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1.
BMC Pregnancy Childbirth ; 22(1): 523, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35764981

RESUMO

BACKGROUND: Ethiopia has low skilled birth attendance rates coupled with low quality of care within health facilities contributing to one of the highest maternal mortality rates in Sub-Saharan Africa, at 412 deaths per 100,000 live births. There is lack of evidence on the readiness of health facilities to deliver quality labor and delivery (L&D) care. This paper describes the structural quality of routine L&D care in government hospitals of Ethiopia. METHODS: A facility-based cross-sectional study design, involving census of all government hospitals in Southern Nations Nationalities and People's Region (SNNPR) (N = 20) was conducted in November 2016 through facility audit using a structured checklist. Data collectors verified the availability and functioning of the required items through observation and interview with the heads of labor and delivery case team. An overall mean score of structural quality was calculated considering domain scores such as general infrastructure, human resource and essential drugs, supplies, equipment and laboratory services. Summary statistics such as proportion, mean and standard deviation were computed to describe the degree of adherence of the hospitals to the standards related to structural quality of routine labor and delivery care. RESULTS: One third of hospitals had low readiness to provide quality routine L&D care, with only two approaching near fulfilment of all the standards. Hospitals had fulfilled 68.2% of the standards for the structural aspects of quality of L&D care. Of the facility audit criteria, the availability of essential equipment and supplies for infection prevention scored the highest (88.8%), followed by safety, comfort and woman friendliness of the environment (76.4%). Availability skilled health professionals and quality management practices scored 72.5% each, while availability of the required items of general infrastructure was 64.6%. The two critical domains with the lowest score were availability of essential drugs, supplies and equipment (52.2%); and laboratory services and safe blood supply (50%). CONCLUSION: Substantial capacity gaps were observed in the hospitals challenging the provision of quality routine L&D care services, with only two thirds of required resources available. The largest gaps were in laboratory services and safe blood, and essential drugs, supplies and equipment. The results suggest the need to ensure that all public hospitals in SNNPR meet the required structure to enable the provision of quality routine L&D care with emphases on the identified gaps.


Assuntos
Medicamentos Essenciais , Estudos Transversais , Etiópia , Feminino , Governo , Hospitais Públicos , Humanos , Gravidez
2.
Am J Obstet Gynecol ; 217(4): 441.e1-441.e14, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28645573

RESUMO

BACKGROUND: The risk of unexplained fetal death or stillbirth increases late in pregnancy, suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA, and lipids. We hypothesized that placentas at >41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. OBJECTIVE: We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging. We also aimed to develop an in vitro term placental explant culture model to test the aging pathways. STUDY DESIGN: We collected placentas from women at 37-39 weeks' gestation (early-term and term), late-term, and with unexplained stillbirth. We used immunohistochemistry to compare the 3 groups for: DNA/RNA oxidation (8-hydroxy-deoxyguanosine), lysosomal distribution (lysosome-associated membrane protein 2), lipid oxidation (4-hydroxynonenal), and autophagosome size (microtubule-associated proteins 1A/1B light chain 3B, LC3B). The expression of aldehyde oxidase 1 was measured by real-time polymerase chain reaction. Using a placental explant culture model, we tested the hypothesis that aldehyde oxidase 1 mediates oxidative damage to lipids in the placenta. RESULTS: Placentas from late-term pregnancies show increased aldehyde oxidase 1 expression, oxidation of DNA/RNA and lipid, perinuclear location of lysosomes, and larger autophagosomes compared to placentas from women delivered at 37-39 weeks. Stillbirth-associated placentas showed similar changes in oxidation of DNA/RNA and lipid, lysosomal location, and autophagosome size to placentas from late-term. Placental explants from term deliveries cultured in serum-free medium also showed evidence of oxidation of lipid, perinuclear lysosomes, and larger autophagosomes, changes that were blocked by the G-protein-coupled estrogen receptor 1 agonist G1, while the oxidation of lipid was blocked by the aldehyde oxidase 1 inhibitor raloxifene. CONCLUSION: Our data are consistent with a role for aldehyde oxidase 1 and G-protein-coupled estrogen receptor 1 in mediating aging of the placenta that may contribute to stillbirth. The placenta is a tractable model of aging in human tissue.


