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1.
AJR Am J Roentgenol ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38838235

ABSTRACT

Myositis is defined as inflammation within skeletal muscle and is a subcategory of myopathy, which is more broadly defined as any disorder affecting skeletal muscle. Myositis may be encountered as a component of autoimmune and connective tissue disease, where it is described as idiopathic inflammatory myopathy. Myositis can also be caused by infections, as well as toxins and drugs, including newer classes of medications. MRI plays an important role in the diagnosis and evaluation of patients with suspected myositis, but many entities may have imaging features similar to myositis and can be considered myositis mimics. These include muscular dystrophies, denervation, deep venous thrombosis, diabetic myonecrosis, muscle injury, heterotopic ossification, and even neoplasms. In patients with suspected myositis, definitive diagnosis may require integrated analysis of imaging findings with clinical, laboratory, and pathology data. The objectives of this article are to review the fundamental features of myositis, including recent updates in terminology and consensus guidelines for idiopathic inflammatory myopathies, the most important MRI differential diagnostic considerations for myositis (i.e., myositis mimics), and new horizons, including the potential importance of artificial intelligence and multimodal integrated diagnostics in the evaluation of patients with muscle disorders.

3.
Magn Reson Imaging ; 111: 256-264, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38621551

ABSTRACT

BACKGROUND: 3D multi-spectral imaging (MSI) of metal implants necessitates relatively long scan times. OBJECTIVE: We implemented a fast isotropic 3D MSI technique at 3 T and compared its image quality and clinical utility to non-isotropic MSI in the evaluation of hip implants. METHODS: Two musculoskeletal radiologists scored images from coronal proton density-weighted conventional MAVRIC-SL and an isotropic MAVRIC-SL sequence accelerated with robust-component-analysis on a 3-point scale (3: diagnostic, 2: moderately diagnostic, 1: non-diagnostic) for overall image quality, metal artifact, and visualization around femoral and acetabular components. Grades were compared using a signed Wilcoxon test. Images were evaluated for effusion, synovitis, osteolysis, loosening, pseudotumor, fracture, and gluteal tendon abnormalities. Reformatted axial and sagittal images for both sequences were subsequently generated and compared for image quality with the Wilcoxon test. Whether these reformats increased diagnostic confidence or revealed additional pathology, including findings unrelated to arthroplasty that may contribute to hip pain, was also compared using the McNemar test. Inter-rater agreement was measured by Cohen's kappa. RESULTS: 39 symptomatic patients with a total of 59 hip prostheses were imaged (mean age, 70 years ±9, 14 males, 25 females). Comparison scores between coronal images showed no significant difference in image quality, metal artifact, or visualization of the femur and acetabulum. Except for loosening, reviewers identified more positive cases of pathology on the original coronally-acquired isotropic sequence. In comparison of reformatted axial and sagittal images, the isotropic sequence scored significantly (p < 0.01) higher for overall image quality (3.0 vs 2.0) and produced significantly (p < 0.01) more cases of increased diagnostic confidence (42.4% vs 7.6%) or additional diagnoses (50.8% vs 22.9%). Inter-rater agreement was substantial (k = 0.798) for image quality. Mean scan times were 4.2 mins (isotropic) and 7.1 mins (non-isotropic). CONCLUSION: Compared to the non-isotropic sequence, isotropic 3D MSI was acquired in less time while maintaining diagnostically acceptable image quality. It identified more pathology, including postoperative complications and potential pain-generating pathology unrelated to arthroplasty. This fast isotropic 3D MSI sequence demonstrates promise for improving diagnostic evaluation of symptomatic hip prostheses at 3 T while simultaneously reducing scan time.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Humans , Male , Female , Aged , Magnetic Resonance Imaging/methods , Middle Aged , Imaging, Three-Dimensional/methods , Artifacts , Hip Joint/diagnostic imaging , Hip Joint/surgery , Aged, 80 and over , Reproducibility of Results , Adult
4.
Diagnostics (Basel) ; 14(2)2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38275464

