Impedance-based cell monitoring: barrier properties and beyond

In multicellular organisms epithelial and endothelial cells form selective permeable interfaces between tissue compartments of different chemical compositions. Tight junctions which connect adjacent cells, control the passage of molecules across the barrier and, in addition, facilitate active transport processes. The cellular barriers are not static but can be deliberately modulated by exposure to specific external stimuli. In vitro models representing the essential absorption barriers of the body are nowadays available, thus allowing investigation of the parameters that control permeability as well as transport processes across those barriers. Independent of the origin of the barrier forming cells, techniques are needed to quantify their barrier integrity. One simple assay is to measure the permeability for given hydrophilic substrates possessing different molecular weights like sucrose or dextrans. However, this technique is time-consuming and labor-intensive. Moreover, radioactive or fluorescently-labeled substrates are needed to allow easy analytical detection. Finally, if transport processes are investigated, the standard permeant may interfere with the transport process under investigation or might even alter the barrier integrity by itself. Thus, independent, non-invasive techniques are needed to quantify the barrier integrity continuously during the experiment. Such techniques are available and are mainly based on the measurement of the transendothelial or transepithelial electrical resistance (TEER) of barrier forming cells grown on porous membranes. Simple devices using two sets of electrodes (so-called Voltohmeters) are widely used. In addition, an easy-to-use physical technique called impedance spectroscopy allows the continuous analysis of both the TEER and the electrical capacitance giving additional information about the barrier properties of cells grown on permeable membranes. This technique is useful as a quality control for barrier forming cells. Another impedance-based approach requires cells to be grown directly on solid, micro-structured electrodes. Here, we will discuss the physical background of the different techniques; advantages, disadvantages, and applications will be scrutinized. The aim is to give the reader a comprehensive understanding concerning the range and limits of the application, mainly focusing on endothelial cells.</p

A Survey of University Students’ Preferences for Midwifery Care and Community Birth Options in 8 High‐Income Countries

Background: Midwifery care is associated with positive birth outcomes, access to community birth options, and judicious use of interventions. The aim of this study was to characterize and compare maternity care preferences of university students across a range of maternity care systems and to explore whether preferences align with evidence- based recommendations and options available. Methods: A cross-sectional, web-based survey was completed in 2014-2015 by a convenience sample of university students in 8 high-income countries across 4 continents (n=4,569). In addition to describing preferences for midwifery care and community birth options across countries, socio-demographic characteristics, psychological factors, knowledge about pregnancy and birth, and sources of information that shaped students’ attitudes towards birth were examined in relation to preferences for midwifery care and community birth options. Results: Approximately half of the student respondents (48. 2%) preferred midwifery-led care for a healthy pregnancy, 9.5% would choose to birth in a birthing center, and 4.5% preferred a home birth. Preference for midwifery care varied from 10.3% among women in the United States to 78.6% among women in England. Preferences for home birth varied from 0.3% among US women to 18.3% among Canadian women. Women, health science students, those with low childbirth fear, who learned about pregnancy and birth from friends (compared to other sources, e.g. the media) and those who responded from Europe were significantly more likely to prefer midwifery care and community birth. High confidence in knowledge of pregnancy and birth was linked to significantly higher odds of community birth preferences and midwifery care preferences Conclusions: It would be beneficial to integrate childbirth education into high school curricula, to promote knowledge of midwifery care, pregnancy and childbirth and reduce fear among prospective parents. Community birth options need to be expanded, to meet demand among the next generation of maternity service users

Preference for cesarean section in young nulligravid women in eight OECD countries and implications for reproductive health education

Background: Efforts to reduce unnecessary Cesarean sections (CS) in high and middle income countries have focused on changing hospital cultures and policies, care provider attitudes and behaviors, and increasing women’s knowledge about the benefits of vaginal birth. These strategies have been largely ineffective. Despite evidence that women have well-developed preferences for mode of delivery prior to conceiving their first child, few studies and no interventions have targeted the next generation of maternity care consumers. The objectives of the study were to identify how many women prefer Cesarean section in a hypothetical healthy pregnancy, why they prefer CS and whether women report knowledge gaps about pregnancy and childbirth that can inform educational interventions. Methods: Data was collected via an online survey at colleges and universities in 8 OECD countries (Australia, Canada, Chile, England, Germany, Iceland, New Zealand, United States) in 2014/2015. Childless young men and women between 18 and 40 years of age who planned to have at least one child in the future were eligible to participate. The current analysis is focused on the attitudes of women (n = 3616); rates of CS preference across countries are compared, using a standardized cohort of women aged 18–25 years, who were born in the survey country and did not study health sciences (n = 1390). Results: One in ten young women in our study preferred CS, ranging from 7.6% in Iceland to 18.4% in Australia. Fear of uncontrollable labor pain and fear of physical damage were primary reasons for preferring a CS. Both fear of childbirth and preferences for CS declined as the level of confidence in women’s knowledge of pregnancy and birth increased. Conclusion: Education sessions delivered online, through social media, and face-to-face using drama and stories told by peers (young women who have recently had babies) or celebrities could be designed to maximize young women’s capacity to understand the physiology of labor and birth, and the range of methods available to support them in coping with labor pain and to minimize invasive procedures, therefore reducing fear of pain, bodily damage, and loss of control. The most efficacious designs and content for such education for young women and girls remains to be tested in future studies.Applied Science, Faculty ofMedicine, Faculty ofNon UBCFamily Practice, Department ofMidwifery, Division ofNursing, School ofPopulation and Public Health (SPPH), School ofReviewedFacult

