Evaluating the association between hybrid magnetic resonance positron emission tomography and cardiac-related outcomes in cardiac sarcoidosis

Objectives: To evaluate an extended hybrid MR/PET imaging strategy in cardiac sarcoidosis (CS) employing qualitative and quantitative assessment of PET tracer uptake, and to evaluate its association with cardiac-related outcomes. Background: Invasive endomyocardial biopsy is the gold standard to diagnose CS, but it has poor sensitivity due to the patchy distribution of disease. Imaging with hybrid late gadolinium enhancement (LGE) MR and 18F-fluorodexyglucose (18F-FDG) PET allows simultaneous assessment of myocardial injury and disease activity and has shown promise for improved diagnosis of active CS based on the combined positive imaging outcome, MR(+)PET(+). Methods: 148 patients with suspected CS were enrolled for hybrid MR/PET imaging. Patients were classified based on presence/absence of LGE (MR+/MR-), presence/absence of 18F-FDG (PET+/PET-), and pattern of 18F-FDG uptake (focal/diffuse) into the following categories: MR(+)PET(+)FOCAL, MR(+)PET(+)DIFFUSE, MR(+)PET(-), MR(-)PET(+)FOCAL, MR(-)PET(+)DIFFUSE, MR(-)PET(-). Patients classified as MR(+)PET(+)FOCAL were designated as having active CS [aCS(+)], while all others were considered as having inactive or absent CS and designated aCS(-). Quantitative values of standard uptake value (SUVmax), target-to-background ratio (TBRmax), target-to-normal-myocardium ratio (TNMRmax) and T2 were measured. Occurrence of a cardiac-related clinical outcome was defined as any of the following during the 6-month period after imaging: cardiac arrest, ventricular arrhythmia, complete heart block, need for cardiac resynchronization/defibrillator/pacemaker/monitoring device (CRT-D, ICD/WCD, or ILR). MR/PET imaging results were compared to the presence of the composite clinical outcome. Results: Patients designated aCS(+) had more than 4-fold increased odds of meeting the clinical endpoint compared to aCS(-) (unadjusted odds ratio 4.8; 95% CI 2.0-11.4; p<0.001). TNMRmax achieved an area under the receiver operating characteristic curve of 0.90 for separating aCS(+) from aCS(-). Conclusions: Hybrid MR/PET imaging with an extended image-based classification of CS was statistically associated with clinical outcomes in CS. TNMRmax had high sensitivity and excellent specificity for quantifying the imaging-based classification of active CS.

Molecular Mechanisms of Epileptic Encephalopathy Caused by KCNMA1 Loss-of-Function Mutations

The gene kcnma1 encodes the α-subunit of high-conductance calcium- and voltage-dependent K+ (BK) potassium channel. With the development of generation gene sequencing technology, many KCNMA1 mutants have been identified and are more closely related to generalized epilepsy and paroxysmal dyskinesia. Here, we performed a genetic screen of 26 patients with febrile seizures and identified a novel mutation of KCNMA1 (E155Q). Electrophysiological characterization of different KCNMA1 mutants in HEK 293T cells, the previously-reported R458T and E884K variants (not yet determined), as well as the newly-found E155Q variant, revealed that the current density amplitude of all the above variants was significantly smaller than that of the wild-type (WT) channel. All the above variants caused a positive shift of the I-V curve and played a role through the loss-of-function (LOF) mechanism. Moreover, the β4 subunit slowed down the activation of the E155Q mutant. Then, we used kcnma1 knockout (BK KO) mice as the overall animal model of LOF mutants. It was found that BK KO mice had spontaneous epilepsy, motor impairment, autophagic dysfunction, abnormal electroencephalogram (EEG) signals, as well as possible anxiety and cognitive impairment. In addition, we performed transcriptomic analysis on the hippocampus and cortex of BK KO and WT mice. We identified many differentially expressed genes (DEGs). Eight dysregulated genes [i.e., (Gfap and Grm3 associated with astrocyte activation) (Alpl and Nlrp10 associated with neuroinflammation) (Efna5 and Reln associated with epilepsy) (Cdkn1a and Nr4a1 associated with autophagy)] were validated by RT-PCR, which showed a high concordance with transcriptomic analysis. Calcium imaging results suggested that BK might regulate the autophagy pathway from TRPML1. In conclusion, our study indicated that newly-found point E155Q resulted in a novel loss-of-function variant and the dysregulation of gene expression, especially astrocyte activation, neuroinflammation and autophagy, might be the molecular mechanism of BK-LOF meditated epilepsy.