ABSTRACT

The purpose of our study was to determine differences in adaptative and injury patterns in the elbow related to valgus extension overload (VEO) in overhead throwing athletes by age. A total of 86 overhead throwing athletes and 23 controls underwent MRI or MR arthrography (MRA) of the elbow. Throwing athletes were divided by age into three groups: ≤16 years (26 subjects), 17-19 years (25 subjects), and ≥20 years (35 subjects). Consensus interpretation of each MRI was performed, with measurements of ulnar collateral ligament (UCL) thickness and subchondral sclerosis at the radial head, humeral trochlea, and olecranon process. A higher frequency of apophyseal and stress injuries was seen in adolescent athletes and increased incidence of soft tissue injuries was observed in older athletes. Early adaptive and degenerative changes were observed with high frequency independent of age. Significant differences were observed between athletes and controls for UCL thickness (p < 0.001) and subchondral sclerosis at the radial head (p < 0.001), humeral trochlea (p < 0.001), and olecranon process (p < 0.001). Significant differences based on athlete age were observed for UCL thickness (p < 0.001) and subchondral sclerosis at the olecranon process (p = 0.002). Our study highlights differences in anatomic adaptations related to VEO at the elbow between overhead throwing athletes and control subjects, as well as across age in throwing athletes.

5.
Nat Microbiol ; 8(11): 2006-2019, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37814071

ABSTRACT

Histone proteins bind DNA and organize the genomes of eukaryotes and most archaea, whereas bacteria rely on different nucleoid-associated proteins. Homology searches have detected putative histone-fold domains in a few bacteria, but whether these function like archaeal/eukaryotic histones is unknown. Here we report that histones are major chromatin components in the bacteria Bdellovibrio bacteriovorus and Leptospira interrogans. Patterns of sequence evolution suggest important roles for histones in additional bacterial clades. Crystal structures (<2.0 Å) of the B. bacteriovorus histone (Bd0055) dimer and the histone-DNA complex confirm conserved histone-fold topology but indicate a distinct DNA-binding mode. Unlike known histones in eukaryotes, archaea and viruses, Bd0055 binds DNA end-on, forming a sheath of dimers encasing straight DNA rather than wrapping DNA around their outer surface. Our results demonstrate that histones are present across the tree of life and highlight potential evolutionary innovation in how they associate with DNA.


Subject(s)
Bdellovibrio bacteriovorus , Histones , Histones/genetics , Chromatin , Bdellovibrio bacteriovorus/genetics , Bacteria/genetics , DNA/chemistry , Archaea/genetics
6.
Kidney Int Rep ; 8(8): 1648-1656, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37547534

ABSTRACT

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) causes autoimmune-mediated inflammation of small blood vessels in multiple organs, including the kidneys. The ability to accurately predict kidney outcomes would enable a more personalized therapeutic approach. Methods: We used our national renal biopsy registry to validate the ability of ANCA Renal Risk Score (ARRS) to predict end-stage kidney disease (ESKD) for individual patients. This score uses histopathological and biochemical data to stratify patients as high, medium, or low risk for developing ESKD. Results: A total of 288 patients were eligible for inclusion in the study (low risk n = 144, medium risk n = 122, high risk n = 12). Using adjusted Cox proportional hazard models with the low-risk group as reference, we show that outcome differs between the categories: high-risk hazard ratio (HR) 16.69 (2.91-95.81, P = 0.002); medium risk HR 4.14 (1.07-16.01, P = 0.039). Incremental multivariable-adjusted Cox proportional hazards models demonstrated that adding ARRS to a model adjusted for multiple clinical parameters enhanced predictive discrimination (basic model C-statistic 0.864 [95% CI 0.813-0.914], basic model plus ARRS C-statistic 0.877 [95% CI 0.823-0.931]; P <0.01). Conclusion: The ARRS better discriminates risk of ESKD in AAV and offers clinicians more prognostic information than the use of standard biochemical and clinical measures alone. This is the first time the ARRS has been validated in a national cohort. The proportion of patients with high-risk scores is lower in our cohort compared to others and should be noted as a limitation of this study.

