Stakeholders' perspectives of mobile x-ray services in support of healthcare-in-place in residential aged care facilities: a qualitative study.

BACKGROUND: There is interest in reducing avoidable emergency department presentations from residential aged care facilities (RACF). Mobile x-ray services may enable the delivery of healthcare in residential aged care facilities. Accordingly, the Australian Government in November 2019 introduced a Medicare Benefit Schedule rebate providing for a 'call-out' fee payable to radiology service providers. This study aims to understand stakeholder perspectives on the benefits of mobile x-ray services and the factors influencing their adoption by RACFs. DESIGN, SETTING, PARTICIPANTS: Twenty-two semi-structured interviews were conducted between October 2020 and February 2021 with a range of stakeholders involved in healthcare delivery to residents: a) general practitioners; b) emergency department clinicians; c) paramedic clinicians; d) a hospital avoidance clinician; e) radiology clinicians and managers; and f) aged care clinicians and managers. Thematic analysis was conducted. RESULTS: Mobile x-ray services were considered valuable for RACF residents. Lack of timely general practitioner in-person assessment and referral, as well as staffing deficits in residential aged care facilities, reduces optimal use of mobile x-ray services and results in potentially unnecessary hospital transfers. CONCLUSIONS: The use of mobile x-ray services, as a hospital avoidance strategy, depends on the capacity of RACFs to provide more complex healthcare-in-place. However, this requires greater access to general practitioners for in-person assessment and referral, adequate staffing numbers and appropriately skilled nursing staff within residential aged care facilities.

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses.

There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine against SARS-CoV-2. The vaccine is based on the display of coronavirus spike glycoprotein receptor-binding domain (RBD) on a synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses of RBD-SpyVLP in a prime-boost regimen induce a strong neutralising antibody response in mice and pigs that is superior to convalescent human sera. We evaluate antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we show that RBD-SpyVLP induces a polyclonal antibody response that recognises key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. Moreover, RBD-SpyVLP is thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence. The data suggests that RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic.

Evaluation of a population health strategy to reduce distracted driving: Examining all "Es" of injury prevention.

BACKGROUND: Cell phone use while driving (CPWD) increases the risk of crashing and is a major contributor to injuries and deaths. The objective of this study was to describe the evaluation of a multifaceted, evidence-based population health strategy for the reduction of distracted driving. METHODS: A multipronged campaign was undertaken from 2014 to 2016 for 16- to 44-year-olds, based on epidemiology, focused on personal stories and consequences, using the "Es" of injury prevention (epidemiology, education, environment, enforcement, and evaluation). Education consisted of distracted driving videos, informational cards, a social media AdTube campaign, and a movie theater trailer, which were evaluated with a questionnaire regarding CPWD attitudes, opinions, and behaviors. Spatial analysis of data within a geographic information system was used to target advertisements. A random sample telephone survey evaluated public awareness of the campaign. Increased CPWD enforcement was undertaken by police services and evaluated by ARIMA time series modeling. RESULTS: The AdTube campaign had a view rate of >10% (41,101 views), slightly higher for females. The top performing age group was 18- to 24-year-olds (49%). Our survey found 61% of respondents used handheld CPWD (14% all of the time) with 80% reporting our movie trailer made them think twice about future CPWD. A stakeholder survey and spatial analysis targeted our advertisements in areas of close proximity to high schools, universities, near intersections with previous motor vehicle collisions, high traffic volumes, and population density. A telephone survey revealed that 41% of the respondents were aware of our campaign, 17% from our print and movie theater ads and 3% from social media. Police enforcement campaign blitzes resulted in 160 tickets for CPWD. Following campaign implementation, there was a statistically significant mean decrease of 462 distracted driving citations annually (p = 0.001). CONCLUSION: A multifaceted, evidence-based population health strategy using the Es of injury prevention with interdisciplinary collaboration is a comprehensive method to be used for the reduction of distracted driving. LEVEL OF EVIDENCE: Therapeutic, level IV.

Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19.

Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres.

Substitution of warthog NF-κB motifs into RELA of domestic pigs is not sufficient to confer resilience to African swine fever virus.

African swine fever virus (ASFV) causes a lethal, haemorrhagic disease in domestic swine that threatens pig production across the globe. Unlike domestic pigs, warthogs, which are wildlife hosts of the virus, do not succumb to the lethal effects of infection. There are three amino acid differences between the sequence of the warthog and domestic pig RELA protein; a subunit of the NF-κB transcription factor that plays a key role in regulating the immune response to infections. Domestic pigs with all 3 or 2 of the amino acids from the warthog RELA orthologue have been generated by gene editing. To assess if these variations confer resilience to ASF we established an intranasal challenge model with a moderately virulent ASFV. No difference in clinical, virological or pathological parameters were observed in domestic pigs with the 2 amino acid substitution. Domestic pigs with all 3 amino acids found in warthog RELA were not resilient to ASF but a delay in onset of clinical signs and less viral DNA in blood samples and nasal secretions was observed in some animals. Inclusion of these and additional warthog genetic traits into domestic pigs may be one way to assist in combating the devastating impact of ASFV.

Intervention with citrus flavonoids reverses obesity and improves metabolic syndrome and atherosclerosis in obese Ldlr-/- mice.

Obesity and its associated metabolic dysfunction and cardiovascular disease risk represent a leading cause of adult morbidity worldwide. Currently available pharmacological therapies for obesity have had limited success in reversing existing obesity and metabolic dysregulation. Previous prevention studies demonstrated that the citrus flavonoids, naringenin and nobiletin, protect against obesity and metabolic dysfunction in Ldlr-/- mice fed a high-fat cholesterol-containing (HFHC) diet. However, their effects in an intervention model are unknown. In this report, we show that, in Ldlr-/- mice with diet-induced obesity, citrus flavonoid supplementation to a HFHC diet reversed existing obesity and adipocyte size and number through enhanced energy expenditure and increased hepatic fatty acid oxidation. Caloric intake was unaffected and no evidence of white adipose tissue browning was observed. Reversal of adiposity was accompanied by improvements in hyperlipidemia, insulin sensitivity, hepatic steatosis, and a modest reduction in blood monocytes. Together, this resulted in atherosclerotic lesions that were unchanged in size, but characterized by reduced macrophage content, consistent with a more stable plaque phenotype. These studies further suggest potential therapeutic utility of citrus flavonoids, especially in the context of existing obesity, metabolic dysfunction, and cardiovascular disease.

Bempedoic Acid Lowers Low-Density Lipoprotein Cholesterol and Attenuates Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient (LDLR+/- and LDLR-/-) Yucatan Miniature Pigs.

OBJECTIVE: Bempedoic acid (BemA; ETC-1002) is a novel drug that targets hepatic ATP-citrate lyase to reduce cholesterol biosynthesis. In phase 2 studies, BemA lowers elevated low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients. In the present study, we tested the ability of BemA to decrease plasma cholesterol and LDL-C and attenuate atherosclerosis in a large animal model of familial hypercholesterolemia. APPROACH AND RESULTS: Gene targeting has been used to generate Yucatan miniature pigs heterozygous (LDLR+/-) or homozygous (LDLR-/-) for LDL receptor deficiency (ExeGen). LDLR+/- and LDLR-/- pigs were fed a high-fat, cholesterol-containing diet (34% kcal fat; 0.2% cholesterol) and orally administered placebo or BemA for 160 days. In LDLR+/- pigs, compared with placebo, BemA decreased plasma cholesterol and LDL-C up to 40% and 61%, respectively. In LDLR-/- pigs, in which plasma cholesterol and LDL-C were 5-fold higher than in LDLR+/- pigs, BemA decreased plasma cholesterol and LDL-C up to 27% and 29%, respectively. Plasma levels of triglycerides and high-density lipoprotein cholesterol, fasting glucose and insulin, and liver lipids were unaffected by treatment in either genotype. In the aorta of LDLR+/- pigs, BemA robustly attenuated en face raised lesion area (-58%) and left anterior descending coronary artery cross-sectional lesion area (-40%). In LDLR-/- pigs, in which lesions were substantially more advanced, BemA decreased aortic lesion area (-47%) and left anterior descending coronary artery lesion area (-48%). CONCLUSIONS: In a large animal model of LDLR deficiency and atherosclerosis, long-term treatment with BemA reduces LDL-C and attenuates the development of aortic and coronary atherosclerosis in both LDLR+/- and LDLR-/- miniature pigs.