Exploring the Correlation Between Fibrosis Biomarkers and Clinical Disease Severity in PLN p.Arg14del Patients

Background: Pathogenic variants in phospholamban (PLN, like p. Arg14del), are found in patients diagnosed with arrhythmogenic (ACM) and dilated cardiomyopathy (DCM). Fibrosis formation in the heart is one of the hallmarks in PLN p.Arg14del carriers. During collagen synthesis and breakdown, propeptides are released into the circulation, such as procollagen type I carboxy-terminal propeptide (PICP) and C-terminal telopeptide collagen type I (ICTP).Aim: To investigate if PICP/ICTP levels in blood are correlative biomarkers for clinical disease severity and outcome in PLN p.Arg14del variant carriers.Methods: Serum and EDTA blood samples were collected from 72 PLN p.Arg14del carriers (age 50.5 years, 63% female) diagnosed with ACM (n = 12), DCM (n = 14), and preclinical variant carriers (n = 46). PICP levels were measured with an enzyme-linked immune sorbent assay and ICTP with a radio immuno-assay. Increased PICP/ICTP ratios suggest a higher collagen deposition. Clinical data including electrocardiographic, and imaging results were adjudicated from medical records.Results: No correlation between PICP/ICTP ratios and late gadolinium enhancement (LGE) was found. Moderate correlations were found between the PICP/ICTP ratio and end-diastolic/systolic volume (both rs = 0.40, n = 23, p = 0.06). PICP/ICTP ratio was significantly higher in patients with T wave inversion (TWI), especially in leads V4–V6, II, III, and aVF (p &lt; 0.022) and in patients with premature ventricular contractions (PVCs) during an exercise tolerance test (p = 0.007).Conclusion: High PICP/ICTP ratios correlated with clinical parameters, such as TWI and PVCs. Given the limited size and heterogeneity of the patient group, additional studies are required to substantiate the incremental prognostic value of these fibrosis biomarkers in PLN p.Arg14del patients.

BEDSIDE LAPAROSCOPY AS DIAGNOSTIC TOOL REVIEW OF ABDOMINAL PATHOLOGIES IN CRITICALLY ILL PATIENTS: REVIEW

Introduction: The diagnosis of abdominal pathologies in critically ill patients is often difficult because of inconclusive laboratory tests or imaging results, or the inability to safely transfer a patient to the radiology room. These causes give a delayed diagnosis of abdominal pathology in the intensive care unit (ICU) and increase rate of morbidity and mortality. The aim of this retrospective study is to evaluate the safety and diagnostic accuracy of bedside diagnostic laparoscopy in the identification of intra-abdominal pathology in critically ill patients. Aim: The aim of this retrospective study is to evaluate the safety and diagnostic accuracy of bedside diagnostic laparoscopy in the identification of intra-abdominal pathology in critically ill patients. Materials and Methods: A literature research was carried out including PubMed, Medline, Embase, Cochrane and Google Scholar databases to identify articles reporting on importance of diagnostic accuracy of bedside diagnostic laparoscopy in the identification of intra-abdominal pathology in critically ill patients. Conclusions: Bedside diagnostic laparoscopy represents a safe and accurate technique for diagnosing intraabdominal pathology in an ICU setting and should be taken into consideration when patient transfer to radiology or the operating room is considered unsafe or when routine radiological examinations are not conclusive enough to reach a definite diagnosis. Keywords: Bedside laparoscopy, critically ill patients, ultrasonography (US), computed tomography (CT) , emergency surgery

Fused Ultrasound And Electromyography-Driven Neuromuscular Model To Improve Plantarflexion Moment Prediction Across Walking Speeds

