Looking for novel physiological regulators of lung development

Tese de doutoramento em MedicinaPediatric and adult diseases characterized by lung hypoplasia or dysplasia are an epidemiological relevant issue, involving important morbidity and mortality rates. The understanding of the complex process of lung development, regulated by several genetic, chemical and physical determinants, has clinical relevance since it can open new perspectives in the treatment of these lung diseases as well as modulation of lung repair. Regardless of the advanced knowledge of normal lung growth, there are several possible regulators and determinants that need to be investigated. Therefore, the main aim of the present dissertation was to discover novel physiological regulators of normal lung morphogenesis, expecting to contribute for the development of new strategies for lung diseases, namely for fetal lung hypoplasia, in context of congenital diaphragmatic hernia (CDH). Using different laboratorial approaches, namely histological, molecular, and functional studies, the role of glycoprotein 130 (gp130) family of cytokines and renin-angiotensin system (RAS) was evaluated throughout fetal lung development, in rat model of either normal and hypoplastic (the nitrofen-induced CDH model) lung development.. In this thesis, it was demonstrated that interleukin 6 (IL-6) and leukemia-inhibitory factor (LIF) are constitutively expressed during fetal lung development and they have a physiological role on pulmonary branching mechanisms. Indeed, cytokines signaling through gp130 homodimers (IL-6 and IL-11) stimulate lung branching, whereas cytokines acting in a gp130 heterodimer receptor (LIF, oncostatin M) inhibit lung growth. It was also established that there is a local and physiologically active RAS during lung morphogenesis. In fact, all RAS components are constitutively expressed in the lung throughout gestation and angiotensin II (ANG II), the physiologically active peptide of RAS, induces a stimulatory effect on lung branching, mediated by type 1 (AT1) receptor of ANG II, through p44/42 and Akt phosphorylation. After the description of these two new physiological regulators/modulators of fetal lung growth, gp130 family of cytokines and RAS, their role in pulmonary hypoplasia, in the CDH context, were assessed. First of all, it was showed that hypoplastic fetal lung has the intrinsic ability to regulate its growth and to recover from growth retardation through a way that resembles the catch-up growth phenomenon. Moreover, IL-6 might be involved in the mechanisms underlying this phenomenon. Finally, the discovery of RAS as a new regulator of fetal lung growth allowed the establishment of an antagonist of type 2 (AT2) receptor of ANG II (PD-123319) as a putative antenatal therapy for pathologies characterized by fetal lung hypoplasia, such as CDH. In vivo, in nitrofen-induced CDH model, antenatal PD-123319 treatment improved the key determinants of mortality associated with CDH, namely lung hypoplasia and pulmonary hypertension, and also improved lung function and survival, without maternal or fetal deleterious effects. In summary, in this thesis, according to the proposed aims, two novel physiological regulators of fetal lung development were identified: gp130 family of cytokines and local lung RAS. Moreover, we demonstrated that fetal lung has the intrinsic ability to regulate its growth and proposed a model for regulation of correct lung size and growth. Nonetheless, future studies are necessary to clarify this regulatory loop and the mediators (afferent arms, sensors, efferent arms) involved on this hypothetic feedback mechanism of compensatory growth. Finally, we established that selective inhibition of AT2 receptor is a putative antenatal therapy for pathologies characterized by lung hypoplasia, such as CDH, which open perspectives for future pre-clinical studies.As doenças pulmonares pediátricas ou do adulto, que cursam com hipoplasia ou displasia pulmonar, associam-se