Free-breathing abdominal chemical exchange saturation transfer imaging using water presaturation and respiratory gating at 3.0 T.

Free-breathing abdominal chemical exchange saturation transfer (CEST) has great potential for clinical application, but its technical implementation remains challenging. This study aimed to propose and evaluate a free-breathing abdominal CEST sequence. The proposed sequence employed respiratory gating (ResGat) to synchronize the data acquisition with respiratory motion and performed a water presaturation module before the CEST saturation to abolish the influence of respiration-induced repetition time variation. In vivo experiments were performed to compare different respiratory motion-control strategies and B0 offset correction methods, and to evaluate the effectiveness and necessity of the quasi-steady-state (QUASS) approach for correcting the influence of the water presaturation module on CEST signal. ResGat with a target expiratory phase of 0.5 resulted in a higher structural similarity index and a lower coefficient of variation on consecutively acquired CEST S0 images than breath-holding (BH) and respiratory triggering (all p < 0.05). B0 maps derived from the abdominal CEST dataset itself were more stable for B0 correction, compared with the separately acquired B0 maps by a dual-echo time scan and B0 maps derived from the water saturation shift referencing approach. Compared with BH, ResGat yielded more homogeneous magnetization transfer ratio asymmetry maps at 3.5 ppm (standard deviation: 3.96% vs. 3.19%, p = 0.036) and a lower mean squared difference between scan and rescan (27.52‱ vs. 16.82‱, p = 0.004). The QUASS approach could correct the water presaturation-induced CEST signal change, but its necessity for in vivo scanning needs further verification. The proposed free-breathing abdominal CEST sequence using ResGat had an acquisition efficiency of approximately four times that using BH. In conclusion, the proposed free-breathing abdominal CEST sequence using ResGat and water presaturation has a higher acquisition efficiency and image quality than abdominal CEST using BH.

Double lung transplantation is better than single lung transplantation for end-stage chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND: Lung transplantation is one of the most common treatment options for patients with end-stage chronic obstructive pulmonary disease. However, the choice between single and double lung transplantation for these patients remains a matter of debate. Therefore, we performed a systematic search of medical databases for studies on single lung transplantation, double lung transplantation, and chronic obstructive pulmonary disease. METHODS: The rate ratio and hazard ratio of survival were analyzed. The meta-analysis included 15 case-control and retrospective registry studies. RESULTS: The rate ratios of the 3-year survival (0.937 and P = 0.041) and 5-year survival (0.775 and P = 0.000) were lower for single lung transplantation than for double lung transplantation. However, the hazard ratio did not differ significantly between the two. CONCLUSIONS: Double lung transplantation was found to provide better benefits than single lung transplantation in terms of the long-term survival in patients with chronic obstructive pulmonary disease.

Melatonin enhanced the cardioprotective effects of HTK solution on Langendorff-perfused mouse hearts subjected to ischemia/reperfusion.

Objectives: Cardiac arrest is a crucial procedure in various cardiac surgeries, during which the heart is subjected to an ischemic state. The occurrence of ischemia/reperfusion (I/R) injury is inevitable due to aortic blockage and opening. The Histidine-tryptophan-ketoglutarate (HTK) solution is commonly used as an organ protection liquid to mitigate cardiac injury during cardiac surgery. Despite its widespread use, there is significant potential for improving its protective efficacy. Materials and Methods: The cardioprotective effect of HTK solution with and without melatonin was evaluated using the isolated Langendorff-perfused mouse heart model. The isolated C57bL/6 mouse hearts were randomly divided into four groups: control, I/R, HTK solution treatment before reperfusion (HTK+I/R), and HTK solution combined with melatonin before reperfusion (HTK+M+I/R). Cardiac function and myocardial injury markers were then measured. AMP-activated protein kinase α2 (AMPKα2) KO mice were used to investigate the underlying mechanism. Results: In our study, we found that melatonin significantly improved the protective effects of HTK solution in an isolated Langendorff-perfused mouse model, mechanistically by reducing mitochondrial damage, improving energy metabolism, inhibiting cardiomyocyte apoptosis, and reducing myocardial infarction size. We also observed that the HTK solution alone was ineffective in inhibiting ER stress, but when melatonin was added, there was a significant reduction in ER stress. Furthermore, melatonin was found to alleviate carbonyl stress during cardiac I/R. Interestingly, our results showed that the cardioprotective properties of melatonin were dependent on AMPKα2. Conclusion: The findings presented in this study offer a valuable empirical foundation for the development of perioperative cardioprotective strategies.