Background: Improving the prediction ability of a human-machine interface (HMI) is critical to accomplish a bio-inspired or model-based control strategy for rehabilitation interventions, which are of increased interest to assist limb function post neurological injuries. A fundamental role of the HMI is to accurately predict human intent by mapping signals from a mechanical sensor or surface electromyography (sEMG) sensor. These sensors are limited to measuring the resulting limb force or movement or the neural signal evoking the force. As the intermediate mapping in the HMI also depends on muscle contractility, a motivation exists to include architectural features of the muscle as surrogates of dynamic muscle movement, thus further improving the HMI's prediction accuracy. Objective: The purpose of this study is to investigate a non-invasive sEMG and ultrasound (US) imaging-driven Hill-type neuromuscular model (HNM) for net ankle joint plantarflexion moment prediction. We hypothesize that the fusion of signals from sEMG and US imaging results in a more accurate net plantarflexion moment prediction than sole sEMG or US imaging. Methods: Ten young non-disabled participants walked on a treadmill at speeds of 0.50, 0.75, 1.00, 1.25, and 1.50 m/s. The proposed HNM consists of two muscle-tendon units. The muscle activation for each unit was calculated as a weighted summation of the normalized sEMG signal and normalized muscle thickness signal from US imaging. The HNM calibration was performed under both single-speed mode and inter-speed mode, and then the calibrated HNM was validated across all walking speeds. Results: On average, the normalized moment prediction root mean square error was reduced by 14.58 % (p = 0.012) and 36.79 % (p < 0.001) with the proposed HNM when compared to sEMG-driven and US imaging-driven HNMs, respectively. Also, the calibrated models with data from the inter-speed mode were more robust than those from single-speed modes for the moment prediction.Conclusions: The proposed sEMG-US imaging-driven HNM can significantly improve the net plantarflexion moment prediction accuracy across multiple walking speeds. The findings imply that the proposed HNM can be potentially used in bio-inspired control strategies for rehabilitative devices due to its superior prediction.

Multielement Imaging Reveals the Diagenetic Features and Varied Water Redox Conditions of a Lacustrine Dolomite Nodule

The genesis of dolostone has long been puzzling for more than two centuries. Although much work has been done on investigating the process of dolomitization, little emphasis has been put on examining the diagenetic water redox condition with the wealthy geochemical information preserved in primary dolomite, which is believed to archive the aqueous environment as well as biotic and/or abiotic effects during formation. In situ interpretation with high resolution is a prerequisite in refined research of dolomite. Here, we reported the multielement imaging results of a lacustrine dolomite nodule with the host black shale from the Songliao Basin, northeast of China. Micro X-ray fluorescence (μ-XRF) with a spatial resolution down to 10 μm was used for in situ scanning. Two key parameter settings of the μ-XRF, including single-point exposure time and spatial resolution, were optimized to achieve a better result in a reasonable scanning time scale. The final imaging data graphically revealed dynamic variation of elemental distributions, including elements enriched in dolomite (e.g., Ca, Mg, Fe, and Mn), clastic quartz (Si), and clay minerals (e.g., Al and K) and redox-sensitive trace elements (e.g., Cr, Mo, V, and U). The well-preserved laminated structures inside the nodule and the features with a magnesium-rich core wrapped with an iron-concentric outer layer and a manganese-concentric shell together indicated its primary form as dolomite and a gradual transformation into ankerite as well as manganese-ankerite. The elemental variation indicates a varied bottom water redox condition, which involved from sulfidic to ferruginous and manganous zones. Here, we propose that the intermittent supplies of sulfate and Fe-/Mn-oxidized minerals interrupting the black shale deposition while favoring dolomitization might be brought by the oxidized and salted seawater. And this lacustrine dolomite is expected to be a potential fingerprint mineral in tracking the seawater intrusions to the Songliao Basin which happened 91 million years ago.

CXCR4 peptide-based fluorescence endoscopy in a mouse model of Barrett’s esophagus

