InThe Modern Architectural LandscapeCaroline Constant examines diverse approaches to landscape in the work of architects practicing in Europe and the United States between 1915 and the mid-1980s. ...Case studies highlight landscapes in the public realm rather than the private garden, which had been a primary focus of much Western landscape theory and practice during the early decades of the century. These landscapes do more than accommodate the functional needs of the evolving mass society in parks, playgrounds, and places of assembly; they give formal expression to Modern Movement social and political ideologies, engaging the symbolic potential of the modern landscape-particularly in its ability to take on new, more democratic forms of social organization.
Constant probes the cultural significance of specific landscapes designed by architects, understanding them as ways of interpreting the world and the place of humankind in the world. The examples she scrutinizes extend widely across the century (from the works of Erik Gunnar Asplund and Jože Plečnik to those of Le Corbusier and Rem Koolhaas) and around the globe (from suburban Los Angeles to Barcelona and Chandigarh).
Approaching landscape as an essential component of modern architecture's constructive endowment of material with social value,The Modern Architectural Landscapefocuses on the precise material forms and ideological underpinnings of landscapes conceived by architects, revealing them as salient to the formulation of both modern architecture and the modern landscape.
Background and Objectives: Fracture healing is currently assessed through qualitative evaluation of radiographic images, which is highly subjective in nature. Radiographs can only provide snapshots ...in time, which are limited due to logistics and radiation exposure. We recently proposed assessing the bone healing status through continuous monitoring of the implant load, utilizing an implanted sensor system, the Fracture Monitor. The device telemetrically transmits statistically derived implant parameters via the patient’s mobile phone to assist physicians in diagnostics and treatment decision-making. This preclinical study aims to systematically investigate the device safety and performance in an animal setting. Materials and Methods: Mid-shaft tibial osteotomies of different sizes (0.6–30 mm) were created in eleven Swiss mountain sheep. The bones were stabilized with either a conventional Titanium or stainless-steel locking plate equipped with a Fracture Monitor. Data were continuously collected over the device’s lifetime. Conventional radiographs and clinical CT scans were taken longitudinally over the study period. The radiographs were systematically scored and CTs were evaluated for normalized bone volume in the defect. The animals were euthanized after 9 months. The sensor output was correlated with the radiologic parameters. Tissue samples from the device location were histologically examined. Results: The sensors functioned autonomously for 6.5–8.4 months until energy depletion. No macroscopic or microscopic adverse effects from device implantation were observed. The relative implant loads at 4 and 8 weeks post-operation correlated significantly with the radiographic scores and with the normalized bone volume metric. Conclusions: Continuous implant load monitoring appears as a relevant approach to support and objectify fracture healing assessments and carries a strong potential to enable patient-tailored rehabilitation in the future.
Background and Objectives: Spinal fusion is an effective and widely accepted intervention. However, complications such as non-unions and hardware failures are frequently observed. Radiologic imaging ...and physical examination are still the gold standards in the assessment of spinal fusion, despite multiple limitations including radiation exposure and subjective image interpretation. Furthermore, current diagnostic methods only allow fusion assessment at certain time points and require the patient’s presence at the hospital or medical practice. A recently introduced implantable sensor system for continuous and wireless implant load monitoring in trauma applications carries the potential to overcome these drawbacks, but transferability of the principle to the spine has not been demonstrated yet. Materials and Methods: The existing trauma sensor was modified for attachment to a standard pedicle-screw-rod system. Two lumbar segments (L2 to L4) of one Swiss white alpine sheep were asymmetrically instrumented. After facetectomy, three sensors were attached to the rods between each screw pair and activated for measurement. The sheep was euthanized 16 weeks postoperatively. After radiological assessment the spine was explanted and loaded in flexion-extension to determine the range of motion of the spinal segments. Sensor data were compared with mechanical test results and radiologic findings. Results: The sensors measured physiological rod loading autonomously over the observation period and delivered the data daily to bonded smartphones. At euthanasia the relative rod load dropped to 67% of the respective maximum value for the L23 segment and to 30% for the L34 segment. In agreement, the total range of motion of both operated segments was lower compared to an intact reference segment (L23: 0.57°; L34: 0.49°; intact L45: 4.17°). Radiologic assessment revealed fusion mass in the facet joint gaps and bilateral bridging bone around the joints at both operated segments. Conclusions: Observations of this single-case study confirm the basic ability of continuous rod load measurement to resolve the spinal fusion process as indicated by a declining rod load with progressing bone fusion. A strong clinical potential of such technology is eminent, but further data must be collected for final proof of principle.