7.
PRiMER ; 7: 276659, 2023.
Article in English | MEDLINE | ID: mdl-36845847

ABSTRACT

Introduction: The incidence of melanoma is on the rise. In trained hands, dermoscopy aids in the differentiation of melanoma from benign skin growths, including melanocytic nevi. This study evaluated the impact of dermoscopy training for primary care practitioners (PCPs) on the number of nevi needed to biopsy (NNB) to detect a melanoma. Methods: We conducted an educational intervention that included a foundational dermoscopy training workshop and subsequent monthly telementoring video conferences. We performed a retrospective observational study to evaluate the impact of this intervention on the number of nevi needed to biopsy to detect a melanoma. Results: The number of nevi biopsied to detect one melanoma decreased from 34.3 to 11.3 following the training intervention. Conclusion: Dermoscopy training for primary care practitioners resulted in a significant reduction in the NNB to detect melanoma.

8.
Semin Cell Dev Biol ; 135: 50-58, 2023 02 15.
Article in English | MEDLINE | ID: mdl-35221208

ABSTRACT

Exchanging core histones in the nucleosome for paralogous variants can have important functional ramifications. Many of these variants, and their physiological roles, have been characterized in exquisite detail in model eukaryotes, including humans. In comparison, our knowledge of histone biology in archaea remains rudimentary. This is true in particular for our knowledge of histone variants. Many archaea encode several histone genes that differ in sequence, but do these paralogs make distinct, adaptive contributions to genome organization and regulation in a manner comparable to eukaryotes? Below, we review what we know about histone variants in archaea at the level of structure, regulation, and evolution. In all areas, our knowledge pales when compared to the wealth of insight that has been gathered for eukaryotes. Recent findings, however, provide tantalizing glimpses into a rich and largely undiscovered country that is at times familiar and eukaryote-like and at times strange and uniquely archaeal. We sketch a preliminary roadmap for further exploration of this country; an undertaking that may ultimately shed light not only on chromatin biology in archaea but also on the origin of histone-based chromatin in eukaryotes.


Subject(s)
Archaea , Histones , Humans , Histones/genetics , Archaea/genetics , Archaea/chemistry , Nucleosomes/genetics , Chromatin , Eukaryotic Cells
9.
J Radiol Case Rep ; 17(12): 1-7, 2023 May.
Article in English | MEDLINE | ID: mdl-38828028

ABSTRACT

A 52-year-old male developed right knee pain after hiking in Guatemala. On his return he underwent a knee MRI for an indication of medial knee pain, which demonstrated a medial meniscal tear. However, the MRI demonstrated marked tortuosity and dense calcification of the popliteal artery, confirmed on subsequent radiographs. Review of previous CT studies of the abdomen and lower extremities showed severe ectasia and arterial calcification in the femoral and popliteal arteries bilaterally, but no calcifications in the aorta and common iliac arteries. Dual energy CT studies of the extremities demonstrated extensive periarticular soft tissue calcification throughout the wrists, hands, ankle and feet without evidence of uric acid. Review of the electronic medical records revealed a diagnosis of Arterial Calcification due to Deficiency of CD73 (ACDC), a rare genetic disorder presenting with debilitating pain in the wrists and hands, claudication of the calves, thighs and buttocks, progressing to chronic ischemia of the feet which may be limb-threatening. The patient was enrolled in an NIH trial of bisphosphonates and dual-antiplatelet therapy with stabilization of symptoms. This case discusses the imaging findings of this rare condition, differential diagnosis to consider, and current management.


