Search

Ming-Chang Ku,1,2 Victor C Kok,3,4 Ming-Yung Lee,5 Soa-Min Hsu,1 Pei-Yu Lee,1 Che-Wei Chang,1 Yeu-Sheng Tyan,6 Chi-Wen Juan7,8 1Department of Radiology, Kuang Tien General Hospital, Taichung, 2Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, 3Department of Internal Medicine, Division of Medical Oncology, Kuang Tien General Hospital, 4Department of Bioinformatics and Medical Engineering, Asia University, 5Department of Statistics and Informatics Science, Providence University, 6Department of Medical Imaging, Chung Shan Medical University Hospital, 7Department of Emergency Medicine, Kuang Tien General Hospital, 8Department of Nursing, HungKuang University, Taichung, Taiwan Objectives: Gallbladder opacification (GBO) on computed tomography (CT) imaging may obscure certain pathological or emergent conditions in the gallbladder, such as neoplasms, stones, and hemorrhagic cholecystitis. This study aimed to investigate the clinical contributing factors that could predict the presence of delayed GBO determined by CT.Methods: This study retrospectively evaluated 243 consecutive patients who received enhanced CT or intravenous pyelography imaging and then underwent abdominal CT imaging within 5 days. According to the interval between imaging, the patients were divided into group A (1 day), group B (2 or 3 days), and group C (4 or 5 days). Three radiologists evaluated CT images to determine GBO. Fisher’s exact test and multivariate backward stepwise elimination logistic regression were performed.Results: Positive GBO was significantly associated with the interval between imaging studies, contrast type, contrast volume, renal function, and hypertransaminasemia (P

Roasted carob pulp (Ceratonia siliqua) is a cocoa substitute known for its faint cocoa-like resemblance. However, the cocoa-carob flavour gap remains poorly uncharacterised. This study aimed to elucidate the sensory and molecular aspects of this flavour gap in a 70 % dark chocolate formulation via a two-pronged instrumental-sensorial approach. Descriptive Sensory Analysis (DSA) revealed carob-based chocolate was significantly sweeter, less sour and astringent than conventional dark chocolate due to the high total sugar content (45-50 % DM; HPLC/RID), low titratable acidity and tannin content, respectively. As for aroma, a distinct, albeit weak, cocoa-like aroma was present in carob-based chocolate. HS-SPME-GC-MS/FID revealed this was attributed to branched-chain Strecker aldehyde generation during roasting (2-methylbutanal, 1.17 μg/g; 3-methylbutanal, 2.89 μg/g). Notably, there was a distinct lack of alkylpyrazines. Additionally, a distinct woody, tree bark-like odour was uniquely associated with carob-based chocolates. This was due to furfural generation during roasting (2.33 μg/g). In conclusion, the aroma and taste gap between cocoa and carob was successfully characterised in this study. These findings substantiate the potential of carob application in chocolate manufacturing, thus empowering confectioners to make evidence-based decisions when evaluating cocoa substitutes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

B0 field inhomogeneity is a long-lasting issue for Cardiac MRI (CMR) in high-field (3T and above) scanners. The inhomogeneous B0 fields can lead to corrupted image quality, prolonged scan time, and false diagnosis. B0 shimming is the most straightforward way to improve the B0 homogeneity. However, today's standard cardiac shimming protocol requires manual selection of a shim volume, which often falsely includes regions with large B0 deviation (e.g., liver, fat, and chest wall). The flawed shim field compromises the reliability of high-field CMR protocols, which significantly reduces the scan efficiency and hinders its wider clinical adoption. This study aims to develop a dual-channel deep learning model that can reliably contour the cardiac region for B0 shim without human interaction and under variable imaging protocols. By utilizing both the magnitude and phase information, the model achieved a high segmentation accuracy in the B0 field maps compared to the conventional single-channel methods (Dice score: 2D-mag = 0.866, 3D-mag = 0.907, and 3D-mag-phase = 0.938, all p < 0.05). Furthermore, it shows better generalizability against the common variations in MRI imaging parameters and enables significantly improved B0 shim compared to the standard method (SD(B0Shim): Proposed = 15 ± 11% vs. Standard = 6 ± 12%, p < 0.05). The proposed autonomous model can boost the reliability of cardiac shimming at 3T and serve as the foundation for more reliable and efficient high-field CMR imaging in clinical routines.

Background/aim: Lenvatinib, an oral multikinase inhibitor, has demonstrated promising activity in patients with osteosarcoma (OS). Therefore, it is worth exploring the inhibitory efficacy and mechanism of action of lenvatinib in osteosarcoma. The primary goal of this study was to examine the inhibitory effectiveness and mechanism of lenvatinib on the growth and invasion of OS cells., Materials and Methods: The effects of lenvatinib on cell viability, apoptosis, protein kinase B (AKT) activation, its downstream effector proteins involved in tumor progression, and invasion capability were assessed using MTT assay, flow cytometry, western blotting, and invasion/migration assay on U-2 OS and MG63 cells., Results: Lenvatinib effectively induced cytotoxicity, apoptosis, as well as extrinsic and intrinsic apoptotic signaling in OS cells. Lenvatinib also significantly decreased the invasion/migration capability, AKT activation, and downstream effector proteins., Conclusion: The anti-OS effect of lenvatinib may be associated with the induction of apoptosis and the inactivation of AKT., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background and Objectives: Adequate pain management during early rehabilitation is mandatory for improving the outcomes of patients undergoing total knee arthroplasty (TKA). Conventional pain management, mainly comprising opioids and epidural analgesia, may result in certain adverse effects such as dizziness, nausea, and motor blockade. We proposed a multimodal analgesic (MA) strategy involving the use of peripheral nerve block (NB), periarticular injection (PAI), and intravenous patient-controlled analgesia (IVPCA). This study compared the clinical efficacy and adverse effects of the proposed MA strategy and patient-controlled epidural analgesia (PCEA). Materials and Methods: We enrolled 118 patients who underwent TKA under spinal anesthesia. The patients followed either the MA protocol or received PCEA after surgery. The analgesic effect was examined using a numerical rating scale (NRS). The adverse effects experienced by the patients were recorded. Results: A lower proportion of patients in the MA group experienced motor blockade (6.45% vs. 22.98%) compared to those in the PCEA group on the first postoperative day. Furthermore, a lower proportion of patients in the MA group experienced numbness (18.52% vs. 43.33%) than those in the PCEA group on the first postoperative day. Conclusions: The MA strategy can be recommended for reducing the occurrence of motor blockade and numbness in patients following TKA. Therefore, the MA strategy ensures early rehabilitation while maintaining adequate pain relief.

