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Objectives The aim of this study was to compare the stress reduction effects of spending 25 minutes reclining in a SolTec™ Lounge between 2 intervention groups. Group 1 experienced the Lounge with multilayered music on an external speaker, while group 2 experienced the Lounge with multilayered music and synchronous vibration and magnetic stimulation from within the chair. Subjects In total, 110 participants with a self-reported stress level of 4 or higher on a 0- to 10-point scale were recruited from the local community including employees. Participants were randomized into receiving 1 of the 2 interventions. There were no significant differences between the group’s average stress levels prior to the interventions. Interventions Both groups received a 25-minute session in a dimly lit, quiet area on the Lounge with multilayered music. The second group also received vibration and magnetic stimulation that were synchronized with the music. Design Current stress level as well as ratings or feelings of anxiety, tenseness, energy, focus, happiness, relaxation, nervousness, creativeness, and being rested were recorded before and after the session. Results Both groups of participants reported equivalent decreased feelings of stress after using the Lounge. Participants receiving the synchronous multilayered music, vibration, and magnetic stimulation did report significantly reduced feelings of tenseness, feeling more relaxed, and feeling more creative when compared with the group that received music only. Conclusion Spending 25 minutes in the SolTec™ Lounge with multilayered music is an effective way to reduce self-reported stress in individuals who self-report having a high stress level. If confirmed by future studies, including synchronous vibration and magnetic stimulation with the multilayered music might be an effective stress reduction strategy.

Purpose: Intraplaque haemorrhage (IPH) is a well-known risk factor for faster plaque progression (volume increase); however, its etiology is unclear. We aimed at determining what other local plaque- and systemic factors contribute to plaque progression and to the development and progression of IPH., Methods: We examined 98 asymptomatic participants with carotid plaque using serial multi-contrast magnetic resonance imaging. We measured the percent of wall volume (%WV=100 x [wall volume] / [total vessel volume]) and measured IPH and calcification volumes. We used generalized estimating equations-based regression to analyze predictors of %WV change and new IPH while accounting for covariates (sex, age and statin use), and multiple non-independent observations per participant., Results: Total follow-up was 1.8 ± 0.8 years on average. The presence of IPH (β: 0.6 %/y, p = 0.033) and calcification (β: 1.2 %/y, p = 0.028) were each associated with faster plaque progression. New IPH, detected on a subsequent scan in 4 % of arteries that did not initially have IPH, was associated with larger calcification (odds ratio [OR]: 2.6 per 1-SD increase, p = 0.038) and higher pulse pressure (OR: 2.3 per 1-SD increase, p = 0.016). Larger calcification was associated with greater increases in pulse pressure (β: 1.4 mm Hg/y per 1-SD increase, p = 0.040)., Conclusions: IPH and calcification are each independently associated with faster plaque progression. The association of carotid calcification to increased pulse pressure and new IPH development suggests a possible mechanism by which calcification drives IPH development and plaque progression., 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 B.V. All rights reserved.)

The clinical significance of measuring vessel wall thickness is widely acknowledged. Recent advancements have enabled high-resolution 3D scans of arteries and precise segmentation of their lumens and outer walls; however, most existing methods for assessing vessel wall thickness are 2D. Despite being valuable, reproducibility and accuracy of 2D techniques depend on the extracted 2D slices. Additionally, these methods fail to fully account for variations in wall thickness in all dimensions. Furthermore, most existing approaches are difficult to be extended into 3D and their measurements lack spatial localization and are primarily confined to lumen boundaries. We advocate for a shift in perspective towards recognizing vessel wall thickness measurement as inherently a 3D challenge and propose adapting the Laplacian method as an outstanding alternative. The Laplacian method is implemented using convolutions, ensuring its efficient and rapid execution on deep learning platforms. Experiments using digital phantoms and vessel wall imaging data are conducted to showcase the accuracy, reproducibility, and localization capabilities of the proposed approach. The proposed method produce consistent outcomes that remain independent of centerlines and 2D slices. Notably, this approach is applicable in both 2D and 3D scenarios. It allows for voxel-wise quantification of wall thickness, enabling precise identification of wall volumes exhibiting abnormal wall thickness. Our research highlights the urgency of transitioning to 3D methodologies for vessel wall thickness measurement. Such a transition not only acknowledges the intricate spatial variations of vessel walls, but also opens doors to more accurate, localized, and insightful diagnostic insights.

