Maternal outcomes in subsequent delivery after previous obstetric anal sphincter injury (OASI): a multi-centre retrospective cohort study.

INTRODUCTION AND HYPOTHESIS: Women with a history of obstetric anal sphincter injury (OASI) are at increased risk of recurrence (rOASI) at subsequent delivery; however, evidence regarding the factors influencing this risk is limited. Furthermore, little is known about what factors influence the decision to alternatively deliver by elective caesarean section (ELLSCS). METHODS: Retrospective univariate and multivariate logistic regression analysis of prospectively collected data from four NHS electronic maternity databases including primiparous women sustaining OASIS during a singleton, term, cephalic, vaginal delivery between 2004 and 2015, who had a subsequent delivery. RESULTS: Two thousand two hundred seventy-two women met the criteria; 10.2% delivering vaginally had a repeat OASI and 59.4% had a second-degree tear. Women having an ELLSCS were more likely to be Caucasian, older, have previously had an operative vaginal delivery (OVD) and have a more severe degree of OASI. Positive predictors for rOASI were increased birth weight and maternal age at both index and subsequent deliveries, a more severe degree of initial OASI and Asian ethnicity. The overall mediolateral episiotomy (MLE) rate was 15.6%; 77.2% of those who had an episiotomy sustained no spontaneous perineal trauma. Only 4.4% of women with a rOASI had an MLE, whilst the MLE rate was 16.9% in those without a recurrence (p  4 kg increased the risk 2.5 fold. CONCLUSIONS: Women with previous OASIS are at an increased risk of recurrence. A more liberal use of MLE during subsequent vaginal delivery could significantly reduce the risk of recurrence

Does shear wave ultrasound independently predict axillary lymph node metastasis in women with invasive breast cancer?

Shear wave elastography (SWE) shows promise as an adjunct to greyscale ultrasound examination in assessing breast masses. In breast cancer, higher lesion stiffness on SWE has been shown to be associated with features of poor prognosis. The purpose of this study was to assess whether lesion stiffness at SWE is an independent predictor of lymph node involvement. Patients with invasive breast cancer treated by primary surgery, who had undergone SWE examination were eligible. Data were retrospectively analysed from 396 consecutive patients. The mean stiffness values were obtained using the Aixplorer(®) ultrasound machine from SuperSonic Imagine Ltd. Measurements were taken from a region of interest positioned over the stiffest part of the abnormality. The average of the mean stiffness value obtained from each of two orthogonal image planes was used for analysis. Associations between lymph node involvement and mean lesion stiffness, invasive cancer size, histologic grade, tumour type, ER expression, HER-2 status and vascular invasion were assessed using univariate and multivariate logistic regression. At univariate analysis, invasive size, histologic grade, HER-2 status, vascular invasion, tumour type and mean stiffness were significantly associated with nodal involvement. Nodal involvement rates ranged from 7 % for tumours with mean stiffness <50 kPa to 41 % for tumours with a mean stiffness of >150 kPa. At multivariate analysis, invasive size, tumour type, vascular invasion, and mean stiffness maintained independent significance. Mean stiffness at SWE is an independent predictor of lymph node metastasis and thus can confer prognostic information additional to that provided by conventional preoperative tumour assessment and staging

Calcitization of aragonitic bryozoans in Cenozoic tropical carbonates from East Kalimantan, Indonesia

© The Author(s) 2016. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The file attached is the published version of the article

