio parabronquial apresentou numerosos parabrônquios entre 15 a 21 dias. Este estudo permitiu a identificação de eventos normais que ocorrem durante o desenvolvimento do sistema respiratório de emas, importante modelo ainda não descrito. As informações geradas serão úteis para o diagnóstico de patologias que acometem este sistema orgânico, visando a melhoria dos sistemas de produção em cativeiro.(AU)

Morphogenesis of the rhea (Rhea americana) respiratory system in different embryonic and foetal stages

ABSTRACT: The rhea (Rhea americana) is an important wild species that has been highlighted in national and international livestock. This research aims to analyse embryo-foetal development in different phases of the respiratory system of rheas. Twenty-three embryos and foetuses were euthanized, fixed and dissected. Fragments of the respiratory system, including the nasal cavity, larynx, trachea, syrinx, bronchi and lungs, were collected and processed for studies using light and scanning electron microscopy. The nasal cavity presented cubic epithelium in the early stages of development. The larynx exhibited typical respiratory epithelium between 27 and 31 days. The trachea showed early formation of hyaline cartilage after 15 days. Syrinx in the mucous membrane of 18-day foetuses consisted of ciliated epithelium in the bronchial region. The main bronchi had ciliated epithelium with goblet cells in the syringeal region. In the lung, the parabronchial stage presented numerous parabronchi between 15 and 21 days. This study allowed the identification of normal events that occur during the development of the rhea respiratory system, an important model that has not previously been described. The information generated here will be useful for the diagnosis of pathologies that affect this organic system, aimed at improving captive production systems.

RESUMO: A ema (Rhea americana) representa importante espécie silvestre que vem se destacando na pecuaria nacional e internacional. Esta pesquisa objetiva analisar o desenvolvimento embrionário-fetal, em diferentes fases, do sistema respiratório de emas. Vinte e três embriões e fetos foram eutanasiados, fixados e dissecados. Fragmentos do sistema respiratório: cavidade nasal, laringe, traqueia, siringe, brônquios e pulmões, foram coletados e processados para estudos por meio de microscopia de luz e microscopia eletrônica de varredura. A cavidade nasal apresentou, nas primeiras fases de desenvolvimento, epitélio estratificado cúbico. A laringe exibiu epitélio respiratório típico entre 27 e 31 dias. A traqueia aos 15 dias apresentou início de formação da cartilagem hialina. Na siringe a túnica mucosa de fetos de 18 dias e formada por epitélio estratificado ciliado na região bronquial. Os brônquios principais apresentavam epitélio estratificado ciliado com células caliciformes na região siringeal. No pulmão, o estágio parabronquial apresentou numerosos parabrônquios entre 15 a 21 dias. Este estudo permitiu a identificação de eventos normais que ocorrem durante o desenvolvimento do sistema respiratório de emas, importante modelo ainda não descrito. As informações geradas serão úteis para o diagnóstico de patologias que acometem este sistema orgânico, visando a melhoria dos sistemas de produção em cativeiro.

Porocarcinoma Ecrino / Ecrine Porocarcinoma

Resumen:El porocarcinoma ecrino es un tipo muy poco frecuente de cáncer de piel, originado en la porción epidérmica de las glándulas sudoríparas ecrinas. Representa no más del 0.01% de los tumores cutáneos. El 20% de los porocarcinomas ecrinos son recurrentes y el 20% producen metástasis a ganglios linfáticos. Se ha reportado escasos casos de metástasis a distancia. Tiene un índice de mortalidad del 67% de los pacientes con metástasis.El diagnóstico es basado en los hallazgos histopatológicos y los estudios complementarios de inmunohistoquímica, a veces necesarios para el diagnóstico diferencial con otros tipos más frecuentes de cáncer de piel.No existen pruebas de que este tipo de carcinoma responda a la quimioterapia ni la radioterapia. Se considera que el manejo principal debe ser la resección quirúrgica y la electroquimioterapia.

Abstract:Eccrine porocarcinoma is a rare type of skin cáncer arising from the intraepidermal portion of eccrine sweat glands, representing no more tan 0.01% of all cutaneous tumors. 20% of the Eccrine porocarcinoma will recur and 20% will metastasize to regional lymph nodes. Few cases of distant metastases has been reported . There is a mortality rate of 67% in patients with metastases. The diagnosis is primarily based on histopathologic findings and complementary immunohistochemistry for differential diagnosis mainly with more frequent skin cáncer.Neither chemotherapy nor radiation therapy has been proven to be of clinical benefit in treating this type of carcinoma. It is considered that the management should be based on surgical resection and electrochemotherapy.

Dealing with nanosafety around the globe-Regulation vs. innovation.

In recent years, nanotechnology has become increasingly important for global industries. Today, many nanomaterials are used as ingredients in cosmetics, food products, medical devices and pharmaceuticals. In some cases they exert unexpected risks and potentially pose a threat to human health and the environment. Regulatory authorities all over the world carefully observe recent developments in this area, striving to find a balance between consumer safety and the interests of the industry. In the following, the current legislation in the United States of America, the European Union, Asia and Brazil will be presented. Further, the requirements defined by these different authorities and methodology to investigate relevant characteristics of nanomaterials will be discussed.

