[Proactively embracing the challenges of multimorbidity].

With rapid socio-economic development and the acceleration of population aging, the average life span of human beings has increased significantly. Individuals suffering from the co-existence of multiple diseases (multimorbidity) have become a new normal in public health and posed severe challenge to human health. Multimorbidity significantly reduces the quality of life, increases disability and mortality risks, complicates disease treatment and care and increases burden of the healthcare system with higher costs. This commentary discusses the definition of multimorbidity and common public misconceptions, then assesses its profound impact on overall public health, socio-economic development and healthcare system. We also proposes the potential strategies to meet the challenges posed by multimorbidity. The main aim is to raise awareness of multimorbidity, advocate proactive responses to improve public health and build a healthy society through the development of prevention and treatment systems and promote precision prevention and treatment for multimorbidity.

[Research progress on global health competency and its models].

At present, the research on Global Health Competencies is mainly conducted in the field of the establishment of competency models and application of indicators. This review summarizes the research progress of the Global Health Competency and its models, and focuses on cutting-edge research from the aspects of target audience, purpose, content, classical model, methods and future development. The competency model is suggested to be adjusted and updated according to the practices of different countries and regions. The research and funding of the competency model in the field of public health is suggested to be strengthened, and the global health and diplomacy are suggested to be combined to enrich and improve the competency model. Finally, this review aims to promote Global Health Competencies research in China, especially to improve the global health talent training system and relevant policies in further research.

Individual perceptions of community efficacy for non-communicable disease management in twelve communities in China: cross-sectional and longitudinal analyses.

OBJECTIVES: This objective of this study was to use empirical data to assess cross-sectional variation singular and changes over time in community efficacy for non-communicable diseases (NCDs) management (COEN) and to examine individual factors associated with changes in COEN. STUDY DESIGN: This was a longitudinal observational study. METHODS: Participants with hypertension and diabetes were randomly selected from 12 communities from three cities in eastern China, and a baseline survey and a 1-year follow-up were conducted. The COEN scale has five dimensions: community physical environment (CPE), behavioral risk factors (BRF), mental health and social relationships (MHSR), community health management (CHM), and community organisations and activities (COA). Mixed-effects models were used to investigate the change in COEN over time and the association between individual factors and changes in COEN. RESULTS: COEN scores showed significant variation singular among the 12 communities (P < 0.001) at the baseline. In the mixed-effects model, CPE (ß coefficient: 1.62, P < 0.001), BRF (0.90, P < 0.001), MHSR (0.86, P < 0.001), CHM (0.46, P < 0.001), and total scores (ß = 3.57, P < 0.001) increased significantly over time. The changes in COEN were associated with individual characteristics (e.g., older, men, more educated). CONCLUSIONS: Cross-sectional variations and changes over time in COEN demonstrated the utility of a sensitive instrument. Factors such as age, gender, marriage, education level, and employment may affect the financial and social resources assignment for NCD management. Our findings suggest that further high-quality studies are needed to better evaluate the effect of community empowerment on the prevention and control of NCDs.

[Exploration of the classification of public health intervention and its implication for China].

Public health interventions refer to a series of organized and specific measures implemented in specific situations to achieve goals related to improving health, preventing and controlling diseases, and more. As research on intervention measures has deepened, the classification of public health interventions has gradually developed, clarifying the nature, categories and intervention targets of these measures. This typological study can help standardize the concepts of public health interventions, develop, select, and evaluate the effectiveness of intervention measures, and improve the effectiveness of public health actions. This paper reviews the main international classification models of intervention measures, analyzes and summarizes five classification methods of public health interventions, namely, based on goals, nature, objects, hierarchies, and modes of action, and introduces relevant cases. The paper proposes that China should conduct further in-depth and systematic research on public health interventions, develop evidence-based intervention measures and practices, promote the effective transformation of intervention measures and results, and facilitate the development of public health.

Deep Learning Enables 60% Accelerated Volumetric Brain MRI While Preserving Quantitative Performance: A Prospective, Multicenter, Multireader Trial.

