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Background Multiple sclerosis (MS) is a neuroinflammatory disease in which pregnancy leads to a temporary amelioration in disease activity as indicated by the profound decrease in relapses rate during the 3rd trimester of pregnancy. CD4+ and CD8+ T cells are implicated in MS pathogenesis as being key regulators of inflammation and brain lesion formation. Although Tcells are prime candidates for the pregnancy-associated improvement of MS, the precise mechanisms are yet unclear, and in particular, a deep characterization of the epigenetic and transcriptomic events that occur in peripheral T cells during pregnancy in MS is lacking. Methods Women with MS and healthy controls were longitudinally sampled before, during (1st, 2nd and 3rd trimesters) and after pregnancy. DNA methylation array and RNA sequencing were performed on paired CD4+ and CD8+ T cells samples. Differential analysis and network-based approaches were used to analyze the global dynamics of epigenetic and transcriptomic changes. Results Both DNA methylation and RNA sequencing revealed a prominent regulation, mostly peaking in the 3rd trimester and reversing post-partum, thus mirroring the clinical course with improvement followed by a worsening in disease activity. This rebound pattern was found to represent a general adaptation of the maternal immune system, with only minor differences between MS and controls. By using a network-based approach, we highlighted several genes at the core of this pregnancy-induced regulation, which were found to be enriched for genes and pathways previously reported to be involved in MS. Moreover, these pathways were enriched for in vitro stimulated genes and pregnancy hormones targets. Conclusion This study represents, to our knowledge, the first in-depth investigation of the methylation and expression changes in peripheral CD4+ and CD8+ T cells during pregnancy in MS. Our findings indicate that pregnancy induces profound changes in peripheral T cells, in both MS and healthy controls, which are associated with the modulation of inflammation and MS activity.

Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory and neurodegenerative disorder of the central nervous system. Pregnancy represents a natural modulation of the disease course, where the relapse rate decreases, especially in the 3

A negative childbirth experience may have long term negative effects on maternal health. New international guidelines allow a slower progress of labor in the early active phase. However, a longer time in labor may influence the childbirth experience. In this population-based cohort study including 26,429 women, who gave birth from January 2016 to March 2020, the association between duration of different phases of active labor and childbirth experience was studied. The women assessed their childbirth experience by visual analogue scale (VAS) score. Data was obtained from electronic medical records. The prevalence of negative childbirth experience (VAS 1-3) was 4.9%. A significant association between longer duration of all labor phases and a negative childbirth experience was found for primi- and multipara. The adjusted odds ratio (aOR (95%CI)) of negative childbirth experience and longer time in active labor (above the 90th percentile) in primipara was 2.39 (1.98-2.90) and in multipara 2.23 (1.78-2.79). In primi-and multipara with duration of labor >= 12 h or >= 6 h the aOR (95%CI) of negative childbirth experience were 2.22 (1.91-2.58) and 1.91 (1.59-2.26) respectively. It is of great importance to identify and optimize the clinical care of women with longer time in labor to reduce the risk of negative childbirth experience and associated adverse long-term effects. Funding Agencies|Linkoping University; County Council of Ostergotland; Linkoping University, Sweden (ALF grants, Region Ostergotland); Medical Research Council of Southeast Sweden (FORSS) [FORSS-909171]

Background: Preterm birth (PTB), defined as birth before 37 weeks of gestation, accounts for most neonatal death and morbidity. Accurate prediction is a pre-requisite for the prevention and proper ...

Genital mucosal transmission is the most common route of HIV spread. The initial responses triggered at the site of viral entry are reportedly affected by host factors, especially complement components present at the site, and this will have profound consequences on the outcome and pathogenesis of HIV infection. We studied the initial events associated with host-pathogen interactions by exposing cervical biopsies to free or complement-opsonized HIV. Opsonization resulted in higher rates of HIV acquisition/infection in mucosal tissues and emigrating dendritic cells. Transcriptomic and proteomic data showed a significantly more pathways and higher expression of genes and proteins associated with viral replication and pathways involved in different aspects of viral infection including interferon signaling, cytokine profile and dendritic cell maturation for the opsonized HIV. Moreover, the proteomics data indicate a general suppression by the HIV exposure. This clearly suggests that HIV opsonization alters the initial signaling pathways in the cervical mucosa in a manner that promotes viral establishment and infection. Our findings provide a foundation for further studies of the role these early HIV induced events play in HIV pathogenesis.