An assessment of the quality of randomised controlled trials conducted in China

Background: Despite the rapid increase in research in China, little is known about the quality of clinical trials conducted there.Methods: A systematic review and critical appraisal of randomised controlled trials (RCTs) conducted in China and published in 2004 was undertaken to describe their characteristics, assess the quality of their reporting, and where possible, the quality of their conduct. Randomised controlled trials in all disease areas and types of interventions, which took place in China and included Chinese citizens were identified using PubMed and hand searching the Journal Series of the Chinese Medical Association. Quality was assessed against a subset of criteria adapted from the CONSORT statement.Results: Three hundred and seven RCTs were included. One hundred and ninety-nine (64.8%) failed to report methods of randomization and 254 (82.4%) did not mention blinding of either participants or investigators. Reporting of baseline characteristics, primary outcome and length of follow-up was inadequate in a substantial proportion of studies. Fewer than 11% of RCTs mentioned ethical approval and only 18.0% adequately discussed informed consent. However, dropout rates were very favourable with nearly 44% of trials reporting a zero dropout rate.Conclusion: Reporting of RCTs in China requires substantial improvement to meet the targets of the CONSORT statement. The conduct of Chinese RCTs cannot be directly inferred from the standard of reporting; however without good reporting the methods of the trials cannot be clearly ascertained

Comparison of the Safety and Pharmacokinetics of ST-246® after IV Infusion or Oral Administration in Mice, Rabbits and Monkeys

ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV) formulation may be required for some hospitalized patients who are unable to take oral medication. An IV formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation. plasma concentrations. These effects were eliminated using slower IV infusions. associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and IV administration. The administration of ST-246 was well tolerated as a slow IV infusion

Nurse-Led Medicines' Monitoring for Patients with Dementia in Care Homes: A Pragmatic Cohort Stepped Wedge Cluster Randomised Trial

People with dementia are susceptible to adverse drug reactions (ADRs). However, they are not always closely monitored for potential problems relating to their medicines: structured nurse-led ADR Profiles have the potential to address this care gap. We aimed to assess the number and nature of clinical problems identified and addressed and changes in prescribing following introduction of nurse-led medicines' monitoring.Pragmatic cohort stepped-wedge cluster Randomised Controlled Trial (RCT) of structured nurse-led medicines' monitoring versus usual care.Five UK private sector care homes.41 service users, taking at least one antipsychotic, antidepressant or anti-epileptic medicine.Nurses completed the West Wales ADR (WWADR) Profile for Mental Health Medicines with each participant according to trial step.Problems addressed and changes in medicines prescribed.Information was collected from participants' notes before randomisation and after each of five monthly trial steps. The impact of the Profile on problems found, actions taken and reduction in mental health medicines was explored in multivariate analyses, accounting for data collection step and site.Five of 10 sites and 43 of 49 service users approached participated. Profile administration increased the number of problems addressed from a mean of 6.02 [SD 2.92] to 9.86 [4.48], effect size 3.84, 95% CI 2.57-4.11, P <0.001. For example, pain was more likely to be treated (adjusted Odds Ratio [aOR] 3.84, 1.78-8.30), and more patients attended dentists and opticians (aOR 52.76 [11.80-235.90] and 5.12 [1.45-18.03] respectively). Profile use was associated with reduction in mental health medicines (aOR 4.45, 1.15-17.22).The WWADR Profile for Mental Health Medicines can improve the quality and safety of care, and warrants further investigation as a strategy to mitigate the known adverse effects of prescribed medicines.ISRCTN 48133332