Part 1: Evaluating Neck-Strengthening Protocols to Reduce the Incidence of Traumatic Brain Injury: Traditional vs. Nontraditional Neck-Strengthening Techniques.

ABSTRACT: Schroeder, LH, McDaniel, AT, Wang, Y, Dickens, GM, Pantani, V, and Kubinak, H. Part 1: evaluating neck-strengthening protocols to reduce the incidence of traumatic brain injury: traditional vs. nontraditional neck-strengthening techniques. J Strength Cond Res 38(1): 21-29, 2024-A common cause of traumatic brain injuries (TBIs) is the head's kinematic response to rapid movement, which can be reduced with dynamic neck strengthening. This study aimed to determine the most effective neck-strengthening program by comparing a traditional and nontraditional program. Isometric neck strength was assessed in 32 subjects randomly assigned to one of the traditional and nontraditional neck-strengthening programs. The nontraditional program used a novel neck-strengthening device. After weeks 6 and 10 of training, isometric neck strength was reassessed. With the collected data, linear mixed models were established to compare the changes in neck strength between the 2 groups during the 10-week training period. Statistical analysis results suggest that, for both cervical extension (CE) and cervical flexion (CF), subjects in the novel neck-strengthening device group had a significantly higher gain of strength during the 10 weeks than the traditional group. With test statistics of -2.691 and -3.203 and corresponding 2-sided p-value of 0.01289 and 0.003889, respectively, we conclude that there is a statistically significant difference in the linear slopes of increase for both CE and CF between the 2 groups. As to left cervical lateral flexion and right cervical lateral flexion, the novel neck strength group had increased strength gains compared with the traditional group. However, the increase was not enough to demonstrate significant findings. Results were considered significant at p < 0.05. The results of this study show that the novel neck-strengthening device may be an effective mechanism for preventing mild TBIs.

Application of Quantitative MRI in Thyroid Eye Disease: Imaging Techniques and Clinical Practices.

Thyroid eye disease (TED) is a complex autoimmune disorder that impairs various orbital structures, leading to cosmetic damage and vision loss. Magnetic resonance imaging (MRI) is a fundamental diagnostic tool utilized in clinical settings of TED, for its accurate demonstration of orbital lesions and indication of disease conditions. The application of quantitative MRI has brought a new prospect to the management and research of TED, offering more detailed information on morphological and functional changes in the orbit. Therefore, many researchers concentrated on the implementation of different quantitative MRI techniques on TED for the exploration of clinical practices. Despite the abundance of studies utilizing quantitative MRI in TED, there remain considerable barriers and disputes on the best exploitation of this tool. This could possibly be attributed to the complexity of TED and the fast development of MRI techniques. It is necessary that clinical and radiological aspects of quantitative MRI in TED be better integrated into comprehensive insights. Hence, this review traces back 30 years of publications regarding quantitative MRI utilized in TED and elucidates this promising application in the facets of imaging techniques and clinical practices. We believe that a deeper understanding of the application of quantitative MRI in TED will enhance the efficacy of the multidisciplinary management of TED. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Identification and analysis of key hypoxia- and immune-related genes in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM), an autosomal dominant genetic disease, is the main cause of sudden death in adolescents and athletes globally. Hypoxia and immune factors have been revealed to be related to the pathology of HCM. There is growing evidence of a role for hypoxia and inflammation as triggers and enhancers in the pathology in HCM. However, the role of hypoxia- and immune-related genes in HCM have not been reported. METHODS: Firstly, we obtained four HCM-related datasets from the Gene Expression Omnibus (GEO) database for differential expression analysis. Immune cells significantly expressed in normal samples and HCM were then screened by a microenvironmental cell population counter (MCP-counter) algorithm. Next, hypoxia- and immune-related genes were screened by the LASSO + support vector machine recursive feature elimination (SVM-RFE) and weighted gene co-expression network analysis (WGCNA). Single-gene enrichment analysis and expression validation of key genes were then performed. Finally, we constructed a competing endogenous RNA (ceRNA) network of key genes. RESULTS: In this study, 35 differentially expressed hypoxia genes were found. By using LASSO + SVM-RFE analysis, 10 more targets with differentially expressed hypoxia genes were identified. The MCP-count algorithm yielded five differentially expressed immune cells, and after assessing them for WGCNA characteristics, 612 immune genes were discovered. When hypoxia and immune genes were combined for cross-tabulation analysis, three hypoxia- and immune-related genes (ATP2A2, DDAH1, and OMA1) were identified. CONCLUSION: Based on hypoxia characteristic genes, three key genes were identified. These were also significantly related to immune activation, which proves a theoretical basis and reference value for studying the relationship between HCM and hypoxia and immunity.

