Temporal and spatial variation of the human microbiota during pregnancy

Despite the critical role of the human microbiota in health, our understanding of microbiota compositional dynamics during and after pregnancy is incomplete. We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. From 40 of these women, we analyzed bacterial taxonomic composition of 3,767 specimens collected prospectively and weekly during gestation and monthly after delivery from the vagina, distal gut, saliva, and tooth/gum. Linear mixed-effects modeling, medoid-based clustering, and Markov chain modeling were used to analyze community temporal trends, community structure, and vaginal community state transitions. Microbiota community taxonomic composition and diversity remained remarkably stable at all four body sites during pregnancy (P > 0.05 for trends over time). Prevalence of a Lactobacillus-poor vaginal community state type (CST 4) was inversely correlated with gestational age at delivery (P = 0.0039). Risk for preterm birth was more pronounced for subjects with CST 4 accompanied by elevated Gardnerella or Ureaplasma abundances. This finding was validated with a set of 246 vaginal specimens from nine women (four of whom delivered preterm). Most women experienced a postdelivery disturbance in the vaginal community characterized by a decrease in Lactobacillus species and an increase in diverse anaerobes such as Peptoniphilus, Prevotella, and Anaerococcus species. This disturbance was unrelated to gestational age at delivery and persisted for up to 1 y. These findings have important implications for predicting premature labor, a major global health problem, and for understanding the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals.The human body harbors diverse, complex, and abundant microbiota whose composition is determined largely by body site but also by host genetics, environmental exposures, and time (1, 2). The microbiota plays critical roles in health and in disease, including nutrient acquisition, immune programming, and protection from pathogens (3). Normal pregnancy represents a unique, transient, and dynamic state of altered anatomy, physiology, and immune function. Preterm birth, i.e., before 37 wk of gestation, occurs in 11% of pregnancies and is the leading cause of neonatal death (4). In both term and preterm pregnancies, the interplay between the microbiota and the host remains poorly understood.Approximately 25% of preterm births are associated with occult microbial invasion of the amniotic cavity (5). Evidence suggests that the most common source of invading microbes is the host microbiota. In studies of amniotic fluid from women with preterm labor and either intact or ruptured membranes, 16S ribosomal RNA (rRNA) sequences of known vaginal, gut, and oral indigenous bacterial species have been recovered in 15–50% of cases, and their relative abundances have correlated directly with markers of inflammation and inversely with time to delivery (6–9). Preterm birth also is associated with bacterial vaginosis, a community-wide alteration of the vaginal microbiota (10, 11) that increases the risk of preterm birth approximately twofold (12, 13).Several studies have examined the vaginal microbiota during pregnancy using cultivation-independent techniques (14–19). Collectively, these studies found the vaginal communities of pregnant women to be dominated by Lactobacillus species and characterized by lower richness and diversity than in nonpregnant women but with higher stability. Of the two studies that evaluated pregnancy outcomes, one found preterm birth to be linked with higher intracommunity (alpha) diversity in the vagina (16), but the other found no significant association between preterm birth and any specific community type or microbial taxon (17).Other (nonvaginal) body sites have been even less well studied in the setting of pregnancy. The subgingival crevice has been investigated only with cultivation (20, 21) or with taxon-specific molecular approaches (22). Two studies of the fecal microbiota reported differences in bacterial community structure between the first and third trimesters (23, 24); in each study, however, samples were collected at only two time points. These limited findings support the need for longitudinal investigations of the microbiota at multiple body sites during pregnancy.As part of a larger ongoing study, we examined a total of 49 women who were divided into two groups, each of which included controls (term deliveries) and cases (preterm deliveries). We characterized the temporal dynamics of microbiota composition based on prospective weekly sampling during pregnancy from four body sites: vagina, distal gut (stool), saliva, and tooth/gum, as well as after delivery. Our data reveal microbiota compositional stability during pregnancy at all body sites, a diverse vaginal community state early during pregnancy in women who subsequently delivered prematurely, and a dramatic shift in vaginal microbiota composition at the time of delivery that in some cases persisted for the maximum duration of postpartum sampling (1 y).     

Issues in vaccinology: Present challenges and future directions

Vaccination is a principal and highly cost‐effective means of controlling infectious diseases, providing direct protection against pathogens by conferring long‐lasting immunological memory and inducing population‐level herd immunity. Despite rapid ongoing progress in vaccinology, there remain many obstacles to the development and deployment of novel or improved vaccines; these include the underlying science of how to induce and sustain appropriate protective immune responses as well as bureaucratic, logistic and socio‐political hurdles. The failure to distribute and administer existing vaccines to at‐risk communities continues to account for a large proportion of infant mortality worldwide: almost 20 million children do not have access to basic vaccines and several million still die each year as a result. While emerging epidemic or pandemic diseases pose a significant threat to global health and prosperity, there are many infectious diseases which provide a continuous or cyclical burden on healthcare systems which also need to be addressed. Gaps in knowledge of the human immune system stand in the way of developing technologies to overcome individual and pathogenic variation. The challenges in tackling infectious disease and directions that the field of preventive medicine may take to improve the current picture of global health are the focus of this review.     

Experience of managing open fractures of the lower limb at a major trauma centre

Introduction

In April 2012 the John Radcliffe Hospital in Oxford became a major trauma centre (MTC). The British Orthopaedic Association and British Association of Plastic, Reconstructive and Aesthetic Surgeons joint standards for the management of open fractures of the lower limb (BOAST 4) require system-wide changes in referral practice that may be facilitated by the MTC and its associated major trauma network.

Methods

From 2008 to 2013 a multistep audit of compliance with BOAST 4 was conducted to assess referral patterns, timing of surgery and outcomes (surgical site infection rates), to determine changes following local intervention and the establishment of the MTC.

Results

Over the study period, 50 patients had soft tissue cover for an open lower limb fracture and there was a significant increase in the proportion of patients receiving definitive fixation in our centre (p=0.036). The median time from injury to soft tissue cover fell from 6.0 days to 3.5 days (p=0.051) and the median time from definitive fixation to soft tissue cover fell from 5.0 days to 2.0 days (p=0.003). The deep infection rate fell from 27% to 8% (p=0.247). However, in 2013 many patients still experienced a delay of >72 hours between injury and soft tissue cover, primarily owing to a lack of capacity for providing soft tissue cover.

Conclusions

Our experience may be relevant to other MTCs seeking to identify barriers to optimising the management of patients with these injuries.     

Invisibility of the self: Reaching for the telos of nursing within a context of moral distress

Many studies have examined clinical and institutional moral problems in the practice of nurses that have led to the experience of moral distress. The causes and implications of moral distress in nurses, however, have not been understood in terms of their implications from the perspective of virtue ethics. This paper analyzes how nurses reach for the telos of their practice, within a context of moral distress. A qualitative case study was carried out in a private hospital in Brazil. Observation and semi‐semistructured interviews were conducted with 13 nurse participants. With the aid of ATLAS.ti software, the data were analyzed by using thematic content analysis using virtue ethics to theorize the findings. These nurses experienced a loss of their nursing identity as they encountered an ambiguous telos and the domination of institutional values. In their reach for the telos of their practice, nurses found an environment permeated by ethical challenges, which not only created moral distress but also created professional invisibility, a phenomenon referred to as ‘invisibility of the self’.