Geological archive of the onset of plate tectonics

© 2018 The Author(s) Published by the Royal Society. All rights reserved. Plate tectonics, involving a globally linked system of lateral motion of rigid surface plates, is a characteristic feature of our planet, but estimates of how long it has been the modus operandi of lithospheric formation and interactions range from the Hadean to the Neoproterozoic. In this paper, we review sedimentary, igneous and metamorphic proxies along with palaeomagnetic data to infer both the development of rigid lithospheric plates and their independent relative motion, and conclude that significant changes in Earth behaviour occurred in the mid- to late Archaean, between 3.2 Ga and 2.5 Ga. These data include: sedimentary rock associations inferred to have accumulated in passive continental margin settings, marking the onset of seafloor spreading; the oldest foreland basin deposits associated with lithospheric convergence; a change from thin, new continental crust of mafic composition to thicker crust of intermediate composition, increased crustal reworking and the emplacement of potassic and peraluminous granites, indicating stabilization of the lithosphere; replacement of dome and keel structures in granite-greenstone terranes, which relate to vertical tectonics, by linear thrust imbricated belts; the commencement of temporally paired systems of intermediate and high dT/dP gradients, with the former interpreted to represent subduction to collisional settings and the latter representing possible hinterland back-arc settings or ocean plateau environments. Palaeomagnetic data from the Kaapvaal and Pilbara cratons for the interval 2780-2710Ma and from the Superior, Kaapvaal and Kola-Karelia cratons for 2700-2440Ma suggest significant relative movements. We consider these changes in the behaviour and character of the lithosphere to be consistent with a gestational transition from a non-plate tectonic mode, arguably with localized subduction, to the onset of sustained plate tectonics

Griseofulvin stabilizes microtubule dynamics, activates p53 and inhibits the proliferation of MCF-7 cells synergistically with vinblastine

<p>Abstract</p> <p>Background</p> <p>Griseofulvin, an antifungal drug, has recently been shown to inhibit proliferation of various types of cancer cells and to inhibit tumor growth in athymic mice. Due to its low toxicity, griseofulvin has drawn considerable attention for its potential use in cancer chemotherapy. This work aims to understand how griseofulvin suppresses microtubule dynamics in living cells and sought to elucidate the antimitotic and antiproliferative action of the drug.</p> <p>Methods</p> <p>The effects of griseofulvin on the dynamics of individual microtubules in live MCF-7 cells were measured by confocal microscopy. Immunofluorescence microscopy, western blotting and flow cytometry were used to analyze the effects of griseofulvin on spindle microtubule organization, cell cycle progression and apoptosis. Further, interactions of purified tubulin with griseofulvin were studied <it>in vitro </it>by spectrophotometry and spectrofluorimetry. Docking analysis was performed using autodock4 and LigandFit module of Discovery Studio 2.1.</p> <p>Results</p> <p>Griseofulvin strongly suppressed the dynamic instability of individual microtubules in live MCF-7 cells by reducing the rate and extent of the growing and shortening phases. At or near half-maximal proliferation inhibitory concentration, griseofulvin dampened the dynamicity of microtubules in MCF-7 cells without significantly disrupting the microtubule network. Griseofulvin-induced mitotic arrest was associated with several mitotic abnormalities like misaligned chromosomes, multipolar spindles, misegregated chromosomes resulting in cells containing fragmented nuclei. These fragmented nuclei were found to contain increased concentration of p53. Using both computational and experimental approaches, we provided evidence suggesting that griseofulvin binds to tubulin in two different sites; one site overlaps with the paclitaxel binding site while the second site is located at the αβ intra-dimer interface. In combination studies, griseofulvin and vinblastine were found to exert synergistic effects against MCF-7 cell proliferation.</p> <p>Conclusions</p> <p>The study provided evidence suggesting that griseofulvin shares its binding site in tubulin with paclitaxel and kinetically suppresses microtubule dynamics in a similar manner. The results revealed the antimitotic mechanism of action of griseofulvin and provided evidence suggesting that griseofulvin alone and/or in combination with vinblastine may have promising role in breast cancer chemotherapy.</p

Orthokeratinized Odontogenic Cyst of the Mandible with Heterotopic Cartilage

Cartilaginous metaplasia is a rare but well-documented phenomenon occurring in the wall of odontogenic keratocyst. The mural cartilage not associated with odontogenic keratocyst has been reported only once in a maxillary teratoid cyst of congenital origin to our knowledge. A case presented is a 38-year-old man with intraosseous keratinizing epidermoid cyst in the mandible, the wall of which contained a nodule of mature hyaline cartilage. The present lesion likely represents a previously undescribed, histologic hybrid consisting of orthokeratinized odontogenic cyst and cartilaginous heterotopia