Assuntos
Envelhecimento/fisiologia , Morte Fetal , Placenta/metabolismo , Natimorto , 8-Hidroxi-2'-Desoxiguanosina , Aldeído Oxidase/metabolismo , Autofagossomos/metabolismo , DNA/química , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Feminino , Idade Gestacional , Humanos , Lipídeos/química , Lisossomos/metabolismo , Oxirredução , Gravidez , RNA/química
3.
PLoS One ; 19(6): e0285058, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38889169

RESUMO

BACKGROUND: Ethiopia has one of the highest maternal mortality ratios in Africa. Few have examined the quality of labour and delivery (L&D) care in the country. This study evaluated the quality of routine L&D care and identified patient-level and hospital-level factors associated with the quality of care in a subset of government hospitals. MATERIALS AND METHODS: This was a facility-based, cross-sectional study using direct non-participant observation carried out in 2016. All mothers who received routine L&D care services at government hospitals (n = 20) in one of the populous regions of Ethiopia, Southern Nations Nationalities and People's Region (SNNPR), were included. Mixed effects multilevel linear regression modeling was employed in two stages using hospital as a random effect, with quality of L&D care as the outcome and selected patient and hospital characteristics as independent variables. Patient characteristics included woman's age, number of previous births, number of skilled attendants involved in care process, and presence of any danger sign in current pregnancy. Hospital characteristics included teaching hospital status, mean number of attended births in the previous year, number of fulltime skilled attendants in the L&D ward, whether the hospital had offered refresher training on L&D care in the previous 12 months, and the extent to which the hospital met the 2014 Ethiopian Ministry of Health standards regarding to resources available for providing quality of L&D care (measured on a 0-100% scale). These standards pertain to availability of human resource by category and training status, availability of essential drugs, supplies and equipment in L&D ward, availability of laboratory services and safe blood, and availability of essential guidelines for key L&D care processes. RESULTS: On average, the hospitals met two-thirds of the standards for L&D care quality, with substantial variation between hospitals (standard deviation 10.9 percentage points). While the highest performing hospital met 91.3% of standards, the lowest performing hospital met only 35.8% of the standards. Hospitals had the highest adherence to standards in the domain of immediate and essential newborn care practices (86.8%), followed by the domain of care during the second and third stages of labour (77.9%). Hospitals scored substantially lower in the domains of active management of third stage of labour (AMTSL) (42.2%), interpersonal communication (47.2%), and initial assessment of the woman in labour (59.6%). We found the quality of L&D care score was significantly higher for women who had a history of any danger sign (ß = 5.66; p-value = 0.001) and for women who were cared for at a teaching hospital (ß = 12.10; p-value = 0.005). Additionally, hospitals with lower volume and more resources available for L&D care (P-values < 0.01) had higher L&D quality scores. CONCLUSIONS: Overall, the quality of L&D care provided to labouring mothers at government hospitals in SNNPR was limited. Lack of adherence to standards in the areas of the critical tasks of initial assessment, AMTSL, interpersonal communication during L&D, and respect for women's preferences are especially concerning. Without greater attention to the quality of L&D care, regardless of how accessible hospital L&D care becomes, maternal and neonatal mortality rates are unlikely to decrease substantially.


Assuntos
Parto Obstétrico , Qualidade da Assistência à Saúde , Humanos , Etiópia , Feminino , Gravidez , Adulto , Estudos Transversais , Parto Obstétrico/normas , Parto Obstétrico/estatística & dados numéricos , Adulto Jovem , Trabalho de Parto , Análise Multinível , Adolescente , Mortalidade Materna , Serviços de Saúde Materna/normas , Hospitais/normas , Hospitais Públicos/normas
4.
Clin Endocrinol (Oxf) ; 76(6): 887-93, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22168508

RESUMO

OBJECTIVES: Circulating concentrations of the peptide kisspeptin have been proposed as a novel biomarker for early detection of pre-eclampsia. Our aims were to assess analytical and clinical performance characteristics of a commercial kisspeptin assay and to determine sensitivity and specificity of the test for pre-eclampsia. DESIGN: Prospective, longitudinal study in a United Kingdom tertiary referral Antenatal Metabolic Clinic. PATIENTS: Severely obese (body mass index, BMI > 40 kg/m(2), n = 194) and lean (BMI < 25 kg/m(2), n = 78) pregnant women. MEASUREMENTS: A commercial kisspeptin ELISA (Phoenix Pharmaceuticals) was assessed for analytical sensitivity, specificity, precision, linearity, recovery and stability in maternal plasma samples at 16, 28 and 36 weeks gestation. Pre-eclampsia, defined using International Society for the Study of Hypertension in Pregnancy guidelines; blood pressure; delivery gestation; birthweight. RESULTS: Kisspeptin concentrations were lower in early pregnancy in obese women (P < 0.001), and in women who later developed pre-eclampsia (P < 0.05), compared with women with uncomplicated pregnancies. For 16-week plasma kisspeptin in prediction of pre-eclampsia, area under the receiver-operator characteristic curve was 0.80 (P < 0.01), positive and negative likelihood ratios were 3.0 and 0.2, and test sensitivity and specificity were 85.7 and 71.4%, respectively. In regression analyses, kisspeptin (16 weeks) associated positively with delivery gestation (P < 0.05) and birthweight (P < 0.0001), and negatively with 28- and 36-week blood pressure (P < 0.0001). CONCLUSIONS: Kisspeptin concentration in early pregnancy is a promising biomarker for pre-eclampsia and low birthweight but cannot be recommended, in isolation, for universal screening because of inadequate test sensitivity and specificity. Large-scale studies are required to assess its potential in a panel of biomarkers.


