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The toxin ricin is a biological weapon that may be used for bioterrorist purposes. As a member of the group of ribosome-inactivating proteins (RIPs), ricin has an A-chain possessing N-giycosidase activity which irreversibly inhibits protein synthesis. In this paper, we demonstrate that provided appropriate sample preparation is used, this enzymatic activity can be exploited for functional ricin detection with sensitivity similar to the best ELISA and specificity allowing application to environmental samples. Ricin is first captured by a monoclonal antibody directed against the B chain and immobilized on magnetic beads. Detection is then realized by determination of the adenine released by the A chain from an RNA template using liquid chromatography coupled to tandem mass spectrometry. The immunoaffinity step combined with the enzymatic activity detection leads to a specific assay for the entire functional ricin with a lower limit of detection of 0.1 ng/ mL (1.56 pM) after concentration of the toxin from a 500 [micro]L sample size. The variability of the assay was 10%. Finally, the method was applied successfully to milk and tap or bottled water samples.

Study of normotensive male Wistar/Rij rats indicates that some age-related changes include fixed systemic blood pressure, enhanced intrarenal vascular resistance and a corresponding step-wise reduction in renal blood flow and glomerular filtration rate per kidney weight. The morphological changes that occur include glomerular hypertrophy, glomerular basement thickening and reduced capillary surface.

LC/ESI-MS/MS is a promising alternative to immunoassays in improving the analysis of recombinant therapeutic proteins in biological fluids for toxicity and pharmacokinetics purposes. To assess the sensitivity and validation issues associated with this technique, we use here as a model EPI-hNE4, a 56-amino acid recombinant protein, and demonstrate that a method based on tandem mass spectrometry combined with liquid chromatography and electrospray interface can reach sensitivity similar to that of EUSA but without its potential cross-reactivity. For this purpose, a triple quadrupole mass spectrometer operating in positive ion and single reaction monitoring mode with transition, m/z 1040 →1224.5, was used for selective peak detection. Particular issues related to the internal standard, i.e., elution and ionization patterns similar to the protein without stable isotope labeling, and to analytical interference due to endogenous binding antibodies were addressed. A limit of quantification in human or monkey plasma of 5 ng/mL was reached with a sample volume of 100 μL, corresponding to 40 fmol injected into the HPLC column. Intra- and interassay precision and accuracy were below 15%. No matrix effect was detected. [ABSTRACT FROM AUTHOR]