Subject(s)
5'-Nucleotidase , Vascular Calcification , Humans , Male , Middle Aged , Vascular Calcification/diagnostic imaging , 5'-Nucleotidase/deficiency , GPI-Linked Proteins , Diagnosis, Differential , Tomography, X-Ray Computed , Magnetic Resonance Imaging , Popliteal Artery/diagnostic imaging
10.
JAMA Netw Open ; 5(10): e2238300, 2022 10 03.
Article in English | MEDLINE | ID: mdl-36282503

ABSTRACT

Importance: Kidney function is usually estimated from serum creatinine level, whereas an alternative glomerular filtration marker (cystatin C level) associates more closely with future risk of cardiovascular disease (CVD) and mortality. Objectives: To evaluate whether testing concordance between estimated glomerular filtration rates based on cystatin C (eGFRcys) and creatinine (eGFRcr) levels would improve risk stratification for future outcomes and whether estimations differ by age. Design, Setting, and Participants: A prospective population-based cohort study (UK Biobank), with participants recruited between 2006-2010 with median follow-up of 11.5 (IQR, 10.8-12.2) years; data were collected until August 31, 2020. Participants had eGFRcr greater than or equal to 45 mL/min/1.73 m2, albuminuria (albumin <30 mg/g), and no preexisting CVD or kidney failure. Exposures: Chronic kidney disease status was categorized by concordance between eGFRcr and eGFRcys across the threshold for hronic kidney disease (CKD) diagnosis (60 mL/min/1.73 m2). Main Outcomes and Measures: Ten-year probabilities of CVD, mortality, and kidney failure were assessed according to CKD status. Multivariable-adjusted Cox proportional hazards models tested associations between CVD and mortality. Area under the receiving operating curve tested discrimination of eGFRcr and eGFRcys for CVD and mortality. The Net Reclassification Index assessed the usefulness of eGFRcr and eGFRcys for CVD risk stratification. Analyses were stratified by older (age 65-73 years) and younger (age <65 years) age. Results: There were 428 402 participants: median age was 57 (IQR, 50-63) years and 237 173 (55.4%) were women. Among 76 629 older participants, there were 9335 deaths and 5205 CVD events. Among 351 773 younger participants, there were 14 776 deaths and 9328 CVD events. The 10-year probability of kidney failure was less than 0.1%. Regardless of the eGFRcr, the 10-year probabilities of CVD and mortality were low when eGFRcys was greater than or equal to 60 mL/min/1.73 m2; conversely, with eGFRcys less than 60 mL/min/1.73 m2, 10-year risks were nearly doubled in older adults and more than doubled in younger adults. Use of eGFRcys better discriminated CVD and mortality risk than eGFRcr. Across a 7.5% 10-year risk threshold for CVD, eGFRcys improved case Net Reclassification Index by 0.7% (95% CI, 0.6%-0.8%) in older people and 0.7% (95% CI, 0.7%-0.8%) in younger people; eGFRcr did not add to CVD risk estimation. Conclusions and Relevance: The findings of this study suggest that eGFRcr 45 to 59 mL/min/1.73 m2 includes a proportion of individuals at low risk and fails to capture a substantial proportion of individuals at high-risk for CVD and mortality. The eGFRcys appears to be more sensitive and specific for CVD and mortality risks in mild CKD.


Subject(s)
Cardiovascular Diseases , Renal Insufficiency, Chronic , Female , Humans , Aged , Middle Aged , Male , Cystatin C , Creatinine , Cohort Studies , Prospective Studies , Cardiovascular Diseases/epidemiology , Risk Assessment , Albumins
11.
Nat Commun ; 13(1): 2915, 2022 05 25.
Article in English | MEDLINE | ID: mdl-35614055

ABSTRACT

The controlled assembly of replication forks is critical for genome stability. The Dbf4-dependent Cdc7 kinase (DDK) initiates replisome assembly by phosphorylating the MCM2-7 replicative helicase at the N-terminal tails of Mcm2, Mcm4 and Mcm6. At present, it remains poorly understood how DDK docks onto the helicase and how the kinase targets distal Mcm subunits for phosphorylation. Using cryo-electron microscopy and biochemical analysis we discovered that an interaction between the HBRCT domain of Dbf4 with Mcm2 serves as an anchoring point, which supports binding of DDK across the MCM2-7 double-hexamer interface and phosphorylation of Mcm4 on the opposite hexamer. Moreover, a rotation of DDK along its anchoring point allows phosphorylation of Mcm2 and Mcm6. In summary, our work provides fundamental insights into DDK structure, control and selective activation of the MCM2-7 helicase during DNA replication. Importantly, these insights can be exploited for development of novel DDK inhibitors.