a elevadas taxas de morbilidade e mortalidade. A compreensão dos mecanismos complexos do desenvolvimento pulmonar, regulados por determinantes genéticos, químicos e mecânicos, apresenta relevância clínica ao permitir o desenho de novas abordagens terapêuticas que mimetizem o normal crescimento e maturação pulmonares, bem como a regeneração pulmonar. Nos últimos anos, o conhecimento sobre desenvolvimento pulmonar normal muito ter evoluído. Contudo, são vários os fatores de crescimento e reguladores que permanecem por esclarecer. Assim, nesta dissertação investigaram-se novos reguladores fisiológicos da morfogénese pulmonar, procurando contribuir para o desenvolvimento de novas estratégias terapêuticas para as doenças pulmonares, nomeadamente a hipoplasia pulmonar fetal, no contexto da hérnia diafragmática congénita (HDC). No modelo animal do rato, quer em animais controlo quer no modelo de HDC induzida pelo nitrofeno, a função da família das citocinas da glicoproteína 130 (gp130) e do sistema reninaangiotensina (SRA) foi avaliada ao longo do desenvolvimento pulmonar fetal. Diferentes técnicas laboratoriais foram utilizadas, nomeadamente estudos histológicos, moleculares e funcionais. Os nossos resultados demonstraram que a interleucina 6 (IL-6) e o fator inibidor da leucemia (LIF) são constitutivamente expressos ao longo do desenvolvimento pulmonar fetal e desempenham um papel fisiológico nos mecanismos de ramificação pulmonar. Assim, a IL-6 e a IL-11, cujos recetores são homodímeros da gp130, estimulam a ramificação pulmonar. Por sua vez, o LIF, a oncostatina M, que sinalizam via heterodímeros de gp130, inibem o crescimento pulmonar. Para além disso, foi também descrita a presença de um SRA local e fisiologicamente ativo durante a morfogénese pulmonar. Na verdade, todos os componentes do SRA são expressos no pulmão em todas as idades gestacionais estudadas e a angiotensina II (ANG II), o peptídeo fisiologicamente ativo deste sistema, estimula a ramificação pulmonar, via recetor de tipo 1 (AT1) e a fosforilação da p44/42 e Akt. Uma vez descritos estes dois novos reguladores/moduladores do crescimento pulmonar fetal, a família das citocinas da gp130 e o SRA, o seu papel na hipoplasia pulmonar fetal, no contexto da HDC, foi avaliado. Foi possível demonstrar que o pulmão fetal hipoplásico apresenta capacidade intrínseca para regular o seu crescimento e recuperar do atraso de crescimento por um mecanismo similar ao clássico fenómeno de catch-up growth. A IL-6 revelou-se como um dos mediadores envolvidos nos mecanismos subjacentes a este fenómeno. Finalmente, a descoberta do SRA como um novo regulador do crescimento pulmonar fetal permitiu apresentar o PD-123319, um antagonista específico do recetor de tipo 2 da ANG II (AT2), como um potencial alvo terapêutico para patologias caraterizadas por hipoplasia pulmonar fetal, das quais a HDC é um exemplo. No modelo de HDC induzida pelo nitrofeno, in vivo, a administração materna antenatal de PD-123319 melhorou os determinantes chave associados a esta patologia, nomeadamente a hipoplasia e hipertensão pulmonares, e melhorou a função pulmonar e a taxa de sobrevida, sem aparentes efeitos deletérios maternos ou fetais. Em resumo, nesta tese, de acordo com os objetivos inicialmente estabelecidos, foram identificados dois novos reguladores fisiológicos do desenvolvimento pulmonar fetal: a família das citocinas da gp130 e o SRA pulmonar. Foi, também, demonstrado que o pulmão fetal apresenta capacidade intrínseca para regular o seu crescimento e foi proposta a existência de um modelo de regulação do crescimento pulmonar. Contudo, estudos futuros são necessários a fim de se clarificar este hipotético mecanismo de regulação do crescimento e os seus mediadores (vias aferentes, sensor e vias eferentes). Por fim, a apresentação do recetor AT2 como um potencial alvo terapêutico antenatal para patologias caraterizadas por hipoplasia pulmonar, tais como a HDC, promove o desenvolvimento de estudos pré-clínicos futuros

