Blood-based cerebral biomarkers in preeclampsia: Plasma concentrations of NfL, tau, S100B and NSE during pregnancy in women who later develop preeclampsia - A nested case control study

OBJECTIVE: To evaluate if concentrations of the neuronal proteins neurofilament light chain and tau are changed in women developing preeclampsia and to evaluate the ability of a combination of neurofilament light chain, tau, S100B and neuron specific enolase in identifying neurologic impairment before diagnosis of preeclampsia. METHODS: A nested case-control study within a longitudinal study cohort was performed. 469 healthy pregnant women were enrolled between 2004–2007 and plasma samples were collected at gestational weeks 10, 25, 28, 33 and 37. Plasma concentrations of tau and neurofilament light chain were analyzed in 16 women who eventually developed preeclampsia and 36 controls throughout pregnancy with single molecule array (Simoa) method and compared within and between groups. S100B and NSE had been analyzed previously in the same study population. A statistical model with receiving characteristic operation curve was constructed with the four biomarkers combined. RESULTS: Plasma concentrations of neurofilament light chain were significantly increased in women who developed preeclampsia in gestational week 33 (11.85 ng/L, IQR 7.48–39.93 vs 6.80 ng/L, IQR 5.65–11.40) and 37 (22.15 ng/L, IQR 10.93–35.30 vs 8.40 ng/L, IQR 6.40–14.30) and for tau in gestational week 37 (4.33 ng/L, IQR 3.97–12.83 vs 3.77 ng/L, IQR 1.91–5.25) in contrast to healthy controls. A combined model for preeclampsia with tau, neurofilament light chain, S100B and neuron specific enolase in gestational week 25 displayed an area under the curve of 0.77, in week 28 it was 0.75, in week 33 it was 0.89 and in week 37 it was 0.83. Median week for diagnosis of preeclampsia was at 38 weeks of gestation. CONCLUSION: Concentrations of both tau and neurofilament light chain are increased in the end of pregnancy in women developing preeclampsia in contrast to healthy pregnancies. Cerebral biomarkers might reflect cerebral involvement before onset of disease

NMRDyn: A Program for NMR Relaxation Studies of Protein Association

Self-association is an important biological phenomenon that is associated with many cellular processes. NMR relaxation measurements provide data about protein molecular dynamics at the atomic level and are sensitive to changes induced by self-association. Thus, measurements and analysis of NMR relaxation data can provide structurally resolved information on self-association that would not be accessible otherwise. Here, we present a computer program, NMRdyn, which analyses relaxation data to provide parameters defining protein self-association. Unlike existing relaxation analysis software, NMRdyn can explicitly model the monomer-oligomer equilibrium while fitting measured relaxation data. Additionally, the program is packaged with a user-friendly interface, which is important because relaxation data can often be large and complex. NMRdyn is available from http://research1t.imb.uq.edu.au/nmr/NMRdyn

Sexual orientation of women does not affect outcome of fertility treatment with donated sperm

Is there a difference in fertility between heterosexual women and lesbians undergoing sperm donation? Women undergoing treatment with donated sperm are equally fertile regardless of sexual orientation. Lesbians have an increased prevalence of smoking, obesity, sexually transmitted diseases and, possibly, polycystic ovary syndrome, all factors known to affect fertility. Previous studies on sperm donation inseminations (D-IUI) show conflicting results regarding pregnancy outcome. This is a national study of 171 lesbians and 124 heterosexual women undergoing sperm donation both as D-IUI (lesbian n 438, heterosexual n 298) and as embryo transfers (ET) after IVF with donated sperm (lesbians n 225, heterosexuals n 230) during 20052010. All clinics in Sweden offering sperm donation recruited patients. Differences in patients medical history, treatment results and number of treatments to live birth were analyzed using independent samples t-test, Pearsons (2) test or Fishers exact probability test. 71.8 of heterosexuals and 69.0 of lesbians had a child after treatment. The mean number of treatments was 4.2 for heterosexual women and 3.9 for lesbians. The total live birth rate, regardless of treatment type, was 19.7 for heterosexuals and 19.5 for lesbians. For D-IUI, the live birth rate was 12.8 for heterosexuals and 16.0 for lesbians and the live birth rate for all IVF embryo transfers (fresh and thawed cycles) was 28.7 for heterosexuals and 26.2 for lesbians. There were no differences in live birth rate between the groups for each of the different types of insemination stimulations (natural cycle; clomiphene citrate; FSH; clomiphene citrate and FSH combined). Nor was there a difference in live birth rate between the groups for either fresh or thawed embryo transfer. There was no difference between the proportions of women in either group or the number of treatments needed to achieve a live birth. Heterosexuals had a higher prevalence of smokers (9.2), uterine polyps (7.2) or previous children (11.3) than lesbians (smokers 2.8, P 0.03; polyps 1.8, P 0.03; child 2.5, P 0.003). This study is limited to women living in stable relationships undergoing treatment with donated sperm in a clinical setting and may not apply to single women or those undergoing home inseminations. These results may influence healthcare policy decisions as well as increase the quality of clinical care and medical knowledge of healthcare professionals. The data also have important implications for individuals regarding screening, infertility diagnostic procedures and treatment types offered to heterosexuals and lesbians seeking pregnancy through sperm donation. Funding was granted by the Stiftelsen Familjeplaneringsfonden i Uppsala; the Swedish Research Council for Health, Working Life and Welfare; and the Marianne and Marcus Wallenberg Foundation. The authors report no conflicts of interest

Sexual orientation of women does not affect outcome of fertility treatment with donated sperm Sexual orientation of women does not affect outcome of fertility treatment with donated sperm

PARTICIPANTS/MATERIALS, SETTING, METHODS: All clinics in Sweden offering sperm donation recruited patients. Differences in patients' medical history, treatment results and number of treatments to live birth were analyzed using independent-samples t-test, Nor was there a difference in live birth rate between the groups for either fresh or thawed embryo transfer. There was no difference between the proportions of women in either group or the number of treatments needed to achieve a live birth. Heterosexuals had a higher prevalence of smokers (9.2%), uterine polyps (7.2%) or previous children (11.3%) than lesbians (smokers 2.8%, p = 0.03; polyps 1.8%, p = 0.03; child 2.5%, p = 0.003). LIMITATIONS, REASONS FOR CAUTION: This study is limited to women living in stable relationships undergoing treatment with donated sperm in a clinical setting and may not apply to single women or those undergoing home inseminations. WIDER IMPLICATIONS OF THE FINDINGS: These results may influence healthcare policy decisions as well as increase the quality of clinical care and medical knowledge of healthcare professionals. The data also have important implications for individuals regarding screening, infertility diagnostic procedures and treatment types offered to heterosexuals and lesbians seeking pregnancy through sperm donation