Background/aim: Osteosarcoma is an aggressive primary malignant bone tumor that occurs in childhood. Although the diagnostic and treatment options have been improved, osteosarcoma confers poor prognosis. Magnolol, an active component of Magnoliae officinalis cortex, has been widely applied in herb medicine and has been shown to have multiple pharmacological activities. However, whether magnolol possesses anti-osteosarcoma capacity remains unknown., Materials and Methods: We examined magnolol is cytotoxicity, and whether it regulates apoptosis and oncogene expression using MTT, flow cytometry and Western blotting assays in osteosarcoma cells., Results: Magnolol exerted toxicity towards U-2 OS cells by inducing intrinsic/extrinsic apoptosis pathways. Additionally, treatment of U-2 OS cells with magnolol inhibited MAPK1 mitogen-activated protein kinase 1 (ERK)/Nuclear factor kappa B (NF-B) signaling involved in tumor progression and reduced the expression of anti-apoptotic and metastasis-associated genes., Conclusion: Magnolol may induce apoptosis and inactivate ERK/NF-B signal transduction in osteosarcoma cells., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Hypertrophic cardiomyopathy (HCM) related myocardial vascular remodelling may lead to the reduction of myocardial blood supply and a subsequent progressive loss of cardiac function. This process has been difficult to observe and thus their connection remains unclear. Here we used non-invasive myocardial blood flow sensitive CMR to show an impairment of resting myocardial perfusion in a mouse model of naturally occurring HCM., Methods: We used a mouse model (DBA/2 J; D2 mouse strain) that spontaneously carries variants in the two most susceptible HCM genes-Mybpc3 and Myh7 and bears the key features of human HCM. The C57BL/6 J (B6) was used as a reference strain. Mice with either B6 or D2 backgrounds (male: n = 4, female: n = 4) underwent cine-CMR for functional assessment at 9.4 T. Left ventricular (LV) wall thickness was measured in end diastolic phase by cine-CMR. Quantitative myocardial perfusion maps (male: n = 5, female: n = 5 in each group) were acquired from arterial spin labelling (cine ASL-CMR) at rest. Myocardial perfusion values were measured by delineating different regions of interest based on the LV segmentation model in the mid ventricle of the LV myocardium. Directly after the CMR, the mouse hearts were removed for histological assessments to confirm the incidence of myocardial interstitial fibrosis (n = 8 in each group) and small vessel remodelling such as vessel density (n = 6 in each group) and perivascular fibrosis (n = 8 in each group)., Results: LV hypertrophy was more pronounced in D2 than in B6 mice (male: D2 LV wall thickness = 1.3 ± 0.1 mm vs B6 LV wall thickness = 1.0 ± 0.0 mm, p < 0.001; female: D2 LV wall thickness = 1.0 ± 0.1 mm vs B6 LV wall thickness = 0.8 ± 0.1 mm, p < 0.01). The resting global myocardial perfusion (myocardial blood flow; MBF) was lower in D2 than in B6 mice (end-diastole: D2 MBF global  = 7.5 ± 0.6 vs B6 MBF global  = 9.3 ± 1.6 ml/g/min, p < 0.05; end-systole: D2 MBF global  = 6.6 ± 0.8 vs B6 MBF global  = 8.2 ± 2.6 ml/g/min, p < 0.01). This myocardial microvascular dysfunction was observed and associated with a reduction in regional MBF, mainly in the interventricular septal and inferior areas of the myocardium. Immunofluorescence revealed a lower number of vessel densities in D2 than in B6 (D2 capillary = 31.0 ± 3.8% vs B6 capillary = 40.7 ± 4.6%, p < 0.05). Myocardial collagen volume fraction (CVF) was significantly higher in D2 LV versus B6 LV mice (D2 CVF = 3.7 ± 1.4% vs B6 CVF = 1.7 ± 0.7%, p < 0.01). Furthermore, a higher ratio of perivascular fibrosis (PFR) was found in D2 than in B6 mice (D2 PFR = 2.3 ± 1.0%, B6 PFR = 0.8 ± 0.4%, p < 0.01)., Conclusions: Our work describes an imaging marker using cine ASL-CMR with a potential to monitor vascular and myocardial remodelling in HCM.

Objective: Untreated obstructive sleep apnea syndrome (OSAS) increases the risk of cardiovascular, dementia, and motor vehicle accident events. However, continuous positive airway pressure (CPAP) which is the gold standard treatment is not acceptable for many patients with OSAS. Development of devices for the patients of nonadherence to CPAP is necessary., Materials and Methods: We evaluated the effect of the smart antisnore pillow (SAP) in patients with OSAS in a prospective, noncontrolled, nonrandomized, pilot study. According to the apnea-hypopnea index (AHI), they were divided into two groups: mild-to-moderate OSAS group and severe OSAS group. Single-night polysomnography (PSG) with application of a SAP was performed. Thirty patients, 15 males and 15 females, 33-82 years old (mean age, 59.3 ± 12.9 years), completed the smart antisnore pillow therapy test. Among them, 23 patients had mild-to-moderate OSAS., Results: The SAP significantly improved the snore number ( p = 0.018), snore index ( p = 0.013), oxygen denaturation index ( p = 0.001), total AHI ( p = 0.002), and supine AHI ( p = 0.002) in the mild-to-moderate OSAS group, but there was no significant improvement in the severe OSAS group., Conclusions: We concluded that the SAP is an effective positional therapy device for patients with OSAS of mild-to-moderate severity., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Tsung-Te Chung et al.)

Inflammation is one underlying contributing factor in the pathology of acute and chronic kidney disorders. Phagocytes such as monocytes, neutrophils and dendritic cells are considered to play a deleterious role in the progression of kidney disease but may also contribute to organ homeostasis. The kidney is a target of life-threatening autoimmune disorders such as the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). Neutrophils and monocytes express ANCA antigens and play an important role in the pathogenesis of AAV. Noninvasive in vivo methods that can quantify the distribution of inflammatory cells in the kidney as well as other organs in vivo would be vital to identify the causality and significance of inflammation during disease progression. Here we describe an noninvasive technique to study renal inflammation in rodents in vivo using fluorine ( 19 F) MRI. In this protocol we chose a murine ANCA-AAV model of renal inflammation and made use of nanoparticles prepared from perfluoro-5-crown-15-ether (PFCE) for renal 19 F MRI.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by two separate chapters describing the basic concept and data analysis.

The signal intensity differences measured by an arterial-spin-labelling (ASL) magnetic resonance imaging (MRI) experiment are proportional to the local perfusion, which can be quantified with kinetic modeling. Here we present a step-by-step tutorial for the data post-processing needed to calculate an ASL perfusion map. The process of developing an analysis software is described with the essential program code, which involves nonlinear fitting a tracer kinetic model to the ASL data. Key parameters for the quantification are the arterial transit time (ATT), which is the time the labeled blood takes to flow from the labeling area to the tissue, and the tissue T 1 . As ATT varies with vasculature, physiology, anesthesia and pathology, it is recommended to measure it using multiple delay times. The tutorial explains how to analyze ASL data with multiple delay times and a T 1 map for quantification.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

A noninvasive, robust, and reproducible method to measure renal perfusion is important to understand the physiology of kidney. Arterial spin labeling (ASL) MRI technique labels the endogenous blood water as freely diffusible tracers to measure perfusion quantitatively without relying on exogenous contrast agent. Therefore, it alleviates the safety concern involving gadolinium chelates. To obtain quantitative tissue perfusion information is particularly relevant for multisite and longitudinal imaging of living subjects.This chapter is based upon work from the PARENCHIMA COST Action, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by two separate chapters describing the basic concept and data analysis.

