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

Improved timed-mating, non-invasive method using fewer unproven female rats with pregnancy validation via early body mass increases

For studies requiring accurate conception-timing, reliable, efficient methods of detecting oestrus reduce time and costs, whilst improving welfare. Standard methods use vaginal cytology to stage cycle, and breeders are paired–up using approximately five proven females with proven males to achieve at least one conception on a specific day. We describe an alternative, fast, consistent, non-invasive method of timed-mating using detection of lordosis behaviour in Wistar and Lister-Hooded rats that used unproven females with high success rates. Rats under reverse-lighting had body masses recorded pre-mating, day (d) 3-4, d8, d10 and d18 of pregnancy. Using only the presence of the oestrus dance to time-mate females for 24-hrs, 89% Wistar and 88% Lister-Hooded rats successfully conceived. We did not observe behavioural oestrus in Sprague-Dawleys without males present. Significant body mass increases following mating distinguished pregnant from non-pregnant rats, as early as d4 of pregnancy (10% ± 1.0 increase cf 3% ± 1.2). The pattern of increases throughout gestation was similar for all pregnant rats until late pregnancy, when there were smaller increases for primi- and multiparous rats (32% ± 2.5; 25% ± 2.4), whereas nulliparous rats had highest gains (38% ± 1.5). This method demonstrated a distinct refinement of the previous timed-mating common practice used, as disturbance of females was minimised. Only the number required of nulli-, primi- or multiparous rats were mated, and body mass increases validated pregnancy status. This new breeding-management method is now established practice for two strains of rat and resulted in a reduction in animal use

Primary enucleation for group D retinoblastoma in the era of systemic and targeted chemotherapy: the price of retaining an eye

BACKGROUND: Chemotherapy is increasingly used as primary treatment for group D retinoblastoma, whereas primary enucleation is considered to have a diminishing role. This study aimed to compare the management course, including number of examinations under anaesthesia (EUAs), of group D patients treated by enucleation versus chemotherapy. METHODS: A retrospective analysis of 92 group D patients, of which 40 (37 unilateral) underwent primary enucleation and 52 (17 unilateral) were treated with intravenous chemotherapy. Number of EUAs was compared between the treatment groups with respect to the whole cohort, using univariate and multivariate analysis, and to unilateral cases only. RESULTS: Patients were followed up for a median of 61 months (mean: 66, range: 14-156), in which time primary enucleated patients had on average seven EUAs and chemotherapy-treated patients 21 EUAs (p<0.001). Chemotherapy, young age, bilateral disease, multifocal tumours, familial and germline retinoblastoma were found on univariate analysis to correlate with increased number of EUAs (p≤0.019). On multivariate analysis, however, only treatment type and presentation age were found significant (p≤0.001). On subanalysis of the unilateral cases, patients undergoing primary enucleation had in average seven EUAs, as compared with 16 in the chemotherapy group (p<0.001). Of the 55 unilateral-presenting patients, a new tumour developed in the fellow eye only in a single familial case. CONCLUSION: Group D patients' families should be counselled regarding the significant difference in number of EUAs following primary enucleation versus chemotherapy when deciding on a treatment strategy. In this regard, primary enucleation would be most beneficial for older patients with unilateral disease

Ultrasonic Wave Dispersion and Attenuation in Fluid Filled Porous Media

The study of ultrasonic wave propagation in granular materials can lead to a better understanding of wave interaction with such materials as uncured cement and concrete. The measured parameters can then be used to investigate the curing process in particular the time required for a given mixture to consolidate. The cohesionless granular materials having loose contact between the constituent grains form a matrix that has negligible shear modulus. Sediment, sandy ground and concrete before solidification can be considered as examples of cohesionless granular materials. The shear and rigidity moduli of these materials can differ greatly from the values obtained by effective medium theories. In particular these differences could affect the ultrasonic wave propagation in such a material. In the case of cohesionless granular material the complete description of mechanical properties requires the consideration of discrete nature of the solid frame and the contact areas between the grains. Therefore wave interaction with such a material should also include the above mentioned effects. The goal of this work is to investigate the ultrasonic wave dispersion and attenuation in cohesionless granular materials the results can be to applied to the monitoring of cement and concrete during the curing process

Safety and efficacy of fluticasone propionate in the topical treatment of skin diseases

Fluticasone propionate - the first carbothioate corticosteroid - has been classified as a potent anti-inflammatory drug for dermatological use. It is available as 0.05% cream and 0.005% ointment formulations for the acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis and vitiligo. This glucocorticoid is characterized by high lipophilicity, high glucocorticoid receptor binding and activation, and a rapid metabolic turnover in skin. Although skin blanching following fluticasone propionate exceeds that of corticosteroids of medium strength, several clinical trials demonstrate a low potential for cutaneous and systemic side-effects, even in difficult-to-treat areas like the face, the eyelids and intertriginous areas. Even among paediatric patients with atopic dermatitis, fluticasone propionate proved to be safe and effective. These pharmacological and clinical properties are reflected by the high therapeutic index of this glucocorticoid

Primary intravenous chemotherapy for group D retinoblastoma: a 13-year retrospective analysis.

