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Abstract 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.

Abstract 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.

The authors introduce a consistency-based approach to detecting examiner bias. On comparing intra-class correlation coefficients on transformed data for supervisor continuous performance and report marks (ICC1*) with those for supervisor continuous performance and second marker report marks (ICC2*), a highly significant difference was obtained for both the entire cohort (ICC1* = 0.72, ICC2* = 0.30, F = 2.47, p less than 0.0005 (N = 1085)) and the subgroup with high supervisor ratings for continuous performance (ICC1* = 0.62, ICC2* = 0.24, F = 1.97, p less than 0.0005 (n = 952)). A strong halo effect was detected and preliminary evidence was obtained for the presence of a strong horn effect for students with lower scores, thus providing a basis for future research. (Contains 1 footnote, 1 table, and 1 figure.)

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 (β = 5.66; p-value = 0.001) and for women who were cared for at a teaching hospital (β = 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The notion of students as partners in the co-creation of curricula and indeed co-evaluating or co-grading has shown positive outcomes that include increased engagement and motivation (Cook-Sather, Bovill, & Felten, 2014; Cook-Sather 2014; Cook- Sather & Motz-Storey 2016). In order for a student to be a pedagogical co-designer or indeed a change agent it is reasonable to suggest that they must already possess a substantial level of social and cultural capital (Woolcock, 2001) to enable this engagement. However, students from lower socio-economic status backgrounds are more likely to lack such capital and to not understand the "rules of the game" (Bourdieu, 1990; Bourdieu, 1984). In this situation, the value or pay-off of being involved in such co-design in terms of attribute development through a novel sense of experiential learning, may not be fully appreciated. Therefore, there are likely limits to the extent that co-creation and radical collegiality (Fielding, 1999), will lead to the democratisation of curricula and enhance students' experiences, irrespective of social background. Despite the barriers outlined above, Student-Led, Individually-Created Courses (SLICCs) are an emerging area of practice at the University of Edinburgh through which widening participation (WP) students are successfully being engaged in the graduate attributes and employability agendas and ultimately in the pedagogical co-design of their own credit-bearing curriculum. SLICCs provide a flexible reflectivelearning framework for experiential learning that enables individuals and groups of students to work across disciplinary and structural boundaries. These courses broaden the scope of what is considered to be 'curricular', bringing what was previously co- and extra-curricular into the credit-bearing provision. This paper will explore how WP students are engaged in the radical collegiality of SLICCs, despite the many barriers related to capital, through a rational pedagogy as outlined by Bourdieu and Passeron (1979). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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<0.001) 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Prototype hormonal male contraceptive regimens generally achieve only incomplete suppression to azoospermia with potentially adverse metabolic effects. We have carried out a short-term dose-finding study to investigate the potential of an oral gestogen, desogestrel, with testosterone pellets. Normal men received a single dose of 300 mg testosterone with 75 microg, 150 microg or 300 microg desogestrel daily for 8 weeks (n = 10 per group). LH and FSH were rapidly suppressed, with little difference between groups. Testosterone concentrations fell slightly during treatment with evidence of a linear dosage effect. Plasma inhibin B showed minor changes, but in seminal plasma it was suppressed, becoming undetectable in all men in the 300 microg desogestrel group. There were no significant changes in lipoproteins, fibrinogen or sexual behaviour during treatment, and minor falls in haematocrit and haemoglobin concentration. Sperm concentration fell in a dose-dependent manner, with three men, one man and seven men in the three groups respectively achieving severe oligozoospermia (<3 x 10(6)/ml), and three men achieving azoospermia in the 300 microg group despite the short duration of the study. The combination of oral desogestrel with depot testosterone thus results in profound suppression of gonadotrophin secretion without adverse metabolic or behavioural effects. Desogestrel with a long-acting testosterone preparation is a promising approach to hormonal male contraception. [ABSTRACT FROM AUTHOR]