Subject(s)
Cell Cycle Proteins , Minichromosome Maintenance Proteins , Protein Serine-Threonine Kinases , Saccharomyces cerevisiae Proteins , Cell Cycle Proteins/metabolism , Cryoelectron Microscopy , DNA Replication , Minichromosome Maintenance Proteins/metabolism , Phosphorylation , Protein Serine-Threonine Kinases/metabolism , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/metabolism
13.
Semin Arthritis Rheum ; 53: 151980, 2022 04.
Article in English | MEDLINE | ID: mdl-35183935

ABSTRACT

INTRODUCTION: Calcinosis cutis is a debilitating complication of systemic sclerosis (SSc). We previously developed a radiographic scoring system to assess severity of calcinosis affecting the hands in patients with SSc. We sought to further validate our radiographic scoring system to assess for change over 1 year and to identify factors associated with improvement or progression. MATERIALS AND METHODS: Baseline and 1-year antero-posterior hand radiographs were obtained in 39 SSc patients with calcinosis prospectively enrolled at 6 centers within the US, Canada, Mexico and Australia. Two readers (one radiologist and one rheumatologist) scored all radiographs using the calcinosis scoring system and a 5-point Likert scale (1 = A lot better, 2 = A little better, 3=No change, 4 = A little worse, 5 = A lot worse) on follow-up. By maximizing the Kappa coefficient of agreement between grouped Likert scale (better/no change/worse) and the percentage of change of calcinosis in the radiographic scoring system, we defined progressive calcinosis as >25% increase in score from baseline at 1-year, stable calcinosis as change in score between -25% to 25%, and improvement of calcinosis as decrease in score by >25%. Nineteen SSc patients from an independent cohort were used for validation. RESULTS: Inter-rater reliability of the calcinosis scoring system was high with intra-class correlation coefficient of 0.93 (0.89-0.95). The median percentage of change from baseline to 1 year was 12.8% (range -89.3 to 290.2%). Sixteen patients (41%) experienced progression of calcinosis over 1 year; 18 (46%) remained stable; and 5 (13%) had improvement. Patients with progressive calcinosis had lower T-score on bone densitometry (-3.3 vs -1.7, p = 0.044) and higher prevalence of loss of digital pulp on physical exam (56% vs 22%, p = 0.027), with a trend towards lower baseline modified Rodnan skin score (mRSS) (3.8 vs. 5.9, p = 0.057), than patients who did not progress. Patients who experienced improvement in calcinosis had lower prevalence of digital pitting scars (20% vs 71%, p = 0.047) than patients whose calcinosis did not improve. In multivariable analysis, loss of digital pulp remained a predictor of calcinosis progression (OR 5.8, p = 0.023, CI 1.27 - 26.36). In the validation cohort, 2 (11%) patients improved, 10 (53%) remained stable, and 7 (37%) progressed. CONCLUSIONS: We confirmed the excellent inter-rater reliability of our radiographic calcinosis scoring system and demonstrated its usefulness to detect change over time. Approximately 40% of patients experienced progression of calcinosis over 1 year. Loss of digital pulp was predictive of progressive calcinosis providing further evidence that digital ischemia contributes to the progression of calcinosis.


Subject(s)
Calcinosis , Scleroderma, Localized , Scleroderma, Systemic , Calcinosis/etiology , Hand/diagnostic imaging , Humans , Reproducibility of Results , Scleroderma, Systemic/complications , Scleroderma, Systemic/diagnostic imaging
14.
J Digit Imaging ; 35(3): 524-533, 2022 06.
Article in English | MEDLINE | ID: mdl-35149938

