The role of laparoscopic biopsies in lumbar spondylodiscitis.

Infection of an intervertebral disk is a serious condition. Diagnosis often is elusive and difficult. It is imperative to obtain appropriate microbiological specimens before initiation of treatment. The authors describe a 51-year-old woman with lumbar spondylodiscitis that was because of infection after the placement of an epidural catheter for postoperative analgesia. A spinal magnetic resonance imaging confirmed the diagnosis, but computed tomography-guided fine needle biopsy did not provide adequate material for a microbiologic diagnosis. Laparoscopic biopsies of the involved disk provided good specimens and a diagnosis of Propionibacterium acnes infection. The authors believe that this minimally invasive procedure should be performed when computed tomography-guided fine needle biopsy does not provide a microbiologic diagnosis in spondylodiscitis.

PAX3/FOXO1 fusion gene status is the key prognostic molecular marker in rhabdomyosarcoma and significantly improves current risk stratification.

PURPOSE: To improve the risk stratification of patients with rhabdomyosarcoma (RMS) through the use of clinical and molecular biologic data. PATIENTS AND METHODS: Two independent data sets of gene-expression profiling for 124 and 101 patients with RMS were used to derive prognostic gene signatures by using a meta-analysis. These and a previously published metagene signature were evaluated by using cross validation analyses. A combined clinical and molecular risk-stratification scheme that incorporated the PAX3/FOXO1 fusion gene status was derived from 287 patients with RMS and evaluated. RESULTS: We showed that our prognostic gene-expression signature and the one previously published performed well with reproducible and significant effects. However, their effect was reduced when cross validated or tested in independent data and did not add new prognostic information over the fusion gene status, which is simpler to assay. Among nonmetastatic patients, patients who were PAX3/FOXO1 positive had a significantly poorer outcome compared with both alveolar-negative and PAX7/FOXO1-positive patients. Furthermore, a new clinicomolecular risk score that incorporated fusion gene status (negative and PAX3/FOXO1 and PAX7/FOXO1 positive), Intergroup Rhabdomyosarcoma Study TNM stage, and age showed a significant increase in performance over the current risk-stratification scheme. CONCLUSION: Gene signatures can improve current stratification of patients with RMS but will require complex assays to be developed and extensive validation before clinical application. A significant majority of their prognostic value was encapsulated by the fusion gene status. A continuous risk score derived from the combination of clinical parameters with the presence or absence of PAX3/FOXO1 represents a robust approach to improving current risk-adapted therapy for RMS.

A formin-nucleated actin aster concentrates cell wall hydrolases for cell fusion in fission yeast.

Cell-cell fusion is essential for fertilization. For fusion of walled cells, the cell wall must be degraded at a precise location but maintained in surrounding regions to protect against lysis. In fission yeast cells, the formin Fus1, which nucleates linear actin filaments, is essential for this process. In this paper, we show that this formin organizes a specific actin structure-the actin fusion focus. Structured illumination microscopy and live-cell imaging of Fus1, actin, and type V myosins revealed an aster of actin filaments whose barbed ends are focalized near the plasma membrane. Focalization requires Fus1 and type V myosins and happens asynchronously always in the M cell first. Type V myosins are essential for fusion and concentrate cell wall hydrolases, but not cell wall synthases, at the fusion focus. Thus, the fusion focus focalizes cell wall dissolution within a broader cell wall synthesis zone to shift from cell growth to cell fusion.

Insertion of a malE B-Galactosidase fusion protein into the envelope of Escherichia coli disrupts biogenesis of outer membrane proteins and processing of inner membrane proteins