The kidney is a complex organ involved in the excretion of metabolic products as well as the regulation of body fluids, osmolarity, and homeostatic status. These functions are influenced in large part by alterations in the regional distribution of blood flow between the renal cortex and medulla. Renal perfusion is therefore a key determinant of glomerular filtration. Therefore the quantification of regional renal perfusion could provide important insights into renal function and renal (patho)physiology. Arterial spin labeling (ASL) based perfusion MRI techniques, can offer a noninvasive and reproducible way of measuring renal perfusion in animal models. This chapter addresses the basic concept of ASL-MRI.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Renal MRI holds incredible promise for making a quantum leap in improving diagnosis and care of patients with a multitude of diseases, by moving beyond the limitations and restrictions of current routine clinical practice. Clinical and preclinical renal MRI is advancing with ever increasing rapidity, and yet, aside from a few examples of renal MRI in routine use, it is still not good enough. Several roadblocks are still delaying the pace of progress, particularly inefficient education of renal MR researchers, and lack of harmonization of approaches that limits the sharing of results among multiple research groups.Here we aim to address these limitations for preclinical renal MRI (predominantly in small animals), by providing a comprehensive collection of more than 40 publications that will serve as a foundational resource for preclinical renal MRI studies. This includes chapters describing the fundamental principles underlying a variety of renal MRI methods, step-by-step protocols for executing renal MRI studies, and detailed guides for data analysis. This collection will serve as a crucial part of a roadmap toward conducting renal MRI studies in a robust and reproducible way, that will promote the standardization and sharing of data.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers.

Background: Malignant tumours release factors, which attract myeloid cells and induce their polarisation to pro-invasive, immunosuppressive phenotypes. Brain-resident microglia and peripheral macrophages accumulate in the tumour microenvironment of glioblastoma (GBM) and induce immunosuppression fostering tumour progression. Macrophage colony stimulating factors (CSFs) control the recruitment of myeloid cells during peripheral cancer progression, but it is disputable, which CSFs drive their accumulation in gliomas., Methods: The expression of CSF2 (encoding granulocyte-macrophage colony stimulating factor) was determined in TCGA datasets and five human glioma cell lines. Effects of stable CSF2 knockdown in glioma cells or neutralising CSF2 or receptor CSF2Rα antibodies on glioma invasion were tested in vitro and in vivo., Results: CSF2 knockdown or blockade of its signalling reduced microglia-dependent glioma invasion in microglia-glioma co-cultures. CSF2-deficient human glioma cells encapsulated in cell-impermeable hollow fibres and transplanted to mouse brains, failed to attract microglia, but stimulated astrocyte recruitment. CSF2-depleted gliomas were smaller, attracted less microglia and macrophages, and provided survival benefit in tumour-bearing mice. Apoptotic microglia/macrophages were detected in CSF2-depleted tumours., Conclusions: CSF2 is overexpressed in a subset of mesenchymal GBMs in association with high immune gene expression. Tumour-derived CSF2 attracts, supports survival and induces pro-tumorigenic polarisation of microglia and macrophages.

Thermal magnetic resonance (ThermalMR) accommodates radio frequency (RF)-induced temperature modulation, thermometry, anatomic and functional imaging, and (nano)molecular probing in an integrated RF applicator. This study examines the feasibility of ThermalMR for the controlled release of a model therapeutics from thermoresponsive nanogels using a 7.0-tesla whole-body MR scanner en route to local drug-delivery-based anticancer treatments. The capacity of ThermalMR is demonstrated in a model system involving the release of fluorescein-labeled bovine serum albumin (BSA-FITC, a model therapeutic) from nanometer-scale polymeric networks. These networks contain thermoresponsive polymers that bestow environmental responsiveness to physiologically relevant changes in temperature. The release profile obtained for the reference data derived from a water bath setup used for temperature stimulation is in accordance with the release kinetics deduced from the ThermalMR setup. In conclusion, ThermalMR adds a thermal intervention dimension to an MRI device and provides an ideal testbed for the study of the temperature-induced release of drugs, magnetic resonance (MR) probes, and other agents from thermoresponsive carriers. Integrating diagnostic imaging, temperature intervention, and temperature response control, ThermalMR is conceptually appealing for the study of the role of temperature in biology and disease and for the pursuit of personalized therapeutic drug delivery approaches for better patient care.

Objective: Design, implementation, evaluation and application of a quadrature birdcage radiofrequency (RF) resonator tailored for renal and cardiac sodium ( 23 Na) magnetic resonance imaging (MRI) in rats at 9.4 T., Materials and Methods: A low pass birdcage resonator (16 rungs, d in  = 62 mm) was developed. The transmission field (B 1 + ) was examined with EMF simulations. The scattering parameter (S-parameter) and the quality factor (Q-factor) were measured. For experimental validation B 1 + -field maps were acquired with the double-angle method. In vivo sodium imaging of the heart (spatial resolution: (1 × 1 × 5) mm 3 ) and kidney (spatial resolution: (1 × 1 × 10) mm 3 ) was performed with a FLASH technique., Results: The RF resonator exhibits RF characteristics, transmission field homogeneity and penetration that afford 23 Na MR in vivo imaging of the kidney and heart at 9.4 T. For the renal cortex and medulla a SNRs of 8 and 13 were obtained and a SNRs of 14 and 15 were observed for the left and right ventricle., Discussion: These initial results obtained in vivo in rats using the quadrature birdcage volume RF resonator for 23 Na MRI permit dedicated studies on experimental models of cardiac and renal diseases, which would contribute to translational research of the cardiorenal syndrome.

Diffusion-weighted magnetic resonance imaging (DWI) is a non-invasive imaging technique sensitive to tissue water movement. By enabling a discrimination between tissue properties without the need of contrast agent administration, DWI is invaluable for probing tissue microstructure in kidney diseases. DWI studies commonly make use of single-shot Echo-Planar Imaging (ss-EPI) techniques that are prone to suffering from geometric distortion. The goal of the present study was to develop a robust DWI technique tailored for preclinical magnetic resonance imaging (MRI) studies that is free of distortion and sensitive to detect microstructural changes. Since fast spin-echo imaging techniques are less susceptible to B 0 inhomogeneity related image distortions, we introduced a diffusion sensitization to a split-echo Rapid Acquisition with Relaxation Enhancement (RARE) technique for high field preclinical DWI at 9.4 T. Validation studies in standard liquids provided diffusion coefficients consistent with reported values from the literature. Split-echo RARE outperformed conventional ss-EPI, with ss-EPI showing a 3.5-times larger border displacement (2.60 vs. 0.75) and a 60% higher intra-subject variability (cortex = 74%, outer medulla = 62% and inner medulla = 44%). The anatomical integrity provided by the split-echo RARE DWI technique is an essential component of parametric imaging on the way towards robust renal tissue characterization, especially during kidney disease.

We hypothesized that sorafenib plus transarterial chemoembolization (TACE) would confer survival benefits over sorafenib alone for advanced hepatocellular carcinoma (aHCC). We investigated this while using the population-based All-Cancer Dataset to assemble a cohort ( n = 3674; median age, 60; 83% men) of patients receiving sorafenib for aHCC (Child-Pugh A) with macro-vascular invasion or nodal/distant metastases. The patients were classified into the sorafenib-TACE group ( n = 426) or the propensity score-matched sorafenib-alone group ( n = 1686). All of the participants were followed up until death or the end of the study. Time-dependent Cox model and the Mantel-Byar test were used for survival analysis. During the median follow-ups of 221 and 133 days for the sorafenib-TACE and sorafenib-alone groups, 164 (39%) and 916 (54%) deaths occurred, respectively; the corresponding median overall survivals (OS) were 381 and 204 days, respectively (hazard ratio, HR: 0.74; 95% confidence interval, CI, 0.63-0.88; p = 0.021). The one-year and six-month OS were 53.5% and 80.3% in the sorafenib-TACE group and 32.4% and 54.4% in the sorafenib-alone group, respectively. The major complications were comparable between the two groups. The addition of TACE to sorafenib improves survival, with a 26% reduction in mortality. These findings provide strong real-world evidence that supports this combination strategy for eligible Child-Pugh A aHCC patients.