BACKGROUND AND PURPOSE: In this prospective, multicenter, multireader study, we evaluated the impact on both image quality and quantitative image-analysis consistency of 60% accelerated volumetric MR imaging sequences processed with a commercially available, vendor-agnostic, DICOM-based, deep learning tool (SubtleMR) compared with that of standard of care. MATERIALS AND METHODS: Forty subjects underwent brain MR imaging examinations on 6 scanners from 5 institutions. Standard of care and accelerated datasets were acquired for each subject, and the accelerated scans were enhanced with deep learning processing. Standard of care, accelerated scans, and accelerated-deep learning were subjected to NeuroQuant quantitative analysis and classified by a neuroradiologist into clinical disease categories. Concordance of standard of care and accelerated-deep learning biomarker measurements were assessed. Randomized, side-by-side, multiplanar datasets (360 series) were presented blinded to 2 neuroradiologists and rated for apparent SNR, image sharpness, artifacts, anatomic/lesion conspicuity, image contrast, and gray-white differentiation to evaluate image quality. RESULTS: Accelerated-deep learning was statistically superior to standard of care for perceived quality across imaging features despite a 60% sequence scan-time reduction. Both accelerated-deep learning and standard of care were superior to accelerated scans for all features. There was no difference in quantitative volumetric biomarkers or clinical classification for standard of care and accelerated-deep learning datasets. CONCLUSIONS: Deep learning reconstruction allows 60% sequence scan-time reduction while maintaining high volumetric quantification accuracy, consistent clinical classification, and what radiologists perceive as superior image quality compared with standard of care. This trial supports the reliability, efficiency, and utility of deep learning-based enhancement for quantitative imaging. Shorter scan times may heighten the use of volumetric quantitative MR imaging in routine clinical settings.

Tissue at Risk and Ischemic Core Estimation Using Deep Learning in Acute Stroke.

BACKGROUND AND PURPOSE: In acute stroke patients with large vessel occlusions, it would be helpful to be able to predict the difference in the size and location of the final infarct based on the outcome of reperfusion therapy. Our aim was to demonstrate the value of deep learning-based tissue at risk and ischemic core estimation. We trained deep learning models using a baseline MR image in 3 multicenter trials. MATERIALS AND METHODS: Patients with acute ischemic stroke from 3 multicenter trials were identified and grouped into minimal (≤20%), partial (20%-80%), and major (≥80%) reperfusion status based on 4- to 24-hour follow-up MR imaging if available or into unknown status if not. Attention-gated convolutional neural networks were trained with admission imaging as input and the final infarct as ground truth. We explored 3 approaches: 1) separate: train 2 independent models with patients with minimal and major reperfusion; 2) pretraining: develop a single model using patients with partial and unknown reperfusion, then fine-tune it to create 2 separate models for minimal and major reperfusion; and 3) thresholding: use the current clinical method relying on apparent diffusion coefficient and time-to-maximum of the residue function maps. Models were evaluated using area under the curve, the Dice score coefficient, and lesion volume difference. RESULTS: Two hundred thirty-seven patients were included (minimal, major, partial, and unknown reperfusion: n = 52, 80, 57, and 48, respectively). The pretraining approach achieved the highest median Dice score coefficient (tissue at risk = 0.60, interquartile range, 0.43-0.70; core = 0.57, interquartile range, 0.30-0.69). This was higher than the separate approach (tissue at risk = 0.55; interquartile range, 0.41-0.69; P = .01; core = 0.49; interquartile range, 0.35-0.66; P = .04) or thresholding (tissue at risk = 0.56; interquartile range, 0.42-0.65; P = .008; core = 0.46; interquartile range, 0.16-0.54; P < .001). CONCLUSIONS: Deep learning models with fine-tuning lead to better performance for predicting tissue at risk and ischemic core, outperforming conventional thresholding methods.

[A retrospective analysis of single preterm birth incidence and high-risk factors based on maternal age stratification].