Frecuencia de anticuerpos anti-transglutaminasa y antiendomisio en pacientes con diabetes tipo 1 / Association of type 1 diabetes mellitus with celiac disease

Background: Type 1 diabetes mellitus and celiac disease share common genetic and immunological aspects and celiac disease is more common among type 1 diabetic patients. Aim: To determine the frequency of anti endomysial and anti transglutaminase antibodies among patients with type 1 diabetes. Material and Methods: Anti endomysialantibodies determined by indirect immunofluorescence an anti transglutaminase antibodies determined by ELISA were measured in 410 serum samples of patients with type 1 diabetes. Results: Seventy one samples (17 percent) had positive anti transglutaminase antibodies. Among these, 17 had also positive anti endomysial antibodies. In 11 of these 17 patients, the presence of celiac disease was confirmed. Conclusions: Among patients with type 1 diabetes mellitus, the frequency of celiac disease is three times higher than in the general population.

Development and characterization of 47 novel microsatellite markers for Vellozia squamata (Velloziaceae).

UNLABELLED: • PREMISE OF THE STUDY: We developed and validated microsatellite primers for Vellozia squamata (Velloziaceae), an endemic species of the cerrado (Brazilian savannas), to investigate the influence of different fire regimes on its genetic diversity and population structure. • METHODS AND RESULTS: Using a selective hybridization method, we tested 51 SSR loci using a natural population of V. squamata and obtained 47 amplifiable loci. Among these, 26 loci were polymorphic and the average values of genetic diversity were: average number of alleles per locus ([Formula: see text]) = 6.54, average number of alleles per polymorphic locus ([Formula: see text]) = 7.13, average observed heterozygosity [Formula: see text] = 0.22, average expected heterozygosity [Formula: see text] = 0.49, and average fixation index [Formula: see text] = 0.55. • CONCLUSIONS: These 26 loci allowed us to assess the effects of distinct fire regimes on the genetic structure of V. squamata populations with the aim of establishing strategies for the conservation of this endemic species. The markers can also be useful for future pharmaceutical studies, as the species has great potential for medicinal and cosmetic applications.

Cholangiocarcinoma in an American Rhea (Rhea Americana araneipes) / Colangiocarcinoma em uma ema

Cholangiocarcinomas are neoplasms that originate from the bile duct epithelium. The present case described a cholangiocarcinoma in an adult female American Rhea (Rhea Americana araneipes) by means of gross, histopathology and immunohistochemistry. Irregular, firm, multifocal, yellow-white masses, measuring from 0.4 to 6cm in diameter were observed in both liver lobes. At the cut surface, multiple firm nodules filled with connective tissue were present. Microscopically, the neoplasia was composed of small, irregular, gland-like structures of neoplastic cells surrounded by connective tissue. The cells resembled epithelial cells of the hepatic biliary ducts. Neoplastic cells were positive for cytokeratin and negative for vimentin. This is the first report of a malignant fatal neoplasia in an American Rhea.(AU)

Colangiocarcinomas são neoplasias originárias do epitélio do ducto biliar. O presente caso descreve os achados macroscópicos, microscópicos e imuno-histoquímicos de um colangiocarcinoma em uma ema fêmea (Rhea americana araneipes). No fígado, massas irregulares, firmes, multifocais, de coloração amarelo-esbranquiçada, medindo de 0,4 a 6cm de diâmetro foram observadas em ambos os lobos. Ao corte, múltiplos nódulos firmes preenchidos por tecido conjuntivo foram observados. Microscopicamente, a neoplasia era composta de células pequenas, irregulares, semelhantes às células do epitélio biliar, que formavam estruturas glandulares. A imuno-histoquímica foi positiva para citoqueratina e negativa para vimentina. Este trabalho constitui o primeiro relato de uma neoplasia maligna fatal em uma ema.(AU)

Cholangiocarcinoma in an American Rhea (Rhea Americana araneipes) / Colangiocarcinoma em uma ema

Cholangiocarcinomas are neoplasms that originate from the bile duct epithelium. The present case described a cholangiocarcinoma in an adult female American Rhea (Rhea Americana araneipes) by means of gross, histopathology and immunohistochemistry. Irregular, firm, multifocal, yellow-white masses, measuring from 0.4 to 6cm in diameter were observed in both liver lobes. At the cut surface, multiple firm nodules filled with connective tissue were present. Microscopically, the neoplasia was composed of small, irregular, gland-like structures of neoplastic cells surrounded by connective tissue. The cells resembled epithelial cells of the hepatic biliary ducts. Neoplastic cells were positive for cytokeratin and negative for vimentin. This is the first report of a malignant fatal neoplasia in an American Rhea.

Colangiocarcinomas são neoplasias originárias do epitélio do ducto biliar. O presente caso descreve os achados macroscópicos, microscópicos e imuno-histoquímicos de um colangiocarcinoma em uma ema fêmea (Rhea americana araneipes). No fígado, massas irregulares, firmes, multifocais, de coloração amarelo-esbranquiçada, medindo de 0,4 a 6cm de diâmetro foram observadas em ambos os lobos. Ao corte, múltiplos nódulos firmes preenchidos por tecido conjuntivo foram observados. Microscopicamente, a neoplasia era composta de células pequenas, irregulares, semelhantes às células do epitélio biliar, que formavam estruturas glandulares. A imuno-histoquímica foi positiva para citoqueratina e negativa para vimentina. Este trabalho constitui o primeiro relato de uma neoplasia maligna fatal em uma ema.