A survey of university students’ preferences for midwifery care and community birth options in 8 high‐income countries

Introduction Midwifery care is associated with positive birth outcomes, access to community birth options, and judicious use of interventions. The aim of this study was to characterize and compare maternity care preferences of university students across a range of maternity care systems and to explore whether preferences align with evidence‐based recommendations and options available. Methods A cross‐sectional, web‐based survey was completed in 2014 and 2015 by a convenience sample of university students in 8 high‐income countries across 4 continents (N = 4569). In addition to describing preferences for midwifery care and community birth options across countries, this study examined sociodemographic characteristics, psychological factors, knowledge about pregnancy and birth, and sources of information that shaped students’ attitudes toward birth in relation to preferences for midwifery care and community birth options. Results Approximately half of the student respondents (48.2%) preferred midwifery‐led care for a healthy pregnancy; 9.5% would choose to give birth in a birthing center, and 4.5% preferred a home birth. Preference for midwifery care varied from 10.3% among women in the United States to 78.6% among women in the United Kingdom. Preferences for home birth varied from 0.3% among US women to 18.3% among Canadian women. Women, health science students, those with low childbirth fear, those who learned about pregnancy and birth from friends (compared with other sources, eg, the media), and those who responded from Europe were significantly more likely to prefer midwifery care and community birth. High confidence in knowledge of pregnancy and birth was linked to significantly higher odds of community birth preferences and midwifery care preferences. Discussion It would be beneficial to integrate childbirth education into high school curricula to promote knowledge of midwifery care, pregnancy, and childbirth and to reduce fear among prospective parents. Community birth options need to be expanded to meet demand among the next generation of maternity service users

Deep sequencing in conjunction with expression and functional analyses reveals activation of FGFR1 in ewing sarcoma

PURPOSE: A low mutation rate seems to be a general feature of pediatric cancers, in particular in oncofusion gene-driven tumors. Genetically, Ewing sarcoma is defined by balanced chromosomal EWS/ETS translocations, which give rise to oncogenic chimeric proteins (EWS-ETS). Other contributing somatic mutations involved in disease development have only been observed at low frequency. EXPERIMENTAL DESIGN: Tumor samples of 116 Ewing sarcoma patients were analyzed here. Whole-genome sequencing was performed on two patients with normal, primary, and relapsed tissue. Whole-exome sequencing was performed on 50 Ewing sarcoma and 22 matched normal tissues. A discovery dataset of 14 of these tumor/normal pairs identified 232 somatic mutations. Recurrent nonsynonymous mutations were validated in the 36 remaining exomes. Transcriptome analysis was performed in a subset of 14 of 50 Ewing sarcomas and DNA copy number gain and expression of FGFR1 in 63 of 116 Ewing sarcomas. RESULTS: Relapsed tumors consistently showed a 2- to 3-fold increased number of mutations. We identified several recurrently mutated genes at low frequency (ANKRD30A, CCDC19, KIAA0319, KIAA1522, LAMB4, SLFN11, STAG2, TP53, UNC80, ZNF98). An oncogenic fibroblast growth factor receptor 1 (FGFR1) mutation (N546K) was detected, and the FGFR1 locus frequently showed copy number gain (31.7%) in primary tumors. Furthermore, high-level FGFR1 expression was noted as a characteristic feature of Ewing sarcoma. RNA interference of FGFR1 expression in Ewing sarcoma lines blocked proliferation and completely suppressed xenograft tumor growth. FGFR1 tyrosine kinase inhibitor (TKI) therapy in a patient with Ewing sarcoma relapse significantly reduced 18-FDG-PET activity. CONCLUSIONS: FGFR1 may constitute a promising target for novel therapeutic approaches in Ewing sarcoma