Kypho-IORT - a novel approach of intraoperative radiotherapy during kyphoplasty for vertebral metastases

<p>Abstract</p> <p>Background</p> <p>Instable and painful vertebral metastases in patients with progressive visceral metastases present a common therapeutic dilemma. We developed a novel approach to deliver intraoperative radiotherapy (IORT) during kyphoplasty and report the first treated case.</p> <p>Methods/Results</p> <p>60 year old patient with metastasizing breast cancer under chemotherapy presented with a newly diagnosed painful metastasis in the 12^ththoracic vertebra. Under general anaesthesia, a bipedicular approach into the vertebra was chosen with insertion of specially designed metallic sleeves to guide the electron drift tube of the miniature X-ray generator (INTRABEAM, Carl Zeiss Surgical, Oberkochen, Germany). This was inserted with a novel sheet designed for this approach protecting the drift tube. A radiation dose of 8 Gy in 5 mm distance (50 kV X-rays) was delivered. The kyphoplasty balloons (KyphX, Kyphon Inc, Sunnyvale) were inflated after IORT and polymethylmethacrylate cement was injected. The whole procedure lasted less than 90 minutes.</p> <p>Conclusion</p> <p>In conclusion, this novel, minimally invasive procedure can be performed in standard operating rooms and may become a valuable option for patients with vertebral metastases providing immediate stability and local control. A phase I/II study is under way to establish the optimal dose prescription.</p

Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections

Copyright: © 2013 Baron et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by ANR (ANR-07-BLAN-0214 and ANR-12-EMMA-00O7-01), CNRS and INRA. PvW was financially supported by the BBSRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Temperature-Dependent Modulation of Chromosome Segregation in msh4 Mutants of Budding Yeast

BACKGROUND:In many organisms, homologous chromosomes rely upon recombination-mediated linkages, termed crossovers, to promote their accurate segregation at meiosis I. In budding yeast, the evolutionarily conserved mismatch-repair paralogues, Msh4 and Msh5, promote crossover formation in conjunction with several other proteins, collectively termed the Synapsis Initiation Complex (SIC) proteins or 'ZMM's (Zip1-Zip2-Zip3-Zip4-Spo16, Msh4-Msh5, Mer3). zmm mutants show decreased levels of crossovers and increased chromosome missegregation, which is thought to cause decreased spore viability. PRINCIPAL FINDINGS:In contrast to other ZMM mutants, msh4 and msh5 mutants show improved spore viability and chromosome segregation in response to elevated temperature (23 degrees C versus 33 degrees C). Crossover frequencies in the population of viable spores in msh4 and msh5 mutants are similar at both temperatures, suggesting that temperature-mediated chromosome segregation does not occur by increasing crossover frequencies. Furthermore, meiotic progression defects at elevated temperature do not select for a subpopulation of cells with improved segregation. Instead, another ZMM protein, Zip1, is important for the temperature-dependent improvement in spore viability. CONCLUSIONS:Our data demonstrate interactions between genetic (zmm status) and environmental factors in determining chromosome segregation

Reconnaissance of the HR 8799 exosolar system. II. Astrometry and orbital motion

This is the final version of the article. Available from the American Astronomical Society / IOP Publishing via the DOI in this record.We present an analysis of the orbital motion of the four substellar objects orbiting HR 8799. Our study relies on the published astrometric history of this system augmented with an epoch obtained with the Project 1640 coronagraph with an integral field spectrograph (IFS) installed at the Palomar Hale telescope. We first focus on the intricacies associated with astrometric estimation using the combination of an extreme adaptive optics system (PALM-3000), a coronagraph, and an IFS. We introduce two new algorithms. The first one retrieves the stellar focal plane position when the star is occulted by a coronagraphic stop. The second one yields precise astrometric and spectrophotometric estimates of faint point sources even when they are initially buried in the speckle noise. The second part of our paper is devoted to studying orbital motion in this system. In order to complement the orbital architectures discussed in the literature, we determine an ensemble of likely Keplerian orbits for HR 8799bcde, using a Bayesian analysis with maximally vague priors regarding the overall configuration of the system. Although the astrometric history is currently too scarce to formally rule out coplanarity, HR 8799d appears to be misaligned with respect to the most likely planes of HR 8799bce orbits. This misalignment is sufficient to question the strictly coplanar assumption made by various authors when identifying a Laplace resonance as a potential architecture. Finally, we establish a high likelihood that HR 8799de have dynamical masses below 13 MJup, using a loose dynamical survival argument based on geometric close encounters. We illustrate how future dynamical analyses will further constrain dynamical masses in the entire system

A new efficient trial design for assessing reliability of ankle-brachial index measures by three different observer groups

BACKGROUND: The usual method of assessing the variability of a measure such as the ankle brachial index (ABI) as a function of different observer groups is to obtain repeated measurements. Because the number of possible observer-subject combinations is impractically large, only a few small studies on inter- and intraobserver variability of ABI measures have been carried out to date. The present study proposes a new and efficient study design. This paper describes the study methodology. METHODS: Using a partially balanced incomplete block design, six angiologists, six primary-care physicians and six trained medical office assistants performed two ABI measurements each on six individuals from a group of 36 unselected subjects aged 65–70 years. Each test subject is measured by one observer from each of the three observer groups, and each observer measures exactly six of the 36 subjects in the group. Each possible combination of two observers occurs exactly once per patient and is not repeated on a second subject. The study involved four groups of 36 subjects (144), plus standbys. RESULTS: The 192 volunteers present at the study day were similar in terms of demographic characteristics and vascular risk factors: mean age 68.6 ± 1.7; mean BMI 29.1 ± 4.6; mean waist-hip ratio 0.92 ± 0.09; active smokers 12%; hypertension 60.9%; hypercholesterolemia 53.4%; diabetic 17.2%. A complete set of ABI measurements (three observers performing two Doppler measurements each) was obtained from 108 subjects. From all other subjects at least one ABI measurement was obtained. The mean ABI was 1.08 (± 0.13), 15 (7.9%) volunteers had an ABI <0.9, and none had an ABI >1.4, i.e. a ratio that may be associated with increased stiffening of the arterial walls. CONCLUSION: This is the first large-scale study investigating the components of variability and thus reliability in ABI measurements. The advantage of the new study design introduced here is that only one sixth of the number of theoretically possible measurements is required to obtain information about measurement errors. Bland-Altman plots show that there are only small differences and no systematic bias between the observers from three occupational groups with different training backgrounds

Aromatase gene and its effects on growth, reproductive and maternal ability traits in a multibreed sheep population from Brazil

We determined the polymorphism C242T of the aromatase gene (Cyp19) and its allelic frequency, as well as the effect of the variants on productive and reproductive traits in 71 purebred Santa Inês sheep, 13 purebred Brazilian Somali sheep, nine purebred Poll Dorset sheep, and 18 crossbred 1/2 Dorper sheep. The animals were genotyped using the PCR-RFLP technique. The influence of the animal's genotype on its performance or on the performance of its lambs was analyzed by the least square method. Another factor assessed was the importance of the animal's genotype in analysis models for quantitative breeding value estimates, and whether there were differences among the averages of breeding values of animals with different genotypes for this gene. In the sample studied, no AA individuals were observed; the AB and BB frequencies were 0.64 and 0.36, respectively. All Brazilian Somali sheep were of genotype BB. All 1/2 Dorper BB animals presented a lower age at first lambing, and the Santa Inês BB ewes presented a lower lambing interval. In these same genetic groups, AB ewes presented higher litter weight at weaning. This is evidence that BB ewes have a better reproductive performance phenotype, whereas AB ewes present a better maternal ability phenotype. However, in general, animals with genotype AB presented better average breeding values than those with genotype BB

Osteopoikilosis and multiple exostoses caused by novel mutations in LEMD3 and EXT1 genes respectively - coincidence within one family