Recent studies report that the rate of recurrent stroke is highest in the stages immediately following cerebral infarction and decreases over time in patients with atherosclerotic carotid stenosis. The purpose of this study was to identify temporal differences in early stage carotid plaque components from acute cerebrovascular ischemic events using carotid MRI. Carotid plaque images were obtained on 3 T MRI from 128 patients enrolled in MR-CAS. Among the 128 subjects, 53 were symptomatic and 75 asymptomatic. The symptomatic patients were classified into three groups based on interval from onset of symptoms to the date of the carotid MRI (Group <14 days; 15-30 days; and > 30 days). The volume of each plaque component was identified and quantified from MR images. The presence of juxtaluminal loose matrix/inflammation (LM/I) was identified as a possible indicator of inflammation on the luminal side. Plaque components were compared between groups using the Wilcoxon rank-sum or the Chi-square test. Patient characteristics and carotid plaque morphology were similar among all four groups. The median volume of LM/I in Group >30 days was significantly lower than in other groups (0 mm3 vs 12.3 mm3 and 18.1 mm3; p = 0.003). In addition, the prevalence of juxtaluminal LM/I decreased over time (ptrend = 0.002). There were no statistically significant differences in other plaque components between the symptomatic groups. The volume of LM/I was significantly smaller in Group >30 days and prevalence of juxtaluminal LM/I in the atherosclerotic carotid plaque was high in the early stages after events. This suggests that carotid plaques undergo rapid evolution after an acute cerebrovascular ischemic event., Competing Interests: Declaration of Competing Interest D.S. Hippe received research grants from GE Healthcare, Philips Healthcare, Toshiba America Medical Systems, and Siemens Medical Solutions. N. Balu received research grant from Philips Healthcare. T.S. Hatsukami received research grants from Philips Healthcare. C. Yuan received research grants from Philips Healthcare. All other authors have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: Obesity prevalence has reached an all-time high in the US, affecting >40% of the population. This study's objective was to evaluate associations between demographics and self-reported calorie knowledge and self-perceived confidence in calorie knowledge ("calorie confidence"). The relationships between body mass index (BMI) and calorie knowledge and confidence were also explored., Methods: We analyzed data from participants (n = 2171) in the crosssectional, nationally representative 2019 FDA Food Safety and Nutrition Survey using logistic regression to estimate adjusted odds ratios (AORs) and confidence intervals (95% CIs) for associations between BMI and calorie knowledge (correct/incorrect), calorie confidence (confident/not confident), and demographic characteristics, and the Wald chi square test to evaluate relationships between BMI and both calorie knowledge and confidence., Results: Many of the same subgroups were more likely than others to report lack of calorie knowledge and lack of confidence in knowing the typical daily calorie intake needed to maintain a healthy weight [respective AORs (95% CIs): age (years), >60 vs 51-60, 1.7 (1.1-2.5), and 1.4 (1.0-2.0); sex, male vs female, 1.7 (1.3-2.3), and 1.7 (1.3-2.1); race/ethnicity, non-Hispanic Black vs non-Hispanic white, 3.4 (2.1-5.5), and 2.4 (1.6-3.8); education, ≤high school vs college grad, 1.5 (1.0- 2.3), and 1.9 (1.3-2.7)]. BMI was significantly correlated with calorie confidence ( P  = .047), such that those reporting less confidence were more likely overweight or obese [underweight/healthy (BMI < 25): 29%, overweight (25 ≤ BMI < 30): 34%, obese (BMI ≥ 30): 37%]., Conclusion: In certain demographic subgroups associations between calorie knowledge and confidence differed. Tailored education and outreach for these groups may help to address these disparities.

Tumor-targeting oncolytic viruses such as vaccinia virus (VV) are attractive cancer therapeutic agents that act through multiple mechanisms to provoke both tumor lysis and anti-tumor immune responses. However, delivery of these agents remains restricted to intra-tumoral administration, which prevents effective targeting of inaccessible and disseminated tumor cells. In the present study we have identified transient pharmacological inhibition of the leukocyte-enriched phosphoinositide 3-kinase δ (PI3Kδ) as a novel mechanism to potentiate intravenous delivery of oncolytic VV to tumors. Pre-treatment of immunocompetent mice with the PI3Kδ-selective inhibitor IC87114 or the clinically approved idelalisib (CAL-101), prior to intravenous delivery of a tumor-tropic VV, dramatically improved viral delivery to tumors. This occurred via an inhibition of viral attachment to, but not internalization by, systemic macrophages through perturbation of signaling pathways involving RhoA/ROCK, AKT, and Rac. Pre-treatment using PI3Kδ-selective inhibitors prior to intravenous delivery of VV resulted in enhanced anti-tumor efficacy and significantly prolonged survival compared to delivery without PI3Kδ inhibition. These results indicate that effective intravenous delivery of oncolytic VV may be clinically achievable and could be useful in improving anti-tumor efficacy of oncolytic virotherapy., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Conventional reference multi-contrast black-blood (BB) MRI can be used for measuring luminal stenosis severity and plaque components, and its performance has been validated by intra- and inter-reader reproducibility test and histology. Recently, a set of 3D multi-contrast BB sequences have been developed, but its accuracy and reliability have not been well investigated. In this study, we evaluated the performance of 3D multi-contrast MRI (3D-MERGE, T2-VISTA, and SNAP) by comparing it with reference multi-contrast vessel wall MRI and assessing the inter-reader reproducibility., Methods: In total, 27 patients were recruited in this study. Twenty-six participants underwent reference and 3D multi-contrast imaging in a 3.0T MR scanner. One participant underwent carotid endarterectomy (CEA) after 3D MR imaging. Two trained reviewers interpreted reference and 3D datasets. Lumen area (LA), wall area (WA), normalized wall index (NWI), maximum wall thickness (MaxWT), and mean wall thickness (MWT) were measured, and the presence of lipid-rich necrotic core (LRNC), intra-plaque hemorrhage (IPH) and calcification (CA) were identified. Inter-reader reproducibility of 3D interpretation was assessed., Results: 3D imaging provided comparable measurements with reference imaging in LA (43.81±25.74 vs. 43.35±24.66 mm 2 ) and MaxWT (1.65±1.33 vs. 1.62±1.10 mm), with a lower NWI (0.40±0.15 vs. 0.43±0.11), WA (29.40±21.92 vs. 30.64±16.17 mm 2 ) and MWT (1.09±0.69 vs. 1.14±0.47), and showed good agreement for identification of LRNC (κ=0.66, 95% CI: 0.30-1.00) and CA (κ=0.69, 95% CI: 0.42-0.97), and excellent agreement for IPH (κ=1.00, 95% CI: 1.00-1.00). Inter-reader agreement of 3D analysis was good (LRNC, κ=0.87, 95% CI: 0.61-1.00; CA, κ=0.66, 95% CI: 0.36-0.96; IPH, κ=1.00, 95% CI: 1.00-1.00)., Conclusions: 3D multi-contrast vessel wall imaging provides comparable performance in morphological measurements and identification of carotid plaque components as reference multi-contrast MRI, with good inter-reader reproducibility., Competing Interests: Conflicts of Interest: Dr. Hatsukami received research grants from Philips Healthcare unrelated to this work. The other authors have no conflicts of interest to declare., (2020 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: US obesity rates are at historically high levels, increasing the risk of negative health and economic outcomes at individual and population levels. Findings from earlier studies indicate that many consumers lack a clear understanding of calorie needs, potentially affecting their ability to manage caloric intake., Objective: Our aim was to determine the knowledge of typical daily calorie needs of US adults by demographic and other characteristics, using a nationally representative sample., Design: Data were analyzed from 6,267 respondents to the 2007-2008 and 2009-2010 National Health and Nutrition Examination Survey and its supplemental data source, the Flexible Consumer Behavior Survey, to assess reported knowledge of typical daily calorie requirements and associations with demographic and other characteristics of interest., Statistical Analyses Performed: Logistic regression for complex sample surveys was used to estimate associations between self-reported daily calorie needs for men and women aged 21 years and older and participant characteristics., Results: Most respondents accurately reported typical daily calorie needs for a person of their sex, age group, and physical activity level, however, distinct differences emerged between demographic groups. Women, non-Hispanic whites, and those with higher income and education levels were more likely to estimate typical daily calorie needs accurately; men were almost four times more likely than women to indicate a lack of knowledge of daily calorie needs., Conclusions: Knowledge of typical daily calorie requirements is a foundational concept of nutrition literacy. Educational efforts to increase awareness, knowledge, and use of calorie information for certain groups may be helpful to refine interventions and ultimately improve public health in the United States., (Published by Elsevier Inc.)