Background: Revision total joint arthroplasties are physically demanding cases. Recent studies have shown increased cardiovascular stress in surgeons performing revision total knee arthroplasty (rTKA) and revision total hip arthroplasty (rTHA) compared with primary cases. To our knowledge, no study has compared surgeon ergonomics during these cases. The purpose of this study was to analyze surgeon posture during primary and revision THA and TKA., Methods: We prospectively evaluated 286 consecutive cases (103 primary TKAs, 95 primary THAs, 57 rTKAs, and 31 rTHAs) performed by three high-volume, fellowship-trained arthroplasty surgeons. Throughout each case, surgeons wore a posture-tracking device to evaluate time spent slouching. The threshold for slouching was set to 30 degrees of flexion from the neutral spinal axis. Demographic and surgical factors were collected. Two-tailed t-tests and multivariate analysis were used to assess differences between groups., Results: After controlling for individual differences in posture, we found an increase in percentage and duration of time spent slouching between rTHA and primary THA cases (58.9% vs. 43.2%, P < 0.001; 65.1 vs. 32.6 minutes, P < 0.001). In the multivariate analysis, patient body mass index and rTHA were found to be an individual contributor to slouching percentage in THAs (P = 0.001). We found increased duration of time spent slouching between rTKA and primary TKA (80.2 vs. 45.7 minutes, P < 0.001); however, percentage time slouching showed no difference (67.1% vs. 58.5%, P = 0.175). Active fellow involvement was an individual contributor to decreased time slouching in both TKA and THA groups (P < 0.001)., Conclusions: Surgeons performing revision total joint arthroplasty spend markedly more case time in a slouched posture compared with primary arthroplasty, particularly in patients with a higher body mass index. Awareness of the surgical and patient factors that can affect posture in TKAs and THAs can help arthroplasty surgeons gain more awareness about injury prevention and potentially help prolong their career., (Copyright © 2025 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Introduction: Health disparities have been widely studied in the primary care and surgical settings. The purpose of this study was to examine surgical access disparities for orthopaedic surgical cases performed at a large academic health center by comparing the relationship between patient demographic factors and surgical wait time., Methods: A total of 24,778 orthopaedic surgical cases from 2018 to 2022 at a public, tertiary care, Level I trauma center were retrospectively analyzed to assess for surgical timing disparities based on patient-specific factors, including race, sex, language, and socioeconomic status., Results: Elective surgical cases were completed with an average surgical wait time of 28.11 ± 26.34 days. Urgent surgical cases were completed with an average surgical wait time of 1.23 ± 1.50 days. Patient race, sex, language, and socioeconomic status had no effect on surgical wait time for urgent case scheduling. Female patients had longer average wait times in elective cases, whereas race had a weak association with increased wait time. Two-factor interaction analysis showed no multifactorial effects of patient demographic factors on surgical wait time. Patient race and socioeconomic status were associated with increased distance from surgical sites, although increased distance did not correlate with increased surgical wait time., Conclusion: Patient demographic factors did not demonstrate clinically notable associations with surgical timing in this patient cohort, in contrast to previous studies demonstrating the effects of race and socioeconomic status on healthcare outcomes and access. Race and socioeconomic status did correlate with increased distance from surgical centers although distance from surgical sites did not correlate with surgical wait time. This contributes to previous literature on healthcare equity and indicates that surgical wait time may not contribute to the known healthcare inequalities seen in minority and marginalized patients., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: Pes cavovarus has an estimated incidence of 8%-17% in patients with spina bifida (SB). The majority of the current literature on surgical treatment of cavovarus feet in children and adolescents includes a variety of diagnoses. There are currently no case series describing a treatment algorithm for deformity correction in this specific patient population. The authors of this study present the results of a retrospective case series performed to assess the radiographic outcomes of two-stage corrective surgery in patients with SB., Aim: To assess the radiographic outcomes of a staged operation consisting of radical plantar release followed by osteotomy for pes cavovarus in patients with SB., Methods: Retrospective chart review was performed on patients with SB with a diagnosis of pes cavovarus at a freestanding children's hospital who underwent surgical correction of the deformity. Patients were excluded for lack of two-stage corrective operation, nonambulatory status, lack of at least six months follow-up, and age > 18 years at the time of surgery. This resulted in a cohort of 19 patients. Radiographic analysis was performed on 11 feet that had a complete series of preoperative and postoperative weightbearing X-rays. Preoperative and postoperative radiographic outcome measurements were compared using a two-sample t -test., Results: Significant changes between the preoperative and postoperative measurements were seen in Meary's angle, the anteroposterior talo-first metatarsal (AP TMT1) angle, and the talonavicular coverage. Mean values of Meary's angle were 17.9 ± 13.1 preoperatively and 4.7 ± 10.3 postoperatively ( P = 0.016). Mean AP TMT1 angle was 20.6 ± 15.1 preoperatively and 9.3 ± 5.5 postoperatively ( P = 0.011). Mean talonavicular coverage values were -10.3 ± 9.6 preoperatively and -3.8 ± 10.1 postoperatively ( P = 0.025)., Conclusion: The two-stage corrective procedure demonstrated efficacy in correcting cavovarus deformity in patients with SB. Providers should strongly consider employing the staged surgical algorithm presented in this manuscript for management of these patients., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Nanomaterials are present in a wide variety of health products, drugs and medical devices and their use is constantly increasing, varying in terms of diversity and quantity. The topic is vast because it covers nanodrugs, but also excipients (that includes varying proportions of NMs) and medical devices (with intended or not-intended (by-products of wear) nanoparticles). Although researchers in the field of nanomedicines in clinical research and industry push for clearer definitions and relevant regulations, the endeavor is challenging due to the enormous diversity of NMs in use and their specific properties. In addition, regulatory hurdles and discrepancies are often cited as obstacles to the clinical development of these innovative products. The scientific council of the Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM) undertook a multidisciplinary analysis encompassing fundamental, environmental and societal dimensions with the aim of identifying topics of interest for regulatory assessment and surveillance. This analysis allowed for proposing some recommendations for approximation and harmonization of international regulatory practices for the assessment of the risk/benefit balance of these products, considering as well the public expectations as regards efficacy and safety of nanomaterials used in Health products, in terms of human and environmental health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Oualikene-Gonin, Sautou, Ezan, Bastos, Bellissant, Belgodère, Maison, Ankri and the Scientific Advisory Board of the ANSM.)