Prevention of Diet-Induced Metabolic Dysregulation, Inflammation, and Atherosclerosis in Ldlr-/- Mice by Treatment With the ATP-Citrate Lyase Inhibitor Bempedoic Acid.

OBJECTIVE: Bempedoic acid (ETC-1002, 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel low-density lipoprotein cholesterol-lowering compound. In animals, bempedoic acid targets the liver where it inhibits cholesterol and fatty acid synthesis through inhibition of ATP-citrate lyase and through activation of AMP-activated protein kinase. In this study, we tested the hypothesis that bempedoic acid would prevent diet-induced metabolic dysregulation, inflammation, and atherosclerosis. APPROACH AND RESULTS: Ldlr-/- mice were fed a high-fat, high-cholesterol diet (42% kcal fat, 0.2% cholesterol) supplemented with bempedoic acid at 0, 3, 10 and 30 mg/kg body weight/day. Treatment for 12 weeks dose-dependently attenuated diet-induced hypercholesterolemia, hypertriglyceridemia, hyperglycemia, hyperinsulinemia, fatty liver and obesity. Compared to high-fat, high-cholesterol alone, the addition of bempedoic acid decreased plasma triglyceride (up to 64%) and cholesterol (up to 50%) concentrations, and improved glucose tolerance. Adiposity was significantly reduced with treatment. In liver, bempedoic acid prevented cholesterol and triglyceride accumulation, which was associated with increased fatty acid oxidation and reduced fatty acid synthesis. Hepatic gene expression analysis revealed that treatment significantly increased expression of genes involved in fatty acid oxidation while suppressing inflammatory gene expression. In full-length aorta, bempedoic acid markedly suppressed cholesteryl ester accumulation, attenuated the expression of proinflammatory M1 genes and attenuated the iNos/Arg1 ratio. Treatment robustly attenuated atherosclerotic lesion development in the aortic sinus by 44%, with beneficial changes in morphology, characteristic of earlier-stage lesions. CONCLUSIONS: Bempedoic acid effectively prevents plasma and tissue lipid elevations and attenuates the onset of inflammation, leading to the prevention of atherosclerotic lesion development in a mouse model of metabolic dysregulation.

Evaluation of hydrophobic chitosan-based particulate formulations of porcine reproductive and respiratory syndrome virus vaccine candidate T cell antigens.

PRRS control is hampered by the inadequacies of existing vaccines to combat the extreme diversity of circulating viruses. Since immune clearance of PRRSV infection may not be dependent on the development of neutralising antibodies and the identification of broadly-neutralising antibody epitopes have proven elusive, we hypothesised that conserved T cell antigens represent potential candidates for development of a novel PRRS vaccine. Previously we had identified the M and NSP5 proteins as well-conserved targets of polyfunctional CD8 and CD4 T cells. To assess their vaccine potential, peptides representing M and NSP5 were encapsulated in hydrophobically-modified chitosan particles adjuvanted by incorporation of a synthetic multi-TLR2/TLR7 agonist and coated with a model B cell PRRSV antigen. For comparison, empty particles and adjuvanted particles encapsulating inactivated PRRSV-1 were prepared. Vaccination with the particulate formulations induced antigen-specific antibody responses, which were most pronounced following booster immunisation. M and NSP5-specific CD4, but not CD8, T cell IFN-γ reactivity was measurable following the booster immunisation in a proportion of animals vaccinated with peptide-loaded particles. Upon challenge, CD4 and CD8 T cell reactivity was detected in all groups, with the greatest responses being detected in the peptide vaccinated group but with limited evidence of an enhanced control of viraemia. Analysis of the lungs during the resolution of infection showed significant M/NSP5 specific IFN-γ responses from CD8 rather than CD4 T cells. Vaccine primed CD8 T cell responses may therefore be required for protection and future work should focus on enhancing the cross-presentation of M/NSP5 to CD8 T cells.