Assuntos
Kisspeptinas/sangue , Obesidade/sangue , Pré-Eclâmpsia/sangue , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Obesidade/complicações , Gravidez , Estudos Prospectivos , Fatores de Risco
5.
BMC Med Educ ; 10: 83, 2010 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-21092088

RESUMO

BACKGROUND: Much has been written in the educational literature on the value of communities of practise in enhancing student learning. Here, we take the experience of senior undergraduate medical students involved in short-term research as a member of a team as a paradigm for learning in a community of practise. Based on feedback from experienced supervisors, we offer recommendations for initiating students into the research culture of their team. In so doing, we endeavour to create a bridge between theory and practise through disseminating advice on good supervisory practise, where the supervisor is perceived as an educator responsible for designing the research process to optimize student learning. METHODS: Using the questionnaire design tool SurveyMonkey and comprehensive lists of contact details of staff who had supervised research projects at the University of Edinburgh during 1995-2008, current and previous supervisors were invited to recommend procedures which they had found successful in initiating students into the research culture of a team. Text responses were then coded in the form of derivative recommendations and categorized under general themes and sub-themes. RESULTS: Using the chi-square tests of linear trend and association, evidence was found for a positive trend towards more experienced supervisors offering responses (χ2 = 16.833, p < 0.0005, n = 215) while there was a lack of evidence of bias in the gender distribution of respondents (χ2 = 0.482, p = 0.487, n = 203), respectively. A total of 126 codes were extracted from the text responses of 65 respondents. These codes were simplified to form a complete list of 52 recommendations, which were in turn categorized under seven derivative overarching themes, the most highly represented themes being Connecting the student with others and Cultivating self-efficacy in research competence. CONCLUSIONS: Through the design of a coding frame for supervisor responses, a wealth of ideas has been captured to make communities of research practise effective mediums for undergraduate student learning. The majority of these recommendations are underpinned by educational theory and have the potential to take the learner beyond the stage of initiation to that of integration within their community of research practise.


Assuntos
Atitude do Pessoal de Saúde , Pesquisa Biomédica/educação , Educação de Graduação em Medicina , Mentores , Comportamento Cooperativo , Currículo , Feminino , Humanos , Comunicação Interdisciplinar , Masculino , Escócia , Inquéritos e Questionários
6.
Prenat Diagn ; 29(10): 982-5, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19582702

RESUMO

OBJECTIVE: To investigate whether pregnancies with development of subsequent pre-eclampsia and intra-uterine growth restriction are associated with altered levels of kisspeptin in maternal serum in the second trimester. STUDY DESIGN: Retrospective case-control study of 16-20 week serum samples matched for duration of storage at -70 degrees C. Levels of kisspeptin were measured in serum from women with pregnancies with subsequent development of pre-eclampsia (n = 57), intra-uterine growth restriction (n = 118), and matched controls (n = 317). RESULTS: Serum kisspeptin levels were significantly lower in those women who subsequently developed pre-eclampsia than in controls [median (quartile range) 1109 (449) vs 1188 (365) pg/mL, p = 0.029] and in those with intra-uterine growth restriction [1164 (386) vs 1188 (365) pg/mL, p = 0.016]. CONCLUSIONS: Kisspeptin levels are lower in maternal serum in the second trimester, in pregnancies associated with placental dysfunction. The differences in kisspeptin are modest, so although not forming a single screening marker in pre-eclampsia and intra-uterine growth restriction, measurement of kisspeptin may be useful in combination with other markers. Understanding the role of kisspeptin in the establishment of the placenta may further our knowledge of the mechanisms underlying placental function.


Assuntos
Retardo do Crescimento Fetal/sangue , Pré-Eclâmpsia/sangue , Segundo Trimestre da Gravidez/sangue , Proteínas Supressoras de Tumor/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Gonadotropina Coriônica Humana Subunidade beta/sangue , Regulação para Baixo , Feminino , Idade Gestacional , Humanos , Kisspeptinas , Gravidez , Estudos Retrospectivos , alfa-Fetoproteínas/análise
7.
Med Teach ; 31(10): 885-94, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19877860

RESUMO

Student Selected Components (SSCs) are one of the more innovative recent developments in medical education. Initially established in the UK in the 1990s in response to the General Medical Council's recommendations in Tomorrow's Doctors (1993), they provide students with a significant element of choice and depth of study in the curriculum. SSCs have become an integral part of medical curricula throughout the UK, and to a limited extent the rest of the world. In most cases they contribute to the delivery of learning outcomes broadly encompassing personal, professional and research skills, whilst creating opportunities for students to explore future career options. This AMEE Guide is written for developers of new medical curricula, where SSC-like initiatives offering choice and depth of study, in conjunction with core learning, are being considered. Its aim is to provide insight into the structure of an SSC programme and its various important component parts. It is also relevant for those already involved in SSC development by offering insight into effectively managing, assessing and improving existing programmes, to deliver effective, coherent and core-integrated teaching valued by students and faculty alike.


