Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy.

Charcot neuroarthropathy is a rare but serious complication of diabetes, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and an increased risk of ulceration. Management is complicated by a lack of consensus on diagnostic criteria and an incomplete understanding of the pathogenesis. In this review, we consider recent insights into the development of Charcot neuroarthropathy. It is likely to be dependent on several interrelated factors which may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (nitric oxide and calcitonin gene-related peptide), which may affect the normal coupling of bone formation and resorption, and increased levels of Receptor activator of nuclear factor kappa-B ligand, potentiating osteoclastogenesis. Repetitive unrecognized trauma due to neuropathy increases levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumour necrosis factor α) which could also contribute to increased bone resorption, in combination with a pre-inflammatory state, with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts - cluster of differentiation 14 (CD14). Increased blood glucose and loss of circulating Receptor for Advanced Glycation End-Products (AGLEPs), leading to increased non-enzymatic glycation of collagen and accumulation of AGLEPs in the tissues of the foot, may also contribute to the pathological process. An understanding of the relative contributions of each of these mechanisms and a final common pathway for the development of Charcot neuroarthropathy are still lacking. Cite this article: S. E. Johnson-Lynn, A. W. McCaskie, A. P. Coll, A. H. N. Robinson. Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy. Bone Joint Res 2018;7:373-378. DOI: 10.1302/2046-3758.75.BJR-2017-0334.R1

Coexistence of Magnetic Order and Two-dimensional Superconductivity at LaAlO3_3/SrTiO3_3 Interfaces

A two dimensional electronic system with novel electronic properties forms at the interface between the insulators LaAlO$_3$ and SrTiO$_3$. Samples fabricated until now have been found to be either magnetic or superconducting, depending on growth conditions. We combine transport measurements with high-resolution magnetic torque magnetometry and report here evidence of magnetic ordering of the two-dimensional electron liquid at the interface. The magnetic ordering exists from well below the superconducting transition to up to 200 K, and is characterized by an in-plane magnetic moment. Our results suggest that there is either phase separation or coexistence between magnetic and superconducting states. The coexistence scenario would point to an unconventional superconducting phase in the ground state.Comment: 10 pages, 4 figure

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial

Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI

Audit of short term outcomes of surgical and medical second trimester termination of pregnancy

<p>Abstract</p> <p>Background</p> <p>As comparisons of modern medical and surgical second trimester termination of pregnancy (TOP) are limited, and the optimum method of termination is still debated, an audit of second trimester TOP was undertaken, with the objective of comparing the outcomes of modern medical and surgical methods.</p> <p>Methods</p> <p>All cases of medical and surgical TOP between the gestations of 13 and 20 weeks from 1st January 2007 to 30th June 2008, among women residing in the local health board district, a tertiary teaching hospital in an urban setting, were identified by a search of ICD-10 procedure codes (surgical terminations) and from a ward database (medical terminations). Retrospective review of case notes was undertaken. A total of 184 cases, 51 medical and 133 surgical TOP, were identified. Frequency data were compared using Chi-squared or Fischer's Exact tests as appropriate and continuous data are presented as mean and standard deviation if normally distributed or median and interquartile range if non-parametric.</p> <p>Results</p> <p>Eighty-one percent of surgical terminations occurred between 13 to 16 weeks gestation, while 74% of medical terminations were performed between 17 to 20 weeks gestation. The earlier surgical TOP occurred in younger women and were more often indicated for maternal mental health. Sixteen percent of medical TOP required surgical delivery of the placenta. Evacuation of retained products was required more often after medical TOP (10%) than after surgical TOP (1%). Other serious complications were rare.</p> <p>Conclusion</p> <p>Both medical and surgical TOP are safe and effective for second trimester termination. Medical TOP tend to be performed at later gestations and are associated with a greater likelihood of manual removal of the placenta and delayed return to theatre for retained products. This case series does not address long term complications.</p

A review of duodenal metastases from squamous cell carcinoma of the cervix presenting as an upper gastrointestinal bleed

Upper gastrointestinal bleeding due to duodenal metastases is extremely uncommon. Extra-pelvic spread of squamous cell carcinoma (SCC) of the cervix to the small bowel is rare with only 6 reported cases in the English literature since 1981(PubMed, Medline)

New Insights into Human Nondisjunction of Chromosome 21 in Oocytes

Nondisjunction of chromosome 21 is the leading cause of Down syndrome. Two risk factors for maternal nondisjunction of chromosome 21 are increased maternal age and altered recombination. In order to provide further insight on mechanisms underlying nondisjunction, we examined the association between these two well established risk factors for chromosome 21 nondisjunction. In our approach, short tandem repeat markers along chromosome 21 were genotyped in DNA collected from individuals with free trisomy 21 and their parents. This information was used to determine the origin of the nondisjunction error and the maternal recombination profile. We analyzed 615 maternal meiosis I and 253 maternal meiosis II cases stratified by maternal age. The examination of meiosis II errors, the first of its type, suggests that the presence of a single exchange within the pericentromeric region of 21q interacts with maternal age-related risk factors. This observation could be explained in two general ways: 1) a pericentromeric exchange initiates or exacerbates the susceptibility to maternal age risk factors or 2) a pericentromeric exchange protects the bivalent against age-related risk factors allowing proper segregation of homologues at meiosis I, but not segregation of sisters at meiosis II. In contrast, analysis of maternal meiosis I errors indicates that a single telomeric exchange imposes the same risk for nondisjunction, irrespective of the age of the oocyte. Our results emphasize the fact that human nondisjunction is a multifactorial trait that must be dissected into its component parts to identify specific associated risk factors

The Drosophila melanogaster PeptideAtlas facilitates the use of peptide data for improved fly proteomics and genome annotation

<p>Abstract</p> <p>Background</p> <p>Crucial foundations of any quantitative systems biology experiment are correct genome and proteome annotations. Protein databases compiled from high quality empirical protein identifications that are in turn based on correct gene models increase the correctness, sensitivity, and quantitative accuracy of systems biology genome-scale experiments.</p> <p>Results</p> <p>In this manuscript, we present the <it>Drosophila melanogaster </it>PeptideAtlas, a fly proteomics and genomics resource of unsurpassed depth. Based on peptide mass spectrometry data collected in our laboratory the portal <url>http://www.drosophila-peptideatlas.org</url> allows querying fly protein data observed with respect to gene model confirmation and splice site verification as well as for the identification of proteotypic peptides suited for targeted proteomics studies. Additionally, the database provides consensus mass spectra for observed peptides along with qualitative and quantitative information about the number of observations of a particular peptide and the sample(s) in which it was observed.</p> <p>Conclusion</p> <p>PeptideAtlas is an open access database for the <it>Drosophila </it>community that has several features and applications that support (1) reduction of the complexity inherently associated with performing targeted proteomic studies, (2) designing and accelerating shotgun proteomics experiments, (3) confirming or questioning gene models, and (4) adjusting gene models such that they are in line with observed <it>Drosophila </it>peptides. While the database consists of proteomic data it is not required that the user is a proteomics expert.</p