Inhibins are regulators of paracrine and endocrine function during pregnancy, but their intrauterine sites of secretion are not well established. In amniotic fluid, inhibin A-, inhibin B- and inhibin pro-αC-containing isoforms were present in high concentrations, whereas in maternal serum, inhibin A and pro-αC forms were present in high amounts, with low concentrations of inhibin B. In fetal cord serum, inhibin pro-αC was present in all samples, inhibin B was detectable in male but not female fetuses, with no detectable inhibin A in either sex. From cultured explants, both inhibin A and B were secreted by chorion laeve, whereas only inhibin A was secreted by placenta, with both tissues secreting inhibin pro-αC. Only low concentrations of both dimeric inhibins and pro-αC forms were secreted by decidua parietalis and amnion. The dual perfused placental cotyledon secreted both inhibin A and pro-αC into maternal perfusate, but only inhibin pro-αC into the fetal circulation and less than to the maternal side. We conclude that trophoblast is the predominant source of dimeric inhibins, but with markedly different secretion depending on its intrauterine location. There was a significant decrease in inhibin A and pro-αC in amniotic fluid collected at term active labour compared to elective Caesarean section (P < 0.001). This may reflect a local change in inhibin/activin processing at labour, likely in chorion laeve trophoblast cells, which may be important in the paracrine control of the feto-maternal communication required to maintain pregnancy and initiate labour. [ABSTRACT FROM PUBLISHER]

We have investigated the presence of matrix metalloproteinases (MMP)-2 and -9 and their tissue inhibitors (TIMP) in the human uterine cervix. We postulate that during the process of cervical ripening, there is an increase in the activity of MMP in order to facilitate cervical connective tissue change. We have previously demonstrated that nitric oxide (NO) donors induce cervical ripening in vivo. A secondary hypothesis is that NO donors regulate MMP activity within the human uterine cervix. Cervical tissue biopsies were obtained from both pregnant and non-pregnant subjects. Cervical fibroblasts were cultured from the non-pregnant tissue. MMP-2 was present in conditioned media from pregnant and non-pregnant cervical explants and non-pregnant cervical fibroblasts. MMP-9 secretion was only detected in explants from non-pregnant women. TIMP-1, -2 and -4 were released by all cervical explants and fibroblast preparations. Pregnant women, in the first trimester, were treated with an NO donor (isosorbide mononitrate) in vivo. Cervical explants and fibroblasts from non-pregnant women were treated with the NO donor spermine nonoate in vitro. Treatment with an NO donor either in vivo or in vitro had no effect on the secretion of the MMP or TIMP studied. Further studies evaluating the mechanisms involved in cervical ripening are required. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are important enzymes in tissue remodelling, a key event for the development of the fetal membranes and placenta and establishing the feto–maternal interface during early pregnancy. This study has examined the secretion of the gelatinases, MMP-2 (72 kDa) and MMP-9 (92 kDa), and the endogenous tissue inhibitors of metalloproteinases (TIMPs) into extra-embryonic coelomic and amniotic fluids, the two principal intra-uterine compartments of the first trimester, and compared them to amniotic fluid collected later in gestation. In extra-embryonic coelomic fluid, gelatin zymography demonstrated that MMP-2 (72 kDa) was the predominant gelatinase, with some MMP-9 present. A broad range of TIMPs corresponding to TIMP-1 and TIMP-2, glycosylated and unglycosylated TIMP-3 and TIMP-4 was detected in this compartment by reverse zymography and immunoblot analyses. There was little gelatinase or TIMP activity in amniotic fluid in the first trimester. In amniotic fluid from the second trimester after fusion of the membranes obliterating the extra-embryonic coelom, and at term elective caesarean section, MMP-2 is the predominant gelatinase present, with a broad spectrum of TIMPs. These findings demonstrate that predominantly MMP-2 and also MMP-9, regulated by a range of TIMPs, are involved in intra-uterine tissue remodelling during the establishment of pregnancy. [ABSTRACT FROM AUTHOR]