Intercellular mitochondrial component transfer triggers ischemic cardiac fibrosis.

Myocardial fibrosis is the villain of sudden cardiac death. Myocardial ischemia/reperfusion (MI/R) injury induces cardiomyocyte damage or even death, which in turn stimulates fibroblast activation and fibrosis, but the intercellular communication mechanism remains unknown. Recent studies have shown that small extracellular vesicles (sEVs) significantly contribute to intercellular communication. Whether and how sEV might mediate post-MI/R cardiomyocyte/fibroblasts communication remain unknown. Here, in vivo and in vitro MI/R models were established. We demonstrate that sEVs derived from cardiomyocyte (Myo-sEVs) carry mitochondrial components, which enter fibroblasts to initiate myocardial fibrosis. Based on bioinformatics screening and experimental verification, the activating molecule in Beclin1-regulated autophagy protein 1 (autophagy/beclin-1 regulator 1, Ambra1) was found to be a critical component of these sEV and might be a new marker for Myo-sEVs. Interestingly, release of Ambra1+-Myo-sEVs was caused by secretory rather than canonical autophagy after MI/R injury and thereby escaped degradation. In ischemic and peripheral areas, Ambra1+-Myo-sEVs were internalized by fibroblasts, and the delivered mtDNA components to activate the fibroblast cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway to promote fibroblast activation and proliferation. In addition, our data show that Ambra1 is expressed on the EV surface and cardiac-specific Ambra1 down regulation inhibits the Ambra1+-Myo-sEVs release and fibroblast uptake, effectively inhibiting ischemic myocardial fibrosis. This finding newly provides the evidence that myocardial secretory autophagy plays a role in intercellular communication during cardiac fibrosis. Ambra1 is a newly characterized molecule with bioactivity and might be a marker for Myo-sEVs, providing new therapeutic targets for cardiac remodeling.

Frataxin inhibits the sensitivity of the myocardium to ferroptosis by regulating iron homeostasis.

RATIONALE: Myocardial ischemia/reperfusion (I/R) injury is characterized by cell death via various cellular mechanisms upon reperfusion. As a new type of cell death, ferroptosis provides new opportunities to reduce myocardial cell death. Ferroptosis is known to be more active during reperfusion than ischemia. However, the mechanisms regulating ferroptosis during ischemia and reperfusion remain largely unknown. METHODS: The contribution of ferroptosis in ischemic and reperfused myocardium were detected by administered of Fer-1, a ferroptosis inhibitor to C57BL/6 mice, followed by left anterior descending (LAD) ligation surgery. Ferroptosis was evaluated by measurement of cell viability, ptgs2 mRNA level, iron production, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels. H9C2 cells were exposed to hypoxia/reoxygenation to mimic in vivo I/R. We used LC-MS/MS to identify potential E3 ligases that interacted with frataxin in heart tissue. Cardiac-specific overexpression of frataxin in whole heart was achieved by intracardiac injection of frataxin, carried by adeno-associated virus serotype 9 (AAV9) containing cardiac troponin T (cTnT) promoter. RESULTS: We showed that regulators of iron metabolism, especially iron regulatory protein activity, were increased in the ischemic myocardium or hypoxia cardiomyocytes. In addition, we found that frataxin, which is involved in iron metabolism, is differentially expressed in the ischemic and reperfused myocardium and involved in the regulation of cardiomyocytes ferroptosis. Furthermore, we identified an E3 ligase, NHL repeat-containing 1 (NHLRC1), that mediates frataxin ubiquitination degradation. Cardiac-specific overexpression of frataxin ameliorated myocardial I/R injury through ferroptosis inhibition. CONCLUSIONS: Through a multi-level study from molecule to animal model, these findings uncover the key role of frataxin in inhibiting cardiomyocyte ferroptosis and provide new strategies and perspectives for the treatment of myocardial I/R injury.

Nitrilotriacetic acid-assisted Mn(II) activated periodate for rapid and long-lasting degradation of carbamazepine: The importance of Mn(IV)-oxo species.