Inducing Supervision Practices among peers in a Community of Practice

O processo de Bolonha e a criação do Espaço Europeu de Educação Superior e de Investigação têm-se revelado verdadeiramente desafiantes, quer na dimensão conceptual quer na dimensão da intervenção, sobre novos modelos de aprendizagem e, consequentemente, novas práticas de ensino consonantes. Enquanto docentes de uma Instituição de Ensino Superior responsável pela formação de professores, os modelos de formação destes profissionais merecem-nos, pois, particular reflexão. Consideramos que a formação de professores é um importante período na socialização dos sujeitos, no qual a criticidade inerente ao processo de construção do conhecimento profissional (no sentido de Shulman (1986) – nos domínios do conhecimento do conteúdo, do conhecimento pedagógico e curricular) se deverá assumir como eixo central na construção da sua profissionalidade docente. Apresentando-se como uma organização capaz de conceber, projetar, atuar e refletir, preconizamos um modelo de supervisão que ajude a Escola a problematizar e a projetar o futuro, verdadeiramente ambiciosa, que questione os momentos menos bem conseguidos para conhecer as suas causas, sendo capaz de traçar novas linhas de ação. A partir da constituição de uma Comunidade de Prática, neste texto propomo-nos apresentar alguns instrumentos de suporte à supervisão pedagógica entre pares assim como resultados preliminares obtidos. Estes resultados apontam no sentido de ser fundamental desenvolver e apresentar a indução de novas práticas supervisivas no docente do ES, identificando mecanismos facilitadores/constrangedores da implementação de processos de regulação da atividade de ensino entre pares, beneficiando, em nosso entender, o processo de aprendizagem dos estudantes. Keywords Pedagogical Supervision; Teacher Training; European Higher Education Area; Community of Practices; Research PracticesAbstract The Bologna process and the creation of the European Higher Education Area have been proving to be a challenge. As teachers trainers in a Higher Education institution, the teacher training models deserve, to us, particular reflection, namely the teaching processes adopted by Higher Education teachers. We believe that teacher training is an important period in the individuals socialization, in which the inherent criticality of the professional knowledge construction process (in the sense of Shulman (1986) – including content, pedagogical and curricular knowledge) should be a central tenet in the construction of teachers professionnality. Presenting itself as an organization capable of conceiving, designing, acting and thinking, we claim for supervision pratices that help school to discuss and plan for the future, truly ambitious, that questions the less well achieved moments to understand their causes, being able to draw new action lines.Thus, having the establishment of a Community of Practice as a starting point, it is our goal with this text to present some of the support tools that are being tested in pedagogical supervision among peers with some preliminary results. We believe these results point towards what it is essential to develop and present the induction of a new pedagogical supervision for Higher Education. By identifying facilitators/constraining mechanisms on the implementation of regulatory processes of educational activity among peers, we aim not only improving the quality of the practices on Higher Education contexts, but also benefiting, from our point of view, the learning process of students in general.Abstract The Bologna process and the creation of the European Higher Education Area have been proving to be a challenge. As teachers trainers in a Higher Education institution, the teacher training models deserve, to us, particular reflection, namely the teaching processes adopted by Higher Education teachers. We believe that teacher training is an important period in the individuals socialization, in which the inherent criticality of the professional knowledge construction process (in the sense of Shulman (1986) – including content, pedagogical and curricular knowledge) should be a central tenet in the construction of teachers professionnality. Presenting itself as an organization capable of conceiving, designing, acting and thinking, we claim for supervision pratices that help school to discuss and plan for the future, truly ambitious, that questions the less well achieved moments to understand their causes, being able to draw new action lines.Thus, having the establishment of a Community of Practice as a starting point, it is our goal with this text to present some of the support tools that are being tested in pedagogical supervision among peers with some preliminary results. We believe these results point towards what it is essential to develop and present the induction of a new pedagogical supervision for Higher Education. By identifying facilitators/constraining mechanisms on the implementation of regulatory processes of educational activity among peers, we aim not only improving the quality of the practices on Higher Education contexts, but also benefiting, from our point of view, the learning process of students in general.Abstract The Bologna process and the creation of the European Higher Education Area have been proving to be a challenge. As teachers trainers in a Higher Education institution, the teacher training models deserve, to us, particular reflection, namely the teaching processes adopted by Higher Education teachers. We believe that teacher training is an important period in the individuals socialization, in which the inherent criticality of the professional knowledge construction process (in the sense of Shulman (1986) – including content, pedagogical and curricular knowledge) should be a central tenet in the construction of teachers professionnality. Presenting itself as an organization capable of conceiving, designing, acting and thinking, we claim for supervision pratices that help school to discuss and plan for the future, truly ambitious, that questions the less well achieved moments to understand their causes, being able to draw new action lines.Thus, having the establishment of a Community of Practice as a starting point, it is our goal with this text to present some of the support tools that are being tested in pedagogical supervision among peers with some preliminary results. We believe these results point towards what it is essential to develop and present the induction of a new pedagogical supervision for Higher Education. By identifying facilitators/constraining mechanisms on the implementation of regulatory processes of educational activity among peers, we aim not only improving the quality of the practices on Higher Education contexts, but also benefiting, from our point of view, the learning process of students in general

A percepción dos futuros profesores do uso pedagóxico dos libros de texto dixitais nos procesos de aprendizaxe

Using digital textbook (from now on, DTB) in the learning context has been gradually gaining importance in the 21 st century educational scenarios. Nevertheless, there is ambiguity in the literature and in the educational field as far as the advantages and efficiency of the widespread use of digital textbook. In order to understand, in the Portuguese context, the implications foreseen, as far as the learning process is concerned, on the use of digital textbook, the present study focuses on students’ perceptions of some pedagogical and functional issues related to the use of digital textbook and was carried on at a higher School of Education in Oporto. A total of sixty-six students from postgraduate classes (future teachers/educators of children from five up to eleven years old) participated in the study by completing a survey questionnaire regarding their representations on their familiarity, perceived pedagogical advantages, textbook format preferences (print vs. digital) and learning potentiality of the digital textbook. The results illustrate the importance given to digital textbook, and despite the fact that the students were, to a large extent, unaware of the concept of digital textbook, their perceptions on the usability and pedagogical aspects indicate, on the one hand, the need for continued growth in the number and variety of digital textbook made available and, on the other hand, that more research on this subject is needed.info:eu-repo/semantics/publishedVersio

