Lactobacillus rhamnosus DSM 14870 and Lactobacillus gasseri DSM 14869 were previously isolated from the vaginal epithelial cells (VEC) of healthy women and selected for the development of the vaginal EcoVag probiotic capsules. EcoVag was subsequently shown to provide long-term cure and reduce relapse of bacterial vaginosis (BV) as an adjunct to antibiotic therapy. To identify genes potentially involved in probiotic activity, we performed genome sequencing and characterization of the two strains. The complete genome analysis of both strains revealed the presence of genes encoding functions related to adhesion, exopolysaccharide (EPS) biosynthesis, antimicrobial activity, and CRISPR adaptive immunity but absence of antibiotic resistance genes. Interesting features of L. rhamnosus DSM 14870 genome include the presence of the spaCBA-srtC gene encoding spaCBA pili and interruption of the gene cluster encoding long galactose-rich EPS by integrases. Unique to L. gasseri DSM 14869 genome was the presence of a gene encoding a putative (1456 amino acid) new adhesin containing two rib/alpha-like repeats. L. rhamnosus DSM 14870 and L. gasseri DSM 14869 showed acidification of the culture medium (to pH 3.8) and a strong adhesion capability to the Caco-2 cell line and VEC. L. gasseri DSM 14869 could produce a thick (40nm) EPS layer and hydrogen peroxide. L. rhamnosus DSM 14870 was shown to produce SpaCBA pili and a 20nm EPS layer, and could inhibit the growth of Gardnerella vaginalis, a bacterium commonly associated with BV. The genome sequences provide a basis for further elucidation of the molecular basis for their probiotic functions.
Background
To reduce acquisition and relapse of bacterial vaginosis (BV), lactobacilli must be maintained in the vaginal microbiome. Probiotic lactobacilli may aid this purpose. We investigated whether vaginal probiotics (containing Lactobacillus rhamnosus DSM 14870 and Lactobacillus gasseri DSM 14869) would result in vaginal colonisation with lactobacilli in women with and without BV.
Methods
This prospective, partially randomised, exploratory pilot study was conducted in Soweto, South Africa. Thirty-nine sexually-active, HIV negative women were enrolled from October 2014 to May 2016 into three arms. Women who did not have BV (Group 1, n = 13) self-administered probiotic capsules vaginally once daily for 30 days, then once a week until Day 190. Women diagnosed with BV were randomized into Group 2 (n = 12) or Group 3 (n = 14) and treated with the triple oral antibiotic combination for vaginal discharge syndrome per South African guidelines (cefixime 400 mg stat, doxycycline 100 mg BD for 7 days and metronidazole 2 g stat). Immediately after antibiotic treatment, women in Group 2 self-administered probiotic capsules vaginally once daily for 30 days then vaginally once a week until Day 190. Women in Group 3 were not given lactobacilli.
Results
During the study, L. rhamnosus DSM 14870 or L. gasseri DSM 14869, were isolated in 5/13 (38.5%) women in Group 1 compared to 10/12 (83.3%) women in Group 2 (p = 0.041). The 1-month and 6-month BV cure rates were similar (P > 0.05) between Group 2 (42 and 25%) compared to Group 3 (36 and 25%). In Group 2, no correlation was observed between the frequency of isolation of the two Lactobacillus strains and the 1-month or 6-month cure rate.
Conclusions
Supplementation with vaginal probiotic capsules resulted in colonisation of the vagina by the Lactobacillus strains (L. rhamnosus DSM 14870 and L. gasseri DSM 14869) contained in the capsules. We observed low initial cure rates of BV after a stat dose of metronidazole and that the probiotic did not improve BV cure rates or alleviate recurrence which could be due to treatment failure or very limited power of the study.
Trial registration
Registered at the Pan African Clinical Trial Registry (www.pactr.org) on April 13, 2018 (retrospectively registered). Trial identification number: PACTR201804003327269.
BackgroundGrief is a normal phenomenon but showing great variation depending on cultural and personal features. Bonanno and Kaltman have nonetheless proposed five aspects of normal grief. The aim of this study was to investigate if women with miscarriage experience normal grief.Material and methodsContent analyses of 25 transcribed conversations with women 4 weeks after their early miscarriages were classified depending on the meaning-bearing units according to Bonanno and Kaltman's categories. In the factor analyses, these categories were compared with the Perinatal Grief Scale and women's age, number of children and number of miscarriages, and gestational weeks.ResultsWomen with miscarriage fulfill the criteria for having normal grief according to Bonanno and Kaltman. All of the 25 women had meaning-bearing units that were classified as cognitive disorganization, dysphoria, and health deficits, whereas disrupted social and occupational functioning and positive aspects of bereavement were represented in 22 of 25 women. From the factor analysis, there are no differences in the expression of the intensity of the grief, irrespective of whether or not the women were primiparous, younger, or had suffered a first miscarriage.ConclusionWomen's experience of grief after miscarriage is similar to general grief after death. After her loss, the woman must have the possibility of expressing and working through her grief before she can finish her pregnancy emotionally. The care-giver must facilitate this process and accept that the intensity of the grief is not dependent on the woman's age, or her number of earlier miscarriages.
Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Infection/inflammation is responsible for a significant percentage of preterm birth, particularly at early gestations. A recent clinical recommendation by a guidelines group of the Danish Society of Obstetrics and Gynecology advised against the use of clindamycin for the treatment of bacterial vaginosis in pregnancy to reduce the risk of spontaneous preterm birth based on lack of evidence of efficacy. We believe that the evidence for the use of clindamycin for this indication is robust and that this recommendation was reached erroneously on the basis of flawed inclusion criteria: the inclusion of an unpublished study with poorly diagnosed bacterial vaginosis and the exclusion of an important pivotal study on the use of clindamycin in early pregnancy for the prevention of preterm birth. Had these errors been corrected, the conclusions would have been different.
The risk of long-term damage to the CNS after exposure to mixed solvents in work environments is controversial. Thirty-six workers were studied who had been exposed to organic solvents for more than 10 years (mean 24 5 years) in a working environment. The workers and unexposed controls were studied with a battery of neuropsychological and cognitive tests. Significant group differences were observed for the Wechsler adult intelligence scale (WAIS) digit span and symbol digit substitution, and on paired associate learning and continuous word recognition. The results suggest that long-term work-related exposure to organic solvents may have chronic toxic effects.
If patients are successfully treated, half of the patients will stay cured indicating that treatment is of benefit. Most relapses occur during the first year. Our results indicate that the etiology of BV might have something to do with new sexual contacts.
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