Background Near-infrared (NIR) fluorescence imaging has been emerging as a promising strategy to overcome the high number of early esophageal adenocarcinomas missed by white light endoscopy and random biopsy collection. We performed a preclinical assessment of fluorescence imaging and endoscopy using a novel CXCR4-targeted fluorescent peptide ligand in the L2-IL1B mouse model of Barrett’s esophagus. Methods Six L2-IL1B mice with advanced stage of disease (12–16 months old) were injected with the CXCR4-targeted, Sulfo-Cy5-labeled peptide (MK007), and ex vivo wide-field imaging of the whole stomach was performed 4 h after injection. Before ex vivo imaging, fluorescence endoscopy was performed in three L2-IL1B mice (12–14 months old) by a novel imaging system with two L2-IL1B mice used as negative controls. Results Ex vivo imaging and endoscopy in L2-IL1B mice showed that the CXCR4-targeted MK007 accumulated mostly in the dysplastic lesions with a mean target-to-background ratio > 2. The detection of the Sulfo-Cy5 signal in dysplastic lesions and its co-localization with CXCR4 stained cells by confocal microscopy further confirmed the imaging results. Conclusions This preliminary preclinical study shows that CXCR4-targeted fluorescence endoscopy using MK007 can detect dysplastic lesions in a mouse model of Barrett’s esophagus. Further investigations are needed to assess its use in the clinical setting.

Research Progress on Cenozoic Volcano Genesis and Fluid Action in Northeast China

The tectonic evolution of northeast China is closely related to the subduction of the Pacific plate. The dehydration of the slab subduction process produces metasomatic agents that have important effects on the physical and chemical properties of the mantle wedge, including the decrease of seismic wave velocity and the increase of Poisson’s ratio and electrical conductivity. In order to investigate the tectonic evolution and fluid action of northeast China, this paper compares the previous seismic and electromagnetic imaging results of northeast China and explores the relationship between the genesis of Cenozoic volcanoes and fluid action in northeast China through rheological analysis. The results show that the western Pacific plate subducted into the mantle transition zone beneath northeast China, and sustained dehydration occurred. The upward migration of these released water caused partial melting at the base of the upper mantle. Some of the upwelling streams pierced the weak tectonic boundary under the buoyancy effect, which finally formed the large-scale Cenozoic volcanic events in northeast China.

Dynamic PET Imaging Using Dual Texture Features

Purpose: This study aims to explore the impact of adding texture features in dynamic positron emission tomography (PET) reconstruction of imaging results.Methods: We have improved a reconstruction method that combines radiological dual texture features. In this method, multiple short time frames are added to obtain composite frames, and the image reconstructed by composite frames is used as the prior image. We extract texture features from prior images by using the gray level-gradient cooccurrence matrix (GGCM) and gray-level run length matrix (GLRLM). The prior information contains the intensity of the prior image, the inverse difference moment of the GGCM and the long-run low gray-level emphasis of the GLRLM.Results: The computer simulation results show that, compared with the traditional maximum likelihood, the proposed method obtains a higher signal-to-noise ratio (SNR) in the image obtained by dynamic PET reconstruction. Compared with similar methods, the proposed algorithm has a better normalized mean squared error (NMSE) and contrast recovery coefficient (CRC) at the tumor in the reconstructed image. Simulation studies on clinical patient images show that this method is also more accurate for reconstructing high-uptake lesions.Conclusion: By adding texture features to dynamic PET reconstruction, the reconstructed images are more accurate at the tumor.

HIV-child with disseminated Talaromyces Marneffei (Penicillium marneffei) infection: a rare severe case report

Background Talaromyces Marneffei (Penicillium marneffei, T.marneffei) has been frequently reported in patients with adult acquired immunodeficiency syndrome. Still, cases of children with HIV combined with T.marneffei infection are very rare. This report describes the case of a HIV-child who is a girl from China. Her special clinical manifestations and laboratory diagnosis results can provide clinicians with the basis for diagnosis and treatment of T.marneffei related rare diseases. Case presntation We reported a single case of 7-year-old Chinese female patient who presented with fever, abdominal pain, multiple lymphadenopathy, hepatosplenomegaly, left lower extremity ecchymosis, and bloody stool. The patient received anti-inflammatory therapy; however, her symptoms did not improve. Consequently, she was diagnosed with T.marneffei and HIV infection; it was also confirmed that her mother did not undergo HIV blocking therapy during pregnancy. Yet, the child’s family refused all treatment, after which the child was discharged from the hospital. The patient died a few days later. Conclusion This case suggested that children with AIDS suffering from fever, lymphadenopathy and coagulation dysfunction, penicilliosis should be suspected. Clinicians should diagnose the disease early through laboratory and imaging results, which can help reduce the mortality, prolong the survival time and improve the quality of life of children.