Objective: To compare the preterm birth rate among different age groups and analyze relative high-risk factors of preterm birth. Methods: A retrospective analysis was conducted on clinical data of single pregnant women ≥28 gestational weeks from January 2013 to May 2019 in the First Affiliated Hospital of Chongqing Medical Hospital. All involved women were divided into three groups according to age, Group 1 (aged<35 years), Group 2 (aged 35-39 years), and Group 3 (aged ≥40 years). The preterm birth rate among 3 groups was compared and their high-risk factors were analyzed. Results: There were 48 288 singleton pregnancies during the study period, of which 3 351 were preterm births， preterm birth rate was 6.94% (3 351/48 288). In Group 1, there were 42 020 women, of which 2 699 were preterm births (6.42%, 2 699/42 020); in Group 2, there were 5 061 women, of which 491 were preterm births (9.70%, 491/5 061); and in Group 3, there were 1 207 women, of which 161 were preterm births (13.34%, 161/1 207). Comparing the spontaneous preterm birth rates among the three groups, Group 1 was the lowest one and Group 3 was the highest one (3.72% vs 4.51% vs 5.88%); comparing the medical preterm birth rates among the three groups, Group 1 also was the lowest one and Group 3 also was the highest one (2.70% vs 5.20% vs 7.46%); the differences were statistically significant (P<0.05). The incidence of spontaneous and medical preterm birth according gestational weeks were compared among three groups and there were no significant differences (P>0.05). Comparing and analyzing the high-risk factors of medical preterm birth, the incidence of intrahepatic cholestasis of pregnancy and fetal distress in Group 1 were higher than those in Group 2 and 3; the incidence of placenta praevia were significantly higher in Group 2 and 3 than that in Group 1; the differences were statistically significant (P<0.05). Conclusions: Maternal age is a significant high-risk factor of both spontaneous preterm birth and medical preterm birth, and the risk of preterm birth increases with age. For medical preterm birth, compared with right-age pregnant women, placenta praevia is the high-risk factor for women in advanced maternal age(AMA), which have great effect on medical preterm birth rate of AMA.

Deep Learning in Neuroradiology.

Deep learning is a form of machine learning using a convolutional neural network architecture that shows tremendous promise for imaging applications. It is increasingly being adapted from its original demonstration in computer vision applications to medical imaging. Because of the high volume and wealth of multimodal imaging information acquired in typical studies, neuroradiology is poised to be an early adopter of deep learning. Compelling deep learning research applications have been demonstrated, and their use is likely to grow rapidly. This review article describes the reasons, outlines the basic methods used to train and test deep learning models, and presents a brief overview of current and potential clinical applications with an emphasis on how they are likely to change future neuroradiology practice. Facility with these methods among neuroimaging researchers and clinicians will be important to channel and harness the vast potential of this new method.

Foxp3 is a key downstream regulator of p53-mediated cellular senescence.

The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-l-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.

Routine endoscopic screening for synchronous esophageal neoplasm in patients with head and neck squamous cell carcinoma: a prospective study.

Early detection of synchronous esophageal squamous cell neoplasm (ESCN) in head and neck squamous cell carcinoma (HNSCC) patients can significantly affect their prognosis. We investigated the prevalence of synchronous ESCN and the risk factors for developing ESCN in patients with HNSCC, and evaluated the effect of routine endoscopic screening in these patients. Subjects who were diagnosed as HNSCC from May 2010 to January 2014 were eligible. All patients underwent conventional white light endoscopic examinations with narrow band imaging and Lugol chromoendoscopy. Among 458 subjects screened, 28 synchronous ESCN were detected in 24 patients (5.2%). The prevalence of ESCN was greatest in patients with hypopharyngeal cancer (20.9%). In multivariate analysis, pyriform sinus involvement was independent risk factor for developing synchronous ESCN (odds ratio 171.2, P < 0.001). During the follow-up period (median, 24 months), the 3-year overall survival rates was significantly lower in patients with ESCN than in patients without ESCN (54.2% vs. 78.3%, P = 0.0013). Routine endoscopic screening for detecting synchronous ESCN should be recommended for patients with HNSCC, especially those with pyriform sinus involvement.

Perioperative effects of caudal and transversus abdominis plane (TAP) blocks for children undergoing urologic robot-assisted laparoscopic surgery.

