Lactobacillus crispatus S-layer proteins modulate innate immune response and inflammation in the lower female reproductive tract.

Lactobacillus species dominance of the vaginal microbiome is a hallmark of vaginal health. Pathogen displacement of vaginal lactobacilli drives innate immune activation and mucosal barrier disruption, increasing the risks of STI acquisition and, in pregnancy, of preterm birth. We describe differential TLR mediated activation of the proinflammatory transcription factor NF-κB by vaginal pathogens and commensals.

Glycomics of cervicovaginal fluid from women at risk of preterm birth reveals immuno-regulatory epitopes that are hallmarks of cancer and viral glycosylation.

During pregnancy the immune system needs to maintain immune tolerance of the foetus while also responding to infection, which can cause premature activation of the inflammatory pathways leading to the onset of labour and preterm birth. The vaginal microbiome is an important modifier of preterm birth risk, with Lactobacillus dominance during pregnancy associated with term delivery while high microbial diversity is associated with an increased risk of preterm birth. Glycans on glycoproteins along the lower female reproductive tract are fundamental to microbiota-host interactions and the mediation of inflammatory responses.

A comparative study of the cutting efficiency of diamond rotary instruments with different grit sizes with a low-speed electric handpiece against zirconia specimens.

Statement Of Problem: The use of zirconia in dentistry has increased. However, little attention has been given to the difficulty experienced by clinicians when cutting zirconia restorations intraorally. Evidence for which grit size and type of rotary instrument is best for cutting zirconia intraorally is lacking.

The effect of duration of untreated psychosis (DUP) on the risk for hospitalization after admission to a first episode service.

Engagement with a first episode-psychosis service (FES) reduces the risk of psychiatric hospitalization. However, the role of the duration of untreated psychosis (DUP) in impacting this outcome is disputed. This study aimed to examine whether DUP was an effect modifier of the post-FES reduction of risk of hospitalization, and to explore associations between patients' characteristics and hospitalization post-FES.

Prostaglandin F2α requires activation of calcium-dependent signalling to trigger inflammation in human myometrium.

Introduction: Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in uterine tissues. This includes increased leukocyte infiltration, and subsequent increase in chemokine and cytokine levels, activation of pro-inflammatory transcription factors as NF-κB and increased prostaglandin synthesis.

Safety, tolerability, and acceptability of CTV-05 (LACTIN-V) in pregnant women at high-risk of preterm birth.

The vaginal microbiota is a determinant for the risk of preterm birth (PTB). Dominance of the vaginal niche by associates with term delivery. This is the first observational clinical study of live vaginal biotherapeutics ( CTV-05 (LACTIN-V)) in pregnant women at high-risk of PTB.

Rhombencephalitis in Pregnancy-A Challenging Case of Probable Infection.

Rhombencephalitis refers to inflammation of the brainstem and cerebellum, and can be caused by infections, autoimmune disorders or paraneoplastic syndromes. The most common infective cause is the bacterium Listeria monocytogenes. Listeria monocytogenes is the predominant species to cause human listeriosis, and is commonly due to the ingestion of contaminated foods.

The Role of Neutrophils in Pregnancy, Term and Preterm Labour.

Neutrophils are surveillance cells, and the first to react and migrate to sites of inflammation and infection following a chemotactic gradient. Neutrophils play a key role in both sterile inflammation and infection, performing a wide variety of effector functions such as degranulation, phagocytosis, ROS production and release of neutrophil extracellular traps (NETs). Healthy term labour requires a sterile pro-inflammatory process, whereas one of the most common causes of spontaneous preterm birth is microbial driven.

N-glycosylation of cervicovaginal fluid reflects microbial community, immune activity, and pregnancy status.

Human cervicovaginal fluid (CVF) is a complex, functionally important and glycan rich biological fluid, fundamental in mediating physiological events associated with reproductive health. Using a comprehensive glycomic strategy we reveal an extremely rich and complex N-glycome in CVF of pregnant and non-pregnant women, abundant in paucimannose and high mannose glycans, complex glycans with 2-4 N-Acetyllactosamine (LacNAc) antennae, and Poly-LacNAc glycans decorated with fucosylation and sialylation. N-glycosylation profiles were observed to differ in relation to pregnancy status, microbial composition, immune activation, and pregnancy outcome.

15-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cells.

Background: Prematurity is the leading cause of childhood death under the age of five. The aetiology of preterm birth is multifactorial; however, inflammation and infection are the most common causal factors, supporting a potential role for immunomodulation as a therapeutic strategy. 15-Deoxy-Delta-12,14-prostaglandin J2 (15dPGJ2) is an anti-inflammatory prostaglandin and has been shown to delay lipopolysaccharide (LPS) induced preterm labour in mice and improve pup survival.

Experiences of Multidisciplinary Working: Perspectives from the Wessex Ghana Stroke Partnership.