BACKGROUND: Eye salvage rate for group D retinoblastoma using intravenous chemotherapy (IVC) as a primary modality is <50%. To report on 13 years' experience with the use of primary IVC for group D retinoblastoma. METHODS: A retrospective analysis of 64 group D eyes (52 patients) treated with primary IVC, from 2002 to 2014. RESULTS: The median age at presentation was 11.0 months (mean: 18.6, range: 0.6-144.0), 35 (67%) patients had bilateral disease, 38 (73%) germline disease and 8 (15%) cases were familial. In addition to IVC, patients received a median number of three treatments (mean: 6, range: 0-24), including thermotherapy/cryotherapy, plaque radiotherapy, intra-ophthalmic artery chemotherapy (IAC) and/or intravitreous chemotherapy. External beam radiotherapy (EBRT) was used in five eyes, all of which were eventually enucleated. In a median follow-up time of 55 months (mean: 64, range: 14-156), 63% of eyes were salvaged. By the Kaplan-Meier survival analysis, globe salvage rate was 83%, 70%, 59% and 45% at 1, 3, 5 and 10 years, respectively. There were no cases of metastatic spread from intraocular retinoblastoma and no deaths. IVC-related adverse events included febrile neutropenia in 21 (40%) patients and anaphylactic reaction to carboplatin in 2 (4%), all conservatively resolved. Of the patients receiving IAC, third and sixth nerve palsies were documented in two (10%) and one (5%) eyes, respectively. CONCLUSIONS: Primary IVC for group D eyes, with adjuvant treatments as required, was found to be a safe and efficient approach, achieving 63% eye salvage rate, no metastatic spread from intraocular retinoblastoma and no deaths. IAC has now replaced EBRT as a successful salvage treatment

Out of hospital cardiac arrest : what do the numbers tell us?

The benefits of sodium bicarbonate use in treating out of hospital cardiac arrest (OHCA) have been debated and have fluctuated over time. Both prospective and retrospective studies have been done. With an aggregate of these studies there is little evidence that sodium bicarbonate is effective in preventing morbidity and mortality in patients experiencing OHCA. Overall OHCA treated by Emergency Medical Services (EMS) has an incidence of 73 per 100,000 and an average survival to hospital discharge of 11.4% for adults. With the information available and more recent guidelines and evidence showing less support for the use in utilizing sodium bicarbonate in a prehospital cardiac arrest, it should be assessed if this evidence extends to the population seen at MU hospital to guide further appropriate care and policies. Additionally, trends in 30-day survival should be evaluated for significance and appropriate change in practice should be considered both for continued aggressive care and limiting nonbeneficial intervention during OHCA.Michael Johnson BSN, RN, CCRN, (M2); Julie AW Stilley PhD; Joshua D Stilley MD, FACEP, FAAEM ; Department of Emergency Medicine, University of Missouri Health Car

Squirrelpox virus: assessing prevalence, transmission and environmental degradation

Red squirrels (Sciurus vulgaris) declined in Great Britain and Ireland during the last century, due to habitat loss and the introduction of grey squirrels (Sciurus carolinensis), which competitively exclude the red squirrel and act as a reservoir for squirrelpox virus (SQPV). The disease is generally fatal to red squirrels and their ecological replacement by grey squirrels is up to 25 times faster where the virus is present. We aimed to determine: (1) the seropositivity and prevalence of SQPV DNA in the invasive and native species at a regional scale; (2) possible SQPV transmission routes; and, (3) virus degradation rates under differing environmental conditions. Grey (n = 208) and red (n = 40) squirrel blood and tissues were sampled. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) techniques established seropositivity and viral DNA presence, respectively. Overall 8% of squirrels sampled (both species combined) had evidence of SQPV DNA in their tissues and 22% were in possession of antibodies. SQPV prevalence in sampled red squirrels was 2.5%. Viral loads were typically low in grey squirrels by comparison to red squirrels. There was a trend for a greater number of positive samples in spring and summer than in winter. Possible transmission routes were identified through the presence of viral DNA in faeces (red squirrels only), urine and ectoparasites (both species). Virus degradation analyses suggested that, after 30 days of exposure to six combinations of environments, there were more intact virus particles in scabs kept in warm (25°C) and dry conditions than in cooler (5 and 15°C) or wet conditions. We conclude that SQPV is present at low prevalence in invasive grey squirrel populations with a lower prevalence in native red squirrels. Virus transmission could occur through urine especially during warm dry summer conditions but, more notably, via ectoparasites, which are shared by both species

Friends of hot Jupiters. II. No correspondence between hot-Jupiter spin-orbit misalignment and the incidence of directly imaged stellar companions

This is the final version of the article. Available from American Astronomical Society / IOP Publishing via the DOI in this record.Multi-star systems are common, yet little is known about a stellar companion's influence on the formation and evolution of planetary systems. For instance, stellar companions may have facilitated the inward migration of hot Jupiters toward to their present day positions. Many observed short-period gas giant planets also have orbits that are misaligned with respect to their star's spin axis, which has also been attributed to the presence of a massive outer companion on a non-coplanar orbit. We present the results of a multi-band direct imaging survey using Keck NIRC2 to measure the fraction of short-period gas giant planets found in multi-star systems. Over three years, we completed a survey of 50 targets ("Friends of Hot Jupiters") with 27 targets showing some signature of multi-body interaction (misaligned or eccentric orbits) and 23 targets in a control sample (well-aligned and circular orbits). We report the masses, projected separations, and confirmed common proper motion for the 19 stellar companions found around 17 stars. Correcting for survey incompleteness, we report companion fractions of 48% ± 9%, 47% ± 12%, and 51% ± 13% in our total, misaligned/eccentric, and control samples, respectively. This total stellar companion fraction is 2.8σ larger than the fraction of field stars with companions approximately 50-2000 AU. We observe no correlation between misaligned/eccentric hot Jupiter systems and the incidence of stellar companions. Combining this result with our previous radial velocity survey, we determine that 72% ± 16% of hot Jupiters are part of multi-planet and/or multi-star systems.This work was supported by NASA grant NNX14AD24G. H.N. is grateful for funding support from the Natural Sciences and Engineering Research Council of Canada. J.A.J. gratefully acknowledges support from generous fellowships from the David & Lucile Packard and Alfred P. Sloan foundations