The surgical technique and the age of the horse both influence the outcome of mosaicplasty in a cadaver equine stifle model

Six pieces of grafts, 6.5 mm in diameter, 20 mm in length, were taken from each of 170 cadaver hindlimbs, using the cranial surface of the medial femoral trochlea for harvesting. The age of the horses varied between 4 months and 23 years. 30 limbs under the age of 12 years were selected for transplantation. Three of six grafts were transplanted into the medial femoral condyle using different combinations of tunnel depth and dilation. With ageing, a significant decline in transplantability was detected. In general, mosaicplasty cannot be recommended in horses above 11 years. Based on a previous clinical case (Bodo et al., 2000), a good surface alignment was indeed achieved with a combination of graft length drilling and dilation in most cases. However, the occasional entrapment of cartilage debris under the graft prevented perfect alignment in the present cadaver study in 27% of the grafts transplanted in this manner. Since the protrusion of grafts never exceeded 1.5 mm, we conclude that drilling 3–5 mm deeper than graft length with graft length deep dilation can avoid disadvantageous protrusion of the transplanted hyaline cartilage caps, achieving bone decompression at the same time

Multimodal Dependent Type Theory

We introduce MTT, a dependent type theory which supports multiple modalities. MTT is parametrized by a mode theory which specifies a collection of modes, modalities, and transformations between them. We show that different choices of mode theory allow us to use the same type theory to compute and reason in many modal situations, including guarded recursion, axiomatic cohesion, and parametric quantification. We reproduce examples from prior work in guarded recursion and axiomatic cohesion, thereby demonstrating that MTT constitutes a simple and usable syntax whose instantiations intuitively correspond to previous handcrafted modal type theories. In some cases, instantiating MTT to a particular situation unearths a previously unknown type theory that improves upon prior systems. Finally, we investigate the metatheory of MTT. We prove the consistency of MTT and establish canonicity through an extension of recent type-theoretic gluing techniques. These results hold irrespective of the choice of mode theory, and thus apply to a wide variety of modal situations

Classic Kaposi's sarcoma in morocco: clinico -epidemiological study at the national institute of oncology

<p>Abstract</p> <p>Background</p> <p>Classic Kaposi's sarcoma (CKS) is a rare disease likely associated with human herpes virus 8 (HHV-8) infection, and occurs predominantly in Jewish, Mediterranean and middle eastern men .There is a dearth of data in Moroccan patients with CKS regarding epidemiology, clinical characteristics and outcomes. This report examines a cohort of patients with CKS evaluated at the national institute of oncology over 11-year period.</p> <p>Methods</p> <p>A retrospective analysis of patients referred to the national institute of oncology with classical Kaposi sarcoma, between January 1998 and February 2008, was performed. Reviewed information included demographics, clinical and pathological staging, death or last follow-up.</p> <p>Results</p> <p>During the study period, 56 patients with a diagnosis of CKS have been referred to our hospital. There were 11(19,7%) females and 45 (80,3%) males (male-to-female ratio: 4:1). Mean age at diagnosis was 61,7 ± 15 (range: 15- 86 years). Nodules and/or plaques were the most frequent type of lesion. The most common location was the lower limbs, particularly the distal lower extremity (90%). In addition to skin involvement, visceral spread was evident in 9 cases. The most common visceral involvement sites were lymph nodes (44%), lung (22%), and gastrointestinal tract (22%). Associated lymphoedema was seen in 24 (42%) of the patients. There were 18 stage I patients (32,14%), 8: stage II (14,28%), 21 stage III(37,5%) and 9 stage IV (16,07%). A second primary malignancy was diagnosed in 6 cases (10,7%), none of the reticuloendothelial system.</p> <p>With a median follow-up of 45 months, 38 (67,8) patients are alive, of whom 25 (65,78%) patients with stable disease, five with progressive disease currently under systemic chemotherapy and 8(21,05%) are alive and free of disease, over a mean interval of 5 years.</p> <p>Conclusion</p> <p>This is the largest reported series in our context. In Morocco, CKS exhibits some special characteristics including a disseminated skin disease at diagnosis especially in men, a more common visceral or lymph node involvement and a less frequent association with second malignancies.</p