Síndrome de hiperestimulação ovárica grave com pancreatite aguda sobreposta: a propósito de um caso clínico

Ovarian hyperstimulation syndrome is an important complication of controlled ovarian stimulation, mainly associated with assisted reproductive techniques. It has a wide severity spectrum. Acute pancreatitis in pregnancy is a rare event. We report a case of a pregnant woman with acute pacreatitis superimposed to a severe ovarian hyperstimulation induced by assisted reproductive techniques

Normal range and lateral symmetry in the skin temperature profile of pregnant women

Body skin temperature is a useful parameter for diagnosing diseases and infrared thermography can, be a powerful tool in providing important information to detect body temperature changes in a noninvasive way. The aim of this work was to study the pattern of skin temperature during pregnancy, to establish skin temperature reference values and to find correlations between these and the pregnant population characteristics. Sixty-one healthy pregnant women (mean age 30.6 +/- 5.1 years) in the 8th-40th gestational week with normal pregnancies were examined in 31 regions of interest (ROI). The ROIs were defined all over the body in order to determine the most influenced by factors such as age or body mass index (BMI). The results obtained in this work highlight that in normal pregnant women the skin temperature is symmetrically distributed, with the symmetrical areas differing less than 0.5 degrees C, with a mean value of 0.25 +/- 0.23 degrees C. This study identified a significant negative correlation between the BMI and temperature. Age has been shown to have great influence on the skin temperature, with a significant increase of temperature observed with age. This work explores a novel medical application of infrared thermography and provides a characterization of thermal skin profile in human pregnancy for a large set of ROIs while also evaluating the effects of age and BMI.This work is funded by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT - Portuguese Foundation for Science and Technology under the project UID/CTM/50025/2013. Thermal equipment provided through the REEQ/ 1033/CTM/ 2005 POCI 2010 program. Project "Do-IT", co-financed by the European Community Fund through COMPETE Programa Operacional Factores de Competitividade. Hospital de Braga for authorizing the study and providing facilities for data collection. We also acknowledge the collaboration from the entire staff at the Department of Obstetrics and Gynecology of the Hospital de Braga.info:eu-repo/semantics/publishedVersio

A indução de práticas supervisivas entre pares numa comunidade de práticas.

The Bologna process and the creation of the European Higher Education Area have beenproving to be a challenge. As teachers trainers in a Higher Education institution, the teacher training models deserve, to us, particular reflection, namely the teaching processes adopted by Higher Education teachers. We believe that teacher training is an important period in the individuals socialization, in which the inherent criticality of the professional knowledge construction process (in the sense of Shulman (1986) – including content, pedagogical and curricular knowledge) should be a central tenet in the construction of teachers professionnality. Presenting itself as an organization capable of conceiving, designing, acting and thinking, we claim for supervision pratices that help school to discuss and plan for the future, truly ambitious, that questions the less well achieved moments to understand their causes, being able to draw new action lines.Thus, having the establishment of a Community of Practice as a starting point, it is our goal with this text to present some of the support tools that are being tested in pedagogical supervision among peers with some preliminary results. We believe these results point towards what it is essential to develop and present the induction of a new pedagogical supervision for Higher Education. By identifying facilitators/constraining mechanisms on the implementation of regulatory processes of educational activity among peers, we aim not only improving the quality of the practices on Higher Education contexts, but also benefiting, from our point of view, the learning process of students in general.The Bologna process and the creation of the European Higher Education Area have been proving to be a challenge. As teachers trainers in a Higher Education institution, the teacher training models deserve, to us, particular reflection, namely the teaching processes adopted by Higher Education teachers. We believe that teacher training is an important period in the individuals socialization, in which the inherent criticality of the professional knowledge construction process (in the sense of Shulman (1986) – including content, pedagogical and curricular knowledge) should be a central tenet in the construction of teachers professionnality. Presenting itself as an organization capable of conceiving, designing, acting and thinking, we claim for supervision pratices that help school to discuss and plan for the future, truly ambitious, that questions the less well achieved moments to understand their causes, being able to draw new action lines.Thus, having the establishment of a Community of Practice as a starting point, it is our goal with this text to present some of the support tools that are being tested in pedagogical supervision among peers with some preliminary results. We believe these results point towards what it is essential to develop and present the induction of a new pedagogical supervision for Higher Education. By identifying facilitators/constraining mechanisms on the implementation of regulatory processes of educational activity among peers, we aim not only improving the quality of the practices on Higher Education contexts, but also benefiting, from our point of view, the learning process of students in general