Assuntos
Currículo , Educação Médica/organização & administração , Aprendizagem , Escolha da Profissão , Avaliação Educacional , Ética Médica , Medicina Baseada em Evidências , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Sistemas de Informação , Cooperação Internacional , Relações Interpessoais , Modelos Educacionais , Autonomia Pessoal , Gerenciamento do Tempo
8.
Med Teach ; 31(10): 895-902, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19877861

RESUMO

BACKGROUND: Student Selected Components (SSCs) are an established feature of UK undergraduate medical curricula that offer students choice. They represent a large investment in time and resources. Although programmes vary between Schools, the major learning objectives remain broadly similar. Providing students engage fully with the activity, the final learning outcomes should also be comparable. However, engaging effectively and purposefully with such programmes may not be a clear and straightforward process for students. AIM: To present the challenges and solutions to inform students how to derive the greatest benefit from the learning activities in their SSC programmes. METHODS: Synthesis of the accumulated experience over more than 10 years of developing, running and evaluating SSCs by the Directors of SSCs in five Scottish Medical Schools, combined with analysis of course evaluation and student feedback. RESULTS: Consensus defined 12 tips aimed at improving the approach taken by students to their SSCs, and to provide a structure to maximise their final learning outcomes. CONCLUSION: SSC programmes provide diverse opportunities for students to develop and expand their learning. With increasing emphasis being placed upon student assessment to judge a wide range of professional skills and standards into foundation and specialist training, much greater importance is now being given to SSCs as an opportunity for personal, professional and academic developments. However, it is important that this is performed in a purposeful manner to maximise this opportunity. These 12 tips provide guidance to students on how they can maximise the opportunity presented to them by SSCs.


Assuntos
Currículo , Educação Médica/organização & administração , Aprendizagem , Estudantes de Medicina , Comunicação , Avaliação Educacional , Humanos , Modelos Educacionais , Autonomia Pessoal , Gerenciamento do Tempo
9.
Placenta ; 77: 19-29, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30827352

RESUMO

INTRODUCTION: The amount of prostaglandin F2α (PGF2α) in the uterine lumen increases during the window of implantation in many mammals, including humans. We hypothesized that PGF2α regulates processes related to human embryo implantation. METHODS: The effect of PGF2α was studied using an in vitro model of human extravillous trophoblast (EVT) cell line (HTR-8/SVneo). Adhesion, proliferation, invasion and migration assays, zymography for metalloproteinases (MMP) activity, and gene/protein expression analyses were applied. Doses of 100 nM and/or 1 µM of PGF2α and fluprostenol were used. PGF2α receptor (PTGFR), MMP9 and MMP2 proteins in the human first trimester placenta were localized by immunohistochemistry and immunofluorescence. RESULTS: This study is the first reporting the expression of PTGFR protein in the first trimester placenta, as well as in HTR-8/SVneo cells. PGF2α and fluprostenol increased HTR-8/SVneo cell proliferation and adhesion to extracellular matrix protein (P < 0.05). This effect was abolished by mitogen activated protein kinases (MAPK) inhibitor. PGF2α induced phosphorylation of focal adhesion kinase and MAPK1/3 (P < 0.05). PGF2α increased mRNA content and protein activity of MMP9, and gene and protein expression of interleukin-6 (P < 0.05). EVT cell migration and invasiveness were stimulated by PGF2α (P < 0.05). The PGF2α effect on cell invasion was reduced by inhibitors of MMP2, MMP9 and mTOR. In all experiments, the stimulatory effects of PGF2α were diminished by using a PTGFR antagonist. DISCUSSION: Our findings suggest a significant role for PGF2α in mechanisms associated with implantation. PGF2α acting by PTGFR in HTR-8/SVneo cells stimulates their adhesion and proliferation through the MAPK signaling pathway and increases invasiveness inducing MMP proteolytic activity and mTOR signaling.


Assuntos
Dinoprosta/fisiologia , Trofoblastos/citologia , Trofoblastos/fisiologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Dinoprosta/farmacologia , Implantação do Embrião/efeitos dos fármacos , Implantação do Embrião/fisiologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Interleucina-6/genética , Interleucina-6/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Fosforilação , Placenta/metabolismo , Gravidez , Primeiro Trimestre da Gravidez/metabolismo , Receptores de Prostaglandina/metabolismo , Transdução de Sinais , Trofoblastos/efeitos dos fármacos
10.
Contraception ; 77(4): 283-8, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18342652