Heading Down the Wrong Pathway: on the Influence of Correlation within Gene Sets

<p>Abstract</p> <p>Background</p> <p>Analysis of microarray experiments often involves testing for the overrepresentation of pre-defined sets of genes among lists of genes deemed individually significant. Most popular gene set testing methods assume the independence of genes within each set, an assumption that is seriously violated, as extensive correlation between genes is a well-documented phenomenon.</p> <p>Results</p> <p>We conducted a meta-analysis of over 200 datasets from the Gene Expression Omnibus in order to demonstrate the practical impact of strong gene correlation patterns that are highly consistent across experiments. We show that a common independence assumption-based gene set testing procedure produces very high false positive rates when applied to data sets for which treatment groups have been randomized, and that gene sets with high internal correlation are more likely to be declared significant. A reanalysis of the same datasets using an array resampling approach properly controls false positive rates, leading to more parsimonious and high-confidence gene set findings, which should facilitate pathway-based interpretation of the microarray data.</p> <p>Conclusions</p> <p>These findings call into question many of the gene set testing results in the literature and argue strongly for the adoption of resampling based gene set testing criteria in the peer reviewed biomedical literature.</p

Antibiotic-induced release of small extracellular vesicles (exosomes) with surface-associated DNA

Recently, biological roles of extracellular vesicles (which include among others exosomes, microvesicles and apoptotic bodies) have attracted substantial attention in various fields of biomedicine. Here we investigated the impact of sustained exposure of cells to the fluoroquinolone antibiotic ciprofloxacin on the released extracellular vesicles. Ciprofloxacin is widely used in humans against bacterial infections as well as in cell cultures against Mycoplasma contamination. However, ciprofloxacin is an inducer of oxidative stress and mitochondrial dysfunction of mammalian cells. Unexpectedly, here we found that ciprofloxacin induced the release of both DNA (mitochondrial and chromosomal sequences) and DNA-binding proteins on the exofacial surfaces of small extracellular vesicles referred to in this paper as exosomes. Furthermore, a label-free optical biosensor analysis revealed DNA-dependent binding of exosomes to fibronectin. DNA release on the surface of exosomes was not affected any further by cellular activation or apoptosis induction. Our results reveal for the first time that prolonged low-dose ciprofloxacin exposure leads to the release of DNA associated with the external surface of exosomes

Comparative Functional Genomics Analysis of NNK Tobacco-Carcinogen Induced Lung Adenocarcinoma Development in Gprc5a-Knockout Mice

Background: Improved understanding of lung cancer development and progression, including insights from studies of animal models, are needed to combat this fatal disease. Previously, we found that mice with a knockout (KO) of G-protein coupled receptor 5A (Gprc5a) develop lung tumors after a long latent period (12 to 24 months). Methodology/Principal Findings: To determine whether a tobacco carcinogen will enhance tumorigenesis in this model, we administered 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) i.p. to 2-months old Gprc5a-KO mice and sacrificed groups (n = 5) of mice at 6, 9, 12, and 18 months later. Compared to control Gprc5a-KO mice, NNK-treated mice developed lung tumors at least 6 months earlier, exhibited 2- to 4-fold increased tumor incidence and multiplicity, and showed a dramatic increase in lesion size. A gene expression signature, NNK-ADC, of differentially expressed genes derived by transcriptome analysis of epithelial cell lines from normal lungs of Gprc5a-KO mice and from NNK-induced adenocarcinoma was highly similar to differential expression patterns observed between normal and tumorigenic human lung cells. The NNK-ADC expression signature also separated both mouse and human adenocarcinomas from adjacent normal lung tissues based on publicly available microarray datasets. A key feature of the signature, up-regulation of Ube2c, Mcm2, and Fen1, was validated in mouse normal lung and adenocarcinoma tissues and cells by immunohistochemistry and western blotting, respectively