A national population-based cohort study to investigate inequalities in maternal mortality in the UK 2009-17

Background: Disparities have been documented in maternal mortality rates between women from different ethnic, age and socio-economic groups in the UK. It is unclear whether there are differential changes in these rates amongst women from different groups over time. The objectives of this analysis were to describe UK maternal mortality rates in different age, ethnic and socio-economic groups between 2009 and 2017, and to identify whether there were changes in the observed inequalities, or different trends amongst population subgroups. Methods: Maternal mortality rates with 95% confidence intervals (CI) in specific age, deprivation and ethnic groups were calculated using numbers of maternal deaths as numerator and total maternities as denominator. Relative risks (RR) with 95% CI were calculated and compared using ratios of relative risk. Change over time was investigated using non-parametric tests for trend across ordered groups. Results: Women from black and Asian groups had a higher mortality rate than white women in most time periods, as did women aged 35 and over and women from the most deprived quintile areas of residence. There was evidence of an increasing trend in maternal mortality amongst black women and a decrease in mortality amongst women from the least deprived areas, but no trends over time in any of the other ethnic, age or IMD groups were seen. There was a widening of the disparity between black and white women (RR 2.59 in 2009-11 compared with 5.27 in 2015-17, ratio of the relative risks 2.03, 95% CI 1.11, 3.72). Conclusions: The clear differences in the patterns of maternal mortality amongst different ethnic, age and socio-economic groups emphasise the importance of research and policies focussed specifically on women from black and minority ethnic groups, together with other disadvantaged groups, to begin to reduce maternal mortality in the UK.</p

A modified protocol for the detection of three different mRNAs with a new-generation in situ hybridization chain reaction on frozen sections

A new multiple fluorescence in situ hybridization method based on hybridization chain reaction was recently reported, enabling simultaneous mapping of multiple target mRNAs within intact zebrafish and mouse embryos. With this approach, DNA probes complementary to target mRNAs trigger chain reactions in which metastable fluorophore-labeled DNA hairpins self-assemble into fluorescent amplification polymers. The formation of the specific polymers enhances greatly the sensitivity of multiple fluorescence in situ hybridization. In this study we describe the optimal parameters (hybridization chain reaction time and temperature, hairpin and salt concentration) for multiple fluorescence in situ hybridization via amplification of hybridization chain reaction for frozen tissue sections. The combined use of fluorescence in situ hybridization and immunofluorescence, together with other control experiments (sense probe, neutralization and competition, RNase treatment, and anti-sense probe without initiator) confirmed the high specificity of the fluorescence in situ hybridization used in this study. Two sets of three different mRNAs for oxytocin, vasopressin and somatostatin or oxytocin, vasopressin and thyrotropin releasing hormone were successfully visualized via this new method. We believe that this modified protocol for multiple fluorescence in situ hybridization via hybridization chain reaction would allow researchers to visualize multiple target nucleic acids in the future

Stochastic Physics, Complex Systems and Biology

In complex systems, the interplay between nonlinear and stochastic dynamics, e.g., J. Monod's necessity and chance, gives rise to an evolutionary process in Darwinian sense, in terms of discrete jumps among attractors, with punctuated equilibrium, spontaneous random "mutations" and "adaptations". On an evlutionary time scale it produces sustainable diversity among individuals in a homogeneous population rather than convergence as usually predicted by a deterministic dynamics. The emergent discrete states in such a system, i.e., attractors, have natural robustness against both internal and external perturbations. Phenotypic states of a biological cell, a mesoscopic nonlinear stochastic open biochemical system, could be understood through such a perspective.Comment: 10 page

Diagnosis and management of subcutaneous implantable cardioverter‐defibrillator infections based on process mapping

Background: Infection is a well‐recognized complication of cardiovascular implantable electronic device (CIED) implantation, including the more recently available subcutaneous implantable cardioverter‐defibrillator (S‐ICD). Although the AHA/ACC/HRS guidelines include recommendations for S‐ICD use, currently there are no clinical trial data that address the diagnosis and management of S‐ICD infections. Therefore, an expert panel was convened to develop consensus on these topics. / Methods: A process mapping methodology was used to achieve a primary goal – the development of consensus on the diagnosis and management of S‐ICD infections. Two face‐to‐face meetings of panel experts were conducted to recommend useful information to clinicians in individual patient management of S‐ICD infections. / Results: Panel consensus of a stepwise approach in the diagnosis and management was developed to provide guidance in individual patient management. / Conclusion: Achieving expert panel consensus by process mapping methodology in S‐ICD infection diagnosis and management was attainable, and the results should be helpful in individual patient management