Background: Presence of intraplaque hemorrhage (IPH) is a known risk factor for stroke and plaque progression. Accurate and reproducible measurement of IPH volume are required for further risk stratification., Purpose: To develop a semiautomatic method to measure carotid IPH volume., Study Type: Retrospective., Population: Patients scheduled for carotid endarterectomy and patients with 16-79% asymptomatic carotid stenosis by ultrasound., Field Strength: 3T., Sequence: Simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) MRI., Assessment: A semiautomated volumetric measurement of IPH using signal intensity thresholding of 3D SNAP volume was implemented. Fourteen carotid endarterectomy patients were enrolled to determine the signal intensity threshold of IPH using histology. Thirty-three patients with 16-79% asymptomatic stenosis were scanned twice within 1 month to evaluate reproducibility. The normalized SNAP intensity with the highest Youden index for predicting IPH on histology was used for thresholding. Scan-rescan reproducibility of IPH measurement was assessed using the intraclass correlation coefficient (ICC) and coefficient of variation (CV)., Statistical Tests: Receiver operating characteristic curve, area under the curve, Cohen's kappa, intraclass correlation coefficient, coefficient of variance (CV), and paired t-test., Results: IPH detection by the algorithm had substantial agreement with manual review (kappa: 0.92; 95% confidence interval [CI]: 0.83, 1.00) and moderate agreement with histology (kappa: 0.55; 95% CI: 0.34, 0.68). IPH volume measurements by the algorithm were strongly correlated with histology (Spearman's rho = 0.76, P = 0.002). IPH measurements were also reproducible, with ICCs of 0.86 (95% CI: 0.57, 0.96), 0.77 (95% CI: 0.32, 0.94), and 0.99 (95% CI: 0.93, 1.00) for maximum/mean normalized intensity and IPH volume, respectively. The corresponding CVs were 10.6%, 5.2%, and 11.8%., Data Conclusion: IPH volume measurements on SNAP MRI are highly reproducible using semiautomatic measurement. Level of Evidence 2 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2019;50:1055-1062., (© 2019 International Society for Magnetic Resonance in Medicine.)

Tunneling spectroscopy of one-dimensional interacting wires can be profoundly sensitive to the boundary conditions of the wire. Here, we analyze the tunneling spectroscopy of a wire coupled to capacitive metallic leads. Strikingly, with increasing many-body interactions in the wire, the impact of the boundary noise becomes more prominent. This interplay allows for a smooth crossover from standard 1D tunneling signatures into a regime where the tunneling is dominated by the fluctuations at the leads. This regime is characterized by an elevated zero-bias tunneling alongside a universal power-law decay at high energies. Furthermore, local tunneling measurements in this regime show a unique spatial dependence that marks the formation of plasmonic standing waves in the wire. Our result offers a tunable method by which to control the boundary effects and measure the interaction strength (Luttinger parameter) within the wire.

Scalable architectures for quantum information technologies require one to selectively couple long-distance qubits while suppressing environmental noise and cross talk. In semiconductor materials, the coherent coupling of a single spin on a quantum dot to a cavity hosting fermionic modes offers a new solution to this technological challenge. Here, we demonstrate coherent coupling between two spatially separated quantum dots using an electronic cavity design that takes advantage of whispering-gallery modes in a two-dimensional electron gas. The cavity-mediated, long-distance coupling effectively minimizes undesirable direct cross talk between the dots and defines a scalable architecture for all-electronic semiconductor-based quantum information processing.

Background: Education to improve health professionals' responses to suicide is considered an important suicide prevention strategy. However, the effectiveness of this approach for nurses is unclear., Aim: To systematically review the peer-reviewed literature regarding the effectiveness of suicide prevention education programs for nurses., Method: Nine academic databases (CINAHL, Cochrane Reviews & Trials, Embase, Informit Health Collection, Joanna Briggs Institute, Medline, PsycINFO, Scopus, and Web of Science) were searched in November 2016, utilizing search terms related to suicide, education, and nurses, with no limits placed on publication date or study design., Results: The search yielded 5,456 identified articles, 11 of which met the inclusion criteria. Studies were primarily quantitative (RCTs n = 3; quasi-experimental n = 6; qualitative n = 2), and involved nurses (range = 16-561) working in a diversity of settings, particularly hospitals (n = 9). Studies revealed positive changes in nurses' competence, knowledge, and attitudes associated with training over the short term., Limitations: The heterogeneity of education programs and methodological weaknesses of included studies limit the conclusions drawn., Conclusion: There is a moderate body of evidence to support the effectiveness of suicide prevention education programs for nurses. Future research should examine longer-term changes in clinical practice and strategies for continuing education, with more rigorous study designs.