Periodate-based (PI, IO4-) oxidation processes for pollutant elimination have gained increased attention in recent years. This study shows that nitrilotriacetic acid (NTA) can assist trace Mn(II) in activating PI for fast and long-lasting degradation of carbamazepine (CBZ) (100% degradation in 2 min). PI can oxidize Mn(II) to permanganate(MnO4-, Mn(VII)) in the presence of NTA, which indicates the important role of transient manganese-oxo species. 18O isotope labeling experiments using methyl phenyl sulfoxide (PMSO) as a probe further confirmed the formation of manganese-oxo species. The chemical stoichiometric relationship (PI consumption: PMSO2 generation) and theoretical calculation suggested that Mn(IV)-oxo-NTA species were the main reactive species. The NTA-chelated manganese facilitated direct oxygen transfer from PI to Mn(II)-NTA and prevented hydrolysis and agglomeration of transient manganese-oxo species. PI was transformed completely to stable and nontoxic iodate but not lower-valent toxic iodine species (i.e., HOI, I2, and I-). The degradation pathways and mechanisms of CBZ were investigated using mass spectrometry and density functional theory (DFT) calculation. This study provided a steady and highly efficient choice for the quick degradation of organic micropollutants and broadened the perspective on the evolution mechanism of manganese intermediates in the Mn(II)/NTA/PI system.

MRI Assessment of Renal Lipid Deposition and Abnormal Oxygen Metabolism of Type 2 diabetes Mellitus Based on mDixon-Quant.

BACKGROUND: Diabetic nephropathy (DN) is the main cause of end-stage renal failure. Multiecho Dixon-based imaging utilizes chemical shift for water-fat separation that may be valuable in detecting changes both fat and oxygen content of the kidney from a single dataset. PURPOSE: To investigate whether multiecho Dixon-based imaging can assess fat and oxygen metabolism of the kidney in a single breath-hold acquisition for patients with type 2 diabetes mellitus (DM). STUDY TYPE: Prospective. SUBJECTS: A total of 40 DM patients with laboratory examination of biochemical parameters and 20 age- and body mass index (BMI)-matched healthy volunteers (controls). FIELD STRENGTH/SEQUENCE: 3D multiecho Dixon gradient-echo sequence at 3.0 T. ASSESSMENT: The DM patients were divided into two groups based on urine albumin-to-creatinine ratio (ACR): type 2 diabetes mellitus (DM, 20 patients, ACR < 30 mg/g) and diabetic nephropathy (DN, 20 patients, ACR ≥ 30 mg/g). In all subjects, fat fraction (FF) and relaxation rate (R2*) maps were derived from the Dixon-based imaging dataset, and mean values in manually drawn regions of interest in the cortex and medulla compared among groups. Associations between MRI and biochemical parameters, including ß2-microglobulin, were investigated. STATISTICAL TESTS: Kruskal-Wallis tests, Spearman correlation analysis, and receiver operating characteristic (ROC) curve analysis. RESULTS: FF and R2* values of the renal cortex and medulla were significantly different among the three groups with control group < DM < DN (FF: control, 1.11± 0.30, 1.10 ± 0.39; DM, 1.52 ± 0.32, 1.57 ± 0.35; DN, 1.99 ± 0.66, 2.21 ± 0.59. R2*: Control, 16.88 ± 0.77, 20.70 ± 0.86; DM, 17.94 ± 0.75, 22.10 ± 1.12; DN, 19.20 ± 1.24, 23.63 ± 1.33). The highest correlation between MRI and biochemical parameters was that between cortex R2* and ß2-microglobulin (r = 0.674). A medulla R2* cutoff of 21.41 seconds-1 resulted in a sensitivity of 80%, a specificity of 85% and achieved the largest area under the ROC curve (AUC) of 0.83 for discriminating DM from the controls. A cortex FF of 1.81% resulted in a sensitivity of 80%, a specificity of 100% and achieved the largest AUC of 0.83 for discriminating DM from DN. DATA CONCLUSION: Multiecho Dixon-based imaging is feasible for noninvasively distinguishing DN, DM and healthy controls by measuring FF and R2* values. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Simultaneous T1, T2, and T2* Mapping of Carotid Plaque: The SIMPLE* Technique.