Patients with rheumatoid arthritis (RA) have a high risk of cardiovascular diseases and fractures. This retrospective cohort study explored whether patients with RA face higher complication risks or longer hospital stays than other patients when they had a lower limb fracture that required the surgery. Patients aged >45 years who received lower limb fracture surgeries between 2005 and 2012 were selected from the National Health Insurance Research Database, and 10 related variables including sex and age were used in propensity score matching to pair RA patients with non-RA patients in a 1:4 ratio. The final study sample comprised 1109 patients with RA and 4436 non-RA patients. The results indicated that 5.57% of the study sample had postoperative complications, accounting for 5.05% of patients with RA and 5.70% of the control group. After conditional logistic regression analysis was performed, the risk of major complications has no significant differences between patients with RA and the control group (odds ratio [OR] = 0.87; 95% confidence interval [CI]: 0.61-1.24; P > .05). However, the comorbidity severity score exerted a significant effect on complications; patients with scores ≥3 were 2.78 times more likely to experience complications (OR = 2.78; 95% CI 1.52-5.07). When considering different types of complications, patients with RA were less likely to be exposed to the risk of stroke (OR = 0.48). After controlling all related factors, no significant differences were observed in the complication risks or deaths between the 2 groups (P > .05). Regarding hospitalization length, the average stay for all patients was 8.12 days; after controlling related factors, the hospitalization length for patients with RA was 0.97 times that of the control group, which was nonsignificant (P > .05). These results may provide some information to healthcare professionals when providing treatments.

Background: Intramedullary (IM) or extramedullary (EM) mechanical guides are used as alignment tools during total knee arthroplasty (TKA) surgery. The EM guide is less invasive; however, the IM mechanical guide is the preferred option since it has shown superior outcomes in several studies. Picture archive and communication system (PACS) images, if available, are extensively used for preoperative planning and intraoperative guidance. This retrospective study compared TKA outcomes using the conventional IM guide and a new EM technique which uses PACS image for preoperative and intraoperative assessment bone resection. To the best of our knowledge, this is the first study with the new EM technique., Materials and Methods: The study was performed on 205 knees (190 patients) for TKA from 2011 to 2013. The perioperative blood loss and the postoperative alignment angles were assessed for both mechanical guides. The angles were measured on the radiographs of the patient. The blood loss was assessed by the blood accumulated in the hemovac drain during the surgery and until 3 days after the surgery., Results: The new EM guide provided similar postoperative alignment as that obtained with the IM guide., Conclusion: The EM-guided method for femoral bone cutting using PACS films in TKA is as good as the IM method. The additional advantages of less injury to the bone and less fat emboli load to the cardiopulmonary system with the EM method makes it an attractive choice for routine, especially in the elderly and/or simultaneous bilateral, TKA in hospitals without modern computer-assisted navigation systems., Competing Interests: There are no conflicts of interest.

To reduce the damage to posteromedial knee capsule, we developed a direct extra-articular arthroscopic approach for excision of symptomatic popliteal cysts. This study aimed to demonstrate the surgical technique and present the 2-year follow-up results. Cystectomy is performed by extra-articular surgical approach through a high posteromedial portal. Twenty-one consecutive patients diagnosed of symptomatic popliteal cysts with failed initial conservative treatments were included. At a median follow-up of 29.4 months, all knees had improved clinical function assessed by Rauschning and Lindgren knee classification (p<0.001). The cysts were either disappeared (95.2%) or reduced in size (4.8%). Only one (4.8%) patient had recurrent cyst, which was solved after ultrasound-guided aspiration. This direct extra-articular arthroscopic technique could be a feasible alternative for treatment of symptomatic popliteal cysts., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Instability of the knee joint after total knee replacement (TKR) is one of the most important reasons for revision TKR. Inadequate release or tightening of the collateral ligaments in the knee joint may cause instability and early failure. This study presents a case series study of a new technique for ligament balancing wherein the collateral ligament is detached from its origin and rotated (twisted) around its longitudinal axis to tighten the ligament before the origin is reattached to its original position. The surgical technique for collateral ligament tightening during TKR was performed on 6 patients with a deformed knee caused by osteoarthritis and rheumatoid arthritis. The range of motion, knee society score, and laxity of the patients' knee joint, after 7 months to 13 years of follow-up, were evaluated. The technique was successful, achieving good range of motion and satisfactory stability of the joint. Further evaluation in a larger number of cases and a comparative analysis with different techniques would further support the usefulness of this rotational ligamentoplasty technique.

As the world's population ages, the number of people receiving total knee arthroplasty (TKA) has been on the rise. Although patients with diabetes mellitus are known to face greater risks of TKA postoperative infection and revision TKA owing to diabetic complications, studies on whether such patients' participation in pay for performance (P4P) programs influences the incidence rates of TKA postoperative infection or revision TKA are still lacking. This study examined the 2002-2012 data of Taiwan's National Health Insurance Research Database to conduct a retrospective cohort analysis of diabetic patients over 50 years old who have received TKA. To reduce any selection bias between patients joining and not joining the P4P program, propensity score matching was applied. The Cox proportional hazards model was used to examine the influence of the P4P program on TKA postoperative infection and revision TKA, and the results indicate that joining P4P lowered the risk of postoperative infection (HR = 0.91, 95% CI: 0.77-1.08), however, which was not statistically significant, and significantly lowered the risk of revision TKA (HR = 0.53, 95% CI: 0.39-0.72). Being younger and male, having multiple comorbid conditions or greater diabetic severity, receiving care at regional or public hospitals, and not having a diagnosis of degenerative or rheumatoid arthritis were identified as factors for higher risk of TKA postoperative infection for patients with diabetes. As for the risk of revision TKA, postoperative infection and being younger were identified as factors for a significantly higher risk (p < 0.05)., Competing Interests: The authors have declared that no competing interests exist.

Background: Because of modern challenges in quality, safety, patient centeredness, and cost, health care is evolving to adopt leadership practices of highly effective organizations. Traditional physician training includes little focus on developing leadership skills, which necessitates further training to achieve the potential of collaborative management., Purpose: The aim of this study was to design a leadership program using established models for continuing medical education and to assess its impact on participants' knowledge, skills, attitudes, and performance., Methodology/approach: The program, delivered over 9 months, addressed leadership topics and was designed around a framework based on how physicians learn new clinical skills, using multiple experiential learning methods, including a leadership active learning project. The program was evaluated using Kirkpatrick's assessment levels: reaction to the program, learning, changes in behavior, and results. Four cohorts are evaluated (2008-2011)., Results: Reaction: The program was rated highly by participants (mean = 4.5 of 5). Learning: Significant improvements were reported in knowledge, skills, and attitudes surrounding leadership competencies. Behavior: The majority (80%-100%) of participants reported plans to use learned leadership skills in their work. Improved team leadership behaviors were shown by increased engagement of project team members., Results: All participants completed a team project during the program, adding value to the institution., Conclusion: Results support the hypothesis that learning approaches known to be effective for other types of physician education are successful when applied to leadership development training. Across all four assessment levels, the program was effective in improving leadership competencies essential to meeting the complex needs of the changing health care system., Practice Implications: Developing in-house programs that fit the framework established for continuing medical education can increase physician leadership competencies and add value to health care institutions. Active learning projects provide opportunities to practice leadership skills addressing real word problems.