Music's Relevance for People Affected by Cancer: A Meta-Ethnography and Implications for Music Therapists.

BACKGROUND: Evidence supports music-based oncologic support interventions including music therapy. By comparison, little is understood about music-based self-care. This meta-ethnography examined five published qualitative studies to extend understanding of music's relevance, including helpfulness, for people affected by cancer; including children, adolescents, and adults with cancer, carers, and the bereaved. OBJECTIVE: To improve understanding of music's broad relevance for those affected by cancer. METHODS: Meta-ethnography strategies informed the analysis. Five studies were synthesized that included 138 participants: 26 children and 28 parents of children with cancer; 12 adolescents and young adults with cancer; 52 adults with cancer; 12 carers; and 8 bereaved. Studies' category and thematic findings were compared and integrated into third-order interpretations, and a line of argument. Perspectives from the five studies that illuminated the line of argument were developed. RESULTS: Music usage can remain incidental, continue normally, and/or change because of cancer's harsh effects. Music can be a lifeline, support biopsychosocial and spiritual well-being, or become elusive, that is, difficult to experience. Music helps or intrudes because it extends self-awareness and social connections, and prompts play, memories, imageries, and legacies. Music therapists may help patients and carers to recover or extend music's helpful effects. CONCLUSIONS: Cancer care can be improved through offering music-based resources/services, which give cancer patients and carers opportunities to extend music usage for personal support and, for carers, to support patients. Music therapists can advocate for such resources and educate health professionals about assessing/recognizing when patients' and carers' changed music behaviors signify additional support needs.

Home safe home: Evaluation of a childhood home safety program.

BACKGROUND: The London Health Sciences Centre Home Safety Program (HSP) provides safety devices, education, a safety video, and home safety checklist to all first-time parents for the reduction of childhood home injuries. The objective of this study was to evaluate the HSP for the prevention of home injuries in children up to 2 years of age. METHODS: A program evaluation was performed with follow-up survey, along with an interrupted time series analysis of emergency department (ED) visits for home injuries 5 years before (2007-2013) and 2 years after (2013-2015) implementation. Spatial analysis of ED visits was undertaken to assess differences in home injury rates by dissemination areas controlling differences in socioeconomic status (i.e., income, education, and lone-parent status) at the neighborhood level. RESULTS: A total of 3,458 first-time parents participated in the HSP (a 74% compliance rate). Of these, 20% (n = 696) of parents responded to our questionnaire, with 94% reporting the program to be useful (median, 6; interquartile range, 2 on a 7-point Likert scale) and 81% learning new strategies for preventing home injuries. The median age of the respondent's babies were 12 months (interquartile range, 1). The home safety check list was used by 87% of respondents to identify hazards in their home, with 95% taking action to minimize the risk. The time series analysis demonstrated a significant decline in ED visits for home injuries in toddlers younger than2 years of age after HSP implementation. The declines in ED visits for home injuries remained significant over and above each socioeconomic status covariate. CONCLUSION: Removing hazards, supervision, and installing safety devices are key facilitators in the reduction of home injuries. Parents found the HSP useful to identify hazards, learn new strategies, build confidence, and provide safety products. Initial finding suggests that the program is effective in reducing home injuries in children up to 2 years of age. LEVEL OF EVIDENCE: Therapeutic/care management study, level V.