RESUMO

BACKGROUND: Communicating about sex with parents has been shown to influence some aspects of sexual behavior in young people. The aim of this study was to investigate how comfortable parents and children find this type of discussion and to compare parental responses with those of their children. STUDY DESIGN: Self-completed questionnaires were distributed to 317 teenagers from a state school in Edinburgh, Scotland, and to 575 of their parents. The questionnaire was designed to appraise relative levels of comfort/discomfort about discussing six sexual health topics. Where a parent and their child had both completed questionnaires, their responses were compared. RESULTS: Three hundred forty-five parents, 162 girls and 155 boys, completed questionnaires. Most parents considered themselves "comfortable" or "very comfortable" discussing sexual health issues with their children, with "boyfriends/girlfriends" as the most comfortable (p< or =.001) and "sexual intercourse" the least comfortable topic (p<.0005). However, many children stated they "definitely would not" talk to parents (19-65% of participants, depending on the topic), citing "embarrassment" as the main reason. Eight-six pairs of parent-child responses were matched and compared showing that on all topics the least communication occurred between fathers and their daughters. CONCLUSIONS: There are clearly barriers to communicating about sexual health issues between parents and their children in this population, and this seems to stem from reluctance on the part of the children rather than of their parents.


Assuntos
Comportamentos Relacionados com a Saúde , Relações Pais-Filho , Educação Sexual , Inquéritos e Questionários , Adolescente , Adulto , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Escócia
11.
Med Teach ; 30(4): 370-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18569657

RESUMO

BACKGROUND: Student selected components (SSCs) represent a significant component of medical curricula in the UK and a new approach in medical education. Despite the prominence given to SSCs by the General Medical Council in each of its seminal papers regarding undergraduate medical education, there remains a diverse view of the purpose, outcomes, structure and assessment of SSCs. Many Schools have adopted their own perspective of SSCs and created different but often innovative courses. AIMS: This article brings together the Scottish Medical Schools and their experience in organising SSCs, highlights some of the challenges and offers possible solutions to some of the difficulties encountered. METHOD: The SSC Director from each of the Scottish medical schools each contributed their own '12 Tips'. From these a consensus was achieved. RESULTS: Even though the Scottish medical schools have a wide range of curriculum and timetable formats, there was a great deal of agreement in the challenges and problems encountered in their SSC programmes, as expressed through these 12 Tips. CONCLUSION: There is much diversity in SSC programmes at different medical schools, although there is also much commonality in the challenges that arise. We hope that this paper will promote thought and discussion amongst those involved, and be useful to those involved in curriculum and programme development and also to those new to medical education.


Assuntos
Comportamento de Escolha , Currículo , Educação de Graduação em Medicina/organização & administração , Estudantes de Medicina , Consenso , Guias como Assunto , Humanos , Escócia
12.
Am J Obstet Gynecol ; 196(3): 255.e1-6, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17346544

RESUMO

OBJECTIVE: The purpose of this study was to determine the expression of natural antimicrobials in primary cultured amnion epithelial cells and to examine their regulation by interleukin-1 beta (IL-1beta). STUDY DESIGN: Primary amnion epithelial cells were cultured from samples that were obtained at prelabor cesarean section (n = 12) and stimulated with IL-1beta. Natural antimicrobial messenger RNA expression was determined by real-time quantitative polymerase chain reaction, and protein was measured by enzyme-linked immunosorbent assay. Data was analyzed by analysis of variance. RESULTS: Primary amnion epithelial cells express messenger RNA for human beta defensin (HBD) 1 to 3, secretory leukocyte protease inhibitor and elafin, but not HBD4. IL-1beta 10 ng/mL stimulates HBD2 messenger RNA in a biphasic pattern, with a 51-fold increase at 6 hours and a 67-fold at 12 hours (P < .001). HBD2 protein production is significantly increased by 24 hours (P < .05). CONCLUSION: The amnion produces potent natural antimicrobials that may help protect the pregnancy from infection. HBD2 production is dramatically upregulated by the labor-associated inflammatory cytokine IL-1beta.


Assuntos
Âmnio/citologia , Defensinas/biossíntese , Células Epiteliais/fisiologia , Células Cultivadas , Defensinas/genética , Células Epiteliais/imunologia , Feminino , Humanos , RNA Mensageiro/biossíntese
13.
Invest Ophthalmol Vis Sci ; 47(5): 1911-7, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16638998

