Predominance of a rare type of HIV-1 in Estonia

An earlier study has indicated that a complex recombinant HIV-1 strain dominates the epidemic in Estonia. The objective of this study was to further investigate the molecular epidemiology and genetic structure of HIV-1 in Estonia. Most of the investigated individuals became infected after August 2000 when HIV-1 started to spread rapidly among Estonian intravenous drug users (IDUs). Two viral DNA regions, gag/pol and gp41, were sequenced and subtyped from peripheral blood mononuclear cells or plasma from 141 individuals. Phylogenetic analysis in the gp41 region revealed that the most frequent type of the virus among IDUs was a circulating recombinant form, CRF06_cpx, whereas a few samples showed highest sequence similarity to a subtype A strain circulating in Ukraine and Russia. Likewise, in the gag/pol region, most of the samples were classified as CRF06_cpx, with a few classified as subtype A. In this region, however, 16% of the sequences turned out to be mosaic unique recombinant forms consisting of CRF06_cpx and subtype A. At least 9 mosaic forms were identified, each with distinct patterns of multiple crossover. To characterize Estonian CRF06_cpx as well as recombinant isolates in more detail, 4 near-full-length HIV-1 genomes were sequenced.     

'Danger' effect of low-density lipoprotein (LDL) and oxidized LDL on human immature dendritic cells

Dendritic cell (DC) maturation may accelerate autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, and may contribute to accelerated atherosclerosis seen in these patients. The immune system responds to both exogenous and endogenous 'dangerous' signals that can induce dendritic cell maturation. We have found that autologous plasma contains danger signals that induce up-regulation of major histocompatibility complex (MHC) class II and co-stimulatory molecules in immature DCs (iDCs). The objective of this study was to determine whether low-density lipoprotein (LDL) and/or oxidized LDL (oxLDL) constitute danger signals, and to assess the effect of exposure to LDL and oxLDL following monocyte differentiation into iDCs in lipoprotein-deficient serum (LPDS). IDCs were generated in the presence of autologous plasma or LPDS. Expression of maturation and migration molecules was evaluated using flow cytometry, and morphology was assessed by light microscopy. Pro- or anti-apoptotic effect was determined using annexin V and propidium iodide binding. Phagocytosis of apoptotic cells was evaluated using autologous plasma or LPDS. LDL and oxLDL were clearly able to slightly up-regulate levels of HLA-DR and co-stimulatory molecule CD86. High oxLDL concentrations (50-100 microg/ml) were associated with expression of additional maturation molecules. Moreover, iDCs that were prepared in LPDS showed partial maturation following exposure to LDL and oxLDL, and improved tolerogenic apoptotic cell uptake. This study suggests that oxLDL, and to some extent LDL, are at least partly responsible for the iDC 'danger' response induced by autologous plasma.     

Altered postural control during the luteal phase in women with premenstrual symptoms

The purpose of this study was to investigate postural control in women with and without premenstrual symptoms (PMS) in three hormonally verified phases of the menstrual cycle. Thirty-two women were recruited to participate in the study and 25 of these women were included in the results. Menstrual cycle phases were determined by sex hormone analyses in serum and LH detection in urine. A prospective rating of PMS was used to divide the subjects into two groups: one with PMS (cyclic) and one without (non-cyclic). For measurement of postural control, subjects stood on a force platform (AMTI) in two-legged stance (eyes open and closed) and one-legged stance (eyes open and closed). There were no significant differences in the two-legged stance between the phases of the menstrual cycle or between groups. In one-legged stance with eyes open, there was a significant increase in postural displacement in the mid-luteal phase in the cyclic group, but no differences were detected between phases in the non-cyclic group. These findings may be related to the previously reported increased injury rate and psychomotor slowing in the luteal phase in women with PMS.     

Genetic characterization of hepatitis C virus strains in Estonia: fluctuations in the predominating subtype with time

During the last decade, there has been a dramatic increase in intravenous drug use in young adults in Estonia with an increased incidence of both hepatitis B and C as a consequence. Since genetic data are limited regarding hepatitis C virus (HCV) strains in Estonia, the aim of the study was to characterize HCV strains in different risk groups to determine their relatedness to strains from other geographical regions. Three hundred fifty-three anti-HCV positive sera collected during 1994-2004 from hospitalized patients, blood donors and health care workers were used as source of HCV RNA. Two hundred nine (59%) of the sera were positive for HCV RNA by PCR directed to the 5'-UTR region. For 174 strains the HCV subtype was determined by analyses of the NS5B and/or the 5'UTR-core regions. 1b (71%) was the most common subtype followed by 3a (24%), 2c (2%), 1a (1%), and 2a (1%). The 1b and 3a strains were similar to strains from other regions of the former USSR. Within genotype 1b there were several HCV lineages. However, for 3a there seemed to be two separate introductions into Estonia. There was a relative shift from subtype 1b to 3a in 1999-2000 with a further replacement of 3a with 1b in intravenous drug users in 2001 and onwards (P < 0.05). However, both subtypes were found to co-circulate in the community independent of risk factors. One patient was infected with the 2k/1b recombinant presumed to originate from St. Petersburg being the first isolate of this recombinant recovered outside Russia.     