Snoring and obstructive sleep apnoea (OSA) are increasingly common conditions, and confer a significant health and socioeconomic burden. Furthermore, untreated OSA represents a significant mortality risk. Patients require careful assessment, including detailed clinical history and examination, sleep study and drug-induced sleep endoscopy (DISE). Although nasal continuous positive airway pressure (nCPAP) is the gold standard treatment for moderate and severe OSA, multidisciplinary team assessment is often required to develop the best treatment plan for an individual, especially when nasal CPAP is poorly tolerated. There is a wide range of medical and surgical treatment options, and following appropriate patient selection and assessment, a focused site-specific, often multilevel, intervention is indicated. There is an increasing body of evidence in the literature supporting these multilevel interventions and with agreement on standardized outcome measures more trials are likely to improve the robustness of these data further.

Background and Aims: Plaque fissuring, a phenomenon morphologically distinct from the classical rupture of a thinned fibrous cap, has not been well characterized in carotid atherosclerosis. The aim of this study was to establish the prevalence of plaque fissures in advanced carotid plaques with an otherwise intact luminal surface, and to determine whether they might be a source of intraplaque hemorrhage (IPH)., Methods: We evaluated 244 surgically intact, 'en bloc' embedded, serially sectioned carotid endarterectomy specimens and included only those plaques with a grossly intact luminal surface., Results: Among the 67 plaques with grossly intact luminal surface, cap fissure was present in 39 (58%) plaques. A total of 60 individual fissures were present, and longitudinally mean fissure length was 1.3 mm. Most fissures were found distal to the bifurcation (63%), proximal to the stenosis (88%), and in the posterior (opposite the flow divider) or lateral quadrants (80%). 36% of the fissures remained in the superficial third of the plaque. 52% extended from the lumen surface to the middle third of the plaque and 12% reached the outer third of the plaque on cross section. Fissures often occurred between two tissue planes and were connected to IPH (fresh: 63%; any type: 92%) and calcifications (43%). No correlation was found with patient characteristics such as symptom status, carotid stenosis, hypertension, diabetes, smoking and medications (statins or antiplatelet agents)., Conclusions: Plaque fissures are common in advanced carotid plaques with an otherwise grossly intact luminal surface and are associated with fresh intraplaque hemorrhage. As they occur on the interface between plaque components with different mechanical properties, further biomechanical studies are needed to unravel the underlying failure mechanisms., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background: Intraplaque hemorrhage (IPH) is associated with atherosclerosis progression and subsequent cardiovascular events. We sought to develop a semi-automatic method with an optimized threshold for carotid IPH detection and quantification on MP-RAGE images using matched histology as the gold standard., Methods: Fourteen patients scheduled for carotid endarterectomy underwent 3D MP-RAGE cardiovascular magnetic resonance (CMR) preoperatively. Presence and area of IPH were recorded using histology. Presence and area of IPH were also recorded on CMR based on intensity thresholding using three references for intensity normalization: the sternocleidomastoid muscle (SCM), the adjacent muscle and the automatically generated local median value. The optimized intensity thresholds were obtained by maximizing the Youden's index for IPH detection. Using leave-one-out cross validation, the sensitivity and specificity for IPH detection based on our proposed semi-automatic method and the agreement with histology on IPH area quantification were evaluated., Results: The optimized intensity thresholds for IPH detection were 1.0 times the SCM intensity, 1.6 times the adjacent muscle intensity and 2.2 times the median intensity. Using the semi-automatic method with the optimized intensity threshold, the following IPH detection and quantification performance was obtained: sensitivities up to 59, 68 and 80 %; specificities up to 85, 74 and 79 %; Pearson's correlation coefficients (IPH area measurement) up to 0.76, 0.93 and 0.90, respectively, using SCM, the adjacent muscle and the local median value for intensity normalization, after heavily calcified and small IPH were excluded., Conclusions: A semi-automatic method with good performance on IPH detection and quantification can be obtained in MP-RAGE CMR, using an optimized intensity threshold comparing to the adjacent muscle. The automatically generated reference of local median value provides comparable performance and may be particularly useful for developing automatic classifiers. Use of the SCM intensity as reference is not recommended without coil sensitivity correction when surface coils are used.

Culturally and linguistically diverse (CALD) communities in Australia face significant challenges in terms of reducing barriers to information and support for depression and anxiety. Increased stigma surrounding mental ill-health in some cultures and related concerns about trust and confidentiality all impact upon timely access to information, services and support for consumers and carers from CALD backgrounds. For health services, there is a need to understand how to better engage CALD communities in mental healthcare. The objective of this narrative review was to identify examples of evidence-based, best practice for what works effectively for engaging with CALD communities to reduce the impact of depression and anxiety. In January 2014, we searched Academic Search Premier, CINAHL, Health-Source Consumer Edition, PsycARTICLES, PsycINFO (all databases within the EbscoHost platform) and PubMed for peer-reviewed articles published between 1994 and 2014. The search revealed a total of 706 records contained within the EbscoHost platform and 689 records in PubMed; 15 matched the inclusion criteria. Six key themes were identified: (i) setting the scene for engagement; (ii) cultural values and preferences; (iii) language considerations; (iv) 'engagers' in the therapeutic process; (v) opening out engagement to include others; and (vi) engaging through the use of technology and alternative mediums. The literature obtained provides a small body of evidence regarding approaches to engaging CALD communities, with findings highlighting the importance of processes which are tailored to the CALD community of interest and which take into account different cultural explanatory models of mental ill-health. Review findings are also discussed within the framework of intersectionality, in which broader structural inequalities and power imbalances - in areas such as gender and social class - collectively impact on help-seeking and mental health outcomes. This review supports further enquiry into how such societal issues influence engagement - and disengagement - in mental health services for CALD communities., (© 2015 John Wiley & Sons Ltd.)