INTRODUCTION: Regional anesthesia is often used in combination with general anesthesia for pediatric surgery, however, it is unknown if adjunctive regional blocks are beneficial to children undergoing urologic laparoscopic or robot-assisted laparoscopic (RAL) procedures. OBJECTIVE: To compare perioperative outcomes in children with adjunctive caudal blocks, transversus abdominis plane (TAP) blocks, or no regional anesthesia for common RAL surgical procedures in pediatric urology. STUDY DESIGN: Inclusion in this retrospective study was limited to children who underwent RAL renal or ureteral/bladder procedures and received a standardized regimen of scheduled intravenous ketorolac and oral acetaminophen for acute postoperative pain control, with opioids as needed (PRN). Perioperative outcomes were compared between patients with an adjunctive caudal block (n = 25), bilateral TAP blocks (n = 44), or no regional anesthesia (n = 51). RESULTS: Children with a preoperative caudal block received less intraoperative opioids than children with TAP blocks or no regional anesthesia (p < 0.001). This difference was observed both for renal procedures (p < 0.01) and ureteral/bladder procedures (p = 0.01). Patients with caudal blocks were also the least likely to require postoperative antiemetics (p = 0.03). There were no significant differences between groups in postoperative opioid use, maximum pain scores within 6 and 24 hours postoperatively, or length of hospital stay (LOS). No complications attributable to regional blocks were identified by chart review. DISCUSSION: Use of adjunctive caudal blocks for pediatric RAL renal or ureteral/bladder surgical procedures may reduce need for alternate analgesic and/or anesthetic agents intraoperatively, as well as decrease postoperative nausea and vomiting. These findings may be related, since nausea and vomiting are common side effects of opioids and inhalational anesthetics. Consideration of the potential impact of caudal blocks on general anesthetic requirements is timely in light of concerns regarding the risk of anesthetic neurotoxicity in young patients. There was no evidence of improved postoperative pain control or shorter LOS for children who received regional anesthesia. It is unknown if regional blocks would have a greater impact in the absence of scheduled pain medications, which all patients in our study received. Limitations of this study include its retrospective nature and moderate sample size. Future randomized controlled trials are necessary to provide a more definitive understanding of regional anesthesia's role in minimizing pediatric surgical and anesthetic morbidity. CONCLUSION: Administration of caudal blocks should be considered for children of suitable age undergoing RAL surgery involving either the upper or lower urinary tract.

Carbon dioxide laser for detrusor tunnel creation in robot-assisted laparoscopic extravesical ureteral reimplant.

OBJECTIVE: Demonstrate and report initial results using a carbon dioxide (CO2) laser for detrusor tunnel creation in robot-assisted laparoscopic extravesical ureteral reimplant (RALUR). METHODS: Retrospective chart review was performed for cases of RALUR from 2011 to 2014. Patients undergoing complex reconstruction (ureteral tailoring, dismembered reimplant, concomitant ureteroureterostomy), and those who had incomplete follow-up were excluded. Variables, including use of the CO2 laser, were collected and correlated with outcomes. RESULTS: 23 patients representing 40 ureteral units were included for analysis. A CO2 laser was used in 9/23 (39%) patients and 16/40 (40%) ureteral units. Intraoperative mucosotomy was reported in 3/14 (21%) patients for the electrocautery group and 1/9 (11%) patients for the CO2 laser group. Resolution of VUR was observed in 11/14 (79%), and 9/9 (100%) of patients for the electrocautery group and the CO2 laser group, respectively. Two complications were identified in the electrocautery group of patients: ileus (Clavien 2), and transient bilateral ureteral obstruction requiring placement of ureteral stents (Clavien 3B). There were no complications in the CO2 laser group. CONCLUSIONS: Creation of the detrusor tunnel with a CO2 laser is safe and effective, and is associated with a lower rate of failure and complication in this cohort.

Microarray expression profiling identifies genes with altered expression in HDL-deficient mice.

Based on the assumption that severe alterations in the expression of genes known to be involved in high-density lipoprotein (HDL) metabolism may affect the expression of other genes, we screened an array of >5000 mouse expressed sequence tags for altered gene expression in the livers of two lines of mice with dramatic decreases in HDL plasma concentrations. Labeled cDNA from livers of apolipoprotein AI (apoAI)-knockout mice, scavenger receptor BI (SR-BI) transgenic mice, and control mice were cohybridized to microarrays. Two-sample t statistics were used to identify genes with altered expression levels in the knockout or transgenic mice compared with control mice. In the SR-BI group we found nine array elements representing at least five genes that were significantly altered on the basis of an adjusted P value < 0.05. In the apoAI-knockout group, eight array elements representing four genes were altered compared with the control group (adjusted P < 0.05). Several of the genes identified in the SR-BI transgenic suggest altered sterol metabolism and oxidative processes. These studies illustrate the use of multiple-testing methods for the identification of genes with altered expression in replicated microarray experiments.

Increased low density lipoprotein degradation in aorta of irradiated mice is inhibited by preenrichment of low density lipoprotein with alpha-tocopherol.