The synthesis of a membrane-bound MalE ,B-galactosidase hybrid protein, when induced by growth of Escherichia coli on maltose, leads to inhibition of cell division and eventually a reduced rate of mass increase. In addition, the relative rate of synthesis of outer membrane proteins, but not that of inner membrane proteins, was reduced by about 50%o. Kinetic experiments demonstrated that this reduction coincided with the period of maximum synthesis of the hybrid protein (and another maltose-inducible protein, LamB). The accumulation of this abnormal protein in the envelope therefore appeared specifically to inhibit the synthesis, the assembly of outer membrane proteins, or both, indicating that the hybrid protein blocks some export site or causes the sequestration of some limiting factor(s) involved in the export process. Since the MalE protein is normally located in the periplasm, the results also suggest that the synthesis of periplasmic and outer membrane proteins may involve some steps in common. The reduced rate of synthesis of outer membrane proteins was also accompanied by the accumulation in the envelope of at least one outer membrane protein and at least two inner membrane proteins as higher-molecular-weight forms, indicating that processing (removal of the N-terminal signal sequence) was also disrupted by the presence of the hybrid protein. These results may indicate that the assembly of these membrane proteins is blocked at a relatively late step rather than at the level of primary recognition of some site by the signal sequence. In addition, the results suggest that some step common to the biogenesis of quite different kinds of envelope protein is blocked by the presence of the hybrid protein.

Detection of Clinically Significant Prostate Cancer Using Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy: A Systematic Review.

CONTEXT: The current standard for diagnosing prostate cancer in men at risk relies on a transrectal ultrasound-guided biopsy test that is blind to the location of the cancer. To increase the accuracy of this diagnostic pathway, a software-based magnetic resonance imaging-ultrasound (MRI-US) fusion targeted biopsy approach has been proposed. OBJECTIVE: Our main objective was to compare the detection rate of clinically significant prostate cancer with software-based MRI-US fusion targeted biopsy against standard biopsy. The two strategies were also compared in terms of detection of all cancers, sampling utility and efficiency, and rate of serious adverse events. The outcomes of different targeted approaches were also compared. EVIDENCE ACQUISITION: We performed a systematic review of PubMed/Medline, Embase (via Ovid), and Cochrane Review databases in December 2013 following the Preferred Reported Items for Systematic reviews and Meta-analysis statement. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. EVIDENCE SYNTHESIS: Fourteen papers reporting the outcomes of 15 studies (n=2293; range: 13-582) were included. We found that MRI-US fusion targeted biopsies detect more clinically significant cancers (median: 33.3% vs 23.6%; range: 13.2-50% vs 4.8-52%) using fewer cores (median: 9.2 vs 37.1) compared with standard biopsy techniques, respectively. Some studies showed a lower detection rate of all cancer (median: 50.5% vs 43.4%; range: 23.7-82.1% vs 14.3-59%). MRI-US fusion targeted biopsy was able to detect some clinically significant cancers that would have been missed by using only standard biopsy (median: 9.1%; range: 5-16.2%). It was not possible to determine which of the two biopsy approaches led most to serious adverse events because standard and targeted biopsies were performed in the same session. Software-based MRI-US fusion targeted biopsy detected more clinically significant disease than visual targeted biopsy in the only study reporting on this outcome (20.3% vs 15.1%). CONCLUSIONS: Software-based MRI-US fusion targeted biopsy seems to detect more clinically significant cancers deploying fewer cores than standard biopsy. Because there was significant study heterogeneity in patient inclusion, definition of significant cancer, and the protocol used to conduct the standard biopsy, these findings need to be confirmed by further large multicentre validating studies. PATIENT SUMMARY: We compared the ability of standard biopsy to diagnose prostate cancer against a novel approach using software to overlay the images from magnetic resonance imaging and ultrasound to guide biopsies towards the suspicious areas of the prostate. We found consistent findings showing the superiority of this novel targeted approach, although further high-quality evidence is needed to change current practice.