This study sought to discover which atherosclerotic plaque components co-localize with enhanced [(18)F]-fluorodeoxyglucose (FDG) uptake in carotid positron emission tomography (PET) images. Although in vivo PET currently lacks the resolution, high-resolution ex vivo FDG-microPET with histology validation of excised carotid plaque might accomplish this goal. Thirteen patients were injected with FDG before carotid endarterectomy. After excision, the plaque specimens were scanned by microPET and magnetic resonance imaging, and then serially sectioned for histological analysis. Two analyses were performed using generalized linear mixed models: (1) a PET-driven analysis which sampled high and low FDG uptake areas from PET images to identify their components in matched histology specimens; and (2) a histology-driven analysis where specific plaque components were selected and matched to corresponding PET images. In the PET-driven analysis, regions of high FDG uptake were more likely to contain inflammatory cells (p < 0.001) and neovasculature (p = 0.008) than regions of low FDG uptake. In the histology-driven analysis, regions with inflammatory cells (p = 0.001) and regions with loose extracellular matrix (p = 0.001) were associated with enhanced FDG uptake. Furthermore, areas of complex inflammatory cell infiltrate (co-localized macrophages, lymphocytes and foam cells) had the highest FDG uptake among inflammatory subgroups (p < 0.001). In conclusion, in carotid plaque, regions of inflammatory cell infiltrate, particularly complex one, co-localized with enhanced FDG uptake in high-resolution FDG-microPET images. Loose extracellular matrix and areas containing neovasculature also produced FDG signal. This study points to the potential ability of FDG-PET to detect the cellular components of the vulnerable plaque.

A human hepatoma cell line (HuH-7) was evaluated as a metabolically competent cell model to investigate cytochrome P450 3A4 (CYP3A4) inhibition, induction, and hepatotoxicity. First, CYP3A4 gene expression and activity were determined in HuH-7 cells under three culture conditions: 1-week culture, 3-week culture, or 1 % dimethyl sulfoxide (DMSO) treatment. HuH-7 cells treated with DMSO for 2 weeks after confluence expressed the highest CYP3A4 gene expression and activity compared to the other two culture conditions. Furthermore, CYP3A4 activity in DMSO-treated HuH-7 cells was compared to that in a human hepatoma cell line (HepG2/C3A) and human bipotent progenitor cell line (HepaRG), which yielded the following ranking: HepaRG > DMSO-treated HuH-7 >> HepG2/C3A cells. The effects of three known CYP3A4 inhibitors were evaluated using DMSO-treated HuH-7 cells. CYP3A4 enzyme inhibition in HuH-7 cells was further compared to human recombinant CYP3A4, indicating similar potency for reversible inhibitors (IC 50 within 2.5-fold), but different potency for the irreversible inhibitor. Next, induction of CYP3A4 activity was compared between DMSO-treated HuH-7 and HepaRG cells using two known inducers. DMSO-treated HuH-7 cells yielded minimal CYP3A4 induction compared to that in the HepaRG cells after 48-h treatments. Finally, the cytotoxicity of five known hepatotoxicants was evaluated in DMSO-treated HuH-7, HepG2/C3A, and HepaRG cells, and significant differences in cytotoxic sensitivity were observed. Overall, DMSO-treated HuH-7 cells are a valuable model for medium- or high-throughput screening of chemicals for CYP3A4 inhibition and hepatotoxicity.

Purpose: The purpose of this systematic review and meta-analysis is to evaluate the effectiveness of diabetes self-management education (DSME) interventions delivered in conjunction with primary care among Hispanic adults with type 2 diabetes mellitus (T2DM)., Methods: A systematic search of PubMed, Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature identified randomized controlled trials (RCT) that tested the effect of DSME interventions in Hispanic adults with T2DM. Studies reporting hemoglobin A1C (A1C) pre and post intervention or change in A1C were eligible for inclusion in the meta-analysis., Results: Of 625 studies identified, 13 RCTs met criteria for inclusion in the systematic review; of these, 11 studies were included in the meta-analysis. The 13 RCTs represent data from 2784 adult Hispanic subjects. DSME interventions (individual, group, telephone/electronic, and multimodal sessions) varied in intensity from 1-time DSME sessions with phone follow-up to contact every 4 to 6 weeks over 5 years. At ≥6 months following intervention, pooled A1C reduction was -0.25 (95% CI, -0.42 to -0.07), favoring the intervention group., Conclusions: DSME in conjunction with primary care is effective in improving glycemic control in Hispanic adults with T2DM. Future comparative effectiveness research is needed to identify best delivery methods to optimize effectiveness of DSME delivered to the Hispanic population., (© 2015 The Author(s).)

Genistein is a widely consumed phytoestrogen in dietary supplements and has been reported to play roles in both cancer prevention and promotion. These conflicting effects may be complicated by sex differences. Cytochrome P450 1A (CYP1A) participates in carcinogen activation and detoxification, and the enzyme may interact with genistein. Therefore, modulation of CYP1A by a combination of genistein and sex hormones could be responsible for sex differences related to cancer prevention and promotion. In the current study, a human liver cell line, HepG2/C3A, cultured in sex hormone-supplemented media was used to investigate the modulatory effect of genistein on CYP1A gene expression and activity. Genistein exerted both long-term (72 h) induction and short-term (immediate) inhibition of CYP1A activity in HepG2/C3A cells. In the long-term study, CYP1A gene expression and enzyme activity were induced to a greater extent in male hormone-supplemented cells than female ones. In the short-term study, CYP1A activity was inhibited more strongly by genistein in the male hormone-supplemented cells than in the female hormone-supplemented cells. These significant differences suggest that male hormones can modulate the effects of genistein on CYP1A gene expression and activity.