Co-localization of Pirt protein and P2X2 receptors in the mouse enteric nervous system

P2X2 receptors, with other P2X receptor subtypes, have an important role mediating synaptic transmission in regulating the functions of the gastrointestinal tract. Our recent work has found a new regulator of P2X receptor function, called phosphoinositide-interacting regulator of transient receptor potential channels (Pirt). In the present work, we have shown that Pirt immunoreactivity was localized in nerve cell bodies and nerve fibers in the myenteric plexus of the stomach, ileum, proximal, and distal colon and in the submucosal plexus of the jejunum, ileum, proximal, and distal colon. Almost all the Pirt-immunoreactive (ir) neurons were also P2X2-ir, and co-immunoprecipitation experiments have shown that Pirt co-precipitated with the anti-P2X2 antibody. This work provides detailed information about the expression of Pirt in the gut and its co-localization with P2X2, indicating its potential role in influencing P2X2 receptor function

Merkel Cell Polyomavirus Small T Antigen Drives Cell Motility via Rho-GTPase-Induced Filopodium Formation

Cell motility and migration is a complex, multistep, and multicomponent process intrinsic to progression and metastasis. Motility is dependent on the activities of integrin receptors and Rho family GTPases, resulting in the remodeling of the actin cytoskeleton and formation of various motile actin-based protrusions. Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high likelihood of recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is associated with the majority of MCC cases, and MCPyV-induced tumorigenesis largely depends on the expression of the small tumor antigen (ST). Since the discovery of MCPyV, a number of mechanisms have been suggested to account for replication and tumorigenesis, but to date, little is known about potential links between MCPyV T antigen expression and the metastatic nature of MCC. Previously, we described the action of MCPyV ST on the microtubule network and how it impacts cell motility and migration. Here, we demonstrate that MCPyV ST affects the actin cytoskeleton to promote the formation of filopodia through a mechanism involving the catalytic subunit of protein phosphatase 4 (PP4C). We also show that MCPyV ST-induced cell motility is dependent upon the activities of the Rho family GTPases Cdc42 and RhoA. In addition, our results indicate that the MCPyV ST-PP4C interaction results in the dephosphorylation of β1 integrin, likely driving the cell motility pathway. These findings describe a novel mechanism by which a tumor virus induces cell motility, which may ultimately lead to cancer metastasis, and provides opportunities and strategies for targeted interventions for disseminated MCC

Purinergic signaling microenvironments: An introduction

The common theme of this introductory article and the minireviews that follow in this special issue is the concept of microenvironments within tissues and surrounding cells that would be ideal signaling venues for a biologically active purinergic ligand. Collectively, the editors/authors and the other contributing authors agree that nucleotides and nucleosides would be most potent within a confined system. A talented cadre of purinergics has been solicited to discuss purinergic signaling in his or her favorite microenvironment within a given organ or tissue. We are gratified by the large number of original articles that also have successfully navigated the peer review process and are part of this special issue. These concepts are not simply purinergic, but the idea of maximal potency in a tissue microenvironment and surrounding specialized cells within a tissue pertains to any autacoid or paracrine agonist

Threat-sensitive anti-predator defence in precocial wader, the northern lapwing Vanellus vanellus

Birds exhibit various forms of anti-predator behaviours to avoid reproductive failure, with mobbing—observation, approach and usually harassment of a predator—being one of the most commonly observed. Here, we investigate patterns of temporal variation in the mobbing response exhibited by a precocial species, the northern lapwing (Vanellus vanellus). We test whether brood age and self-reliance, or the perceived risk posed by various predators, affect mobbing response of lapwings. We quantified aggressive interactions between lapwings and their natural avian predators and used generalized additive models to test how timing and predator species identity are related to the mobbing response of lapwings. Lapwings diversified mobbing response within the breeding season and depending on predator species. Raven Corvus corax, hooded crow Corvus cornix and harriers evoked the strongest response, while common buzzard Buteo buteo, white stork Ciconia ciconia, black-headed gull Chroicocephalus ridibundus and rook Corvus frugilegus were less frequently attacked. Lapwings increased their mobbing response against raven, common buzzard, white stork and rook throughout the breeding season, while defence against hooded crow, harriers and black-headed gull did not exhibit clear temporal patterns. Mobbing behaviour of lapwings apparently constitutes a flexible anti-predator strategy. The anti-predator response depends on predator species, which may suggest that lapwings distinguish between predator types and match mobbing response to the perceived hazard at different stages of the breeding cycle. We conclude that a single species may exhibit various patterns of temporal variation in anti-predator defence, which may correspond with various hypotheses derived from parental investment theory