First report in a river in France of the benthic cyanobacterium Phormidium favosum producing anatoxin-a associated with dog neurotoxicosis.

The first identification of anatoxin-a in a French lotic system is reported. Rapid deaths of dogs occurred in 2003 after the animals drank water from the shoreline of the La Loue River in eastern France. Sediments, stones and macrophytes surfaces at the margin of the river were covered by a thick biofilm containing large quantities of several benthic species of filamentous, non-heterocystous cyanobacteria. Known cyanotoxins, such as microcystins, saxitoxins and anatoxins were screened from biofilm samples by biochemical and analytical assays. A compound with similar UV spectra to the anatoxin-a standard was detected by high-performance liquid chromatography (HPLC) coupled with photo-diode array detector. This toxin was further identified by HPLC coupled with a UV detector and by electrospray ionisation-Quadrupole-Time-Of-Flight mass spectrometer, and confirmed by tandem mass spectrometry. These two techniques were necessary to discriminate anatoxin-a in phenylalanine-containing matrices such as liver samples of poisoned dogs. The toxin and the aromatic amino acid, phenylalanine, present the same pseudomolecular ion at m/z 166, but have differing fragmentation patterns, retention times and UV spectra. Finally, several cyanobacterial strains were isolated from the green biofilm and tested for anatoxin-a production. Phormidium favosum was identified as a new anatoxin-a producing species.     

Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS).

PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.     

Reliability and spatial specificity of rat brain sensorimotor functional connectivity networks are superior under sedation compared with general anesthesia

Functional connectivity networks derived from resting‐state functional MRI (rsfMRI) have received increasing interest to further our understanding of brain function. The anesthesia in rodent models may influence the interpretation and comparison of results from functional connectivity MRI (fcMRI). More research is required on this aspect. In this study, we investigated rat brain connectivity networks under 1.5% isoflurane anesthesia in comparison with medetomidine sedation. rsfMRI data were acquired under both anesthesia conditions within one imaging session. Male Wistar rats (n = 17) were scanned at 11.7 T with focus on the sensorimotor system. The data underwent a per‐subject independent component analysis (ICA), after which individual components were grouped using hierarchical clustering. Consistent and reliable networks were identified under medetomidine in sensorimotor cortex (three networks) and striatum (two networks). The incidence of these networks was drastically reduced under isoflurane. Seed correlation analysis confirmed these results and revealed globally elevated correlations with low topical specificity under isoflurane, stemming from low‐frequency global signal fluctuations. Global signal removal thus enhanced slightly regional specificity under isoflurane and showed anti‐correlations of cortico‐striatal connections in both anesthesia regimes. Functional connectivity networks are thus reliably detected in medetomidine‐sedated animals on an individual basis using ICA. Their occurrence, however, is heavily compromised under isoflurane as a result of global signal fluctuations potentially stemming from burst‐suppression‐like neural activity. Anesthesia and pharmacologically induced modulations may provide insight into network mechanisms in the future. As an agent for fcMRI in brain disease studies, light sedation using medetomidine preserves connectivity networks in a greater level of detail, and may therefore be considered superior to standard isoflurane anesthesia. Copyright © 2013 John Wiley & Sons, Ltd.     

Symptom Validity Testing: A Critical Review

This paper provides a comprehensive review of the published literature on symptom validity tests (SVT) and, with the accompanying tables, serves as a reference to assist in their selection, interpretation, and defense. Because malingering is inherently an applied problem that frequently arises in a medico-legal context, the use of SVTs must meet certain standards. Thus, a number of methodological and theoretical weaknesses of SVT research which limit the use of SVTs as clinical tools and sources of evidence are highlighted. These criticisms incorporate recommendations which must be addressed if conclusions based on SVT data are to meet the increasingly rigorous standards for the admissibility of scientific evidence.     

Has Tranexamic Acid in Total Knee Arthroplasty Made Tourniquet Use Obsolete?

The application of tranexamic acid (TXA) in total joint arthroplasty has dramatically improved peri-operative blood management. In light of these benefits, a study by Huang et al., “Intravenous and Topical Tranexamic Acid Alone Are Superior to Tourniquet Use for Primary Total Knee Arthroplasty,” evaluates the need for continued use of the intra-operative tourniquet, which remains a routine practice with documented benefits and adverse effects. This review evaluates the study’s design and critically interprets its findings for clinical practice. Through a prospective, randomized trial, Huang et al. demonstrated that among selected patients undergoing primary total knee arthroplasty, the use of a tourniquet results in no reduction in blood loss beyond that provided by TXA alone. Moreover, the use of TXA without a tourniquet led to improved early clinical outcomes such as reduced post-operative swelling, improved knee range of motion at discharge, and enhanced patient satisfaction. As medicine is practiced in an increasingly value-driven environment, this study provides a useful method for evaluating the utility of commonly used interventions. Its findings highlight the need for future investigations into the optimal administration of TXA in total knee arthroplasty.