Background Quantitative T1, T2, and T2* measurements of carotid atherosclerotic plaque are important in evaluating plaque vulnerability and monitoring its progression. Purpose To develop a sequence to simultaneously quantify T1, T2, and T2* of carotid plaque. Materials and Methods The simultaneous T1, T2, and T2* mapping of carotid plaque (SIMPLE*) sequence is composed of three modules with different T2 preparation pulses, inversion-recovery pulses, and acquisition schemas. Single-echo data were used for T1 and T2 quantification, while the multiecho (ME) data were used for T2* quantification. The quantitative accuracy of SIMPLE* was tested in a phantom study by comparing its measurements with those of reference standard sequences. In vivo feasibility of the technique was prospectively evaluated between November 2020 and February 2022 in healthy volunteers and participants with carotid atherosclerotic plaque. The Pearson or Spearman correlation test, Student t test, and Wilcoxon rank-sum test were used. Results T1, T2, and T2* estimated with SIMPLE* strongly correlated with inversion-recovery spin-echo (SE) (correlation coefficient [r] = 0.99), ME-SE (r = 0.99), and ME gradient-echo (r = 0.99) sequences in the phantom study. In five healthy volunteers (mean age, 25 years ± 3 [SD]; three women), measurements were similar between SIMPLE* and modified Look-Locker inversion recovery, or MOLLI (1151 msec ± 71 vs 1098 msec ± 64; P = .14), ME turbo SE (31 msec ± 1 vs 31 msec ± 1; P = .32), and ME turbo field echo (24 msec ± 2 vs 25 msec ± 2; P = .19). In 18 participants with carotid plaque (mean age, 65 years ± 9; 16 men), quantitative T1, T2, and T2* of plaque components were consistent with their signal characteristics on multicontrast images. Conclusion A quantitative technique for simultaneous T1, T2, and T2* mapping of carotid plaque with 100-mm3 coverage and 0.8-mm3 resolution was developed using the proposed SIMPLE* sequence and demonstrated high accuracy and in vivo feasibility. © RSNA, 2023 Supplemental material is available for this article.

Free-breathing simultaneous water-fat separation and T1 mapping of the whole liver (SWALI) with isotropic resolution using 3D golden-angle radial trajectory.

Background: Conventional liver T1 mapping techniques are typically performed under breath-holding conditions; they have limited slice coverage and often rely on multiple acquisitions. Furthermore, liver fat affects the accuracy of T1 quantification. Therefore, we aim to propose a free-breathing technique for simultaneous water-fat separation and T1 mapping of the whole liver (SWALI) in a single scan. Methods: The proposed SWALI sequence included an inversion recovery (IR) preparation pulse followed by a series of multiecho three-dimensional (3D) golden-angle radial acquisitions. For each echo time (TE), a series of images containing a mix of water and fat were reconstructed using a sliding window method. For each inversion time (TI), water and fat were separated, and then water and fat T1 estimation was conducted. The fat fraction (FF) was calculated based on the last TI image. The FF and water T1 quantification accuracy were compared with the gold standard sequences in the phantom. The in vivo feasibility was tested in 9 healthy volunteers, 2 patients with fatty liver, and 3 patients with hepatocellular carcinoma (HCC). The reproducibility was evaluated in the patients with fatty liver and in the healthy volunteers. Results: The mean FF and the mean water T1 values obtained by the SWALI sequence showed good agreements with chemical shift-encoded magnetic resonance imaging (CSE-MRI; r=0.998; P<0.001) and fat-suppressed (FS) IR-spin echo (SE; r=0.997; P<0.001) in the phantom. For the patients with fatty liver and the healthy volunteers, the SWALI sequence showed no significant difference with CSE-MRI in FF quantification (P=0.53). In T1 quantification, comparable T1 values were obtained with the SWALI sequence and modified Look-Locker inversion recovery (MOLLI; P=0.10) in healthy volunteers, while the water T1 estimated by the SWALI sequence was significantly lower than the water-fat compound T1 estimated by MOLLI (P<0.001) in patients with fatty liver. In the reproducibility study, the intraclass correlation coefficients (ICCs) for the estimated FF and water T1 were 0.997 and 0.943, respectively. Water T1 of the patients with HCC calculated using the SWALI sequence showed a significant reduction after the contrast administration (P<0.001). Conclusions: Free-breathing water-fat separation and T1 mapping of the whole liver with 2.5 mm isotropic spatial resolution were achieved simultaneously using the SWALI sequence in a 5-min scan.

Inflow Angle Impacts Morphology, Hemodynamics, and Inflammation of Side-wall Intracranial Aneurysms.