Displaying a strong antiproliferative activity on a wide variety of cancer cells, EAPB0203 and EAPB0503 belong to the imidazo1,2-aquinoxalines family of imiquimod structural analogues. EAPB0503 has ...been shown to inhibit tubulin polymerization. The aim of the present study is to characterize the interaction of EAPB0203 and EAPB0503 with tubulin. We combine experimental approaches at the cellular and the molecular level both in vitro and in silico in order to evaluate the interaction of EAPB0203 and EAPB0503 with tubulin. We examine the influence of EAPB0203 and EAPB0503 on the cell cycle and fate, explore the binding interaction with purified tubulin, and use a computational molecular docking model to determine the binding modes to the microtubule. We then use a drug combination study with other anti-microtubule agents to compare the binding site of EAPB0203 and EAPB0503 to known potent tubulin inhibitors. We demonstrate that EAPB0203 and EAPB0503 are capable of blocking human melanoma cells in G2 and M phases and inducing cell death and apoptosis. Second, we show that EAPB0203 and EAPB0503, but also unexpectedly imiquimod, bind directly to purified tubulin and inhibit tubulin polymerization. As suggested by molecular docking and binding competition studies, we identify the colchicine binding site on β-tubulin as the interaction pocket. Furthermore, we find that EAPB0203, EAPB0503 and imiquimod display antagonistic cytotoxic effect when combined with colchicine, and disrupt tubulin network in human melanoma cells. We conclude that EAPB0203, EAPB0503, as well as imiquimod, interact with tubulin through the colchicine binding site, and that the cytotoxic activity of EAPB0203, EAPB0503 and imiquimod is correlated to their tubulin inhibiting effect. These compounds appear as interesting anticancer drug candidates as suggested by their activity and mechanism of action, and deserve further investigation for their use in the clinic.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Orthopedic device-related infections remain a serious challenge to treat. Central to these infections are bacterial biofilms that form on the orthopedic implant itself. These biofilms shield the ...bacteria from the host immune system and most common antibiotic drugs, which renders them essentially antibiotic-tolerant. There is an urgent clinical need for novel strategies to prevent these serious infections that do not involve conventional antibiotics. Recently, a novel antibiofilm coating for titanium surfaces was developed based on 5-(4-bromophenyl)-
-cyclopentyl-1-octyl-1
-imidazol-2-amine as an active biofilm inhibitor. In the current study we present an optimized coating protocol that allowed for a 5-fold higher load of this active compound, whilst shortening the manufacturing process. When applied to titanium disks, the newly optimized coating was resilient to the most common sterilization procedures and it induced a 1 log reduction in biofilm cells of a clinical
isolate (JAR060131)
, without affecting the planktonic phase. Moreover, the antibiofilm effect of the coating in combination with the antibiotic cefuroxime was higher than cefuroxime treatment alone. Furthermore, the coating was successfully applied to a human-scale fracture fixation device resulting in a loading that was comparable to the titanium disk model. Finally, an
biocompatibility and healing study in a rabbit osteotomy model indicated that these coated implants did not negatively affect fracture healing or osteointegration. These findings put our technology one step closer to clinical trials, confirming its potential in fighting orthopedic infections without compromising healing.
•Most deep learning (DL) in imaging studies focused on spinal conditions' detection and diagnosis.•A total of 92% of DL in imaging studies developed a new model while 8% validated a pre-existing ...one.•DL in medical imaging showed promising performance in improving clinical spine care.•Implementation or demonstration of DL in real-world situations was rare.
Artificial intelligence is a revolutionary technology that promises to assist clinicians in improving patient care. In radiology, deep learning (DL) is widely used in clinical decision aids due to its ability to analyze complex patterns and images. It allows for rapid, enhanced data, and imaging analysis, from diagnosis to outcome prediction. The purpose of this study was to evaluate the current literature and clinical utilization of DL in spine imaging.
