Bis(1-substituted-borabenzene)iron complexes Ashe, Arthur J; Meyers, Elizabeth; Shu, Paul ...
Journal of the American Chemical Society,
11/1975, Volume:
97, Issue:
23
Journal Article
Proteases of the malaria parasite Plasmodium falciparum have long been investigated as drug targets. The P. falciparum genome encodes 10 aspartic proteases called plasmepsins, which are involved in ...diverse cellular processes. Most have been studied extensively but the functions of plasmepsins IX and X (PMIX and PMX) were unknown. Here we show that PMIX is essential for erythrocyte invasion, acting on rhoptry secretory organelle biogenesis. In contrast, PMX is essential for both egress and invasion, controlling maturation of the subtilisin-like serine protease SUB1 in exoneme secretory vesicles. We have identified compounds with potent antimalarial activity targeting PMX, including a compound known to have oral efficacy in a mouse model of malaria.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
BACKGROUND AND PURPOSE—Neuroendovascular surgery is a medical subspecialty that uses minimally invasive catheter-based technology and radiological imaging to diagnose and treat diseases of the ...central nervous system, head, neck, spine, and their vasculature. To perform these procedures, the practitioner needs an extensive knowledge of the anatomy of the nervous system, vasculature, and pathological conditions that affect their physiology. A working knowledge of radiation biology and safety is essential. Similarly, a sufficient volume of clinical and interventional experience, first as a trainee and then as a practitioner, is required so that these treatments can be delivered safely and effectively.
METHODS—This document has been prepared under the aegis of the Society of Neurological Surgeons and its Committee for Advanced Subspecialty Training in conjunction with the Joint Section of Cerebrovascular Surgery for the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of NeuroInterventional Surgery, and the Society of Vascular and Interventional Neurology.
RESULTS—The material herein outlines the requirements for institutional accreditation of training programs in neuroendovascular surgery, as well as those needed to obtain individual subspecialty certification, as agreed on by Committee for Advanced Subspecialty Training, the Society of Neurological Surgeons, and the aforementioned Societies. This document also clarifies the pathway to certification through an advanced practice track mechanism for those current practitioners of this subspecialty who trained before Committee for Advanced Subspecialty Training standards were formulated.
CONCLUSIONS—Representing neuroendovascular surgery physicians from neurosurgery, neuroradiology, and neurology, the above mentioned societies seek to standardize neuroendovascular surgery training to ensure the highest quality delivery of this subspecialty within the United States.
Liver tumors are rare in children, and their diagnoses may be challenging particularly because of the lack of a current consensus classification system. Systematic central histopathological review of ...these tumors performed as part of the pediatric collaborative therapeutic protocols has allowed the identification of histologic subtypes with distinct clinical associations. As a result, histopathology has been incorporated within the Children's Oncology Group (COG) protocols, and only in the United States, as a risk-stratification parameter and for patient management. Therefore, the COG Liver Tumor Committee sponsored an International Pathology Symposium in March 2011 to discuss the histopathology and classification of pediatric liver tumors, and hepatoblastoma in particular, and work towards an International Pediatric Liver Tumors Consensus Classification that would be required for international collaborative projects. Twenty-two pathologists and experts in pediatric liver tumors, including those serving as central reviewers for the COG, European Société Internationale d'Oncologie Pédiatrique, Gesellschaft für Pädiatrische Onkologie und Hämatologie, and Japanese Study Group for Pediatric Liver Tumors protocols, as well as pediatric oncologists and surgeons specialized in this field, reviewed more than 50 pediatric liver tumor cases and discussed classic and newly reported entities, as well as criteria for their classification. This symposium represented the first collaborative step to develop a classification that may lead to a common treatment-stratification system incorporating tumor histopathology. A standardized, clinically meaningful classification will also be necessary to allow the integration of new biological parameters and to move towards clinical algorithms based on patient characteristics and tumor genetics, which should improve future patient management and outcome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Whole body-MRI is helpful in directing diagnostic and treatment approaches, and as a research outcome measure. We describe our initial consensus-driven phase towards developing a whole body-MRI ...scoring system for juvenile idiopathic arthritis.
An iterative approach using three rounds of anonymous Delphi surveys followed by a consensus meeting was used to draft the structure of the whole body-MRI scoring system, including the relevant anatomic joints and entheses for assessment, diagnostic item selection, definition and grading, and selection of appropriate MRI planes and sequences. The surveys were completed independently by an international expert group consisting of pediatric radiologists and rheumatologists.
Twenty-two experts participated in at least one of three rounds of Delphi surveys and a concluding consensus meeting. A first iteration scoring system was developed which ultimately included the assessment of 100 peripheral, 23 chest, and 76 axial joints, and 64 entheses, with 2–4 diagnostic items graded in each of the items, using binary (presence/absence) and 2-3-level ordinal scores. Recommendations on anatomic MRI planes and sequences were specified as the minimally necessary imaging protocol for the scoring system.