Introduction: Substantial gaps remain in our understanding of stroke in Africa as well as in stroke care, practice and policy on the continent. The effective organization of preventative, therapeutic and rehabilitative stroke services continue to be challenging in many African countries.

Methodology: In this article we define the nature, function and benefits of effective multidisciplinary team (MDT) working.

Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response.

There has been a surge in studies implicating a role of vaginal microbiota in spontaneous preterm birth (sPTB), but most are associative without mechanistic insight. Here we show a comprehensive approach to understand the causative factors of preterm birth, based on the integration of longitudinal vaginal microbiota and cervicovaginal fluid (CVF) immunophenotype data collected from 133 women at high-risk of sPTB. We show that vaginal depletion of Lactobacillus species and high bacterial diversity leads to increased mannose binding lectin (MBL), IgM, IgG, C3b, C5, IL-8, IL-6 and IL-1β and to increased risk of sPTB.

: Audience-dancer interaction via social media posts and wearable for haptic feedback.

The performative installation utilizes a network of systems toward facilitating interaction between dancer, digital media, and audience. Central to the work is a wearable haptic feedback system able to wirelessly deliver vibrotactile stimuli, with the latter initiated by the audience through posting on Twitter social media platform; the system in use searches for specific mentions, hashtags, and keywords, with positive results causing the system to trigger patterns of haptic biofeedback across the wearable's four actuator motors. The system acts as the intermediator between the audience's online actions and the dancer receiving physical stimuli; the dancer interprets these biofeedback signals according to Laban's Effort movement qualities, with the interpretation informing different states of habitual and conscious choreographic performance.

Antiepileptic drugs for the primary and secondary prevention of seizures after stroke.

Background: Seizures after stroke are an important clinical problem and may result in poor outcomes. The indications of antiepileptic drugs (AEDs) for seizure prophylaxis after stroke remain unclear. This is an updated version of the Cochrane Review previously published in 2014.

Whole Blood Holding Time Prior to Plasma Processing Alters microRNA Expression Profile.

MicroRNAs (miRNAs) can exhibit aberrant expression under different physiological and pathological conditions. Therefore, differentially expressed circulating miRNAs have been a focus of biomarker discovery research. However, the use of circulating miRNAs comes with challenges which may hinder the reliability for their clinical application.

Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth.

The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status.

Euglycaemic ketoacidosis in pregnant women with COVID-19: two case reports.

Background: Euglycaemic ketoacidosis (EKA) is an infrequent but serious condition which usually follows a period of starvation, severe vomiting or illness in individuals with or without diabetes. Ketoacidosis is associated with materno-fetal morbidity and mortality necessitating prompt diagnosis and management. Physiological increases in insulin resistance render pregnancy a diabetogenic state with increased susceptibility to ketosis.

Proteome-wide prediction of bacterial carbohydrate-binding proteins as a tool for understanding commensal and pathogen colonisation of the vaginal microbiome.

Bacteria use carbohydrate-binding proteins (CBPs), such as lectins and carbohydrate-binding modules (CBMs), to anchor to specific sugars on host surfaces. CBPs in the gut microbiome are well studied, but their roles in the vagina microbiome and involvement in sexually transmitted infections, cervical cancer and preterm birth are largely unknown. We established a classification system for lectins and designed Hidden Markov Model (HMM) profiles for data mining of bacterial genomes, resulting in identification of >100,000 predicted bacterial lectins available at unilectin.

Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c.

Genetic variation in CACNA1C, which encodes the alpha-1 subunit of Ca1.2 L-type voltage-gated calcium channels, is strongly linked to risk for psychiatric disorders including schizophrenia and bipolar disorder. To translate genetics to neurobiological mechanisms and rational therapeutic targets, we investigated the impact of mutations of one copy of Cacna1c on rat cognitive, synaptic and circuit phenotypes implicated by patient studies.

Maternal plasma miRNAs as potential biomarkers for detecting risk of small-for-gestational-age births.

Background: Small-for-gestational-age fetuses (SGA) (birthweight <10th centile) are at high risk for stillbirth or long-term adverse outcomes. Here, we investigate the ability of circulating maternal plasma miRNAs to determine the risk of SGA births.

Methods: Maternal plasma samples from 29 women of whom 16 subsequently delivered normally grown babies and 13 delivered SGA (birthweight <5th centile) were selected from a total of 511 women recruited to form a discovery cohort in which expression data for a total of 800 miRNAs was determined using the Nanostring nCounter miRNA assay.

Differential Response of Gestational Tissues to TLR3 Viral Priming Prior to Exposure to Bacterial TLR2 and TLR2/6 Agonists.

Infection/inflammation is an important causal factor in spontaneous preterm birth (sPTB). Most mechanistic studies have concentrated on the role of bacteria, with limited focus on the role of viruses in sPTB. Murine studies support a potential multi-pathogen aetiology in which a double or sequential hit of both viral and bacterial pathogens leads to a higher risk preterm labour.