BACKGROUND: Aneurysm inflow angle has been shown to be associated with hemodynamic changes by computational fluid dynamics. However, these studies were based on single aneurysm model and were limited to side-wall aneurysms. PURPOSE: To investigate the association between inflow angle and morphology, hemodynamic, and inflammation of intracranial side-wall and bifurcation aneurysms. STUDY TYPE: Prospective. POPULATION: A total of 62 patients (aged 58.34 ± 12.39, 44 female) with 59 unruptured side-wall aneurysms and 17 unruptured bifurcation aneurysms were included. FIELD STRENGTH/SEQUENCE: A 3.0 T; 3D fast field echo sequence (TOF-MRA); free-breathing, 3D radio-frequency-spoiled, multi-shot turbo field echo sequence (4D-flow MRI); 3D black-blood T1-weighted volumetric turbo spin echo acquisition sequence (T1 -VISTA) ASSESSMENT: Two neuroradiologists assessed the inflow angle and size for intracranial aneurysms in 3D space with TOF-MRA images. The average and maximum inflow velocity (Vavg-IA , Vmax-IA ), blood flow (Flowavg-IA , Flowmax-IA ), and average wall shear stress (WSSavg-IA ) for aneurysms were assessed from 4D-flow MRI in regions of interest drawn by two neuroradiologists. The aneurysmal wall enhancement (AWE) grades between precontrast and postcontrast T1 -VISTA images were evaluated by three neuroradiologists. STATISTICAL TESTS: Kruskal-Wallis H test, χ2 test, Pearson's correlation coefficient, scatter plots and regression lines, multivariate logistic regression analysis (partial correlation r) were performed. A P < 0.05 was considered statistically significant. RESULTS: The WSSavg-IA (0.52 ± 0.34 vs. 0.27 ± 0.22) and AWE grades (1.38 ± 1.04 vs. 2.02 ± 0.68) between the two inflow angle subgroups of side-wall aneurysms were significantly different. The aneurysm size (rs  = 0.31), WSSavg-IA (rs  = -0.45), and AWE grades (rs  = 0.45) were significantly correlated with inflow angle in side-wall aneurysms. While in bifurcation aneurysms, there were no significant associations between inflow angle and size (P = 0.901), Vavg-IA (P = 0.699), Vmax-IA (P = 0.482), Flowavg-IA (P = 0.550), Flowmax-IA (P = 0.689), WSSavg-IA (P = 0.573), and AWE grades (P = 0.872). DATA CONCLUSION: A larger aneurysm size, a lower WSS and a higher AWE grade were correlated with a larger inflow angle in side-wall aneurysms. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

An alternative approach to TOMM cutoff scores using a large sample of military personnel.

The accuracy of neuropsychological assessments relies on participants exhibiting their true abilities during administration. The Test of Memory Malingering (TOMM) is a popular performance validity test used to determine whether an individual is providing honest answers. While the TOMM has proven to be highly sensitive to those who are deliberately exaggerating their symptoms, there is a limited explanation regarding the significance of using 45 as a cutoff score. The present study aims to further investigate this question by examining TOMM scores obtained in a large sample of active-duty military personnel (N = 859, M = 26 years, SD = 6.14, 97.31% males, 72.44% white). Results indicated that no notable discrepancies existed between the frequency of participants who scored a 45 and those who scored slightly below a 45 on the TOMM. The sensitivity and specificity of the TOMM were derived using the forced-choice recognition (FCR) scores obtained by participants on the California Verbal Learning Test, Second Edition (CVLT-II). The sensitivity for each trial of the TOMM was 0.84, 0.55, and 0.63, respectively; the specificity for each trial of the TOMM was 0.69, 0.93, and 0.92, respectively. Because sensitivity and specificity rates are both of importance in this study, balanced accuracy scores were also reported. Results suggested that various alternative cutoff scores produced a more accurate classification compared to the traditional cutoff of 45. Further analyses using Fisher's exact test also indicated that there were no significant performance differences on the FCR of the CVLT-II between individuals who received a 44 and individuals who received a 45 on the TOMM. The current study provides evidence on why the traditional cutoff may not be the most effective score. Future research should consider employing alternative methods which do not rely on a single score.

The combination of T2-mapping value of lacrimal gland and clinical indicators can improve the stage prediction of Graves' ophthalmopathy compared to clinical activity scores.