RESUMO

PURPOSE: Corneal wound healing involves a cascade of interactions between the epithelium and stroma. Pax6 is upregulated, and early events include epithelial cell migration and apoptosis of superficial keratocytes. The mouse heterozygous Pax6 (Pax6+/-) corneal phenotype mimics human aniridia-related keratopathy (ARK), and some aspects of wound healing have been shown to be abnormal, including matrix metalloproteinase (MMP)-9 expression. The purpose of this study was to test whether the Pax6+/- genotype affects corneal wound-healing responses, including stromal cell apoptosis, epithelial cell migration rate, and MMP secretion in culture. METHOD: Pax6+/- and wild-type (Pax6+/+) mice were killed and their corneas wounded by epithelial debridement. Whole eyes were cultured in organ culture and corneal epithelial healing rates and keratocyte apoptosis were quantified by topical fluorescein staining and TUNEL, respectively. Dissociated corneal epithelial cells from Pax6+/- and wild-type mice were cultured, and the activities of secreted MMP-9 were determined by zymography. RESULTS: Wound-healing rates during the first 6 hours were significantly faster for larger wounds and for Pax6+/- corneas. Compared with wild-type, wounded Pax6+/- eyes showed significantly more stromal cell apoptosis, and cultured Pax6+/- corneal epithelial cells produced lower MMP-9 activity. CONCLUSIONS: The cumulative effect of abnormal wound-healing responses, characterized by increased stromal cell apoptosis and reduced levels of MMP-9 secretion may contribute to the corneal changes in the Pax6+/- mice. Possible contributions of elevated stromal cell apoptosis and other abnormal wound-healing responses to ARK are discussed.


Assuntos
Apoptose , Substância Própria/patologia , Epitélio Corneano/fisiologia , Proteínas do Olho/genética , Regulação da Expressão Gênica/fisiologia , Proteínas de Homeodomínio/genética , Fatores de Transcrição Box Pareados/genética , Proteínas Repressoras/genética , Cicatrização/fisiologia , Animais , Aniridia/genética , Movimento Celular , Feminino , Fibroblastos/patologia , Genótipo , Marcação In Situ das Extremidades Cortadas , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Microscopia de Fluorescência , Técnicas de Cultura de Órgãos , Fator de Transcrição PAX6
14.
Psychoneuroendocrinology ; 63: 135-43, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26444587

RESUMO

BACKGROUND: The maternal hypothalamic-pituitary-adrenal-axis (HPAA) undergoes dramatic activation during pregnancy. Increased cortisol and corticotrophin-releasing-hormone (CRH) associate with low birthweight and preterm labor. In non-pregnant obesity, the HPAA is activated but circulating cortisol levels are normal or lower than in lean women. We hypothesized that maternal cortisol levels would be lower in obese pregnancy, and would associate with increased fetal size and length of gestation. METHOD: Fasting serum cortisol was measured at 16, 28 and 36 weeks gestation and at 3-6 months postpartum in 276 severely obese and 135 lean women. In a subset of obese (n=20) and lean (n=20) we measured CRH, hormones that regulate bioavailable cortisol (corticosteroid-binding-globulin, estradiol, estriol, and progesterone). Urinary glucocorticoid metabolites were measured in pregnant (obese n=6, lean n=5) and non-pregnant (obese n=7, lean n=7) subjects. RESULTS: Maternal cortisol and HPAA hormones were lower in obese pregnancy. Total urinary glucocorticoid metabolites increased significantly in lean pregnancy, but not in obese. Lower maternal cortisol in obese tended to be associated with increased birthweight (r=-0.13, p=0.066). In obese, CRH at 28 weeks correlated inversely with gestational length (r=-0.49, p=0.04), and independently predicted gestational length after adjustment for confounding factors (mean decrease in CRH of -0.25 pmol/L (95% CI -0.45 to -0.043 pmol/L) per/day increase in gestation). CONCLUSION: In obese pregnancy, lower maternal cortisol without an increase in urinary glucocorticoid clearance may indicate a lesser activation of the HPAA than in lean pregnancy. This may offer a novel mechanism underlying increased birthweight and longer gestation in obese pregnancy.


Assuntos
Peso ao Nascer , Idade Gestacional , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Obesidade Mórbida/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Complicações na Gravidez/metabolismo , Adulto , Estudos de Casos e Controles , Hormônio Liberador da Corticotropina/metabolismo , Cortisona/urina , Estradiol/metabolismo , Estriol/metabolismo , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Gravidez , Pregnanos/urina , Progesterona/metabolismo , Tetra-Hidrocortisol/urina , Transcortina/metabolismo
15.
Psychoneuroendocrinology ; 59: 112-22, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26056743