Inhibins are present in maternal serum during pregnancy. However, the presence of inhibins in the compartments surrounding the fetus in early pregnancy is not well defined. Using novel specific enzyme-linked immunosorbent assays we have demonstrated that the bioactive dimeric inhibin forms, inhibin-A and inhibin-B, and the immunoreactive inhibin forms containing pro- and αC sequences are present in different amounts in the extra-embryonic coelomic and amniotic fluids and maternal serum between 8–11 weeks gestation. Of the bioactive dimeric inhibins, both inhibin-A (mean ± SEM 236.0 ± 24.8 pg/ml) and inhibin-B (62.0 ± 8.6 pg/ml) are present in extra-embryonic coelom, whereas no dimeric inhibin is present in the amniotic fluid and only inhibin-A (360.2 ± 32.9 pg/ml) is present in maternal serum. Furthermore, pro-αC-related immuno-reactivity is present at high concentrations in the extra-embryonic coelom (591.7 ± 60.5 pg/ml), amniotic fluid (452.4 ± 76.8 pg/ml) and maternal serum (539.4 ± 39.5 pg/ml). These findings would indicate that at this stage of gestation inhibin-A, inhibin-B and immunoreactive pro-αC-containing inhibin production are likely to arise from different sources including the fetus, placenta and fetal membranes and maternal sources including the ovary. Inhibins may be important regulators of fetal and placental development and involved in the establishment of pregnancy. [ABSTRACT FROM PUBLISHER]

The process of parturition involves a sequence of events that require extensive tissue remodelling. These events include foetal membrane rupture, placental detachment and post-partum involution of the uterus. Normally, foaling in the mare is a quick and dynamic process. Precisely orchestrated tissue remodelling mechanisms are required to control these fast events, hereunder the rupture of the foetal membranes and detachment of the placenta. In tissue remodelling, the matrix metalloproteinases (MMPs) are a much-studied family of enzymes that are involved in extracellular matrix (ECM) degradation. In the mare, invasive chorionic girdle cells have been found to produce MMP-2 and MMP-9, a likely event in the establishment of endometrial cup tissue. The levels of MMP-9 in human and rodent foetal membranes and fluids increased markedly with the onset of labour, relating this enzyme with the rupture of foetal membranes and detachment from the uterus. It is not known whether MMP activity is increased in late gestation or at parturition in mares. The aim of this study was to illustrate the secretion and localisation of MMP-9 and -2 in equine amniotic fluid during late pregnancy and foaling. A longitudinal study was used to determine the activities of MMP-9 and MMP-2 in equine amniotic fluid through gestation and during foaling in pony mares. The concentrations of MMP-9, MMP-2 and TIMP-2 in amniotic fluid were normally distributed and therefore parametric tests were used: Student's t-test to compare between gestational ages and outcome of pregnancy (normal birth, stillbirth or abortion), and the activities during the last 3 days before foaling and during foaling. All zymograms detected MMP-9 and MMP-2, and no significant changes were detected in mid gestation. Approaching normal foaling MMP-9 was present in increasing amounts. Activity of MMP-2 was detected in varying amounts in all samples, but there was no significant change in values through the sampling period. In the days before stillbirth and abortion there was no significant difference in activities of MMP-9 or -2. When values in the last 3 days before normal birth were compared with values during foaling, activities of MMP-9 and MMP-2 were significantly reduced during foaling. Activities of MMP-9 and MMP-2 in the last 3 days before stillbirth or abortion were also significantly higher than during foaling. This study shows that MMP-9 production is induced under specific conditions around normal parturition, and that MMP-2 seems to be constitutively expressed at an unchanging level throughout the last days of gestation. Also, MMP-9 activity is highest in the last three days before foaling and is significantly reduced during foaling. [ABSTRACT FROM AUTHOR]

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.