ABSTRACT

Scoliosis is a condition of abnormal lateral spinal curvature affecting an estimated 2 to 3% of the US population, or seven million people. The Cobb angle is the standard measurement of spinal curvature in scoliosis but is known to have high interobserver and intraobserver variability. Thus, the objective of this study was to build and validate a system for automatic quantitative evaluation of the Cobb angle and to compare AI generated and human reports in the clinical setting. After IRB was obtained, we retrospectively collected 2150 frontal view scoliosis radiographs at a tertiary referral center (January 1, 2019, to January 1, 2021, ≥ 16 years old, no hardware). The dataset was partitioned into 1505 train (70%), 215 validation (10%), and 430 test images (20%). All thoracic and lumbar vertebral bodies were segmented with bounding boxes, generating approximately 36,550 object annotations that were used to train a Faster R-CNN Resnet-101 object detection model. A controller algorithm was written to localize vertebral centroid coordinates and derive the Cobb properties (angle and endplate) of dominant and secondary curves. AI-derived Cobb angle measurements were compared to the clinical report measurements, and the Spearman rank-order demonstrated significant correlation (0.89, p < 0.001). Mean difference between AI and clinical report angle measurements was 7.34° (95% CI: 5.90-8.78°), which is similar to published literature (up to 10°). We demonstrate the feasibility of an AI system to automate measurement of level-by-level spinal angulation with performance comparable to radiologists.


Subject(s)
Scoliosis , Adolescent , Artificial Intelligence , Humans , Lumbar Vertebrae/diagnostic imaging , Machine Learning , Reproducibility of Results , Retrospective Studies , Scoliosis/diagnostic imaging
15.
Skeletal Radiol ; 51(3): 549-556, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34223946

ABSTRACT

OBJECTIVE: To compare the diagnostic performance of a conventional metal artifact suppression sequence MAVRIC-SL (multi-acquisition variable-resonance image combination selective) and a novel 2.6-fold faster sequence employing robust principal component analysis (RPCA), in the MR evaluation of hip implants at 3 T. MATERIALS AND METHODS: Thirty-six total hip implants in 25 patients were scanned at 3 T using a conventional MAVRIC-SL proton density-weighted sequence and an RPCA MAVRIC-SL proton density-weighted sequence. Comparison was made of image quality, geometric distortion, visualization around acetabular and femoral components, and conspicuity of abnormal imaging findings using the Wilcoxon signed-rank test and a non-inferiority test. Abnormal findings were correlated with subsequent clinical management and intraoperative findings if the patient underwent subsequent surgery. RESULTS: Mean scores for conventional MAVRIC-SL were better than RPCA MAVRIC-SL for all qualitative parameters (p < 0.05), although the probability of RPCA MAVRIC-SL being clinically useful was non-inferior to conventional MAVRIC-SL (within our accepted 10% difference, p < 0.05), except for visualization around the acetabular component. Abnormal imaging findings were seen in 25 hips, and either equally visible or visible but less conspicuous on RPCA MAVRIC-SL in 21 out of 25 cases. In 4 cases, a small joint effusion was queried on MAVRIC-SL but not RPCA MAVRIC-SL, but the presence or absence of a small effusion did not affect subsequent clinical management and patient outcome. CONCLUSION: While the overall image quality is reduced, RPCA MAVRIC-SL allows for significantly reduced scan time and maintains almost equal diagnostic performance.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Artifacts , Humans , Magnetic Resonance Imaging , Prostheses and Implants
16.
Genome Biol Evol ; 14(1)2022 01 04.
Article in English | MEDLINE | ID: mdl-34894218