PURPOSE: To explore radiological changes of the lacrimal gland (LG) in Graves' ophthalmopathy (GO) and whether a combination of MRI parameters and clinical indicators would be more effective in predicting individual clinical manifestation of GO compared to clinical activity scores (CAS) assessment. METHODS: A total of 28 patients with GO (56 eyes) and 14 healthy controls (HCs) (28 eyes) were enrolled between July 2020 and July 2021. Patients were classified into the active GO group (CAS ≥ 3) and the inactive GO group (CAS < 3). MRI data and clinical data of LG were collected. The diagnostic performance of MRI parameters and models was assessed by receiver operating characteristic curve analysis. Logistic regression predictive models for staging GO were compared. RESULTS: LG in GO groups had significantly higher Ktrans, Ve, IAUC, ADC, and T2-mapping values (p = 0.006, p < 0.001, p < 0.001, p = 0.048, and p = 0.001, respectively), and significant lower Kep and Vp values (p < 0.001 and p < 0.001 respectively). There were statistically significant differences in T2-mapping value (p < 0.001), the proportion of mild or no obvious redness of conjunctiva (p < 0.001), and the proportion of swelling of caruncle or plica (p < 0.001) between inactive and active groups. In MRI based logistic regression model, the T2-mapping value was an independent risk factor (AUC = 0.832). When combining MRI and clinical indicators, T2-mapping value and age resulted in independent risk factors (AUC = 0.928). Swelling of eyelids, redness of the conjunctiva, swelling of the conjunctiva, swelling of caruncle or plica, and spontaneous retrobulbar pain could be replaced by other objective indicators (AUC = 0.937, 0.852, 0.876, 0.896, and 0.891, respectively). CONCLUSION: There were significant differences in MRI quantitative parameters of LG between HCs and GO patients. The combination of the T2-mapping value of LG and clinical indicators improved the stage prediction of Graves' ophthalmopathy compared to CAS, thus providing a new idea for enhancing the objectification level of GO data collection.

The Function of FoxK Transcription Factors in Diseases.

Forkhead box (FOX) transcription factors play a crucial role in the regulation of many diseases, being an evolutionarily conserved superfamily of transcription factors. In recent years, FoxK1/2, members of its family, has been the subject of research. Even though FoxK1 and FoxK2 have some functional overlap, increasing evidence indicates that the regulatory functions of FoxK1 and FoxK2 are not the same in various physiological and disease states. It is important to understand the biological function and mechanism of FoxK1/2 for better understanding pathogenesis of diseases, predicting prognosis, and finding new therapeutic targets. There is, however, a lack of comprehensive and systematic analysis of the similarities and differences of FoxK1/2 roles in disease, prompting us to perform a literature review.

Kinetics and mechanism of the reaction of hydrogen peroxide with hypochlorous acid: Implication on electrochemical water treatment.

Reduction of HOCl to Cl- by in-situ electrochemical synthesis or ex-situ addition of H2O2 is a feasible method to minimize Cl-DBPs and ClOx- (x = 2, 3, and 4) formation in electrochemical oxidative water treatment systems. This work has investigated the kinetics and mechanism of the reaction between H2O2 and HOCl. The kinetics study showed the species-specific second order rate constants for HOCl with H2O2 (k1), HOCl with HO2- (k2) and OCl- with H2O2 (k3) are 195.5 ± 3.3 M-1s-1, 4.0 × 107 M-1s-1 and 3.5 × 103 M-1s-1, respectively. The density functional theory calculation showed k2 is the most advantageous thermodynamically pathway because it does not need to overcome a high energy barrier. The yields of 1O2 generation from the reaction of H2O2 with HOCl were reinvestigated by using furfuryl alcohol (FFA) as a probe, and an average of 92.3% of 1O2 yields was obtained at pH 7-12. The second order rate constants of the reaction of 1O2 with 13 phenolates were determined by using the H2O2/HOCl system as a quantitative 1O2 production source. To establish a quantitative structure activity relationship, quantum chemical descriptors were more satisfactory than empirical Hammett constants. The potential implications in electrochemical oxidative water treatment were discussed at the end.

SIRT6 Protects Against Myocardial Ischemia-Reperfusion Injury by Attenuating Aging-Related CHMP2B Accumulation.