Apoptotic cell thrombospondin-1 and heparin-binding domain lead to dendritic-cell phagocytic and tolerizing states

Apoptotic cells were shown to induce dendritic cell immune tolerance. We applied a proteomic approach to identify molecules that are secreted from apoptotic monocytes, and thus may mediate engulfment and immune suppression. Supernatants of monocytes undergoing apoptosis were collected and compared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and differentially expressed proteins were identified using tandem mass spectrometry. Thrombospondin-1 (TSP-1) and its cleaved 26-kDa heparin-binding domain (HBD) were identified. We show that TSP-1 is expressed upon induction of monocyte apoptosis in a caspase-dependent pattern and the HBD is cleaved by chymotrypsin-like serine protease. We further show that CD29, CD36, CD47, CD51, and CD91 simultaneously participate in engulfment induction and generation of an immature dendritic cell (iDC) tolerogenic and phagocytic state. We conclude that apoptotic cell TSP-1, and notably its HBD, creates a signalosome in iDCs to improve engulfment and to tolerate engulfed material prior to the interaction with apoptotic cells.     

Effect of mouse interferons on development of Ehrlich's ascites carcinoma

Intraperitoneal injection of various interferons (native cultural, concentrated and partially purified cultural, and also serum) significantly inhibits the development of Ehrlich's ascites carcinoma in noninbred mice. Because of the comparatively low activity of serum interferon, the effect of normal mouse serum on the development of this tumor and its action on the effect of native cultural interferon were investigated. Normal mouse serum was shown to depress the action of cultural interferon and to accelerate the development of Ehrlich's ascites carcinoma.N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 330–332, March, 1980.     

Cup detachment during vacuum-assisted vaginal delivery and birth outcome

Objective

To determine the perinatal outcome associated with cup detachment during vacuum-assisted vaginal delivery (VAVD).

Methods

A retrospective cohort study of all women attempting VAVD in a tertiary hospital (2012–2014). Singleton-term pregnancies were included. Antepartum fetal death and major fetal structural or chromosomal abnormalities were excluded. Primary outcome was neonatal birth trauma (subgaleal hematoma, subarachnoid hematoma, subdural hematoma, skull fracture, and/or erb’s palsy). Secondary outcomes were maternal complications or other neonatal morbidities. Outcomes were compared between women after ≥1 cup detachment (study group) and the rest (control group). Logistic regression analysis was utilized to adjust results to potential confounders.

Results

Overall, 1779 women attempted VAVD during study period. Of them, in 146 (8.2%), the cup detached prior to delivery; 130/146 (89%) had a single detachment. After detachment, 4 (2.7%) delivered by cesarean section, 77 (52.7%) delivered after cup reapplication, and 65 (44.6%) delivered spontaneously. Women in the study group were more likely to undergo VAVD due to prolonged second stage, and were characterized by lower rates of metal cup use. Neonates in the detachment group had higher rates of subarachnoid hematoma and composite neonatal birth trauma (2.7 vs. 0.1% and 4.8 vs. 1.8%, respectively, p < 0.05). This remained significant after adjustment to potential confounders (subarachnoid hematoma aOR = 45.44, 95% CI 6.42–321.62 and neonatal birth trauma aOR = 2.62, 95% CI 1.1–6.22, p < 0.05 for all). Other neonatal and maternal morbidities were similar between groups.

Conclusion

Cup detachment is associated with a higher rate of adverse neonatal outcome. Cup reapplication should be considered carefully.

     

The impact of obstetric gel on the second stage of labor and perineal integrity: a randomized controlled trial

Objective: Dianatal® is a bioadhesive gliding film which reduces the opposing force to vaginal childbirth. We aimed to investigate the safety, applicability, and impact of Dianatal® obstetric gel on second stage of labor and perineal integrity.

Methods: Low-risk singleton pregnancies at term were prospectively enrolled. Eligible women were randomly assigned to either labor management without using obstetric gel, or labor management using intermittent application of obstetric gel into the birth canal during vaginal examinations, starting at active phase of labor (≥4?cm dilation). The primary measured outcome was the length of second stage of labor.

Results: Overall, 200 cases were analyzed. Demographic, obstetrical, and labor characteristics were similar between the groups. Neither adverse events nor maternal or neonatal side effects were observed. The mean lengths of the active and second stages of labor were comparable between the obstetric gel-treated and the control groups (157 versus 219 min and 48 versus 56 min, respectively). None of the women had grade III/IV perineal tears. Maternal and neonatal outcomes were not negatively influenced by using obstetric gel. No difference was found after sub-group analysis for spontaneous vaginal delivery.

Conclusion: Dianatal® obstetric gel is safe in terms of maternal or neonatal use. Albeit a trend toward shorter labor stages using Dianatal® obstetric gel, no significant differences were noted among the groups. In order to further investigate the influence of the obstetric gel on labor stage interval, perineal integrity and maternal and neonatal outcomes, larger randomized clinical trials are needed to be carried out.