PPARδ activation attenuates hepatic steatosis in Ldlr-/- mice by enhanced fat oxidation, reduced lipogenesis, and improved insulin sensitivity.

PPARδ regulates systemic lipid homeostasis and inflammation, but its role in hepatic lipid metabolism remains unclear. Here, we examine whether intervening with a selective PPARδ agonist corrects hepatic steatosis induced by a high-fat, cholesterol-containing (HFHC) diet. Ldlr(-/-) mice were fed a chow or HFHC diet (42% fat, 0.2% cholesterol) for 4 weeks. For an additional 8 weeks, the HFHC group was fed HFHC or HFHC plus GW1516 (3 mg/kg/day). GW1516-intervention significantly attenuated liver TG accumulation by induction of FA ß-oxidation and attenuation of FA synthesis. In primary mouse hepatocytes, GW1516 treatment stimulated AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation in WT hepatocytes, but not AMPKß1(-/-) hepatocytes. However, FA oxidation was only partially reduced in AMPKß1(-/-) hepatocytes, suggesting an AMPK-independent contribution to the GW1516 effect. Similarly, PPARδ-mediated attenuation of FA synthesis was partially due to AMPK activation, as GW1516 reduced lipogenesis in WT hepatocytes but not AMPKß1(-/-) hepatocytes. HFHC-fed animals were hyperinsulinemic and exhibited selective hepatic insulin resistance, which contributed to elevated fasting FA synthesis and hyperglycemia. GW1516 intervention normalized fasting hyperinsulinemia and selective hepatic insulin resistance and attenuated fasting FA synthesis and hyperglycemia. The HFHC diet polarized the liver toward a proinflammatory M1 state, which was reversed by GW1516 intervention. Thus, PPARδ agonist treatment inhibits the progression of preestablished hepatic steatosis.

The oxysterol 24(s),25-epoxycholesterol attenuates human smooth muscle-derived foam cell formation via reduced low-density lipoprotein uptake and enhanced cholesterol efflux.

BACKGROUND: Foam cell formation by intimal smooth muscle cells (SMCs) inhibits the elaboration of extracellular matrix, which is detrimental to plaque stabilization. In the present study, we examined the lipoproteins and receptors involved in human SMC foam cell formation and investigated the ability of 24(S),25-epoxycholesterol [24(S),25-EC], an oxysterol agonist of the liver X receptor, to attenuate SMC foam cell formation. METHODS AND RESULTS: Incubation of human internal thoracic SMCs with atherogenic lipoproteins demonstrated that low-density lipoprotein (LDL), but not oxidized or acetylated LDL, was the primary lipoprotein taken up, resulting in marked cholesteryl ester deposition (6-fold vs 1.8-fold; P<0.05; n=4). Exposure of SMCs to exogenous or endogenously synthesized 24(S),25-EC attenuated LDL uptake (-90% and -47% respectively; P<0.05; n=3) through decreased sterol regulatory element-binding protein-2 expression (-30% and -17%, respectively; P<0.001; n=3), decreased LDL receptor expression (-75% and -40%, respectively; P<0.05; n=3) and increased liver X receptor-mediated myosin regulatory light chain interacting protein expression (7- and 3-fold, respectively; P<0.05; n=4). Furthermore, exogenous 24(S),25-EC increased adenosine triphosphate-binding cassettes A1- and G1-mediated cholesterol efflux to apolipoprotein AI (1.9-fold; P<0.001; n=5) and high-density lipoprotein(3) (1.3-fold; P<0.05; n=5). 24(S),25-EC, unlike a nonsteroidal liver X receptor agonist, T0901317, did not stimulate sterol regulatory element-binding protein-1c-mediated fatty acid synthesis or triglyceride accumulation. 24(S),25-EC preserved the assembly of fibronectin and type I collagen by SMCs. CONCLUSIONS: The oxysterol 24(S),25-EC prevented foam cell formation in human SMCs by attenuation of LDL receptor-mediated LDL uptake and stimulation of cholesterol efflux, restoring the elaboration of extracellular matrix. In contrast to T0901317, 24(S),25-EC prevented the development of a triglyceride-rich foam cell phenotype. (J Am Heart Assoc. 2012;1:e000810 doi: 10.1161/JAHA.112.000810.).