This study is a scoping review and utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to review the scientific literature from 2012 to 2021. A search in PubMed, Web of Science, Embased, and IEEE Xplore databases with syntax specific for DL and medical imaging in spine care applications was conducted to collect all original publications on the subject. Specific data was extracted from the available literature, including algorithm application, algorithms tested, database type and size, algorithm training method, and outcome of interest.
A total of 365 studies (total sample of 232,394 patients) were included and grouped into 4 general applications: diagnostic tools, clinical decision support tools, automated clinical/instrumentation assessment, and clinical outcome prediction. Notable disparities exist in the selected algorithms and the training across multiple disparate databases. The most frequently used algorithms were U-Net and ResNet. A DL model was developed and validated in 92% of included studies, while a pre-existing DL model was investigated in 8%. Of all developed models, only 15% of them have been externally validated.
Based on this scoping review, DL in spine imaging is used in a broad range of clinical applications, particularly for diagnosing spinal conditions. There is a wide variety of DL algorithms, database characteristics, and training methods. Future studies should focus on external validation of existing models before bringing them into clinical use.
Background
The current standard of care for intervertebral disc (IVD) herniation, surgical discectomy, does not repair annulus fibrosus (AF) defects, which is partly due to the lack of effective ...methods to do so and is why new repair strategies are widely investigated and tested preclinically. There is a need to develop a standardized IVD injury model in large animals to enable comparison and interpretation across preclinical study results. The purpose of this study was to compare in vivo IVD injury models in sheep to determine which annulus fibrosus (AF) defect type combined with partial nucleus pulposus (NP) removal would better mimic degenerative human spinal pathologies.
Methods
Six skeletally mature sheep were randomly assigned to one of the two observation periods (1 and 3 months) and underwent creation of 3 different AF defect types (slit, cruciate, and box‐cut AF defects) in conjunction with 0.1 g NP removal in three lumbar levels using a lateral retroperitoneal surgical approach. The spine was monitored by clinical CT scans pre‐ and postoperatively, at 2 weeks and euthanasia, and by magnetic resonance imaging (MRI) and histology after euthanasia to determine the severity of degeneration (disc height loss, Pfirrmann grading, semiquantitative histopathology grading).
Results
All AF defects led to significant degenerative changes detectable on CT and MR images, produced bulging of disc tissue without disc herniation and led to degenerative and inflammatory histopathological changes. However, AF defects were not equal in terms of disc height loss at 3 months postoperatively; the cruciate and box‐cut AF defects showed significantly decreased disc height compared to their preoperative height, with the box‐cut defect creating the greatest disc height loss, while the slit AF defect showed restoration of normal preoperative disc height.
Conclusions
The tested IVD injury models do not all generate comparable disc degeneration but can be considered suitable IVD injury models to investigate new treatments. Results of the current study clearly indicate that slit AF defect should be avoided if disc height is used as one of the main outcomes; additional confirmatory studies may be warranted to generalize this finding.
Staphylococcus aureus is the main causative pathogen of subcutaneous, bone, and implant-related infections, forming structures known as staphylococcal abscess communities (SACs) within tissues that ...also contain immunosuppressive myeloid-derived suppressor cells (MDSCs). Although both SACs and MDSCs are present in chronic S. aureus infections, it remains unknown whether SACs directly trigger MDSC expansion. To investigate this, a previously developed 3D in vitro SAC model was co-cultured with murine and human bone marrow cells. Subsequently, it was shown that SAC-exposed human CD11blow/− myeloid cells or SAC-exposed murine CD11b+ Gr-1+ cells were immunosuppressive mainly by reducing absolute CD4+ and CD8α+ T cell numbers, as shown in T cell proliferation assays and with flow cytometry. Monocytic MDSCs from mice with an S. aureus bone infection also strongly reduced CD4+ and CD8α+ T cell numbers. Using protein biomarker analysis and an immunoassay, we detected in SAC–bone marrow co-cultures high levels of GM-CSF, IL-6, VEGF, IL-1β, TNFα, IL-10, and TGF-β. Furthermore, SAC-exposed neutrophils expressed Arg-1 and SAC-exposed monocytes expressed Arg-1 and iNOS, as shown via immunofluorescent stains. Overall, this study showed that SACs cause MDSC expansion from bone marrow cells and identified possible mediators to target as an additional strategy for treating chronic S. aureus infections.