We previously reported that upper thoracic exposure to ionizing radiation (IR) accelerates fatty streak formation in C57BL/6 mice and that such effects are inhibited by overexpression of the antioxidant enzyme CuZn-superoxide dismutase (SOD). Notably, IR-accelerated lesion formation is strictly dependent on a high fat diet (i.e., atherogenic lipoproteins) but does not involve alterations in circulating lipid or lipoprotein levels. We thus proposed that IR promotes changes in the artery wall that enhance the deposition of lipoprotein lipids. To address this hypothesis, we examined the effects of IR on aortic accumulation and degradation of low density lipoproteins (LDL). Ten-week-old C57BL/6 mice were exposed to a single (8-Gy) dose of (60)Co radiation to the upper thoracic area or were sham irradiated (controls) and were then placed on the high fat diet. Five days postexposure, the mice received either (125)I-labeled LDL ((125)I-LDL) (which was used to measure intact LDL) or (125)I-labeled tyramine cellobiose ((125)I-TC)-LDL (which was used to measure both intact and cell-degraded LDL) via tail vein injection. On the basis of trichloroacetic acid (TCA)-precipitable counts in retroorbital blood samples, > or =95% of donor LDL was cleared within 24 h and there were no differences in time-averaged plasma concentrations of the two forms of LDL among irradiated and control mice. Aortic values increased markedly within the first hour and thereafter exhibited a slow increase up to 24 h. There were no differences between irradiated and control mice at 1 h, when values primarily reflected LDL entry, but a divergence was observed thereafter. At 24 h, (125)I-TC-associated counts were 1.8-fold higher in irradiated mice (P = 0.10). In contrast, (125)I-LDL-associated counts were 30% lower in irradiated mice (P< 0.05), suggesting that most of the retained (125)I-TC was associated with LDL degradation products. Consistent with the proposed involvement of oxidative or redox-regulated events, IR-induced LDL degradation was lower in SOD-transgenic than wild-type mice (P<0.05). The importance of LDL oxidation was suggested by observations that IR-induced LDL degradation was significantly reduced by preenriching LDL with alpha-tocopherol. On the basis of these results, we propose that IR elicits SOD-inhibitable changes in the artery wall that enhance LDL oxidation and degradation leading to the deposition of LDL-borne lipids. These studies provide additional support for the role of oxidation in lipoprotein lipid deposition and atherogenesis and suggest that IR promotes an arterial environment that stimulates this process in vivo.

Relationship between expression levels and atherogenesis in scavenger receptor class B, type I transgenics.

Both in vitro and in vivo studies of scavenger receptor class B type I (SR-BI) have implicated it as a likely participant in the metabolism of HDL cholesterol. To investigate the effect of SR-BI on atherogenesis, we examined two lines of SR-BI transgenic mice with high (10-fold increases) and low (2-fold increases) SR-BI expression in an inbred mouse background hemizygous for a human apolipoprotein (apo) B transgene. Unlike non-HDL cholesterol levels that minimally differed in the various groups of animals, HDL cholesterol levels were inversely related to SR-BI expression. Mice with the low expression SR-BI transgene had a 50% reduction in HDL cholesterol, whereas the high expression SR-BI transgene was associated with 2-fold decreases in HDL cholesterol as well as dramatic alterations in HDL composition and size including the near absence of alpha-migrating particles as determined by two-dimensional electrophoresis. The low expression SR-BI/apo B transgenics had more than a 2-fold decrease in the development of diet-induced fatty streak lesions compared with the apo B transgenics (4448 +/- 1908 micrometer(2)/aorta to 10133 +/- 4035 micrometer (2)/aorta; p < 0.001), whereas the high expression SR-BI/apo B transgenics had an atherogenic response similar to that of the apo B transgenics (14692 +/- 7238 micrometer(2)/aorta) but 3-fold greater than the low SR-BI/apo B mice (p < 0.001). The prominent anti-atherogenic effect of moderate SR-BI expression provides in vivo support for the hypothesis that HDL functions to inhibit atherogenesis through its interactions with SR-BI in facilitating reverse cholesterol transport. The failure of the high SR-BI/apo B transgenics to have similar or even greater reductions in atherogenesis suggests that the changes resulting from extremely high SR-BI expression including dramatic changes in lipoproteins may have both pro- and anti-atherogenic consequences, illustrating the complexity of the relationship between SR-BI and atherogenesis.

Genomic interval engineering of mice identifies a novel modulator of triglyceride production.

