Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors

Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site

Foot pressure distribution during walking in young and old adults

BACKGROUND: Measurement of foot pressure distribution (FPD) is clinically useful for evaluation of foot and gait pathologies. The effects of healthy aging on FPD during walking are not well known. This study evaluated FPD during normal walking in healthy young and elderly subjects. METHODS: We studied 9 young (30 ± 5.2 years), and 6 elderly subjects (68.7 ± 4.8 years). FPD was measured during normal walking speed using shoe insoles with 99 capacitive sensors. Measured parameters included gait phase characteristics, mean and maximum pressure and force, and relative load. Time-series measurements of each variable for all sensors were grouped into 9 anatomical masks. RESULTS: Elderly subjects had lower normalized maximum pressure for the medial and lateral calcaneal masks, and for all medial masks combined. In the medial calcaneus mask, the elderly group also had a lower absolute maximum and lower mean and normalized mean pressures and forces, compared to young subjects. Elderly subjects had lower maximum force and normalized maximum force and lower mean force and normalized mean forces in the medial masks as well. CONCLUSION: FPD differences between the young and elderly groups were confined to the calcaneus and hallux regions and to the medial side of the foot. In elderly subjects, weight bearing on the lateral side of the foot during heel touch and toe-off phases may affect stability during walking

Viral-bacterial co-infection in Australian Indigenous children with acute otitis media

Background: Acute otitis media with perforation (AOMwiP) affects 40% of remote Indigenous children during the first 18 months of life. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the primary bacterial pathogens of otitis media and their loads predict clinical ear state. Our hypothesis is that antecedent respiratory viral infection increases bacterial density and progression to perforation

Professional Development and the Informal Curriculum in End-of-Life Care

Although professionalism has emerged as a key competency for today’s physicians, there exists little insight into how best to teach medical students the relevant skills or instill in them the commitment required to practice according to the highest professional standards. Ten UCSF medical students were interviewed at three time points (second, third, and fourth years of school). Interviews focused on students’ learning and development regarding end-of-life care (EOLC). Students described varying steps in their professional development from their second to fourth years of school, including feeling confused about the definition of professionalism and integrating their personal and professional identities. In addition to professional development, four other themes contributed to the development of medical student understanding of how to provide EOLC as a professional: (1) curricular discordance, (2) role models, (3) the tightrope between trained versus human reactions, and (4) ethical dilemmas. These five themes represent dilemmas that students often learned how to respond to over the course of school. Professional development in EOLC required the acquisition of skills necessary to balance the tension between and navigate conflicting messages present in medical student training

The real risks of steroid injection for plantar fasciitis, with a review of conservative therapies

This article presents a review of conservative therapies for plantar fasciitis pain reduction with a discussion of steroid therapy risks. The therapies reviewed include orthoses, stretching, extracorporeal shockwave, BTX-A, and corticosteroid injection/iontophoresis. These modes were included based on the availability of double blinded randomized controlled trials. We noted the following findings. Orthoses, regardless of type, can improve pain levels. Plantar stretching shows limited short-term benefit (1 month), but can reflect significant long-term improvement (10 months). Extracorporeal shockwave therapy shows equivocal benefit with some studies showing significant improvement and others showing none. Although BTX-A injections were the least studied, significant pain improvement was demonstrated in the short and long term. Steroid injection/iontophoresis showed significant improvement in the short term (1 month). Steroid therapy, when coupled with plantar stretching, can provide efficacious pain relief; however, steroid injections should be combined with ultrasound monitoring to reduce complications

Primordial Black Holes: sirens of the early Universe

Primordial Black Holes (PBHs) are, typically light, black holes which can form in the early Universe. There are a number of formation mechanisms, including the collapse of large density perturbations, cosmic string loops and bubble collisions. The number of PBHs formed is tightly constrained by the consequences of their evaporation and their lensing and dynamical effects. Therefore PBHs are a powerful probe of the physics of the early Universe, in particular models of inflation. They are also a potential cold dark matter candidate.Comment: 21 pages. To be published in "Quantum Aspects of Black Holes", ed. X. Calmet (Springer, 2014

Perceptions and experiences of perinatal mental disorders in rural, predominantly ethnic minority communities in northern Vietnam

BACKGROUND: Preliminary research has suggested that perinatal mental disorders (PMDs), including post-partum depression, are prevalent in Vietnam. However the extent to which these disorders are recognized at the community level remains largely undocumented in the literature. PMDs have also never been investigated within Vietnam’s significant ethnic minority populations, who are known to bear a greater burden of maternal and infant health challenges than the ethnic majority. OBJECTIVE: To investigate knowledge and perceptions of PMDs and their treatments at the community level in a rural, predominantly ethnic minority region of northern Vietnam. METHODS: Qualitative semi-structured interviews were conducted on the topic of common PMDs. Participant groups were primary health workers (PHWs) working at local community health centers, and pregnant or postpartum women enrolled in a program for maternal and infant health that was not mental health related. Interviews included vignette scenarios that asked respondents to interpret cases of women experiencing PMDs, as well as open-ended questions about mental disorders and their treatments. RESULTS: Twelve PHWs and 14 perinatal women completed the study. Major themes that emerged from the interviews included (1) Family relationships impact psychological well-being, (2) Nutrition contributes to perinatal mental health, (3) Both traditional and western medicine play roles in perinatal health, (4) There was a lack of personal experience with women experiencing PMDs, (5) Descriptions of mental health symptoms focused on behaviours, and (6) Community care is the primary mental health support. CONCLUSIONS: PHWs reported having almost never treated a woman with a PMD. However, anecdotal evidence from the women interviewed suggests that there are incidents of mental disorders during the perinatal period that go largely unaddressed. Willingness to present to primary care appears to be high, and presents an opportunity to address this need by training PHWs in effective screening, treatment, and referral. Such training should account for culturally specific presentations of mental disorders as well as the importance of the patient’s social context. To the best of the author’s knowledge, this research presents the first evidence of a PMD burden within Vietnam’s ethnic minority communities