Activation of peroxisome proliferator-activated receptor δ inhibits human macrophage foam cell formation and the inflammatory response induced by very low-density lipoprotein.

OBJECTIVE: Hypertriglyceridemia is an important risk factor for cardiovascular disease. Elevated plasma very low-density lipoprotein (VLDL) puts insulin-resistant patients at risk for atherosclerosis. VLDL readily induces macrophage lipid accumulation and inflammatory responses, for which targeted therapeutic strategies remain elusive. We examined the ability of VLDL to induce macrophage foam cells and the inflammatory response and sought to define the cell signaling cascades involved. We further examined the potential of peroxisome proliferator-activated receptor (PPAR) δ activation to attenuate both VLDL-stimulated lipid accumulation and cytokine expression. METHODS AND RESULTS: THP-1 macrophages exposed to VLDL displayed significant triglyceride accumulation, which was attenuated by PPARδ activation. PPARδ agonists stimulated a transcriptional program resulting in inhibition of lipoprotein lipase activity, activation of fatty acid uptake, and enhanced ß-oxidation. VLDL-treated macrophages significantly increased the expression of activator protein 1 associated cytokines interleukin-1ß, macrophage inflammatory protein 1α, and intercellular adhesion molecule-1. VLDL treatment significantly increased the phosphorylation of both extracellular signal-related kinase 1 and 2 and p38. VLDL reduced AKT phosphorylation as well as its downstream effector forkhead box protein O1, concomitant with increased nuclear forkhead box protein O1. Cells treated with PPARδ agonists were completely resistant to VLDL-induced expression of inflammatory cytokines, mediated by normalization of mitogen-activated protein kinase (MAPK)(erk) and AKT/forkhead box protein O1 signaling. CONCLUSIONS: The combined PPARδ-mediated reductions of lipid accumulation and inflammatory cytokine expression suggest a novel macrophage-targeted therapeutic option in treating atherosclerosis.

Nobiletin attenuates VLDL overproduction, dyslipidemia, and atherosclerosis in mice with diet-induced insulin resistance.

OBJECTIVE: Increased plasma concentrations of apolipoprotein B100 often present in patients with insulin resistance and confer increased risk for the development of atherosclerosis. Naturally occurring polyphenolic compounds including flavonoids have antiatherogenic properties. The aim of the current study was to evaluate the effect of the polymethoxylated flavonoid nobiletin on lipoprotein secretion in cultured human hepatoma cells (HepG2) and in a mouse model of insulin resistance and atherosclerosis. RESEARCH DESIGN AND METHODS: Lipoprotein secretion was determined in HepG2 cells incubated with nobiletin or insulin. mRNA abundance was evaluated by quantitative real-time PCR, and Western blotting was used to demonstrate activation of cell signaling pathways. In LDL receptor-deficient mice (Ldlr(-/-)) fed a Western diet supplemented with nobiletin, metabolic parameters, gene expression, fatty acid oxidation, glucose homeostasis, and energy expenditure were documented. Atherosclerosis was quantitated by histological analysis. RESULTS: In HepG2 cells, activation of mitogen-activated protein kinase-extracellular signal-related kinase signaling by nobiletin or insulin increased LDLR and decreased MTP and DGAT1/2 mRNA, resulting in marked inhibition of apoB100 secretion. Nobiletin, unlike insulin, did not induce phosphorylation of the insulin receptor or insulin receptor substrate-1 and did not stimulate lipogenesis. In fat-fed Ldlr(-/-) mice, nobiletin attenuated dyslipidemia through a reduction in VLDL-triglyceride (TG) secretion. Nobiletin prevented hepatic TG accumulation, increased expression of Pgc1α and Cpt1α, and enhanced fatty acid ß-oxidation. Nobiletin did not activate any peroxisome proliferator-activated receptor (PPAR), indicating that the metabolic effects were PPAR independent. Nobiletin increased hepatic and peripheral insulin sensitivity and glucose tolerance and dramatically attenuated atherosclerosis in the aortic sinus. CONCLUSIONS: Nobiletin provides insight into treatments for dyslipidemia and atherosclerosis associated with insulin-resistant states.