The beneficial or adverse effects of isolated phytochemicals are not always concordant with effects of the botanical dietary supplements from which they were derived. This disparity could be due to interactions between the various phytochemicals present in the whole plant. The phenolic acids, rosmarinic acid (RA), caffeic acid (CA) and ferulic acid (FA) are widely present in foods and dietary supplements, and they are assumed to exert various beneficial biological effects. However, there is little data on the potential biological interactions of these three phenolic acids which commonly occur together and are linked metabolically. In the present study, liver toxicity of the three phenolic acids was assessed on the three compounds singly and in various binary and one ternary combinations. A series of in vitro endpoints relevant to liver toxicity were evaluated in both a human (HepG2/C3A) and rat (MH1C1) hepatocyte cell line. The Combination Index (CI) was calculated for each endpoint from both the concentration responses of the single compounds and the responses of the various binary and ternary mixtures. Both synergistic and antagonistic interactions were observed for some endpoints and some combinations of test agents. Interactions were most prevalent in measures of oxidative stress and cytochrome P450 activities in both cell types. There was only a 53% concordance between the rat and human cells which may be suggestive of species differences. The data suggest an approach for better characterizing the beneficial or adverse effects of complex botanical products through evaluation of interactions between individual phytochemical components., (Published by Elsevier GmbH.)

A simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) MR imaging technique is proposed to detect both luminal stenosis and hemorrhage in atherosclerosis patients in a single scan. Thirteen patients with diagnosed carotid atherosclerotic plaque were admitted after informed consent. All scans were performed on a 3T MR imaging system with SNAP, 2D time-of-flight and magnetization-prepared 3D rapid acquisition gradient echo sequences. The SNAP sequence utilized a phase sensitive acquisition, and was designed to provide positive signals corresponding to intraplaque hemorrhage and negative signals corresponding to lumen. SNAP images were compared to time-of-flight images to evaluate lumen size measurements using linear mixed models and the intraclass correlation coefficient. Intraplaque hemorrhage identification accuracy was evaluated by comparing to magnetization-prepared 3D rapid acquisition gradient echo images using Cohen's Kappa. Diagnostic quality SNAP images were generated from all subjects. Quantitatively, the lumen size measurements by SNAP were strongly correlated (intraclass correlation coefficient = 0.96, P < 0.001) with those measured by time-of-flight. For intraplaque hemorrhage detection, strong agreement (κ = 0.82, P < 0.001) was also identified between SNAP and magnetization-prepared 3D rapid acquisition gradient echo images. In conclusion, a SNAP imaging technique was proposed and shows great promise for imaging both lumen size and carotid intraplaque hemorrhage with a single scan., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Carotid intraplaque hemorrhage (IPH) and lipid rich necrotic core (LRNC) have been associated with accelerated plaque growth, luminal narrowing, future surface disruption and development of symptomatic events. The aim of this study was to evaluate the quantitative relationships between high intensity signals (HIS) in the plaque on TOF-MRA and IPH or LRNC volumes as measured by multicontrast weighted CMR., Methods: Seventy six patients with a suspected carotid artery stenosis or carotid plaque by ultrasonography underwent multicontrast carotid CMR. HIS presence and volume were measured from TOF-MRA MIP images while IPH and LRNC volumes were separately measured from multicontrast CMR., Results: For detecting IPH, HIS on MIP images overall had high specificity (100.0%, 95% CI: 93.0 - 100.0%) but relatively low sensitivity (32%, 95% CI: 20.8 - 47.9%). However, the sensitivity had a significant increasing relationship with underlying IPH volume (p = 0.033) and degree of stenosis (p = 0.022). Mean IPH volume was 2.7 times larger in those with presence of HIS than in those without (142.8 ± 97.7 mm(3) vs. 53.4 ± 56.3 mm(3), p = 0.014). Similarly, mean LRNC volume was 3.4 times larger in those with HIS present (379.8 ± 203.4 mm(3) vs. 111.3 ± 122.7 mm(3), p = 0.001). There was a strong correlation between the volume of the HIS region and the IPH volume measured from multicontrast CMR (r = 0.96, p < 0.001)., Conclusion: MIP images are easily reformatted from three minute, routine, clinical TOF sequences. High intensity signals in carotid plaque on TOF-MRA MIP images are associated with increased intraplaque hemorrhage and lipid-rich necrotic core volumes. The technique is most sensitive in patients with moderate to severe stenosis.

Despite recent advances in both surgery and chemoradiotherapy, mortality rates for advanced cancer remain high. There is a pressing need for novel therapeutic strategies; one option is systemic oncolytic viral therapy. Intravenous administration affords the opportunity to treat both the primary tumour and any metastatic deposits simultaneously. Data from clinical trials have shown that oncolytic viruses can be systemically delivered safely with limited toxicity but the results are equivocal in terms of efficacy, particularly when delivered with adjuvant chemotherapy. A key reason for this is the rapid clearance of the viruses from the circulation before they reach their targets. This phenomenon is mainly mediated through neutralising antibodies, complement activation, antiviral cytokines, and tissue-resident macrophages, as well as nonspecific uptake by other tissues such as the lung, liver and spleen, and suboptimal viral escape from the vascular compartment. A range of methods have been reported in the literature, which are designed to overcome these hurdles in preclinical models. In this paper, the potential advantages of, and obstacles to, successful systemic delivery of oncolytic viruses are discussed. The next stage of development will be the commencement of clinical trials combining these novel approaches for overcoming the barriers with systemically delivered oncolytic viruses.

