Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Pregnant women have a high demand for fetal monitoring and reassurance. Consequently, they use a variety of health applications in pregnancy and tend to visit emergency departments for objectively non-urgent consults. However, the potential of electronic Health (eHealth) and mobile Health (mHealth) solutions is clinically hardly used to prevent non-urgent emergency consultations. To implement modern care solutions a better understanding of the attitudes, fears and hopes of health care professionals towards eHealth and mHealth is needed. Objective: The aim of this study was to investigate the attitudes of health care professionals in obstetrics towards telemedicine. Methods: A quantitative web based survey among health care professionals in Germany was conducted. The participants included nurses, midwives and physicians of all age groups and job positions working in hospitals with various level of care. The questionnaire comprised 24 questions capturing study population characteristics, views about emergency consultations in obstetrics, attitude towards telemedicine, job satisfaction and sleeping behavior. Results: 244 health care professionals participated in the online survey. In general, health care professionals are skeptical (72.9%; n=170) about the use of telemedicine in obstetrics, however, 55.8% (n=130) recognize its potential. Physicians are optimistic with 72% (n=62) considering the use of applications (apps) for pregnancy monitoring reasonable by contrast to just 36% (n=47) of non-physicians (P<.001). Significantly more non-physicians reject such developments categorically, 58% (n=75) compared to 27% (n=24) of physicians (P<.001). We also found, that obstetricians with more than ten years of work-experiences are more skeptical. 49% (n=18) of them believe that telemedicine could reduce non-urgent emergency consultations compared to 73.2% (n=106) among obstetricians with less than 5 years of experience (P=.006). Our survey revealed a high job satisfaction among health care professionals in obstetrics and a prevalence of regular sleeping problems of 46% (n=91). Surprisingly, both job satisfaction and sleeping problems were independent from the number of night shifts served per month (P=.77 and P=.99 respectively). Yet, 56.6% (n=112) of the survey participants thought they would be happier in their job if they had to work fewer night shifts per month. Conclusions: Our study reveals an ambivalent attitude towards telemedicine among health care professionals in obstetrics. Efforts to promote the use of telemedicine should concentrate on nurses and midwives since this group is most skeptical about it in Germany. By contrast, particularly young physicians recognize the potential of apps for patient care and would like to use such technology in pregnancy monitoring.

Heparins have been shown to be beneficial for the prevention of habitual miscarriages and repeated implantation failure, independently of their function as anticoagulants. The pro-inflammatory cytokine tumor necrosis factor (TNF)-α plays a role in the pathogenesis of these early pregnancy complications. Therefore, we examined the impact of heparin on TNF-α signaling in human endometrial stromal cells (ESCs) in vitro. Human ESCs were isolated from hysterectomy specimens and either used as undifferentiated cells or after decidualization in vitro. Cells were incubated with TNF-α, unfractionated heparin and signaling- and transporter-inhibitors. Interleukin (IL)-8 and -6 were measured using ELISAs and real-time RT–PCR. Nuclear factor of transcription (NF)-κB and its inhibitor IκBα were analyzed by in-cell western assays and confocal microscopy. Activation of NF-κB was determined in nuclear extracts using a specific transcription factor assay. Cellular internalization of heparin was detected by a heparin-uptake assay. Unfractionated heparin significantly suppressed the TNF-α-induced and NF-κB-mediated secretion and expression of IL-8 and -6 as well as other molecules in decidualized and undifferentiated human ESCs. Thereby heparin had no influence on the degradation of IκBα and the phosphorylation of NF-κB, but it inhibited the activity of NF-κB in the nucleus. An active heparin-uptake into the cells was the prerequisite for these heparin-effects. Unfractionated heparin is able to inhibit TNF-α/NF-κB-mediated inflammatory effects in the human endometrium independently of its classical function as an anticoagulant. These observations further underline on a molecular level the beneficial anti-inflammatory effects of heparin in women suffering from implantation disorders even in the absence of a thrombophilia.

Heparin modulates the decidualization of human endometrial stromal cells (ESCs), but the molecular mechanisms behind these effects are still unknown. In the present study, we further specified this biological effect of heparin in human ESCs in vitro. ESCs were isolated from hysterectomy specimens, decidualized over 12 days using progesterone and 17β-estradiol and incubated with thrombin, factor Xa (FXa), unfractionated heparin, dextran sulfate, danaparoid or different low-molecular-weight heparins (LMWHs). Production of insulin-like growth factor (IGF)-I, prolactin (PRL) and IGF-binding protein (IGFBP)-1 by ESCs was measured using ELISAs. Like heparin, thrombin and FXa cause an increase in IGF-I in ESCs, suggesting an action of heparin independent from its anticoagulatory effects. This was supported by demonstrating the induction of the same effects on IGF-I, PRL and IGFBP-1 as heparin by dextran sulfate, a polysaccharide of similar size and charge as heparin, but without anticoagulatory properties. LMWHs with the same anti-FXa activity as heparin showed less pronounced effects on ESCs than heparin, whereas the very short pentasaccharide fondaparinux (17 kDa) had barely any effect, further supporting the primary role of molecular size and charge mediating these biological effects of heparin on ESCs. In conclusion, the effects of heparin on the decidualization of human ESCs seem to be independent of its anticoagulatory function, but rather depend on the charge and the size of this polysulfated glycosaminoglycan. Therefore, highly sulfated polysaccharides with a molecular weight >17 kDa might be an interesting pharmacological approach for the therapy of endometrial pathologies, e.g. the treatment of women suffering from recurrent miscarriage or repeated implantation failure.