Fusion weld metal solidification:Continuum from weld interface to centerline

We present a brief résumé of the history of solidification research and key factors affecting the solidification of fusion welds. There is a general agreement of the basic solidification theory, albeit differing - even confusing - nomenclatures do exist, and Cases 2 and 3 (the Chalmers' basic boundary conditions for solidification, categorized by Savage as Cases) are variably emphasized. Model Frame, a tool helping to model the continuum of fusion weld solidification from start to end, is proposed. It incorporates the general solidification models, of which the pertinent ones are selected for the actual modeling. The basic models are the main solidification Cases 1…4. These discrete Cases are joined with Sub-Cases: models of Pfann, Flemings and others, bringing needed Sub-Case variables into the model. Model Frame depicts a grain growing from the weld interface to its centerline. Besides modeling, the Model Frame supports education and academic debate. The new mathematical modeling techniques will extend its use into multi-dimensional modeling, introducing new variables and increasing the modeling accuracy. We propose a model: melting/solidification-model (M/S-model) - predicting the solute profile at the start of the solidification of a fusion weld. This Case 3-based Sub-Case takes into account the melting stage, the solute back-diffusion in the solid, and the growth rate acceleration typical to fusion welds. We propose - based on works of Rutter & Chalmers, David & Vitek and our experimental results on copper - that NEGS-EGS-transition is not associated only with cellular-dendritic-transition. Solidification is studied experimentally on pure and doped copper with welding speed range from 0 to 200 cm/min, with one test at 3000 cm/min. Found were only planar and cellular structures, no dendrites - columnar or equiaxed. Cell sub structures: rows of cubic elements we call "cubelettes", "cell-bands" and "micro-cells", as well as an anomalous crack morphology "crack-eye", were detected, as well as microscopic hot crack nucleus we call "grain-lag cracks", caused by a grain slightly lagging behind its neighbors in arrival to the weld centerline. Varestraint test and R-test revealed a change of crack morphologies from centerline cracks to grainand cell boundary cracks with an increasing welding speed. High speed made the cracks invisible to bare eye and hardly detectable with light microscope, while electron microscope often revealed networks of fine micro-cracks.

Relationship between sedimentation sign and morphological grade in symptomatic lumbar spinal stenosis

Introduction Le canal lombaire étroit symptomatique est de plus en plus fréquent. Le traitement dépend des signes cliniques et des résultats radiologiques. Mais actuellement il n'y a pas de consensus concernant la classification radiologique. Le but de notre article est d'étudier la relation entre deux paramètres morphologiques radiologiques récemment décrits sur des examens par IRM. Le premier est le « signe de sédimentation » (Sedimentation Sign) et le second est le grade morphologique de la sténose lombaire (Morphological Grade), tous deux décrit en 2010. Matériel et méthode Nous avons étudié des examens IRM de 137 patients suivit dans notre établissement. De ces 137, 110 étaient issus d'une base de donnée de patients avec une sténose lombaire dont la Symptomatologie était typique. Dans ce groupe, 73 patients avaient été traité chirurgicalement et 37 conservativement, dépendant de la sévérité des symptômes. Un troisième groupe, le groupe contrôle, était formé de 27 patients ne présentant que des douleurs lombaires basses sans sciatalgie. La sévérité de la sténose a été évaluée sur les examens IRM au niveau du disque en utilisant les 4 grades de la classification morphologique, de A à D. La présence d'un signe de sédimentation a été, quand à lui, notée au niveau du pédicule, au-dessus et au-dessous du niveau présentant la sténose maximale, comme décrit dans l'article original. Résultat La présence d'un signe de sédimentation positif a été observée chez 58% des patients présentant un grade morphologique B, 69% chez les patients avec un grade C et 76% des patients avec un grade D. Dans le groupe de patient traité chirurgicalement pour une sténose canalaire, 67% des patients présentaient un signe de sédimentation positif, 35% dans le groupe du traitement conservateur, et 8 % dans le groupe contrôle. En ce qui concerne la classification du grade morphologique, nous avons regroupé les grade C et D. Il y avait 97% de patients avec un grade C et D dans le groupe du traitement chirurgical, 35 % dans le groupe du traitement conservateur et 18% dans le groupe contrôle. Nous avons donc calculé que la présence d'un signe de sédimentation positif chez les patients avec une sténose lombaire symptomatique augmente le risque d'avoir besoin d'une intervention de l'ordre de 3.5 fois (OR=3.5). En utilisant la classification du grade morphologique, nous avons calculé un risque encore plus élevé. Un patient avec une sténose canalaire de grade C ou D a 65 fois plus de risque d'avoir besoin d'une intervention (OR=65). Conclusion : Les résultats montrent une corrélation entre ces deux paramètres morphologiques. Mais la prédiction du besoin d'une intervention n'est pas équivalente. Un tiers des patients dans le groupe du traitement chirurgical n'avaient pas de signe de sédimentation positif. Ce signe apparaît donc comme un moins bon prédicteur pour le choix du traitement comparé à la sévérité de la sténose jugée avec le grade morphologique (OR 3.5 vs 65).