Toxicity assessment of botanical materials is difficult because they are typically complex mixtures of phytochemicals. In the present study, 16 phenolics were tested in both human (HepG2/C3A) and rat (MH1C1) hepatoma cells using a battery of eight toxicity endpoints. Cluster analysis was used to group the phenolics into four clusters for each cell type. Comparison of overall and individual liver activity of phenolics on both human and rat hepatoma cell lines showed significant differences for some endpoints. However, the cluster membership was similar across both cell types with the majority of phenolics clustering with the solvent control group (cluster 1). Each cell type produced a cluster of compounds with reported in vivo liver toxicity (cluster 2). Five herbal extracts were prepared and then tested as above. Using the cluster model developed with the phenolics, in the HepG2/C3A cells green tea was assigned to cluster 2 and the remaining four extracts to cluster 1. In the MH1C1 cells, green tea and thyme were assigned to cluster 2, cinnamon to cluster 4, and juniper berry and peppermint to cluster 1. The data suggest that this in vitro model may be useful for identifying hepatotoxic phenolics and botanical preparations rich in phenolics., (Published by Elsevier Ltd.)

Objectives: The aim of this study is to compare minimally invasive video-assisted thyroidectomy (MIVAT) to conventional thyroidectomy., Study Design: A systematic review of the literature and meta-analysis., Methods: All published prospective controlled trials that compared MIVAT to conventional thyroidectomy were identified. The trials data were extracted and statistical analyzed using Statsdirect 2.5.7., Results: Five trials were identified. The total number of patients was 318. The primary outcome measures were pain, postoperative hypocalcaemia, and postoperative recurrent laryngeal nerve palsy. There was no difference in rates of postoperative hypocalcaemia or postoperative recurrent laryngeal nerve palsy between the techniques. Reported pain scores at 24 hours were significantly lower in MIVAT compared to conventional surgery. Pooled effect size was -4.496 (95% confidence interval [CI] = -7.146 to -2.045, P = .0004). The secondary outcome measures were operative time, blood loss, and cosmesis. There was significant improvement in patient reported scores for cosmesis with MIVAT. The pooled effect size was 3.669 (95% CI 0.636-60.702, P = .0178). MIVAT was associated with a significant increase in operative time. Pooled effect size was 1.681 (95% CI 0.600-2.762, P = .0023). There was no difference in blood loss between the groups., Conclusions: This study demonstrates that MIVAT is as safe as the existing gold standard operation. Furthermore, it has better cosmetic and pain outcomes for patients when compared to conventional surgery. MIVAT is a promising new technique, with obvious benefits over the established surgery, for small-volume thyroid disease that mainly affects a young female patient population., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objective: We report the first case in the English language literature of an adamantinomatous infrasellar craniopharyngioma, and we describe our management strategy., Case Report: A 46-year-old woman presented with a six-month history of left-sided nasal obstruction and epistaxis. Rhinological examination revealed a left-sided, polypoidal lesion lying medial to the middle turbinate. An urgent examination under anaesthesia was organised; biopsies were considered characteristic of craniopharyngioma. Magnetic resonance imaging and computed tomography demonstrated a well defined, heterogeneous, infrasellar mass centred in the midline, extending anteriorly into the left nasal cavity and posteriorly encasing both internal carotid arteries. Craniofacial resection was performed via a midfacial degloving approach, with adjuvant radiotherapy. The patient was disease-free one year post-operatively., Conclusion: Craniopharyngiomas should be considered in the differential diagnosis of a unilateral nasal polyp. Although technically benign, they are locally aggressive. Therefore, we recommend complete excision with adjuvant radiotherapy if margins are involved or close.

γδ T cells bridge innate and adaptive immunity and function in immunosurveillance, immunoregulation, tumor cell recognition, and as first line of defense against microbial infection. Costimulation of epithelial γδ T cell activation by the JAML receptor can be induced by interaction with its endogenous ligand CAR or by binding of the stimulatory antibody HL4E10. We, therefore, determined the crystal structure of the JAML-HL4E10 Fab complex at 2.95 Å resolution. HL4E10 binds the membrane-proximal domain of JAML through hydrophobic interactions that account for nanomolar affinity and long half-life, contrasting with the fast kinetics and micromolar affinity of the hydrophilic CAR interaction with the membrane-distal JAML domain. Thus, despite different binding sites and mechanisms, JAML interaction with these two disparate ligands leads to the same functional outcome, namely JAML triggering and induction of cell signaling. Several characteristics of the HL4E10 antibody might then be harnessed in therapeutic applications, such as promoting healing of acute or chronic wounds., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Intraplaque hemorrhage in atherosclerotic plaques has been associated with accelerated plaque growth as well as exacerbation of clinical symptoms. The identification of intraplaque hemorrhage using magnetic resonance imaging primarily relies on the detection of methemoglobin on T(1) weighted images. Current techniques are limited by insufficient intraplaque hemorrhage-wall contrast and poor blood suppression. In this study, a slab-selective phase-sensitive inversion-recovery (SPI) technique is proposed by combining a phase-sensitive reconstruction with a T(1) weighted sequence specifically designed to achieve improved intraplaque hemorrhage imaging. The SPI sequence was optimized and then used on ex vivo plaque specimens for histology based validation and intraplaque hemorrhage-wall contrast-to-noise ratio comparison with magnetization-prepared 3D rapid acquisition gradient echo MP-RAGE. SPI and MP-RAGE were also tested on a group of atherosclerosis patients to compare in vivo intraplaque hemorrhage-wall contrast-to-noise ratio and blood suppression effectiveness. On ex vivo specimens SPI had better intraplaque hemorrhage identification accuracy and a significantly higher intraplaque hemorrhage-wall contrast-to-noise ratio (P = 0.01) than MP-RAGE. Similar results were found in the in vivo test: Slab-selective phase-sensitive inversion-recovery provided a significantly improved intraplaque hemorrhage-wall contrast-to-noise ratio (P < 0.01) and blood suppression efficiency (P < 0.01). In conclusion, SPI is a novel technique optimized for intraplaque hemorrhage detection and validated against histology. It has demonstrated its capability for improved in vivo intraplaque hemorrhage identification and blood suppression in atherosclerosis patients., (Copyright © 2010 Wiley-Liss, Inc.)