ABSTRACT

Histones are ubiquitous in eukaryotes where they assemble into nucleosomes, binding and wrapping DNA to form chromatin. One process to modify chromatin and regulate DNA accessibility is the replacement of histones in the nucleosome with paralogous variants. Histones are also present in archaea but whether and how histone variants contribute to the generation of different physiologically relevant chromatin states in these organisms remains largely unknown. Conservation of paralogs with distinct properties can provide prima facie evidence for defined functional roles. We recently revealed deep conservation of histone paralogs with different properties in the Methanobacteriales, but little is known experimentally about these histones. In contrast, the two histones of the model archaeon Thermococcus kodakarensis, HTkA and HTkB, have been examined in some depth, both in vitro and in vivo. HTkA and HTkB exhibit distinct DNA-binding behaviors and elicit unique transcriptional responses when deleted. Here, we consider the evolution of HTkA/B and their orthologs across the order Thermococcales. We find histones with signature HTkA- and HTkB-like properties to be present in almost all Thermococcales genomes. Phylogenetic analysis indicates the presence of one HTkA- and one HTkB-like histone in the ancestor of Thermococcales and long-term maintenance of these two paralogs throughout Thermococcales diversification. Our results support the notion that archaea and eukaryotes have convergently evolved histone variants that carry out distinct adaptive functions. Intriguingly, we also detect more highly diverged histone-fold proteins, related to those found in some bacteria, in several Thermococcales genomes. The functions of these bacteria-type histones remain unknown, but structural modeling suggests that they can form heterodimers with HTkA/B-like histones.


Subject(s)
Histones , Thermococcales , Archaea/genetics , Archaea/metabolism , Chromatin , Histones/genetics , Nucleosomes/genetics , Phylogeny , Thermococcales/genetics , Thermococcales/metabolism
17.
Semin Musculoskelet Radiol ; 25(4): 546-557, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34706384

ABSTRACT

One of the key principles in the interpretation of radiology images is the ability to differentiate between normal and abnormal findings. This article provides a comprehensive overview of normal structures and anatomical variants occurring around the elbow including potential diagnostic pitfalls. We discuss frequently observed anatomical variants found in routine clinical practice associated with osseous, ligamentous, musculotendinous, and neurovascular structures at the elbow that may simulate pathology or predispose to symptoms under specific circumstances.


Subject(s)
Elbow Joint , Elbow , Elbow/diagnostic imaging , Elbow Joint/diagnostic imaging , Humans , Ligaments , Magnetic Resonance Imaging
18.
Transpl Immunol ; 69: 101474, 2021 12.
Article in English | MEDLINE | ID: mdl-34582968

ABSTRACT

INTRODUCTION: End stage renal disease (ESRD) is the irreversible deterioration of renal function requiring renal replacement therapy by dialysis or transplant. Human leucocyte antigens (HLA) have been well examined however research still is required into the non-HLA antibodies. Antibody mediated rejection (AMR) can be seen in the absence of HLA antibodies on biopsies of patients who have received identical transplants; anti-endothelial cell antibodies may explain this. Investigation into endothelial cell antigens on donor and recipient endothelium may elucidate and stratify the degree of risk of any given transplant and may guide towards the best matched donor. METHODS: Protein array analysis was carried out on 8 patient pairs using nitro-cellulose membranes and biotinylated detection antibodies. The fluorescence emitted was captured by X-Ray film and results were recorded with ImageJ software. A fold increase of more than 2 was considered to be positive. RESULTS: 11 proteins identified had a fold increase of increase ≥2 and were present in ≥2 patient pairs which may point to potential clinical utility. Nectin2/CD112 may be measured in order analyse graft survival time in transplant recipients. Prognosticating renal failure has clinical importance and potential markers that have been identified to aid which include MEPE, CRELD2, and TIMP-4. Novel pharmacological therapies for specific biomarkers identified in this study include JAM-A, E-Selectin, CD147, Galectin-3, JAM-C, PAR-1, and TNFR2. CONCLUSION: Protein analysis showed differences in expression of antigens between patients with and without Chronic Kidney Disease (CKD). This information could be used at the matching stage of renal transplantation and also in the treatment of rejection episodes. The results highlight biomarkers that potentially prognosticate and pharmacological therapies that may ameliorate kidney disease and rejection in ESRD and transplant recipients.