Background: ATV (All-Terrain Vehicle) related open fractures are often high energy and may be highly contaminated. We asked whether they were more complicated than other open fractures in pediatric patients., Methods: A retrospective chart review was performed comparing ATV associated open fractures to open fractures sustained in non-ATV related accidents. 97 pediatric open fractures from 2015 to 2021 were identified based on ICD-10 codes. Of these fractures, 62 were non-ATV related and 35 were ATV related. Charts were reviewed to collect basic demographics, fracture pattern, Gustilo-Anderson classification, procedures performed, operative findings, and complications., Results: Our cohort was predominantly male (71% in the ATV group and 76% in the non-ATV group). White race was more common in both the ATV (28 (80%)) and non-ATV (50(78%)) groups. The distribution of AO/OTA fractures was significantly different (p = 0.046), with humerus fractures being more common in the ATV group (8 (22%)) vs. non-ATV group (6 (9.3%)). The ATV group had a higher proportion of more severe type II and III open fractures with 77.1% (n = 27), versus 56% (n = 35) in the non-ATV group (p = 0.020).. Revision and reoperation were more likely in the ATV group (16 (23%)) vs. the non-ATV group (12 (15%)), as was malunion (ATV group 3 (4.3%) Vs. non-ATV 0 (0%))., Conclusion: Open fractures resulting from ATV injuries tend to be more complex and have higher rates of revision and malunion. This information supports the large body of evidence on the dangers of ATVs to children and can help guide expectations of both clinicians and family members of patients presenting with these injuries., Competing Interests: Declaration of Competing Interest Timothy W Torrez, James Hicks, Henry Bonner, Alexandra H Seidenstein, Ezan A Kothari, Gerald McGwin, and Shawn R Gilbert declare that they have no conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Inexpensive simple medical devices allowing fast and reliable counting of whole cells are of interest for diagnosis and treatment monitoring. Magnetic-based labs on a chip are one of the possibilities currently studied to address this issue. Giant magnetoresistance (GMR) sensors offer both great sensitivity and device integrability with microfluidics and electronics. When used on a dynamic system, GMR-based biochips are able to detect magnetically labeled individual cells. In this article, a rigorous evaluation of the main characteristics of this magnetic medical device (specificity, sensitivity, time of use and variability) are presented and compared to those of both an ELISA test and a conventional flow cytometer, using an eukaryotic malignant cell line model in physiological conditions (NS1 murine cells in phosphate buffer saline). We describe a proof of specificity of a GMR sensor detection of magnetically labeled cells. The limit of detection of the actual system was shown to be similar to the ELISA one and 10 times higher than the cytometer one.

Ligand-binding techniques such as immunoassays, the reference for clinical diagnosis, offer a wide range of innovative approaches based on signal DNA amplification, nanotechnologies or digital assays, which result in technologies with sensitivities more than 1000-times that of formats used 20 years ago. Providing that these technologies gain acceptance and translate into robust commercial platforms, we expect that several fields will be impacted in the near future, including the clinical diagnosis of cancer markers, the early detection of infectious diseases and the safety of biotherapeutics. Furthermore, the combination of these techniques with microfluidic systems will allow probing of biological diversity at the single cell level and will lead to the discovery of novel and rare biomarkers.

Lethal and edema toxins are critical virulence factors of Bacillus anthracis. However, little is known about their in vivo dynamics of production during anthrax. In this study, we unraveled for the first time the in vivo kinetics of production of the toxin components EF (edema factor) and LF (lethal factor) during cutaneous infection with a wild-type toxinogenic encapsulated strain in immuno-competent mice. We stratified the asynchronous infection process into defined stages through bioluminescence imaging (BLI), while exploiting sensitive quantitative methods by measuring the enzymatic activity of LF and EF. LF was produced in high amounts, while EF amounts steadily increased during the infectious process. This led to high LF/EF ratios throughout the infection, with variations between 50 to a few thousands. In the bloodstream, the early detection of active LF and EF despite the absence of bacteria suggests that they may exert long distance effects. Infection with a strain deficient in the protective antigen toxin component enabled to address its role in the diffusion of LF and EF within the host. Our data provide a picture of the in vivo complexity of the infectious process.