Introduction Preterm labor is a common clinical problem in obstetrics. Since the majority of women with preterm labor eventually deliver at full term, biomarkers are needed to more accurately predict who will deliver preterm. Oxylipins, given their importance in inflammation regulation, are highly interesting in this respect since labor is an inflammatory process. Methods Eighty women with preterm labor before 34 weeks of gestation were enrolled in a prospective observational multi-center cohort study. Oxylipin levels of 67 analytes in plasma samples were analyzed by liquid chromatography coupled to tandem mass spectrometry. Results Twenty-one (26%) of the women delivered before 34 weeks of gestation, and of those women, fourteen delivered within 48 h of admission. Logistic multivariate regression showed that lower levels of 9,10-DiHODE were associated with delivery before 34 weeks of gestation (aOR 0.12 (0.024–0.62)) and within 48 h ((aOR 0.13 (0.019–0.93)). Furthermore, higher levels of 11,12-DiHETrE were associated with delivery before 34 weeks of gestation ((aOR 6.19 (1.17–32.7)) and higher levels of 8-HETE were associated with delivery within 48 h ((aOR 5.01 (1.13–22.14)). Conclusions The oxylipin 9,10-DiHODE may be protective in preterm labor, both for delivery after 34 weeks of gestation and for delivery later than 48 h of admission, whereas 11,12-DiHETrE and 8-HETE display the opposite effect. Larger studies are needed to validate these mediators as biomarkers for prediction of preterm birth following preterm labor. Medical Research Council of Southeast Sweden (FORSS) [FORSS-931816]; Region Kalmar County; ALF grants; Region Ostergotland

Objective.To determine predictive risk factors for Apgar scores < 7 at 5 minutes at two hospitals providing tertiary care and secondary care, respectively.Methods.A retrospective registry cohort study of 21126 births (2006–2010) using data from digital medical records. Risk factors were analyzed by logistic regression analyses.Results. AS5min⁡<7was multivariately associated with the following: preterm birth; gestational week 32 + 0–36 + 6,OR=3.9(95% CI 2.9–5.3); week 28 + 0–31 + 6,OR=8(5–12); week < 28 + 0,OR=15(8–29); postterm birth,OR=2.0(1.7–2.3); multiple pregnancy,OR=3.53(1.79–6.96); previous cesarean section,OR=3.67(2.31–5.81); BMI 25–29,OR=1.30(1.09–1.55);BMI≥30 OR=1.70(1.20–2.41); nonnormal CTG at admission,OR=1.98(1.48–2.66). ≥1-para was associated with a decreased risk forAS5min⁡<7,OR=0.34(0.25–0.47). In the univariate logistic regression analysisAS5min⁡<7was associated with tertiary level care,OR=1.48(1.17–1.87); however, in the multivariate analysis there was no significant difference.Conclusion.A number of partially preventable risk factors were identified, preterm birth being the most evident. Further, no significant difference between the two hospital levels regarding the risk for low Apgar scores was detected.

The immunological reactivity to major histocompatibility transplantation antigens (MHC) is important in clinical manifestations such as graft rejection and graft-vs.-host disease. To evaluate the allogeneic cytokine response pattern we used a newly developed cytokine mixed leukocyte culture (MLC) technique. Blood mononuclear cells from healthy women (n=6) were exposed to cells from another person and to pooled cells from 28 blood donors (MHC-pool). The secretion kinetics of IL-4 and IFN-gamma from the responder cells was analysed by ELISPOT. We found a higher IFN-gamma response to the MHC-pool compared with the IL-4 secretion. Both the total secretion of IFN-gamma for 7 days and the median value of IFN-gamma in each individual was increased compared with IL-4. The IFN-gamma response showed a bi-phasic pattern with the major peak on day 6-7. Our results indicate that allo-responses are mainly Th1-like responses, displaying a bi-phasic pattern. This knowledge may be useful, and the methods suitable, in the studies of allo-responses in transplantation and pregnancy.

To address the issue of whether Borrelia infection can be asymptomatic, blood donors with no history of borreliosis (n = 408) were screened for antibodies against Borrelia burgdorferi. Seropositive individuals (n = 17) were further investigated with respect to Borrelia-specific T-cell reactivity, using an interferon-gamma ELISPOT assay. Anti-Borrelia antibodies as well as Borrelia-specific T-cell responses were evident in 9 asymptomatic donors, strongly supporting a current or previous asymptomatic Borrelia infection.

SUMMARYBorrelia Lyme disease is a complex disorder that sometimes becomes chronic. There are contradictory reports of experimental Borrelia infections regarding which type of T cell cytokine responses, i.e. Th1 or Th2, are needed to eradicate the Borrelia spirochaetes. In human borreliosis a predominance of Borrelia-specific Th1-like responses has been shown. In this study, spontaneous, as well as Borrelia-specific, secretion of IFN-γ (Th1) and IL-4 (Th2) in Borrelia-seropositive healthy asymptomatic individuals (n = 17) was investigated in peripheral blood by a sensitive ELISPOT assay, and compared with previously reported responses in patients with clinical Borrelia infection (n = 25). The seropositive asymptomatic individuals displayed the same predominance of Borrelia-specific IFN-γ-secreting cells as the patients with clinical Borrelia infection. Interestingly, the proportion of spontaneously IL-4-secreting cells, reflecting the unstimulated in vivo secretion, was lower in the seropositive asymptomatic individuals compared with patients with chronic Borrelia infections (n = 13, P = 0.02), whereas no such difference was found compared with subacute Borrelia infections (n = 12). These findings indicate that IFN-γ secretion alone is not sufficient to eliminate Borrelia spirochaetes in humans, although IFN-γ may still have a beneficial role in borreliosis acting in concert with other mechanisms.