RESUMO

Maternal emotional distress symptoms, including life satisfaction, anxiety and depressed mood, are worse in Severely Obese (SO) than lean pregnancy and may alter placental genes regulating fetal glucocorticoid exposure and placental growth. We hypothesised that the associations between increased maternal distress symptoms and changes in placental gene expression including IGF2 and genes regulating fetal glucocorticoid exposure are more pronounced in SO pregnancy. We also considered whether there were sex-specific effects. Placental mRNA levels of 11ß-HSDs, NR3C1-α, NR3C2, ABC transporters, mTOR and the IGF2 family were measured in term placental samples from 43 lean (BMI≤25kg/m(2)) and 50 SO (BMI≥40kg/m(2)) women, in whom distress symptoms were prospectively evaluated during pregnancy. The mRNA levels of genes with a similar role in regulating fetal glucocorticoid exposure were strongly inter-correlated. Increased maternal distress symptoms associated with increased NR3C2 and IGF2 isoform 1(IGF2-1) in both lean and SO group (p≤0.05). Increased distress was associated with higher ABCB1 and ABCG2 mRNA levels in SO but lower ABCB1 and higher 11ß-HSD1 mRNA levels in lean (p≤0.05) suggesting a protective adaptive response in SO placentas. Increased maternal distress associated with reduced mRNA levels of ABCB1, ABCG2, 11ß-HSD2, NR3C1-α and IGF2-1 in placentas of female but not male offspring. The observed sex differences in placental responses suggest greater vulnerability of female fetuses to maternal distress with potentially greater fetal glucocorticoid exposure and excess IGF2. Further studies are needed to replicate these findings and to test whether this translates to potentially greater negative outcomes of maternal distress in female offspring in early childhood.


Assuntos
Glucocorticoides/metabolismo , Fator de Crescimento Insulin-Like II/genética , Obesidade/genética , Placenta/fisiologia , Complicações na Gravidez/genética , Estresse Psicológico/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Desenvolvimento Fetal/fisiologia , Regulação da Expressão Gênica , Humanos , Hidrocortisona/sangue , Fator de Crescimento Insulin-Like II/metabolismo , Estudos Longitudinais , Troca Materno-Fetal/fisiologia , Obesidade/metabolismo , Placenta/metabolismo , Gravidez , Complicações na Gravidez/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores Sexuais , Estresse Psicológico/genética
16.
Contraception ; 70(2): 135-9, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15288218

RESUMO

Medical students at the University of Edinburgh in Scotland can volunteer to participate in an undergraduate options project that gives them the opportunity to provide sex education for secondary school (high school) pupils. Using a questionnaire presenting a set of fictional case histories, we assessed medical students' theoretical confidence at dealing with sexual health consultations. Students who had participated in delivering peer-led sex education felt significantly more confident at discussing sexual health issues with patients of all age groups (p = 0.001) than students who had not participated in the project. All students felt more comfortable seeing patients of the same gender as themselves but more than half felt that their training left them generally ill-equipped to handle sexual health consultations.


Assuntos
Educação Médica/métodos , Saúde , Educação Sexual , Disfunções Sexuais Fisiológicas , Estudantes de Medicina , Ensino , Atitude do Pessoal de Saúde , Encaminhamento e Consulta , Instituições Acadêmicas , Comportamento Sexual , Inquéritos e Questionários
17.
Anim Reprod Sci ; 81(3-4): 329-39, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-14998657

RESUMO

Profound hormonally controlled tissue remodelling occurs in the equine ovary for follicle growth and development, and also for the alteration in follicle shape directed towards the ovulation fossa, the site where ovulation occurs. The aim of this study was to examine the spatial and temporal regulation of matrix metalloproteinases (MMP)-2 and MMP-9, important enzymes in tissue remodelling, during follicle growth, and ovulation. Using gelatin substrate zymography, we measured these MMPs in follicular fluid of large anovulatory follicles collected during spring transition, early dominant follicles (> 23 mm), and at oestrus in follicles approximately 3 days prior to ovulation, and post-hCG treatment when ovulation was predicted in approximately 4 h. The most abundant activity detected in follicular fluid was MMP-2, although there were no changes in secretion or activation in association with ovulation. The activity of MMP-9 was detected in lower amounts, with no changes prior to ovulation, although it decreased significantly (P < 0.05) post-hCG treatment. At oestrus, when different regions of the ovary were maintained in explant culture for 24 h, there were no significant changes in either MMP-2 or MMP-9 secretion by stromal tissues collected at the ovarian fossa, adjacent to the preovulatory follicle but away from the fossa, and a further site remote from the preovulatory follicle. Over this same time period, follicular progesterone (P < 0.01) and oestradiol (P < 0.05) increased significantly, although oestradiol tended to decrease after hCG administration. These findings indicate that MMP-2 and MMP-9 are not key acute regulators for the changes in follicle shape immediately prior to ovulation.


Assuntos
Cavalos/fisiologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Folículo Ovariano/fisiologia , Ovário/enzimologia , Ovulação , Animais , Gonadotropina Coriônica/administração & dosagem , Técnicas de Cultura , Estradiol/análise , Estro , Feminino , Líquido Folicular/química , Líquido Folicular/enzimologia , Folículo Ovariano/anatomia & histologia , Folículo Ovariano/diagnóstico por imagem , Progesterona/análise , Ultrassonografia
18.
BMC Med Educ ; 4(1): 28, 2004 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-15569395