Women are more susceptible than men to acute liver injury from drugs and other xenobiotics. The biological mechanisms for this sex difference are unknown, but known sex differences in steroid hormone levels and immune response could play a role. A human hepatocyte cell line, HepG2, was cultured for 8 days in either a male hormone, female hormone, or sex hormone-free medium. The cells were then exposed to a mixture of pro-inflammatory cytokines (interleukin (IL)-1beta, IL-6, TNFalpha) for 72h to simulate acute inflammation. Cell viability (total DNA) and various metabolic functions (reactive oxygen species (ROS), neutral and polar lipid (PL) accumulation, mitochondrial membrane potential, cytochrome P450 (CYP) activities) were measured fluorometrically. Acute phase proteins (albumin, IL-1ra) were measured in the culture medium by ELISA. This model gave both significant hormone only effects (ROS, PL accumulation) and cytokine only effects (total DNA, CYP1A, neutral and PL accumulation, albumin, IL-1ra) consistent with known biological responses. Significant hormone-cytokine interactions were observed for several endpoints (total DNA, ROS, neutral and PL accumulation, albumin). These findings suggest that sex hormones and pro-inflammatory cytokines can interact to alter liver metabolism in ways that may contribute to the marked sex difference in susceptibility to chemical-induced acute liver injury., (Published by Elsevier Ireland Ltd.)

Objective: We present the first reported case in the English language literature of an inflammatory myofibroblastic tumour of the right tonsil in a young, pregnant woman, and we report a management strategy for this enigmatic entity., Case Report: A 28-year-old, pregnant woman presented with a 10-day history of odynophagia despite a course of antibiotics. Examination revealed a grade II, erythematous right tonsil with ulceration on the upper pole. A biopsy was arranged, and initial evaluation was suggestive of spindle cell carcinoma. However, this diagnosis was reviewed after immunohistochemical staining confirmed an inflammatory myofibroblastic tumour. Subsequent complete excision was undertaken using CO2 laser., Conclusion: Clinically, inflammatory myofibroblastic tumour of the tonsil is known to be locally aggressive and can present in a manner not dissimilar to a high grade carcinoma of the tonsil. As a result, the recommended treatment is complete local excision with careful follow up.

Purpose: To compare the diagnostic performances of three T1-weighted 3.0-T magnetic resonance (MR) sequences at carotid intraplaque hemorrhage (IPH) imaging, with histo logic analysis as the reference standard., Materials and Methods: Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. Twenty patients scheduled for carotid endarterectomy underwent 3.0-T carotid MR imaging, including two-dimensional fast spin-echo, three-dimensional time-of-flight (TOF), and three-dimensional magnetization-prepared rapid acquisition gradient-echo (RAGE) sequences. Two reviewers blinded to the histologic findings assessed the presence, area, and signal intensity of IPH with each sequence. Detection statistics (sensitivity, specificity, and Cohen kappa values) and agreement between area measurements (Pearson correlation coefficient [r] values) were calculated for each sequence., Results: When all 231 available MR sections were included for analysis, the magnetization-prepared RAGE (kappa = 0.53) and fast spin-echo (kappa = 0.42) sequences yielded moderate agreement between MR and histologic measurements, while the TOF sequence yielded fair agreement (k = 0.33). However, when 47 sections with either small IPHs or heavily calcified IPHs were excluded, sensitivity, specificity, and kappa values, respectively, were 80%, 97%, and 0.80 for magnetization-prepared RAGE imaging; 70%, 92%, and 0.63 for fast spin-echo imaging; and 56%, 96%, and 0.57 for TOF imaging. MR imaging-histologic analysis correlation for IPH area was highest with magnetization-prepared RAGE imaging (r = 0.813), followed by TOF (r = 0.745) and fast spin-echo (r = 0.497) imaging. The capability of these three sequences for IPH detection appeared to be in good agreement with the quantitative contrast of IPH versus background plaque tissue., Conclusion: The magnetization-prepared RAGE sequence, as compared with the fast spin-echo and TOF sequences, demonstrated higher diagnostic capability for the detection and quantification of IPH. Potential limitations of 3.0-T IPH MR imaging are related to hemorrhage size and coexisting calcification., ((c) RSNA, 2010.)

Atherosclerosis is a chronic, progressive, inflammatory disease affecting many vascular beds. Disease progression leads to acute cardiovascular events such as myocardial infarction, stroke and death. The diseased carotid alone is responsible for one third of the 700,000 new or recurrent strokes occurring yearly in the United States. Imaging plays an important role in the management of atherosclerosis, and cardiovascular magnetic resonance (CMR) of the carotid vessel wall is one promising modality in the evaluation of patients with carotid atherosclerotic disease. Advances in carotid vessel wall CMR allow comprehensive assessment of morphology inside the wall, contributing substantial disease-specific information beyond luminal stenosis. Although carotid vessel wall CMR has not been widely used to screen for carotid atherosclerotic disease, many trials support its potential for this indication. This review summarizes the current state of knowledge regarding carotid vessel wall CMR and its potential clinical application for management of carotid atherosclerotic disease.