Minilaparoscopy and sentinel lymph node in uterine cancer

CRSLS MIS Case Reports from SLS.org.Background: The sentinel lymph node (SLN) concept might minimize surgical aggressiveness in gynecological oncology, namely in cervical and endometrial malignancies. Therefore, we assessed the feasibility of SLN identification, dissection, and harvesting by using minilaparoscopic surgical instruments in an animal model. We compared the minilaparoscopic approach, which is known to bring important advantages, with the use of conventional laparoscopic instruments. Methods: Two groups of 7 female pigs were enrolled in this experiment that was performed by the same surgical team. In group A, all animals were approached by a similar minilaparoscopic surgical instrumentation, namely a 5-mm 30° endoscope (supraumbilical port) and 3 ancillary 3.5-mm trocars. In group B, a 5-mm conventional laparoscopic instrument set was used. The patent blue (4.0 mL) was injected on the paracervical region. The time for SLN coloring, identification, localization, dissection, and excision, as well as complications were recorded. The sealing of the lymphatic vessels was observed in the 2 groups. During this experiment, and for the both groups, the Trendelenburg position was kept the same, as well as the carbon dioxide–pneumoperitoneum pressure. Finally, a laparotomy was then performed to evaluate whether any stained SLN still remained. Results: All endoscopic procedures were performed without major complications. SLN were identified and excised in all animals in both groups. The SLN localization varied between animals from external iliac to preaortic regions. The surgical times, from skin incision to SLN removal, was 28.4 ? 5.6 minutes for minilaparoscopy and 25.3 ? 6.8 minutes for conventional laparoscopy (P ? .36). In group B, 1 stained SLN remained and was only detected by laparotomy. Conclusions: We confirmed the feasibility of the minilaparoscopic surgical approach for identification, dissection, and excision of SLN, as well as for sealing the lymphatic vessels that supply the nodes. This procedure might be considered a potentially better alternative to reduce morbidity during staging procedures for gynecological malignancies

Esophageal Atresia: A Challenge from Prenatal Diagnosis to Surgical Treatment

A atrésia esofágica é a anomalia congénita mais comum do desenvolvimento do esófago, caracterizando-se por uma disrupção da sua continuidade, com uma prevalência de cerca de 1 em cada 2500 a 4500 nados vivos. A abordagem desta condição, desde o seu diagnóstico no período pré-natal até ao tratamento cirúrgico no período neonatal, constitui um importante desafo, tanto para o obstetra como para o cirurgião pediátrico. No âmbito do diagnóstico pré-natal, a ecografa, a ressonância magnética, bem como a análise bioquímica do líquido amniótico poderão ser úteis. Por outro lado, no que diz respeito ao tratamento cirúrgico desta condição, dispomos hoje de técnicas cirúrgicas minimamente invasivas, associadas a menor número de sequelas musculoesqueléticas, menor dor no pós-operatório e a um melhor resultado estético fnal. Neste artigo, os autores fazem uma revisão do papel das diferentes técnicas de diagnóstico pré-natal disponíveis, bem como das diferentes abordagens para o tratamento cirúrgico.Esophageal atresia is the most common congenital anomaly of the esophagus, characterized by disruption of its continuity, with a prevalence of 1 per 2500 to 4500 live births. The approach to this condition, since diagnosis in the prenatal period to surgical treatment in the neonatal period, is an important challenge, both for the obstetrician and the pediatric surgeon. Regarding to prenatal diagnosis, ultrasound, mag - netic resonance, and biochemical analysis of amniotic fluid are relevant. On the other hand, concerning to surgical treat - ment, nowadays there are available minimal invasive surgical techniques, with less musculoskeletal sequelae, less pain in the post-operative period and a better esthetic final result. In this article, the authors review the different prenatal diagnostic techniques available, as well as different approaches to the surgical treatmentinfo:eu-repo/semantics/publishedVersio

Adenocarcinoma de células claras do colo do útero em idade jovem: um desafio diagnóstico

Clear cell adenocarcinoma of the cervix is a rare tumor, classically related with in utero diethylstilbestrol (DES) exposure. The authors report a rare case of clear cell adenocarcinoma of the cervix in a 21-yearold woman who had no history of in utero DES exposure, presenting with intermittent vaginal bleeding. It stresses the relevance to always clarify the etiology of abnormal genital bleeding and consider the possibility of cervicovaginal tumors