RESUMO

BACKGROUND: Supervisors are often involved in the assessment of projects they have supervised themselves. Previous research suggests that detailed marking sheets may alleviate leniency and halo effects. We set out to determine if, despite using such a marking schedule, leniency and halo effects were evident in the supervisors' marking of undergraduate short research projects (special study modules (SSM)). METHODS: Review of grades awarded by supervisors, second markers and control markers to the written reports of 4th year medical students who had participated in an SSM during two full academic years (n = 399). Paired t-tests were used to compare mean marks, Pearson correlation to look at agreement between marks and multiple linear regression to test the prediction of one mark from several others adjusted for one another. RESULTS: There was a highly significant difference of approximately half a grade between supervisors and second markers with supervisors marking higher. (t = 3.12, p < 0.01, difference in grade score = 0.42, 95% CI for mean difference 0.18-0.80). There was a high correlation between the two marks awarded for performance of the project and the written report by the supervisor (r = 0.75), but a low-modest correlation between supervisor and second marker (r = 0.28). Linear regression analysis of the influence of the supervisors' mark for performance on their mark for the report gave a non-significant result. This suggests a leniency effect but no halo effect. CONCLUSIONS: This study shows that with the use of structured marking sheet for assessment of undergraduate medical students, supervisors marks are not associated with a halo effect, but leniency does occur. As supervisor assessment is becoming more common in both under graduate and postgraduate teaching new ways to improve objectivity in marking and to address the leniency of supervisors should be sought.


Assuntos
Educação de Graduação em Medicina , Avaliação Educacional/métodos , Aprendizagem Baseada em Problemas/organização & administração , Pesquisa/educação , Pessoal Administrativo , Adulto , Avaliação Educacional/normas , Docentes de Medicina , Humanos , Variações Dependentes do Observador , Projetos Piloto , Reprodutibilidade dos Testes , Pesquisa/normas
19.
Perspect Med Educ ; 2(4): 230-247, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24037741

RESUMO

Student selected components (SSCs), at that time termed special study modules, were arguably the most innovative element in Tomorrow's Doctors (1993), the document from the General Medical Council that initiated the modernization of medical curricula in the UK. SSCs were proposed to make up one-third of the medical curriculum and provide students with choice, whilst allowing individual schools autonomy in how SSCs were utilized. In response, at the University of Edinburgh the undergraduate medical curriculum provides an integrated and sequential development and assessment of research skill learning outcomes, for all students in the SSC programme. The curriculum contains SSCs which provide choice to students in all 5 years. There are four substantial timetabled SSCs where students develop research skills in a topic and speciality of their choice. These SSCs are fully integrated and mapped with core learning outcomes and assessment, particularly with the 'Evidence-Based Medicine and Research' programme theme. These research skills are developed incrementally and applied fully in a research project in the fourth year. One-third of students also perform an optional intercalated one-year honours programme between years 2 and 3, usually across a wide range of honours schools at the biomedical science interface. Student feedback is insightful and demonstrates perceived attainment of research competencies. The establishment of these competencies is discussed in the context of enabling junior graduate doctors to be effective and confident at utilizing their research skills to effectively practice evidence-based medicine. This includes examining their own practice through clinical audit, developing an insight into the complexity of the evidence base and uncertainty, and also gaining a view into a career as a clinical academic.

20.
Theriogenology ; 75(6): 1130-8, 2011 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21220153

RESUMO

During late gestation in the mare, rapid fetal growth is accompanied by considerable placental growth and further invasion of the endometrium by microvilli. This growth requires extensive remodeling of the extracellular matrix (ECM). In early pregnancy, we know that matrix metalloproteinase (MMP)-9 and -2 are involved in the endometrial invasion during endometrial cup formation. The present study investigated whether MMPs are found in fetal fluids later in gestation and during parturition, and if there was a difference in their activities between normal and preterm delivery. Amniotic fluids were collected from pony mares during the latter half of gestation, and amniotic and allantoic fluids from pony and thoroughbred mares at foaling. The fluids were analysed for the activity of MMP-9 and -2, and TIMPs using zymography techniques. There was an increase (P = 0.002) in activity of latent MMP-9 when approaching normal foaling, and a decrease (P < 0.001) during foaling. MMP-2 activity did not change through gestation, or during foaling. When comparing samples from pregnancies resulting in preterm deliveries with samples from foaling mares, the activity of MMP-9 was lower (P < 0.001) and MMP-2 activity was higher (P = 0.004) during foaling than preceding preterm delivery. The activity of MMP-9 was lower (P = 0.002) prior to preterm delivery than before delivery of a live foal at term, whereas no difference (P = 0.07) was demonstrated for latent MMP-2 activity when comparing the same groups. The activity of TIMP-2 was higher (P < 0.001) in the pre-parturient period before normal foaling than preceding preterm delivery. These results suggest that MMPs may have a role as markers for high risk pregnancy in the mare.


Assuntos
Líquido Amniótico/metabolismo , Cavalos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Parto/metabolismo , Prenhez/metabolismo , Inibidores Teciduais de Metaloproteinases/metabolismo , Animais , Biomarcadores/metabolismo , Feminino , Gravidez
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