Which dressing do donor site wounds need?: study protocol for a randomized controlled trial

Donor site wounds after split-skin grafting are rather 'standard' wounds. At present, lots of dressings and topical agents for donor site wounds are commercially available. This causes large variation in the local care of these wounds, while the optimum 'standard' dressing for local wound care is unclear. This protocol describes a trial in which we investigate the effectiveness of various treatment options for these donor site wounds. A 14-center, six-armed randomized clinical trial is being carried out in the Netherlands. An a-priori power analysis and an anticipated dropout rate of 15% indicates that 50 patients per group are necessary, totaling 300 patients, to be able to detect a 25% quicker mean time to complete wound healing. Randomization has been computerized to ensure allocation concealment. Adult patients who need a split-skin grafting operation for any reason, leaving a donor site wound of at least 10 cm2 are included and receive one of the following dressings: hydrocolloid, alginate, film, hydrofiber, silicone dressing, or paraffin gauze. No combinations of products from other intervention groups in this trial are allowed. Optimum application and changes of these dressings are pursued according to the protocol as supplied by the dressing manufacturers. Primary outcomes are days to complete wound healing and pain (using a Visual Analogue Scale). Secondary outcomes are adverse effects, scarring, patient satisfaction, and costs. Outcome assessors unaware of the treatment allocation will assess whether or not an outcome has occurred. Results will be analyzed according to the intention to treat principle. The first patient was randomized October 1, 2009. This study will provide comprehensive data on the effectiveness of different treatment options for donor site wounds. The dressing(s) that will prevail in effectiveness, satisfaction and costs will be promoted among clinicians dealing with such patients. Thus, we aim to contribute a well-designed trial, relevant to all clinicians involved in the care for donor site wounds, which will help enhance uniformity and quality of care for these patients. http://www.trialregister.nl, NTR1849. Date registered: June 9, 200

Viral vectored transmission blocking vaccines against Plasmodium falciparum

Background: Transmission blocking vaccines (TBVs) target sexual develop¬ment of the parasite within the mosquito and aim to prevent transmission of malaria from one individual to another. Antibodies raised against Pfs48/45, Pfs230 Region C, PfHAP2, and Anopheles gambiae Alanyl Aminopeptidase N1 (AgAPN1) proteins reduce transmission i.e. have transmission blocking activity [1–5]. Recombinant simian Adenovirus (AdC63 serotype) and Modified Vaccinia Ankara (MVA) viral vectors have been shown to induce high antibody titres to asexual parasite antigens in animal studies [6]. Materials and methods: Protein sequences for each of the antigens were codon optimised for expression in humans and cloned into shuttle vectors, which were then recombined with the parental virus and purified to obtain virus expressing the antigen of interest. Mice were vaccinated with AdC63 (i.m.), sera was taken after 2 weeks, and will be followed by an MVA boost (i.d.) eight weeks after the prime. Antibodies were assayed by a standardised ELISA, and transmission blocking activity assessed using a standardised membrane feeding assay (SMFA). Conclusion: Induction of high antibody tires using this vaccine platform could be used together with other control measures to achieve elimination and/or eradication of the disease at a local or national level

Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer

<p>Aims: DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer.</p> <p>Methods and Results: DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α.</p> <p>Conclusions: In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.</p&gt

Silicon CMOS photonics platform for enabling high-speed DQPSK transceivers

In this work we review the results obtained under the framework of FP7-HELIOS project for integrated DQPSK transceivers in silicon photonics. A differential DQPSK receiver with balanced zero biased Germanium photodiodes has been demonstrated at 10Gbit/s with an error floor around 10(-15). Furthermore, DPSK modulation up to 10Gbit/s with a bit error rate below 10(-9) is also demonstrated using a silicon push-pull operated dual-drive Mach-Zehnder modulator (MZM) based on carrier depletion. The results indicate the potential of the silicon CMOS photonics platform for boosting next-generation optical networks based on advanced modulation formats

Testosterone Is Associated with Erectile Dysfunction: A Cross-Sectional Study in Chinese Men

Testosterone is essential for the regulation of erectile physiology, but the relationship between low testosterone and erectile dysfunction (ED) has not been firmly established.To examine the association between serum total, free and bio-available testosterone and ED in a population-based sample.A consecutive series of 1776 men aged 20–77 participated in the routine physical examination from September 2009 to December 2009 in Guangxi, China. ED was assessed using the five-item International Index of Erectile Function (IIEF-5) questionnaire. Total testosterone (TT), sex hormone binding globulin (SHBG) and other biochemical profiles were measured. Free testosterone (FT) and bio-available testosterone (BT) were calculated based on Vermeulen’s formula. Data were collected with regard to smoking, alcoholic drinking, physical activity and metabolic syndrome.The prevalence of ED (IIEF-5<22) was 47.6%. Men with ED were significantly older, and more prone to smoke cigarettes (≥20 cigarettes/day) or drink alcohol (≥3 drinks/week), and more likely to have elevated blood pressure (P = 0.036) or hyperglycemia (P<0.001) compared with those without ED. The significant increase in SHBG with age was parallel to its increase with increasing severity of ED (P<0.001). The obscure increase in TT across the ED status was detected without significance (P = 0.418), but TT was positively associated with ED after adjustment for age [odds ratio (OR)  = 1.02, 95% CI (confidence internal): 1.00–1.04]. FT and BT were inversely associated with ED (OR = 0.14, 95%CI: 0.06–0.33; OR = 0.92 (95%CI: 0.89–0.96, respectively) in the univariate analysis, and this inverse association appeared to be independent of smoking status, alcoholic drinking, physical activity, hyper-triglyceridemia and hyperglycemia.FT and BT are inversely related to worsening ED, whereas the positive association between TT and ED is most likely due to the increase in SHBG

The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men

&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor alpha gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD(a)) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMD(a), a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMD(a) and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data replicate previous associations found between SNPs in the 6q25 locus and BMD(a) at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.&lt;/p&gt

Methods for environment: productivity trade-off analysis in agricultural systems

Trade-off analysis has become an increasingly important approach for evaluating system level outcomes of agricultural production and for prioritising and targeting management interventions in multi-functional agricultural landscapes. We review the strengths and weakness of different techniques available for performing trade-off analysis. These techniques, including mathematical programming and participatory approaches, have developed substantially in recent years aided by mathematical advancement, increased computing power, and emerging insights into systems behaviour. The strengths and weaknesses of the different approaches are identified and discussed, and we make suggestions for a tiered approach for situations with different data availability. This chapter is a modified and extended version of Klapwijk et al. (2014)

Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS