Evaluation of Acellular Dermis for Closure of Abdominal Wall Defects in a Rat Model

Background: Abdominal wall repair can be performed with synthetic or biological materials. Biological materials may reduce the risk of infections and fibrosis. The aim of this study was to evaluate two acellular human dermis products. Materials and Methods: A rat model was used to compare the two materials. One was prepared using low concentrations of NaOH; the other material was SureDerm (TM), which is commercially available. Full thickness defects were prepared in the abdominal wall and closed with the materials. Rats were sacrificed at 1 or 4 months after operation and the numbers of adhesions to the bowels were scored. Samples were taken for histological analysis and to measure the breaking strength. Results: In both groups a good functional integration of the implants with the abdominal wall was observed. There was no adhesion formation with the bowels in the group with the NaOH prototype. In the SureDerm group, 4 out of 7 rats showed only small adhesions at 4 months after operation. Breaking strength of the healed tissue was significantly higher in the NaOH prototype group at 4 months after operation (p < 0.0026). Conclusions: The results indicate that both human acellular dermis products may be used in clinical trials for closure of abdominal wall defects

Anti‐dopamine D2 receptor antibodies in chronic tic disorders

AIM: To investigate the association between circulating anti-dopamine D2 receptor (D2R) autoantibodies and the exacerbation of tics in children with chronic tic disorders (CTDs). METHOD: One hundred and thirty-seven children with CTDs (108 males, 29 females; mean age [SD] 10y 0mo [2y 7mo], range 4-16y) were recruited over 18 months. Patients were assessed at baseline, at tic exacerbation, and at 2 months after exacerbation. Serum anti-D2R antibodies were evaluated using a cell-based assay and blinded immunofluorescence microscopy scoring was performed by two raters. The association between visit type and presence of anti-D2R antibodies was measured with McNemar's test and repeated-measure logistic regression models, adjusting for potential demographic and clinical confounders. RESULTS: At exacerbation, 11 (8%) participants became anti-D2R-positive ('early peri-exacerbation seroconverters'), and nine (6.6%) became anti-D2R-positive at post-exacerbation ('late peri-exacerbation seroconverters'). The anti-D2R antibodies were significantly associated with exacerbations when compared to baseline (McNemar's odds ratio=11, p=0.003) and conditional logistic regression confirmed this association (Z=3.49, p<0.001) after adjustment for demographic and clinical data and use of psychotropic drugs. INTERPRETATION: There is a potential association between immune mechanisms and the severity course of tics in adolescents with CTDs

AFLP analysis reveals a lack of phylogenetic structure within Solanum section Petota

<p>Abstract</p> <p>Background</p> <p>The secondary genepool of our modern cultivated potato (<it>Solanum tuberosum </it>L.) consists of a large number of tuber-bearing wild <it>Solanum </it>species under <it>Solanum </it>section <it>Petota</it>. One of the major taxonomic problems in section <it>Petota </it>is that the series classification (as put forward by Hawkes) is problematic and the boundaries of some series are unclear. In addition, the classification has received only partial cladistic support in all molecular studies carried out to date.</p> <p>The aim of the present study is to describe the structure present in section <it>Petota</it>. When possible, at least 5 accessions from each available species and 5 individual plants per accession (totally approx. 5000 plants) were genotyped using over 200 AFLP markers. This resulted in the largest dataset ever constructed for <it>Solanum </it>section <it>Petota</it>. The data obtained are used to evaluate the 21 series hypothesis put forward by Hawkes and the 4 clade hypothesis of Spooner and co-workers.</p> <p>Results</p> <p>We constructed a NJ tree for 4929 genotypes. For the other analyses, due to practical reasons, a condensed dataset was created consisting of one representative genotype from each available accession. We show a NJ jackknife and a MP jackknife tree. A large part of both trees consists of a polytomy. Some structure is still visible in both trees, supported by jackknife values above 69. We use these branches with >69 jackknife support in the NJ jackknife tree as a basis for informal species groups. The informal species groups recognized are: Mexican diploids, Acaulia, Iopetala, Longipedicellata, polyploid Conicibaccata, diploid Conicibaccata, Circaeifolia, diploid Piurana and tetraploid Piurana.</p> <p>Conclusion</p> <p>Most of the series that Hawkes and his predecessors designated can not be accepted as natural groups, based on our study. Neither do we find proof for the 4 clades proposed by Spooner and co-workers. A few species groups have high support and their inner structure displays also supported subdivisions, while a large part of the species cannot be structured at all. We believe that the lack of structure is not due to any methodological problem but represents the real biological situation within section <it>Petota</it>.</p

Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

CFHTLenS: cosmological constraints from a combination of cosmic shear two-point and three-point correlations

Higher order, non-Gaussian aspects of the large-scale structure carry valuable information on structure formation and cosmology, which is complementary to second-order statistics. In this work, we measure second- and third-order weak-lensing aperture-mass moments from the Canada–France–Hawaii Lensing Survey (CFHTLenS) and combine those with cosmic microwave background (CMB) anisotropy probes. The third moment is measured with a significance of 2σ. The combined constraint on Σ8 = σ8(Ωm/0.27)α is improved by 10 per cent, in comparison to the second-order only, and the allowed ranges for Ωm and σ8 are substantially reduced. Including general triangles of the lensing bispectrum yields tighter constraints compared to probing mainly equilateral triangles. Second- and third-order CFHTLenS lensing measurements improve Planck CMB constraints on Ωm and σ8 by 26 per cent for flat Λ cold dark matter. For a model with free curvature, the joint CFHTLenS–Planck result is Ωm = 0.28 ± 0.02 (68 per cent confidence), which is an improvement of 43 per cent compared to Planck alone. We test how our results are potentially subject to three astrophysical sources of contamination: source-lens clustering, the intrinsic alignment of galaxy shapes, and baryonic effects. We explore future limitations of the cosmological use of third-order weak lensing, such as the non-linear model and the Gaussianity of the likelihood function

Blood Flow and Glucose Metabolism in Stage IV Breast Cancer: Heterogeneity of Response During Chemotherapy

Objective: The purpose of the study was to compare early changes in blood flow (BF) and glucose metabolism (MRglu) in metastatic breast cancer lesions of patients treated with chemotherapy. Methods: Eleven women with stage IV cancer and lesions in breast, lymph nodes, liver, and bone were scanned before treatment and after the first course of chemotherapy. BF, distribution volume of water (Vd), MRglu/BF ratio, MRgluand its corresponding rate constants K1and k3were compared per tumor lesion before and during therapy. Results: At baseline, mean BF and MRgluvaried among different tumor lesions, but mean Vdwas comparable in all lesions. After one course of chemotherapy, mean MRgludecreased in all lesions. Mean BF decreased in breast and node lesions and increased in bone lesions. Vddecreased in breast and nodes, but did not change in bone lesions. The MRglu/BF ratio decreased in breast and bone lesions and increased in node lesions. In patients with multiple tumor lesions BF and MRgluresponse could be very heterogeneous, even within similar types of metastases. BF and MRgluincreased in lesions of patients who experienced early disease progression or showed no response during clinical follow-up. Conclusion: BF and MRgluchanges separately give unique information on different aspects of tumor response to chemotherapy. Changes in BF and MRgluparameters can be remarkably heterogeneous in patients with multiple lesions

Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

Background: Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-alpha) and melphalan, followed by delayed surgical resection and adjuvant external-beam radiotherapy is a limb salvage treatment strategy for locally advanced soft tissue sarcomas. The long-term vascular side effects of this combined procedure were evaluated. Methods: Thirty-two patients were treated for a locally advanced sarcoma of the upper (n = 5) or lower limb (n = 27). All patients underwent a noninvasive vascular work-up. Results: Five patients underwent a leg amputation, in two cases due to critical leg ischemia 10 years after ILP. With a median follow-up of 88 (range, 17-159) months, none of the patients with a salvaged lower leg (n = 22) experienced peripheral arterial occlusive disease. Ankle-brachial index (ABI) measurements in the involved leg (median, 1.02; range, .50-1.20) showed a significant decrease compared with the contralateral leg (median, 1.09; range, .91-1.36, P = .001). Pulsatility index (PI) was decreased in the treated leg in 17 of 22 patients at the femoral level (median, 6.30; range, 2.1-23.9 vs. median, 7.35; range, 4.8-21.9; P = .011) and in 19 of 20 patients at popliteal level (median, 8.35; range, 0-21.4 vs. median, 10.95; range, 8.0-32.6; P <.0005). In patients with follow-up of > 5 years, there was more often a decrease in ABI (P = .024) and PI at femoral level (P = .011). Conclusions: ILP followed by resection and external-beam radiotherapy can lead to major late vascular morbidity that requires amputation. Objective measurements show a time-related decrease of ABI and femoral PI in the treated extremity