Background
Intervertebral disc (IVD) disorders (e.g., herniation) directly contribute to back pain, which is a leading cause of global disability. Next‐generation treatments for IVD herniation need ...advanced preclinical testing to evaluate their ability to repair large defects, prevent reherniation, and limit progressive degeneration. This study tested whether experimental, injectable, and nonbioactive biomaterials could slow IVD degeneration in an ovine discectomy model.
Methods
Ten skeletally mature sheep (4–5.5 years) experienced partial discectomy injury with cruciate‐style annulus fibrosus (AF) defects and 0.1 g nucleus pulposus (NP) removal in the L1–L2, L2–L3, and L3–L4 lumbar IVDs. L4–L5 IVDs were Intact controls. IVD injury levels received: (1) no treatment (Injury), (2) poly (ethylene glycol) diacrylate (PEGDA), (3) genipin‐crosslinked fibrin (FibGen), (4) carboxymethylcellulose–methylcellulose (C‐MC), or (5) C‐MC and FibGen (FibGen + C‐MC). Animals healed for 12 weeks, then IVDs were assessed using computed tomography (CT), magnetic resonance (MR) imaging, and histopathology.
Results
All repaired IVDs retained ~90% of their preoperative disc height and showed minor degenerative changes by Pfirrmann grading. All repairs had similar disc height loss and Pfirrmann grade as Injury IVDs. Adhesive AF sealants (i.e., PEGDA and FibGen) did not herniate, although repair caused local endplate (EP) changes and inflammation. NP repair biomaterials (i.e., C‐MC) and combination repair (i.e., FibGen + C‐MC) exhibited lower levels of degeneration, less EP damage, and less severe inflammation; however, C‐MC showed signs of herniation via biomaterial expulsion.
Conclusions
All repair IVDs were noninferior to Injury IVDs by IVD height loss and Pfirrmann grade. C‐MC and FibGen + C‐MC IVDs had the best outcomes, and may be appropriate for enhancement with bioactive factors (e.g., cells, growth factors, and miRNAs). Such bioactive factors appear to be necessary to prevent injury‐induced IVD degeneration. Application of AF sealants alone (i.e., PEGDA and FibGen) resulted in EP damage and inflammation, particularly for PEGDA IVDs, suggesting further material refinements are needed.
This study evaluates the in vivo performance of four injectable, nonbioactive IVD repair biomaterial strategies could slow intervertebral disc (IVD) degeneration in an ovine discectomy model. All repaired IVDs retained ~90% of their preoperative disc height and showed minor degenerative changes by Pfirrmann grading. C‐MC and FibGen + C‐MC IVDs had the best outcomes, these treatments may be appropriate for enhancement with bioactive factors.
Objective
To provide a systematic assessment of the efficacy of preoperative skin asepsis using chlorhexidine versus povidone‐iodine based protocols for surgical site infection (SSI) prevention in ...veterinary surgery.
Study design
Systematic meta‐analytical review according to PRISMA‐P guidelines.
Sample population
Studies comparing preoperative skin asepsis protocols using chlorhexidine versus povidone‐iodine in veterinary surgery identified by systematic search between 1990 and 2020.
Methods
A search using MEDLINE/Pubmed, Web of Science and CAB s was performed, followed by secondary searches of Google Scholar, Proquest Dissertation and Theses, and relevant bibliographic articles. Primary and secondary outcome measures were the efficacy of skin asepsis protocols using chlorhexidine versus povidone‐iodine on SSI incidence and skin bacterial colonization, respectively. A meta‐analysis was performed with a random‐effect model, with effect size calculated as risk ratio (RR) or mean standard deviation (MSD) with 95% CI. Statistical significance was set at P < .05.
Results
Among 1067 publications that met the initial search criteria, 9 relevant studies were eligible for analysis. No difference in the incidence of postoperative SSI or skin bacterial colonization between preoperative asepsis protocols using chlorhexidine versus povidone‐iodine was found. Insufficient information and detail were frequent among studies and precluded a clear assessment of bias.
Conclusion
This study showed that asepsis protocols using chlorhexidine were comparable to povidone‐iodine in preventing postoperative SSI and reducing skin bacterial colonization.
Clinical significance
Given the limitations of the studies that were included in terms of both quality and quantity, more high‐quality randomized controlled trials are needed to confirm these conclusions.
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