Androgenetic alopecia (AGA) is a common hair loss disorder, especially in men and the elderly. In this study, we analyzed the therapeutic effects of platelet-rich plasma (PRP) injections and embedded sutures in patients with AGA. In each participant, we administered different treatments in one area of hair loss that was divided into four sections. Each section received one of the following treatments: No treatment, PRP injection, suture embedding, and combined PRP injection/suture-embedded areas. The thickness of the scalp, and scalp perfusion were measured using an ultrasound imaging system and Moor FLPI full-field laser perfusion imaging system, respectively. The diameters of the hair were measured using optical microscopy. Our results show that PRP injection treatments increased the diameter of the hair (P = 0.034), and the combined PRP injection/suture-embedded treatments had a significant effect on the thickness of the scalp (P = 0.002), the blood flow (P = 0.014) through the scalp, and the diameter of the hair (P= 0.013). This study has demonstrated that there is a synergistic effect between PRP injections and suture embedding for increasing the thickness and blood flow of the scalp, and diameter of the hair. Combined PRP injection/suture-embedded PRP injections might have therapeutic benefit for patients with AGA., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Catechol estrogens (CEs) are metabolic electrophiles that actively undergo covalent interaction with cellular proteins, influencing molecular function. There is no feasible method to identify their binders in a living system. Herein, we developed a click chemistry-based approach using ethinylestradiol (EE2) as the precursor probe coupled with quantitative proteomics to identify protein targets of CEs and classify their binding strengths. Using in situ metabolic conversion and click reaction in liver microsomes, CEs-protein complex was captured by the probe, digested by trypsin, stable isotope labeled via reductive amination, and analyzed by liquid chromatography-mass spectrometry (LC-MS). A total of 334 liver proteins were repeatedly identified ( n ≥ 2); 274 identified proteins were classified as strong binders based on precursor mass mapping. The binding strength was further scaled by D/H ratio (activity probe/solvent): 259 strong binders had D/H > 5.25; 46 weak binders had 5.25 > D/H > 1; 5 nonspecific binders (keratins) had D/H < 1. These results were confirmed using spiked covalent control (strong binder) and noncovalent control (weak binder), as well as in vitro testing of cytochrome c (D/H = 5.9), which showed covalent conjugation with CEs. Many identified strong binders, such as glutathione transferase, catechol-O-methyl transferase, superoxide dismutase, catalase, glutathione peroxidase, and cytochrome c, are involved in cellular redox processes or detoxification activities. CE conjugation was shown to suppress the superoxide oxidase activity of cytochrome c, suggesting that CEs modification may alter the redox action of cellular proteins. Due to structural similarity and inert alkyne group, EE2 probe is very likely to capture protein targets of CEs in general. Thus, this strategy can be adopted to explore the biological impact of CEs modification in living systems.

Purpose To use multiparametric magnetic resonance (MR) imaging to assess for and establish age-related differences in healthy thigh muscles. Materials and Methods Ninety-five subjects (47 men, 48 women; median age, 47 years) with healthy body mass index were grouped according to age: 30-39 years (n = 25), 40-49 years (n = 25), 50-59 years (n = 25), and 60-69 years (n = 20). Multiparametric MR imaging (intravoxel incoherent motion diffusion-weighted, diffusion-tensor, multiecho Dixon, and dynamic contrast material-enhanced MR imaging) was performed at 3.0 T. Two radiologists independently evaluated parametric maps of the anterior, medial, and posterior compartments. Welch-modified one-way analysis of variance and post hoc Dunnet T3 test were used to evaluate differences in apparent diffusion, true diffusion, and pseudodiffusion coefficients; perfusion fraction; fractional anisotropy (FA); fat percentage; volume transfer constant; constant efflux rate from the extravascular-extracellular space to plasma; volume fraction of the extravascular-extracellular space (V e ); incremental area under the curve; and Pearson and Spearman correlation coefficients were used to evaluate relationship strength. Multiple regression analysis was performed to identify independent predictors of age, and interrater reliability was assessed with intraclass correlation coefficients. Results There were significant differences among the age groups in apparent diffusion coefficients (P = .010), true diffusion coefficients (P = .045), FA (P < .001), V e (P = .029) of the anterior compartment muscles, and fat percentages of all three compartments (P ≤ .001). Moreover, FA (Pearson r = 0.428, Spearman ρ = 0.431; P < .001) and V e (r = 0.226, P = .030 and ρ = 0.309, P = .003) in the anterior compartment and fat percentages in all three compartments (r = 0.481, 0.475, and 0.573; ρ = 0.515, 0.487, and 0.667; respectively; P < .001) were positively associated with age. Multiple regression analysis showed that age was predictive of fat percentage in the posterior compartment (β = 0.500, P < .001) and of FA in the anterior compartment (β = 0.194, P = .042). Interrater reliability was excellent (intraclass correlation coefficient, 0.745-0.992). Conclusion Multiple MR imaging parameters were significantly associated with age in thigh muscles. © RSNA, 2017 Online supplemental material is available for this article.

Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the myocardium and bares the risk of progression to heart failure or sudden cardiac death. Identifying patients at risk remains an unmet need. Recognizing the dependence of microscopic susceptibility on tissue microstructure and on cardiac macromorphology we hypothesized that myocardial T 2 * might be altered in HCM patients compared to healthy controls. To test this hypothesis, myocardial T 2 * -mapping was conducted at 7.0 Tesla to enhance T 2 * -contrast. 2D CINE T 2 * -mapping was performed in healthy controls and HCM patients. To ensure that T 2 * is not dominated by macroscopic magnetic field inhomogeneities, volume selective B 0 shimming was applied. T 2 * changes in the interventricular septum across the cardiac cycle were analyzed together with left ventricular radius and ventricular septal wall thickness. The results show that myocardial T 2 * is elevated throughout the cardiac cycle in HCM patients compared to healthy controls. A mean septal T 2 *  = 13.7 ± 1.1 ms (end-systole: T 2 * ,systole  = 15.0 ± 2.1, end-diastole: T 2 * ,diastole  = 13.4 ± 1.3 ms, T 2 * ,systole /T 2 * ,diastole ratio = 1.12) was observed in healthy controls. For HCM patients a mean septal T 2 *  = 17.4 ± 1.4 ms (end-systole: T 2 * ,systole  = 17.7 ± 1.2 ms, end-diastole: T 2 * ,diastole  = 16.2 ± 2.5 ms, T 2 * ,systole /T 2 * ,diastole ratio = 1.09) was found. Our preliminary results provide encouragement that assessment of T 2 * and its changes across the cardiac cycle may benefit myocardial tissue characterization in HCM.