A novel whole body-MRI scoring system for juvenile idiopathic arthritis was developed by consensus among members of MRI in JIA OMERACT working group. Further iterative refinements, reliability testing, and responsiveness are warranted in upcoming studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Contrast-enhanced magnetic resonance imaging (MRI) is the technique of choice for diagnosis and monitoring of temporomandibular joint (TMJ) disorders in patients with juvenile idiopathic arthritis ...(JIA), as it is able to visualize both soft tissue and osteochondral changes. Approximately 40% of children with JIA develop inflammatory and chronic osteochondral changes observable on imaging, which if left untreated can lead to significant facial growth impairment, including facial asymmetry and retrognathia. MRI of the TMJ plays a paramount role in diagnosis and treatment monitoring in JIA since early signs of TMJ involvement are difficult to detect clinically and with physical examination. Findings of TMJ arthritis may be classified into acute and chronic domains. Early or acute manifestations include joint effusion, bone marrow edema, synovial thickening, and increased joint enhancement. With disease progression, there are characteristic osteochondral changes, including deformity of the mandibular condyle with shortening of the mandibular ramus, bone erosions, and disk abnormalities. In this pictorial essay, we describe a consensus MRI protocol for the study of the TMJ and illustrate the degree of normal and pathological MRI findings using currently available MRI scoring systems of the TMJ developed for JIA.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Objective
To determine the relative importance weights of items and grades of a newly developed additive outcome measure called the juvenile idiopathic arthritis (JIA) magnetic resonance imaging ...(MRI) scoring system for the temporomandibular joint (TMJ) (JAMRIS‐TMJ).
Methods
An adaptive partial‐profile, discrete choice experiment (DCE) survey using the 1000Minds platform was independently completed by members of an expert group consisting of radiologists and non‐radiologist clinicians to determine the group‐averaged relative weights for the JAMRIS‐TMJ. Subsequently, an image‐based vignette ranking exercise was done, during which experts individually rank ordered 14 patient vignettes for disease severity while blinded to the weights and unrestricted to JAMRIS‐TMJ assessment criteria. Validity of the weighted JAMRIS‐TMJ was tested by comparing the consensus‐graded, DCE‐weighted JAMRIS‐TMJ score of the vignettes with their unrestricted image‐based ranks provided by the experts.
Results
Nineteen experts completed the DCE survey, and 21 completed the vignette ranking exercise. Synovial thickening and joint enhancement showed higher weights per raw score compared to bone marrow items and effusion in the inflammatory domain, while erosions and condylar flattening showed nonlinear and higher weights compared to disk abnormalities in the damage domain. The weighted JAMRIS‐TMJ score of the vignettes correlated highly with the ranks from the unrestricted comparison method, with median Spearman's ρ of 0.92 (interquartile range IQR 0.87–0.95) for the inflammation and 0.93 (IQR 0.90–0.94) for the damage domain.
Conclusion
A DCE survey was used to quantify the importance weights of the items and grades of the JAMRIS‐TMJ. The weighted score showed high convergent validity with an unrestricted, holistic vignette ranking method.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
We undertook this study to validate the Pediatric Arthritis Ultrasound Scoring System for the knee joint (PAUSS‐knee) in children with juvenile idiopathic arthritis (JIA).
Methods
Children ...with JIA were enrolled to prospectively receive a musculoskeletal ultrasound (MSUS) examination of the knee and a physical examination to determine presence/absence of clinical arthritis. MSUS images were scored using the PAUSS‐knee, a semiquantitative MSUS scoring system (0–3, normal to severe) for B‐mode and power Doppler mode. In addition to MSUS, a subset of participants also received magnetic resonance imaging (MRI) of the knee, which was scored according to the combined Juvenile Arthritis MRI Scoring (JAMRIS) system. Spearman's correlations (rs) were used to calculate associations between variables. Test characteristics of the PAUSS‐knee were calculated with MRI as the reference standard. Inflammatory biomarkers were assessed in synovial fluid from involved knees.
Results
Eighty children with JIA contributed 112 MSUSs and 25 MRIs of the knee. Of the knees, 41% (n = 46) had clinical evidence of arthritis. The B‐mode PAUSS‐knee score moderately correlated with clinically determined arthritis (rs = 0.54, P < 0.001) and strongly correlated with the JAMRIS score (rs = 0.75, P < 0.001). Compared with MRI, the area under the curve for the B‐mode PAUSS‐knee was 0.92. For a cutoff of >1, the B‐mode PAUSS‐knee had a sensitivity of 83% and specificity of 82%. Biomarker analysis indicates that interleukin‐2R levels correlate with PAUSS score.
Conclusion
Our data indicate that the PAUSS‐knee has excellent accuracy for the diagnosis of arthritis when compared with MRI. The PAUSS‐knee has the potential to effectively inform JIA medical decision‐making in real time.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
With powerful new therapies available for management of juvenile idiopathic arthritis (JIA), early diagnosis leading to appropriate treatment may prevent long-term structural joint damage. Although ...magnetic resonance imaging (MRI) is typically used to assess individual body parts, indications for whole body (WB) MRI are increasing. Its utility as a diagnostic and monitoring tool has already been widely investigated in adult rheumatology patients, but less so in pediatric rheumatologic patients. This paper is a comprehensive review of scoring systems and a proposal for the conceptual development of a WB-MRI scoring system for the evaluation of JIA. In this review we identify, summarize, and critically appraise the available literature on the use of WB-MRI in inflammatory arthritis, addressing relevant considerations on components of a classification system that can lead to the development of a future pediatric WB-MRI scoring system for use in children with JIA. We also discuss advantages and challenges of developing such a WB-MRI scoring system for assessment of JIA and outline next steps toward the conceptual development of this scoring system.
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