<p>Abstract</p> <p>Background</p> <p>Osteopoikilosis is a rare autosomal dominant genetic disorder, characterised by the occurrence of the hyperostotic spots preferentially localized in the epiphyses and metaphyses of the long bones, and in the carpal and tarsal bones <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. Heterozygous <it>LEMD3 </it>gene mutations were shown to be the primary cause of the disease <abbrgrp><abbr bid="B2">2</abbr></abbrgrp>. Association of the primarily asymptomatic osteopokilosis with connective tissue nevi of the skin is categorized as Buschke-Ollendorff syndrome (BOS) <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>. Additionally, osteopoikilosis can coincide with melorheostosis (MRO), a more severe bone disease characterised by the ectopic bone formation on the periosteal and endosteal surface of the long bones <abbrgrp><abbr bid="B4">4</abbr><abbr bid="B5">5</abbr><abbr bid="B6">6</abbr></abbrgrp>. However, not all MRO affected individuals carry germ-line <it>LEMD3 </it>mutations <abbrgrp><abbr bid="B7">7</abbr></abbrgrp>. Thus, the genetic cause of MRO remains unknown. Here we describe a familial case of osteopoikilosis in which a novel heterozygous <it>LEMD3 </it>mutation coincides with a novel mutation in <it>EXT1</it>, a gene involved in aetiology of multiple exostosis syndrome. The patients affected with both <it>LEMD3 </it>and <it>EXT1 </it>gene mutations displayed typical features of the osteopoikilosis. There were no additional skeletal manifestations detected however, various non-skeletal pathologies coincided in this group.</p> <p>Methods</p> <p>We investigated <it>LEMD3 </it>and <it>EXT1 </it>in the three-generation family from Poland, with 5 patients affected with osteopoikilosis and one child affected with multiple exostoses.</p> <p>Results</p> <p>We found a novel c.2203C > T (p.R735X) mutation in exon 9 of <it>LEMD3</it>, resulting in a premature stop codon at amino acid position 735. The mutation co-segregates with the osteopoikilosis phenotype and was not found in 200 ethnically matched controls. Another new substitution G > A was found in <it>EXT1 </it>gene at position 1732 (cDNA) in Exon 9 (p.A578T) in three out of five osteopoikilosis affected family members. Evolutionary conservation of the affected amino acid suggested possible functional relevance, however no additional skeletal manifestations were observed other then those specific for osteopoikilosis. Finally in one member of the family we found a splice site mutation in the <it>EXT1 </it>gene intron 5 (IVS5-2 A > G) resulting in the deletion of 9 bp of cDNA encoding three evolutionarily conserved amino acid residues. This child patient suffered from a severe form of exostoses, thus a causal relationship can be postulated.</p> <p>Conclusions</p> <p>We identified a new mutation in <it>LEMD3 </it>gene, accounting for the familial case of osteopoikilosis. In the same family we identified two novel <it>EXT1 </it>gene mutations. One of them A598T co-incided with the <it>LEMD3 </it>mutation. Co-incidence of <it>LEMD3 </it>and <it>EXT1 </it>gene mutations was not associated with a more severe skeletal phenotype in those patients.</p

Staged cardiovascular magnetic resonance for differential diagnosis of Troponin T positive patients with low likelihood for acute coronary syndrome

<p>Abstract</p> <p>Background</p> <p>Cardiac Troponin-T (cTnT) is a cardio-specific indicator of myocardial necrosis due to ischemic or non-ischemic events. Considering the multiple causes of myocardial injury and treatment consequences there is great clinical need to clarify the underlying reason for cTnT release. We sought to implement acute CMR as a non-invasive imaging method for differential diagnosis of elevated cTnT in chest-pain unit (CPU) patients with non-conclusive symptoms and ECG-changes and a low to intermediate probability for coronary artery disease (CAD).</p> <p>Results</p> <p>CPU patients (n = 29) who had positive cTnT were scanned at 1.5T with a new step-by-step CMR algorithm including cine-, perfusion-, T2-, angiography-and late gadolinium enhancement (LGE) imaging. For comparison patients also underwent echocardiography and coronary angiography if necessary. CMR was conducted successfully in all patients and detected 93% of cTnT releases of unknown cause, without adverse hemodynamic or arrhythmic events. Acute myocardial infarction was detected in 11, pulmonary embolism in 6, myocarditis in 5, renal disease and cardiomyopathy in 2, storage disorder in 1 patient. In 2 patients CMR was unable to reveal the cause of cTnT elevations. Mean CMR scan-time was 35 ± 8 min. In 4 patients, CMR led to immediate coronary angiography with correct prediction of the infarct related artery.</p> <p>Conclusions</p> <p>We implemented a novel CMR algorithm to show the clinical value and practical feasibility of acute CMR in a non-conclusive patient cohort with unclear cTnT elevation. Since this pilot study has shown the feasibility of CMR in CPU patients, further prospective studies are warranted to compare CMR with other imaging modalities.</p

The G67E mutation in hMLH1 is associated with an unusual presentation of Lynch syndrome

Germline mutations in the mismatch repair (MMR) genes are associated with Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Here, we characterise a variant of hMLH1 that confers a loss-of-function MMR phenotype. The mutation changes the highly conserved Gly67 residue to a glutamate (G67E) and is reminiscent of the hMLH1-p.Gly67Arg mutation, which is present in several Lynch syndrome cohorts. hMLH1-Gly67Arg has previously been shown to confer loss-of-function (Shimodaira et al, 1998), and two functional assays suggest that the hMLH1-Gly67Glu protein fails to sustain normal MMR functions. In the first assay, hMLH1-Gly67Glu abolishes the protein's ability to interfere with MMR in yeast. In the second assay, mutation of the analogous residue in yMLH1 (yMLH1-Gly64Glu) causes a loss-of-function mutator phenotype similar to yMLH1-Gly64Arg. Despite these molecular similarities, an unusual spectrum of tumours is associated with hMLH1-Gly67Glu, which is not typical of those associated with Lynch syndrome and differs from those found in families carrying the hMLH1-Gly67Arg allele. This suggests that hMLH1 may have different functions in certain tissues and/or that additional factors may modify the influence of hMLH1 mutations in causing Lynch syndrome