Baseline and longitudinal variability of normal tissue uptake values of [F-18]-fluorothymidine-PET images

Purpose [18F]-fluorothymidine ([18F]-FLT) is a PET-tracer enabling in-vivo visualization and quantification of tumor cell proliferation. For qualitative and quantitative analysis, adequate knowledge of normal tissue uptake is indispensable. This study aimed to quantitatively investigate baseline tracer uptake of blood pool, lung, liver and bone marrow and their precision, and to assess the longitudinal effect of systemic treatment on biodistribution. Methods 18F–FLT-PET(/CT) scans (dynamic or static) of 90 treatment-naïve oncological patients were retrospectively evaluated. Twenty-three patients received double baseline scans, and another 39 patients were also scanned early and late during systemic treatment with a tyrosine kinase inhibitor. Reproducible volume of interest were placed in blood pool, lung, liver, and bone marrow. For semi-quantitative analysis, SUVmean, SUVmax, and SUVpeak with several normalizations were derived. Results SUVs of basal lung, liver, and bone marrow were not significantly different between averaged dynamic and static images, in contrast with blood pool and apical lung. Highest repeatability was seen for liver and bone marrow, with repeatability coefficients of 18.6% and 20.4% when using SUVpeak. Systemic treatment with TKIs both increased and decreased normal tissue tracer uptake at early and late time points during treatment. Conclusion Simultaneous evaluation of liver and bone marrow uptake in longitudinal response studies may be used to assess image quality, where changes in uptake outside repeatability limits should trigger investigators to perform additional quality control on individual PET images. Advances in knowledge For [18F]-FLT PET images, liver and bone marrow have low intra-patient variability when quantified with SUVpeak, but may be affected by systemic treatment. Implications for patient care In [18F]-FLT-PET response monitoring trials, liver and bone marrow uptake may be used for quality control of [18F]-FLT PET images

Phenology of Scramble Polygyny in a Wild Population of Chrysolemid Beetles: The Opportunity for and the Strength of Sexual Selection

Recent debate has highlighted the importance of estimating both the strength of sexual selection on phenotypic traits, and the opportunity for sexual selection. We describe seasonal fluctuations in mating dynamics of Leptinotarsa undecimlineata (Coleoptera: Chrysomelidae). We compared several estimates of the opportunity for, and the strength of, sexual selection and male precopulatory competition over the reproductive season. First, using a null model, we suggest that the ratio between observed values of the opportunity for sexual selections and their expected value under random mating results in unbiased estimates of the actual nonrandom mating behavior of the population. Second, we found that estimates for the whole reproductive season often misrepresent the actual value at any given time period. Third, mating differentials on male size and mobility, frequency of male fighting and three estimates of the opportunity for sexual selection provide contrasting but complementary information. More intense sexual selection associated to male mobility, but not to male size, was observed in periods with high opportunity for sexual selection and high frequency of male fights. Fourth, based on parameters of spatial and temporal aggregation of female receptivity, we describe the mating system of L. undecimlineata as a scramble mating polygyny in which the opportunity for sexual selection varies widely throughout the season, but the strength of sexual selection on male size remains fairly weak, while male mobility inversely covaries with mating success. We suggest that different estimates for the opportunity for, and intensity of, sexual selection should be applied in order to discriminate how different behavioral and demographic factors shape the reproductive dynamic of populations