Impaired autophagic flux induces aging-related ischemia vulnerability, which is the hallmark pathology in cardiac aging. Our previous work has confirmed that the accumulation of charged multivesicular body protein 2B (CHMP2B), a subunit of the ESCRT-III complex, in the heart can impair autophagy flux. However, whether CHMP2B accumulation contributes to aging-related intolerance to ischemia/reperfusion (I/R) injury and the regulatory mechanism for CHMP2B in aged heart remain elusive. The cardiac CHMP2B level was significantly higher in aged human myocardium than that in young myocardium. Increased CHMP2B were shown to inhibit autophagic flux leading to the deterioration of MI/R injury in aged mice hearts. Interestingly, a negative correlation was observed between SIRT6 and CHMP2B expression in human heart samples. Specific activation of SIRT6 suppressed CHMP2B accumulation and ameliorated autophagy flux in aged hearts. Using myocardial-specific SIRT6 heterozygous knockout mice and recovery experiments confirmed that SIRT6 regulated myocardial CHMP2B levels. Finally, activation of SIRT6 decreased acetylation of FoxO1 to promote its transcriptional function on Atrogin-1, a muscle-specific ubiquitin ligase, which subsequently enhanced the degradation of CHMP2B by Atrogin-1. This is a novel mechanism for SIRT6 against aging-related myocardial ischemia vulnerability, particularly by preventing excessive accumulation of autophagy key factors.

Optimization of the Contrast Agent Injection Protocol for Carotid Artery Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

BACKGROUND: The injection protocol used in previous carotid artery dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies varied. PURPOSE: To investigate the effect of contrast injection protocol and optimize this protocol for carotid artery DCE-MRI. STUDY TYPE: Prospective. SUBJECTS: Digital phantom and seven patients with carotid atherosclerosis. FIELD STRENGTH/SEQUENCE: 3 T, spoiled gradient recalled echo sequence. ASSESSMENT: Different injection doses (0.01-0.3 mmol/kg) and effective injection rates (0.01-1 mmol/sec) were tested using a digital carotid plaque phantom considering the contrast pharmacokinetics, DCE-MRI imaging, contrast variation and flow-related imaging artifacts, random time delay between the contrast injection and image acquisition, and pharmacokinetic analysis process. For each injection protocol, combining the root mean square relative error (RMSRE) of the measured K trans and v P maps within the adventitial vasa vasorum from 10 tested time delays by the root mean square produced RMSREoverall-vv which was used to measure the overall accuracy of the pharmacokinetic parameters. In vivo validation was performed on seven patients with carotid atherosclerosis by imaging them twice using the traditional commonly used protocol and the recommended protocol found by simulation. STATISTICAL TEST: Student's t-test, chi-square test, and paired t-test, P < 0.05 was considered statistically significant. RESULTS: A low region of RMSREoverall-vv with the combination of medium injection dose and low effective injection rate was found. The protocol with injection dose of 0.07 mmol/kg and effective injection rate of 0.06 mmol/sec achieved the minimal RMSREoverall-vv (4.29%), thus was recommended, which showed more accurate arterial input function. Coinciding with the simulation results, this recommended protocol in in vivo experiments produced significantly fewer image artifacts, lower K trans and v P (P all <0.05) than traditional protocol which overestimated these parameters in simulation. DATA CONCLUSION: The contrast injection protocol influenced the accuracy of the pharmacokinetics parameter estimation in carotid artery DCE-MRI. The injection protocol with injection dose of 0.07 mmol/kg and effective injection rate of 0.06 mmol/sec was recommended. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

Increased aneurysm wall permeability colocalized with low wall shear stress in unruptured saccular intracranial aneurysm.

Aneurysm wall permeability has recently emerged as an in vivo marker of aneurysm wall remodeling. We sought to study the spatial relationship between hemodynamic forces derived from 4D-flow MRI and aneurysm wall permeability by DCE-MRI in a region-based analysis of unruptured saccular intracranial aneurysms (IAs). We performed 4D-flow MRI and DCE-MRI on patients with unruptured IAs of ≥ 5 mm to measure hemodynamic parameters, including wall shear stress (WSS), oscillatory shear index (OSI), WSS temporal (WSSGt) and spatial (WSSGs) gradient, and aneurysm wall permeability (Ktrans) in different sectors of aneurysm wall defined by evenly distributed radial lines emitted from the aneurysm center. The spatial association between Ktrans and hemodynamic parameters measured at the sector level was evaluated. Thirty-one patients were scanned. Ktrans not only varied between aneurysms but also demonstrated spatial heterogeneity within an aneurysm. Among all 159 sectors, higher Ktrans was associated with lower WSS, which was seen in both Spearman's correlation analysis (rho = - 0.18, p = 0.025) and linear regression analysis using generalized estimating equation to account for correlations between multiple sectors of the same aneurysm (regression coefficient = - 0.33, p = 0.006). Aneurysm wall permeability by DCE-MRI was shown to be spatially heterogenous in unruptured saccular IAs and associated with local WSS by 4D-flow MRI.