Objectives: Extracorporeal shockwave therapy (ESWT) and corticosteroid injection (CSI) are treatment options for plantar fasciitis. Their clinical outcome comparison remains a debate. Also, the thickness changes of the plantar fascia on objective evaluation under the medium energy ESWT and CSI therapy are elusive., Methods: A total of 97 patients with chronic plantar fasciitis were enrolled in the randomized prospective trial. Forty-seven patients received extracorporeal shock wave therapy (ESWT), and fifty patients received corticosteroid injection (CSI). The thickness of the plantar fascia was evaluated respectively before ESWT and CSI, and at the 4 th and 12 th week after ESWT and CSI by ultrasonography. Pain level and clinical outcomes were recorded using visual analogue scale (VAS) and 100-points scoring systems. Correlation analysis was performed between the thickness change and clinical outcome., Results: Under ultrasonography, we observed more increase of plantar fascia thickness of ESWT group than CSI group at 4 th week (p=0.048). VAS of plantar fasciitis patients receiving ESWT was lower than those who received corticosteroid injection (0.001 and p⟨0.001, at 4 th and 12 th week). On the assessment of 100-points scoring systems, the pain level of patients with ESWT was lower than those with CSI at the 12 th week (p⟨0.001). On the other hand, the increase of plantar fascia thickness at 4 th week was positively correlated with the decrease of VAS score at 12 th week follow-up (R=0.302, P=0.039)., Conclusions: At 4 th week after treatment, the thickness of plantar fascia increased. Then it decreased gradually, but not to the baseline at 12 th week. On the pain level outcome at 12 th week, extracorporeal shockwave therapy (ESWT) was more efficient than corticosteroid injection (CSI) on chronic plantar fasciitis. The more change of plantar fascia after ESWT, the more efficient on clinical outcome.

Cardiac magnetic resonance (MR) imaging of mice is a valuable tool for the precise in vivo diagnosis and prognosis of heart defects. This detailed protocol describes the method of cardiac MR imaging in mice step by step. A series of MR images captures the contractile function of the mouse heart and post-processing of the image data yields morphometric parameters (myocardial mass, myocardial wall thickness, ventricular end-systolic and end-diastolic volume) as well as functional parameters (stroke volume and ejection fraction). This protocol may also serve as a starting point for MR imaging of rats, by using larger image dimensions (field-of-view) and MR hardware suitable for larger animals.

The integrity of the blood-brain barrier (BBB) can be noninvasively monitored by magnetic resonance imaging (MRI). Conventional MR contrast agents (CAs) containing gadolinium are used in association with MRI in routine clinical practice to detect and quantify BBB leakage. Under normal circumstances CAs do not cross the intact BBB. However due to their small size they extravasate from the blood into the brain tissue even when the BBB is partially compromised. Here we describe an MR method based on T 1 -weighted images taken prior to and after CA injection. This MR method is useful for investigating BBB permeability in in vivo mouse models and can be easily applied in a number of experimental disease conditions including neuroinflammation disorders, or to assess (un)wanted drug effects.

Purpose: To evaluate the presence and causes of left brachiocephalic vein (LBCV) steno-occlusive lesions in patients with loss of normal waveform in Doppler ultrasound of the left internal jugular vein (LIJV)., Materials and Methods: We performed Doppler ultrasound of both internal jugular veins in 1912 patients who received an implantable venous access port from August 2013 to January 2016. Among them, 106 patients showed loss of normal Doppler waveforms of the LIJV (56 men and 50 women; mean age, 61.4 ± 11.6 years). We retrospectively analyzed the presence and causes of the LBCV steno-occlusive lesions on contrast-enhanced chest computed tomography (CT) images., Results: LBCV steno-occlusive lesions were present in 82 patients (77.4%). The causes of these lesions were anatomic structures (n = 70, 85.4%), tumorous lesions (n = 11, 13.4%), and thrombus (n = 1, 1.2%). The anterior anatomic structures to the LBCV causing stenosis were bony structures (n = 50), right upper lobe (n = 11), and mediastinal fat (n = 9). The posterior anatomic structures to the LBCV resulting in stenosis were right brachiocephalic artery (n = 58), left common carotid artery (n = 7), and aortic arch (n = 5). The tumorous lesions resulting in stenosis were mediastinal lymph node (n = 5), thymic lesions (n = 3), lymphoma (n = 1), lung cancer (n = 1), and bone tumor (n = 1)., Conclusions: It is necessary to suspect steno-occlusive lesion of the LBCV from various causes and to use caution when performing central venous catheterization in cases with loss of a normal Doppler waveform.

Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure. Loss of Cadm1 protected mice from obesity, and tract-tracing analysis revealed Cadm1-positive innervation of POMC neurons via afferent projections originating from beyond the arcuate nucleus. Reducing Cadm1 expression in the hypothalamus and hippocampus promoted a negative energy balance and weight loss. These data identify essential roles for Cadm1-mediated neuronal input in weight regulation and provide insight into the central pathways contributing to human obesity.

The blood-brain barrier (BBB) formed by the microvascular endothelium limits cerebral drug delivery. The paraendothelial cleft is sealed by tight junctions (TJs) with a major contribution from claudin-5, which we selected as a target to modulate BBB permeability. For this purpose, drug-enhancer peptides were designed based on the first extracellular loop (ECL) of claudin-5 to allow transient BBB permeabilization. Peptidomimetics (C5C2 and derivatives, nanomolar affinity to claudin-5) size-selectively (≤40 kDa) and reversibly (12-48 h) increased the permeability of brain endothelial and claudin-5-transfected epithelial cell monolayers. Upon peptide uptake, the number of TJ strand particles diminished, claudin-5 was downregulated and redistributed from cell-cell contacts to the cytosol, and the cell shape was altered. Cellular permeability of doxorubicin (cytostatic drug, 580 Da) was enhanced after peptide administration. Mouse studies (3.5 μmol/kg i.v.) confirmed that, for both C5C2 and a d-amino acid derivative, brain uptake of Gd-diethylene-triamine penta-acetic acid (547 Da) was enhanced within 4 h of treatment. On the basis of our functional data, circular dichroism measurements, molecular modeling, and docking experiments, we suggest an association model between β-sheets flanked by α-helices, formed by claudin-5 ECLs, and the peptides. In conclusion, we identified claudin-5 peptidomimetics that improve drug delivery through endothelial and epithelial barriers expressing claudin-5., (© 2017 New York Academy of Sciences.)

