Modeling risk for severe adverse outcomes using angiogenic factor measurements in women with suspected preterm preeclampsia

Introduction: Preeclampsia (PE) is a pregnancy-specific syndrome associated with adverse maternal and fetal outcomes. Patient-specific risks based on angiogenic factors might better categorize those who might have a severe adverse outcome. Methods: Women evaluated for suspected PE at a tertiary hospital (2009–2012) had pregnancy outcomes categorized as ‘referent’ or ‘severe’, based solely on maternal/fetal findings. Outcomes that may have been influenced by a PE diagnosis were considered ‘unclassified’. Soluble fms-like tyrosine kinase (sFlt1) and placental growth factor (PlGF) were subjected to bivariate discriminant modeling, allowing patient-specific risks to be assigned for severe outcomes. Results: Three hundred twenty-eight singleton pregnancies presented at ≤34.0 weeks' gestation. sFlt1 and PlGF levels were adjusted for gestational age. Risks above 5 : 1 (10-fold over background) occurred in 77% of severe (95% CI 66 to 87%) and 0.7% of referent (95% CI <0.1 to 3.8%) outcomes. Positive likelihood ratios for the modeling and validation datasets were 19 (95% CI 6.2–58) and 15 (95% CI 5.8–40) fold, respectively. Conclusions: This validated model assigns patient-specific risks of any severe outcome among women attending PE triage. In practice, women with high risks would receive close surveillance with the added potential for reducing unnecessary preterm deliveries among remaining women. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd

Resistive vibration exercise attenuates bone and muscle atrophy in 56-days of bed-rest: whole body DXA and biochemical markers of bone metabolism

Summary During and after prolonged bed rest, changes in bone metabolic markers occur within 3 days. Resistive vibration exercise during bed rest impedes bone loss and restricts increases in bone resorption markers whilst increasing bone formation. Introduction To investigate the effectiveness of a resistive vibration exercise (RVE) countermeasure during prolonged bed rest using serum markers of bone metabolism and whole-body dual X-ray absorptiometry (DXA) as endpoints. Methods Twenty healthy male subjects underwent 8 weeks of bed rest with 12 months follow-up. Ten subjects performed RVE. Blood drawings and DXA measures were conducted regularly during and after bed rest. Results Bone resorption increased in the CTRL group with a less severe increase in the RVE group (p = 0.0004). Bone formation markers increased in the RVE group but decreased marginally in the CTRL group (p < 0.0001). At the end of bed rest, the CTRL group showed significant loss in leg bone mass (−1.8(0.9)%, p = 0.042) whereas the RVE group did not (−0.7(0.8)%, p = 0.405) although the difference between the groups was not significant (p = 0.12). Conclusions The results suggest the countermeasure restricts increases in bone resorption, increased bone formation, and reduced bone loss during bed rest

Effects of 60-day bed rest with and without exercise on cellular and humoral immunological parameters

Exercise at regular intervals is assumed to have a positive effect on immune functions. Conversely, after spaceflight and under simulated weightlessness (e.g., bed rest), immune functions can be suppressed. We aimed to assess the effects of simulated weightlessness (Second Berlin BedRest Study; BBR2-2) on immunological parameters and to investigate the effect of exercise (resistive exercise with and without vibration) on these changes. Twenty-four physically and mentally healthy male volunteers (20-45&nbsp;years) performed resistive vibration exercise (n=7), resistance exercise without vibration (n=8) or no exercise (n=9) within 60 days of bed rest. Blood samples were taken 2 days before bed rest, on days 19 and 60 of bed rest. Composition of immune cells was analyzed by flow cytometry. Cytokines and neuroendocrine parameters were analyzed by Luminex technology and ELISA/RIA in plasma. General changes over time were identified by paired t-test, and exercise-dependent effects by pairwise repeated measurements (analysis of variance (ANOVA)). With all subjects pooled, the number of granulocytes, natural killer T cells, hematopoietic stem cells and CD45RA and CD25 co-expressing T cells increased and the number of monocytes decreased significantly during the study; the concentration of eotaxin decreased significantly. Different impacts of exercise were seen for lymphocytes, B cells, especially the IgD(+) subpopulation of B cells and the concentrations of IP-10, RANTES and DHEA-S. We conclude that prolonged bed rest significantly impacts immune cell populations and cytokine concentrations. Exercise was able to specifically influence different immunological parameters. In summary, our data fit the hypothesis of immunoprotection by exercise and may point toward even superior effects by resistive vibration exercise.Cellular &amp; Molecular Immunology advance online publication, 10 November 2014; doi:10.1038/cmi.2014.106