Subject(s)
Kidney Transplantation , Graft Rejection , Graft Survival , HLA Antigens , Humans , Kidney/physiology , Renal Dialysis , Transplant Recipients
19.
Dermatol Pract Concept ; 11(2): e2021030, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33954013

ABSTRACT

BACKGROUND: Dermoscopy aids in skin cancer identification. For family physicians who use dermoscopy, there is higher sensitivity for melanoma detection than naked-eye examination. There is a shortage of dermoscopy training for primary care providers. The triage amalgamated dermoscopic algorithm (TADA) is designed for novice dermoscopists. While TADA can be taught in a short dermoscopy workshop, spaced review and blended learning strategies improve knowledge retention. OBJECTIVES: This study determined the impact that the addition of a distance learning platform has on clinical dermoscopy use. Moreover, it evaluated dermoscopic image identification (knowledge retention) following the addition of distance learning via Extension for Community Health Outcomes (ECHO) to a traditional TADA dermoscopy workshop. METHODS: Primary care providers voluntarily attended a 120-minute TADA dermoscopy workshop. Participants completed pre-intervention, post-TADA, and post-ECHO tests of 30 dermoscopic images of benign and malignant skin lesions. A survey was also administered to analyze clinical dermoscopy use and prior dermoscopy training. RESULTS: Twenty-seven residents, faculty, and advanced practice providers participated in this longitudinal observational cohort study. Mean test scores (out of 30) for images of benign and malignant lesions improved from 20.29 pre-intervention to 24.62 post-TADA and 27.63 post-ECHO (P < .001). On average, participants attended 4 ECHO sessions (out of 7 total) and there was a positive correlation (r = 0.77) between the number of ECHOs attended and post-ECHO scores. Dermoscope use increased from 37.0% to 96.3% (P < .001). CONCLUSION: Distance learning and spaced review complement dermoscopy workshop training for primary care.

20.
Eur Radiol ; 31(12): 9369-9379, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33993332

ABSTRACT

OBJECTIVES: To determine whether synovitis graded by radiologists using hybrid quantitative double-echo in steady-state (qDESS) images can be utilized as a non-contrast approach to assess synovitis in the knee, compared against the reference standard of contrast-enhanced MRI (CE-MRI). METHODS: Twenty-two knees (11 subjects) with moderate to severe osteoarthritis (OA) were scanned using CE-MRI, qDESS with a high diffusion weighting (qDESSHigh), and qDESS with a low diffusion weighting (qDESSLow). Four radiologists graded the overall impression of synovitis, their diagnostic confidence, and regional grading of synovitis severity at four sites (suprapatellar pouch, intercondylar notch, and medial and lateral peripatellar recesses) in the knee using a 4-point scale. Agreement between CE-MRI and qDESS, inter-rater agreement, and intra-rater agreement were assessed using a linearly weighted Gwet's AC2. RESULTS: Good agreement was seen between CE-MRI and both qDESSLow (AC2 = 0.74) and qDESSHigh (AC2 = 0.66) for the overall impression of synovitis, but both qDESS sequences tended to underestimate the severity of synovitis compared to CE-MRI. Good inter-rater agreement was seen for both qDESS sequences (AC2 = 0.74 for qDESSLow, AC2 = 0.64 for qDESSHigh), and good intra-rater agreement was seen for both sequences as well (qDESSLow AC2 = 0.78, qDESSHigh AC2 = 0.80). Diagnostic confidence was moderate to high for qDESSLow (mean = 2.36) and slightly less than moderate for qDESSHigh (mean = 1.86), compared to mostly high confidence for CE-MRI (mean = 2.73). CONCLUSIONS: qDESS shows potential as an alternative MRI technique for assessing the severity of synovitis without the use of a gadolinium-based contrast agent. KEY POINTS: The use of the quantitative double-echo in steady-state (qDESS) sequence for synovitis assessment does not require the use of a gadolinium-based contrast agent. Preliminary results found that low diffusion-weighted qDESS (qDESSLow) shows good agreement to contrast-enhanced MRI for characterization of the severity of synovitis, with a relative bias towards underestimation of severity. Preliminary results also found that qDESSLow shows good inter- and intra-rater agreement for the depiction of synovitis, particularly for readers experienced with the sequence.


Subject(s)
Osteoarthritis, Knee , Synovitis , Contrast Media , Humans , Knee Joint/diagnostic imaging , Magnetic Resonance Imaging , Osteoarthritis, Knee/diagnostic imaging , Synovial Membrane , Synovitis/diagnostic imaging
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