Introduction: Osteoporosis is becoming an impending epidemic in the Asia-Pacific region. The association between risk of osteoporotic fracture (OTPF) and chronic obstructive pulmonary disease (COPD) in East Asian patients is yet to be fully examined. We conducted a nationwide population-based retrospective cohort study of 98,700 patients aged ≥50 years with or without COPD using a national administrative claims dataset., Materials and Methods: The patients were divided into COPD and comparison groups comprising 19,740 and 78,960 patients, respectively. The groups were 1 to 4 matched for age, gender, index date, diabetes mellitus, pre-existing osteoporosis and chronic kidney disease. Information such as the geographic area where southern part represented more sunshine exposure, smoking-related diagnoses, alcohol use disorder, whether there was regular use of inhaled corticosteroids and oral corticosteroids, vitamin D prescriptions, Charlson-Deyo comorbidity index score, and other relevant medical comorbidities were extracted for analysis. They were followed up until OTPF or the end of the year 2013. The outcome measure was an osteoporotic vertebral fracture and other long-bone fractures. A multivariate Cox model was constructed to derive adjusted hazard ratios (aHR) for OTPF with corresponding 95% confidence intervals (CI) after controlling for age, sex, insurance premium category, vitamin D prescription, osteoporosis, and coronary heart disease (CHD). Kaplan-Meier curves of the probability of OTPF-free survival for each cohort were compared using the log-rank test. Patients with OTPF during the first follow-up year were excluded from the overall risk calculation. Contributing factors to the increased risk of OTPF in COPD patients were examined in a sensitivity analysis., Results: After a total follow-up of 68,743 patient-years for the COPD group and 278,051 patient-years for the matched comparison group, the HR for OTPF was 1.24 (95% CI [1.02-1.51]; P  = 0.0322) in COPD patients. The aHR was increased by 30% for vertebral OTPF (aHR = 1.297, 95% CI [1.020-1.649]; P  = 0.0339). Differential lag time sensitivity analysis revealed a progressively elevated risk up to 8-fold increase in women (aHR = 8.0 (95% CI [1.81-35.4]; P  < 0.01)) during the fifth follow-up year. COPD patients with pre-existing osteoporosis or given vitamin D prescription harbor a sustained increased risk up to the 5th (aHR, 4.1; 95% CI [1.61-10.35]) and third (aHR, 2.97; 95% CI [1.48-5.97]) follow-up year, respectively., Conclusions: Our nationwide population-based cohort study demonstrates that East Asian COPD patients aged 50 and beyond do harbor a modestly increased risk for osteoporotic vertebral fractures particularly for those who are female, have pre-existing osteoporosis or require vitamin D prescription., Competing Interests: The authors declare there are no competing interests.

Glioma regression requires the recruitment of potent antitumor immune cells into the tumor microenvironment. Dendritic cells (DC) play a role in immune responses to these tumors. The fact that DC vaccines do not effectively combat high-grade gliomas, however, suggests that DCs need to be genetically modified specifically to promote their migration to tumor relevant sites. Previously, we identified extracellular signal-regulated kinase (ERK1) as a regulator of DC immunogenicity and brain autoimmunity. In the current study, we made use of modern magnetic resonance methods to study the role of ERK1 in regulating DC migration and tumor progression in a model of high-grade glioma. We found that ERK1-deficient mice are more resistant to the development of gliomas, and tumor growth in these mice is accompanied by a higher infiltration of leukocytes. ERK1-deficient DCs exhibit an increase in migration that is associated with sustained Cdc42 activation and increased expression of actin-associated cytoskeleton-organizing proteins. We also demonstrated that ERK1 deletion potentiates DC vaccination and provides a survival advantage in high-grade gliomas. Considering the therapeutic significance of these results, we propose ERK1-deleted DC vaccines as an additional means of eradicating resilient tumor cells and preventing tumor recurrence. Mol Cancer Ther; 15(8); 1975-87. ©2016 AACR., (©2016 American Association for Cancer Research.)

Purpose: One challenge academic health centers face is to advance female faculty to leadership positions and retain them there in numbers equal to men, especially given the equal representation of women and men among graduates of medicine and biological sciences over the last 10 years. The purpose of this study is to investigate the explicit and implicit biases favoring men as leaders, among both men and women faculty, and to assess whether these attitudes change following an educational intervention., Method: The authors used a standardized, 20-minute educational intervention to educate faculty about implicit biases and strategies for overcoming them. Next, they assessed the effect of this intervention. From March 2012 through April 2013, 281 faculty members participated in the intervention across 13 of 18 clinical departments., Results: The study assessed faculty members' perceptions of bias as well as their explicit and implicit attitudes toward gender and leadership. Results indicated that the intervention significantly changed all faculty members' perceptions of bias (P < .05 across all eight measures). Although, as expected, explicit biases did not change following the intervention, the intervention did have a small but significant positive effect on the implicit biases surrounding women and leadership of all participants regardless of age or gender (P = .008)., Conclusions: These results suggest that providing education on bias and strategies for reducing it can serve as an important step toward reducing gender bias in academic medicine and, ultimately, promoting institutional change, specifically the promoting of women to higher ranks.

Proteins, covalently modified by catechol estrogens (CEs), were identified recently from the blood serum of diabetic patients and referred to as estrogenized proteins. Estrogenization of circulating insulin may occur and affect its molecular functioning. Here, the chemical reactivity of CEs towards specific amino acid residues of proteins and the structural and functional changes induced by the estrogenization of insulin were studied using cyclic voltammetry, liquid chromatography-mass spectrometry, circular dichroism spectroscopy, molecular modeling, and bioassays. Our results indicate that CEs, namely, 2- and 4-hydroxyl estrogens, were thermodynamically and kinetically more reactive than the catechol moiety. Upon co-incubation, intact insulin formed a substantial number of adducts with one or multiple CEs via covalent conjugation at its Cys 7 in the A or B chain, as well as at His10 or Lys29 in the B chain. Such conjugation was coupled with the cleavage of inter-chain disulfide linkages. Estrogenization on these sites may block the receptor-binding pockets of insulin. Insulin signaling and glucose uptake levels were lower in MCF-7 cells treated with modified insulin than in cells treated with native insulin. Taken together, our findings demonstrate that insulin molecules are susceptible to active estrogenization, and that such modification may alter the action of insulin.

Background: Acute myocardial infarction (AMI) is one of the most important perioperative complications of total knee arthroplasty (TKA). Although risk-stratification tools exist for the prediction of cardiac complications including AMI after noncardiac surgery, such stratification does not differentiate the patients with a coronary stent alone, AMI without a stent, or AMI with a stent. The risk of postoperative AMI in these patient groups may vary. Several studies have recommended suitable times for noncardiac surgery in patients with a coronary stent; however, they do not differentiate between the patients with AMI and no AMI. The suitable time of noncardiac surgery for patients with AMI and stent may vary from those with a stent alone. Moreover, a study to evaluate the risk of AMI within 1 year in an Asian population with a history of AMI or coronary stent who underwent TKA has not been reported., Questions/purposes: (1) What are the risks of AMI within 1 year of TKA in patients who have had a stent alone, AMI without a stent, or AMI with a stent as compared with patients without an AMI/stent? (2) For patients with AMI/stent placement, when can TKA be performed where the risk of subsequent AMI normalizes? (3) What comorbidities are associated with post-TKA AMI? (4) Is the risk of AMI within 1 year after surgery in patients undergoing TKA without a history of AMI/stent higher than that in patients with no surgery?, Methods: This study is a retrospective study of the medical claim records of 128,216 patients who underwent TKA between 1997 and 2010 in Taiwan. The records were retrieved from the research database of the Bureau of National Health Insurance in Taiwan, which maintains the records of 99.68% of the Taiwan population. The patients who had a history of AMI or coronary stent placement within the year before TKA were compared with the patients who had not experienced AMI or stent placement before TKA. The control subjects were matched according to sex, age, Charlson score, and year of surgery. There were 2413 patients in each group. The patients with a history of AMI or stent placement and the timing of TKA after coronary event were further stratified as with a coronary stent alone, AMI without a stent, and AMI with a stent. The effects of the comorbidities of renal failure, diabetes, liver failure, and hypertension were also analyzed individually. The risk of AMI within 1 year after TKA was investigated using bivariate analysis and the Cox proportional hazard model. To compare the risk of AMI within 1 year of surgery in the patients with a history of TKA and no AMI/stent with the population without a history of surgery, a similar bivariate analysis and the Cox proportional hazard model were applied to their matched case and control groups, each containing 110,980 patients., Results: In the adjusted model, using no AMI/stent before TKA as a reference, patients having undergone AMI + stent had the highest risk (hazard ratio [HR], 5.23; 95% confidence interval [CI], 1.81-15.14; p = 0.002), AMI alone without a stent had less risk (HR, 4.88; 95% CI, 1.49-16.01; p = 0.009), and stent alone with AMI had the lowest risk (HR, 3.16; 95% CI, 1.29-7.71; p = 0.012). In all patients, risk of AMI after TKA was not different than reference values after 1 year of initial AMI or stent (stent: HR, 1.67; 95% CI, 0.71-3.94; p = 0.239; AMI: HR, 1.88; 95% CI, 0.42-8.49; p = 0.412; AMI + stent: HR, 1.91; 95% CI, 0.53-6.89; p = 0.321). The risk of post-TKA AMI was elevated within 1 year of the previous episode of AMI/stent (0-180 days: HR, 8.42; 95% CI, 3.03-23.41; p < 0.001; 181-365 days: HR, 7.52; 95% CI, 2.47-22.88; p < 0.001). Only chronic renal failure under hemodialysis was associated with increased risk of AMI within 1 year of TKA (adjusted HR, 4.34; 95% CI, 1.22-15.43; p = 0.023). Patients undergoing TKA with no history of AMI/stent had a lower risk of AMI within 1 year of TKA compared with the patients with no history of surgery (adjusted HR, 0.92; 95% CI, 0.86-0.99; p = 0.016)., Conclusions: This study found the risk of post-TKA AMI remains high within 1 year in patients with a history of AMI/stent. It is recommended that an elective TKA should be performed at least 1 year after an episode of AMI or stent placement. Stents do not provide protection against post-TKA AMI within 6 months of the AMI and patients with AMI + stent have a higher risk of AMI than those with only AMI. Patients of AMI/stent on hemodialysis have a very high risk of post-TKA AMI. However, the risk of AMI is lower in post-TKA patients compared with those with no TKA., Level of Evidence: Level III, prognostic study.