Increased placental sFlt-1 but unchanged PlGF expression in late-onset preeclampsia

<p><i>Objective</i>: To investigate whether differences between late-onset preeclampsia (PE) and intrauterine growth restriction (IUGR) can be explained by differential placental expression patters of sFlt-1, Flt-1, and placental growth factor (PlGF).</p> <p><i>Methods</i>: Placental tissues and maternal blood samples from seven patients with PE, five IUGR, and seven age-matched controls were studied for mRNA and protein levels as well as protein localization and expression intensity.</p> <p><i>Results</i>: Placental PlGF mRNA and protein expression were not altered by placental dysfunction while placental villous trophoblast expression intensity of PlGF was increased.</p> <p><i>Conclusion</i>: High sFlt-1 concentrations may account for diminished maternal serum PlGF levels.</p

Nicotine and Biochanin A, but Not Cigarette Smoke, Induce Anti-Inflammatory Effects on Keratinocytes and Endothelial Cells in Patients with Behçet's Disease

During periods of smoking, patients with Behçet's disease have less oral aphthae than in abstinence. To elucidate this observation, human keratinocytes and dermal microvascular endothelial cells (HMEC-1) were incubated with serum of 20 patients with Behçet's disease and 20 healthy controls for 4hours. Maximum non-toxic concentrations were determined and the cells were further treated with 6μm nicotine, 3.3% cigarette smoke extract (CES), 100μm biochanin A, and 6.25/12.5μm pyrrolidine dithiocarbamate alone and in combinations for 24hours. Serum IL-8 levels of patients were significantly lower than those of controls. However, after 4hours incubation with patients' sera, IL-8 release by both cell types was markedly increased when compared with the corresponding serum levels. The levels of IL-6 and vascular endothelial growth factor (VEGF) release were after 4hours similar with the corresponding levels in serum. IL-1 was not detected. Nicotine significantly decreased IL-8 and -6 release by HMEC-1 maintained in both patients' and controls' sera, but only IL-6 release by keratinocytes maintained in patients' sera. VEGF release by both cells was markedly increased after nicotine treatment in either serum. CES significantly decreased IL-8 release and increased production of VEGF in keratinocytes maintained in patients' serum. The phytoestrogen biochanin A alone and in combination with nicotine further decreased the secretion of IL-8, -6, and VEGF in all experimental settings. Our data support a specific anti-inflammatory effect of nicotine on keratinocytes and endothelial cells maintained in the serum of patients with Behçet's disease. Moreover, biochanin A is likely to exhibit similar and even more profound results than nicotine

Low vagal tone is associated with impaired post stress recovery of cardiovascular, endocrine, and immune markers

Reduced heart rate variability (HRV) and delayed blood pressure recovery are associated with increased cardiovascular risk. Besides this evident link, the vagus is thought to play an inhibitory role in the regulation of other allostatic systems, including inflammation and the hypothalamic-pituitary-adrenal (HPA) axis. However, human evidence is scarce. To further explore these associations and with special regard to the postulated mediating role of the vagus, we hypothesised that subjects with low vagal tone as indexed by reduced resting HRV would show impaired post-stress recovery of cardiovascular, endocrine and immune system markers involved in cardiovascular pathology. 44 healthy men underwent a standardised mental stress test. Besides continuous measurement of systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and HRV serum cortisol, tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured before, after, 20, and 60 min after stress. Low versus high HRV groups was defined by median split on resting HRV (RMSSD). The task elicited significant time effects for SBP, DBP, HR, HRV, cortisol, and TNF-alpha. Subjects with low baseline HRV showed almost no modulation of HRV coupled with overall reduced HRV levels, and impaired recovery of DBP, cortisol, and TNF-alpha. Confirming our hypothesis, low vagal tone was associated with impaired recovery of cardiovascular, endocrine, and immune markers in healthy males. The data support an inhibitory role of the vagus in the regulation of allostatic systems as described in the neurovisceral integration model. We posit reduced resting HRV as a risk marker for future cardiovascular and other stress-related disease