To accelerate the biological annotation of novel genes discovered in sequenced regions of mammalian genomes, we are creating large deletions in the mouse genome targeted to include clusters of such genes. Here we describe the targeted deletion of a 450-kb region on mouse chromosome 11, which, based on computational analysis of the deleted murine sequences and human 5q orthologous sequences, codes for nine putative genes. Mice homozygous for the deletion had a variety of abnormalities, including severe hypertriglyceridemia, hepatic and cardiac enlargement, growth retardation, and premature mortality. Analysis of triglyceride metabolism in these animals demonstrated a several-fold increase in hepatic very-low density lipoprotein triglyceride secretion, the most prevalent mechanism responsible for hypertriglyceridemia in humans. A series of mouse BAC and human YAC transgenes covering different intervals of the 450-kb deleted region were assessed for their ability to complement the deletion induced abnormalities. These studies revealed that OCTN2, a gene recently shown to play a role in carnitine transport, was able to correct the triglyceride abnormalities. The discovery of this previously unappreciated relationship between OCTN2, carnitine, and hepatic triglyceride production is of particular importance because of the clinical consequence of hypertriglyceridemia and the paucity of genes known to modulate triglyceride secretion.

Ionizing radiation accelerates aortic lesion formation in fat-fed mice via SOD-inhibitable processes.

Ionizing radiation promotes formation of reactive oxygen species, including the superoxide anion (O2-). To evaluate whether O2- or O2--mediated perturbations may contribute to the known atherogenic effects of radiation, we examined aortic lesion formation in irradiated C57BL/6 mice and evaluated the effects of CuZn-superoxide dismutase (CuZn-SOD) overexpression. Ten-week-old mice were exposed to a 2-, 4-, or 8-Gy dose of 250-keV x-rays to the upper thorax and then placed on a high-fat diet for 18 weeks. Based on quantitative lipid staining of serial sections of the proximal aorta, mean lesion area was increased with increasing radiation dose and was 3-fold greater in 8-Gy-irradiated than sham-irradiated mice (7800+/-2140 versus 2635+/-709 micrometer(2), P<0.05). These effects were absolutely dependent on a high-fat diet, which had to be introduced within 1 to 2 weeks of the radiation exposure, suggesting the early involvement of atherogenic lipoproteins that were elevated in response to the diet. The importance of radiation-induced oxidative stress was supported by the observation of a 2-fold lower mean lesion area in irradiated CuZn-SOD transgenic mice than in their irradiated, nontransgenic littermates (3026+/-1590 versus 6102+/-1834 micrometer(2), P<0.05). Lucigenin-enhanced chemiluminescence, used as an index of aortic O2- concentrations, was significantly elevated in the postradiation period, and this response was reduced in CuZn-SOD transgenics. On the basis of these results, we propose that radiation may be a useful tool for initiating oxidative or redox-regulated events that promote atherogenesis and for testing the antiatherogenic properties of antioxidants.

Lower plasma levels and accelerated clearance of high density lipoprotein (HDL) and non-HDL cholesterol in scavenger receptor class B type I transgenic mice.

Recent studies have indicated that the scavenger receptor class B type I (SR-BI) may play an important role in the uptake of high density lipoprotein (HDL) cholesteryl ester in liver and steroidogenic tissues. To investigate the in vivo effects of liver-specific SR-BI overexpression on lipid metabolism, we created several lines of SR-BI transgenic mice with an SR-BI genomic construct where the SR-BI promoter region had been replaced by the apolipoprotein (apo)A-I promoter. The effect of constitutively increased SR-BI expression on plasma HDL and non-HDL lipoproteins and apolipoproteins was characterized. There was an inverse correlation between SR-BI expression and apoA-I and HDL cholesterol levels in transgenic mice fed either mouse chow or a diet high in fat and cholesterol. An unexpected finding in the SR-BI transgenic mice was the dramatic impact of the SR-BI transgene on non-HDL cholesterol and apoB whose levels were also inversely correlated with SR-BI expression. Consistent with the decrease in plasma HDL and non-HDL cholesterol was an accelerated clearance of HDL, non-HDL, and their major associated apolipoproteins in the transgenics compared with control animals. These in vivo studies of the effect of SR-BI overexpression on plasma lipoproteins support the previously proposed hypothesis that SR-BI accelerates the metabolism of HDL and also highlight the capacity of this receptor to participate in the metabolism of non-HDL lipoproteins.