Protein adducts covalently modified by catechol estrogens (CEs), referred to as estrogenized proteins, are potential biomarkers for estrogen homeostasis or exposure to environmental toxicants. However, serum proteins endogenously modified by CEs and the modification sites remain elusive. In this study, liquid chromatography-mass spectrometry (LC-MS)-based shotgun proteomics is applied to identify site-specific protein estrogenization in human blood via a systematic approach and stringent validation. We showed CEs, namely 2- and 4-hydroxyl estrogens which are regarded as biomarkers for estrogen homeostasis, form covalent bonds with proteins, mainly via side chain Cys, Lys, or His residue. Estrogenization of purified human serum albumin (HSA) and immunoglobulin G (IgG) at specific sites was achieved by co-incubation and used as the standards to confirm the identified estrogenization in serum proteins. Based on a database search, estrogenized peptides derived from serum proteins in patient blood were identified; endogenous estrogenization of HSA and IgG-1 at multiple sites were confirmed as compared to the standards. Based on a test using Ellman's reagent, estrogenization produced stable products and irreversibly abolished the reactivity of Cys34-HSA, which is the most important antioxidant and nitric oxide carrier in blood. Given the importance of estrogen metabolism in environmental toxicology, further exploration of estrogenized proteins is warranted for biomarker discovery and/or new mechanisms in disease process., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Research in pathologies of the brain, heart and kidney have gained immensely from the plethora of studies that have helped shape new methods in magnetic resonance (MR) for characterizing preclinical disease models. Methodical probing into preclinical animal models by MR is invaluable since it allows a careful interpretation and extrapolation of data derived from these models to human disease. In this review we will focus on the applications of cryogenic radiofrequency (RF) coils in small animal MR as a means of boosting image quality (e.g., by supporting MR microscopy) and making data acquisition more efficient (e.g., by reducing measuring time); both being important constituents for thorough investigational studies on animal models of disease. This review attempts to make the (bio)medical imaging, molecular medicine, and pharmaceutical communities aware of this productive ferment and its outstanding significance for anatomical and functional MR in small rodents. The goal is to inspire a more intense interdisciplinary collaboration across the fields to further advance and progress non-invasive MR methods that ultimately support thorough (patho)physiological characterization of animal disease models. In this review, current and potential future applications for the RF coil technology in cardiovascular, neurovascular, and renal disease will be discussed.

Objective: To report the incidence and findings of brain magnetic resonance imaging (MRI) in patients with hemorrhagic fever with renal syndrome (HFRS)-related encephalopathy along with its clinical course., Methods: Medical records and brain MRI were reviewed from January 2004 to January 2013. The final cohort consisted of 145 patients. Brain MRI findings were correlated with associated clinical stage of disease., Results: The MRI findings associated with clinical course of HFRS-related encephalopathy were posterior reversible encephalopathy syndrome pattern (n=3) in oliguric phase and splenial lesion pattern (n=1) in febrile phase., Conclusions: Brain MRI findings in HFRS-related encephalopathy may be associated with the clinical course of HFRS., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Cellular functions, ranging from focal adhesion (FA) dynamics and cell motility to tumour growth, are orchestrated by signals cells receive from outside via cell surface receptors. Signalling is fine-tuned by the exo-endocytic cycling of these receptors to control cellular responses such as FA dynamics, which determine cell motility. How precisely endocytosis regulates turnover of the various cell surface receptors remains unclear. Here we identify Stonin1, an endocytic adaptor of unknown function, as a regulator of FA dynamics and cell motility, and demonstrate that it facilitates the internalization of the oncogenic proteoglycan NG2, a co-receptor of integrins and platelet-derived growth factor receptor. Embryonic fibroblasts obtained from Stonin1-deficient mice display a marked surface accumulation of NG2, increased cellular signalling and defective FA disassembly as well as altered cellular motility. These data establish Stonin1 as a specific adaptor for the endocytosis of NG2 and as an important factor for FA dynamics and cell migration.

Background: Total joint replacement (TJR) accounts for a substantial proportion of the total expenditures for health care. Efficient utilization of health resources requires information regarding the trends of TJR. This study investigated the association of TJR with the demographic characteristics in Taiwan from 1998 to 2009. It also estimated the demand for total knee replacement (TKR) and total hip replacement (THR) in the next two decades., Methods: International Classification of Diseases-9 (ICD-9) procedure codes were used to identify the data for primary and revision TKRs and THRs between the years 1998 and 2009 from Taiwan's National Health Insurance Research Database. Age- and sex-specific rates of such procedures were calculated. The trend in TJR rate and its future estimation were studied with regression analyses., Results: From 1998 to 2009, the number of primary TKRs increased by 99.1% and that of primary THRs increased by 11.3%. The number of revision TKRs increased by 3.1% and that of revision THRs decreased by 13.2%. Compared with their respective rates in 2005, the rates of primary TKR and primary THR were projected to increase by 508.2% and 69.7%, respectively, in 2030. The rate of revision TKR was predicted to increase by 75.3% and that of revision THR to decrease by 36.1%., Conclusion: This study gives an insight into the current status burden of TJR in Taiwan. TJR rate projection would be useful for future planning of budget and resources for TJR in Taiwan., (Copyright © 2015. Published by Elsevier Taiwan.)