Relationship of nutrition and physical activity behaviors and fitness measures to academic performance for sixth graders in a midwest city school district.

BACKGROUND: To support curriculum and policy, a midwest city school district assessed the association of selected categories of nutrition and physical activity (NUTR/PA) behaviors, fitness measures, and body mass index (BMI) with academic performance (AP) for 800 sixth graders. METHODS: Students completed an adapted Youth Risk Behavior Surveillance Survey (NUTR/PA behaviors), fitness assessments (mile run, curl-ups, push-ups, height, and weight) with results matched to standardized scores (Measures of Academic Progress [MAP]), meal price status, and gender. Differences in mean MAP scores (math and reading) were compared by selected categories of each variable utilizing 1-way analysis of variance. Associations were determined by stepwise multiple regression utilizing mean MAP scores (for math and for reading) as the dependent variable and NUTR/PA behaviors, fitness, and BMI categories as independent variables. Significance was set at α = 0.05. RESULTS: Higher MAP math scores were associated with NUTR (more milk and breakfast; less 100% fruit juice and sweetened beverages [SB]) and PA (increased vigorous PA and sports teams; reduced television), and fitness (higher mile run performance). Higher MAP reading scores were associated with NUTR (fewer SB) and PA (increased vigorous PA, reduced television). Regression analysis indicated about 11.1% of the variation in the mean MAP math scores and 6.7% of the mean MAP reading scores could be accounted for by selected NUTR/PA behaviors, fitness, meal price status, and gender. CONCLUSION: Many positive NUTR/PA behaviors and fitness measures were associated with higher MAP scores supporting the school district focus on healthy lifestyles. Additional factors, including meal price status and gender, contribute to AP.

Worksite education programs by county extension agents to promote colorectal cancer prevention and screening.

The purpose of this study was to determine whether a partnership between university faculty and county extension agents to deliver an Internet-accessible worksite education program effectively promotes awareness of the need for colorectal cancer prevention and screening. Extension agents were recruited to provide colorectal cancer education sessions at worksites in their counties, and a total of 144 participants completed surveys. There was a significant correlation between having insurance and having a discussion with their doctors about colorectal cancer screening at the next office visit; these participants were more likely to share what they learned with friends or family. Neither educational level nor smoking history was significantly correlated with the plan to discuss colorectal cancer screening with their doctors. High-risk smokers without insurance would appear to benefit from additional support for adhering to the American Cancer Society's screening guidelines.

Naringenin prevents dyslipidemia, apolipoprotein B overproduction, and hyperinsulinemia in LDL receptor-null mice with diet-induced insulin resistance.

OBJECTIVE: The global epidemic of metabolic syndrome and its complications demands rapid evaluation of new and accessible interventions. Insulin resistance is the central biochemical disturbance in the metabolic syndrome. The citrus-derived flavonoid, naringenin, has lipid-lowering properties and inhibits VLDL secretion from cultured hepatocytes in a manner resembling insulin. We evaluated whether naringenin regulates lipoprotein production and insulin sensitivity in the context of insulin resistance in vivo. RESEARCH DESIGN AND METHODS: LDL receptor-null (Ldlr(-/-)) mice fed a high-fat (Western) diet (42% calories from fat and 0.05% cholesterol) become dyslipidemic, insulin and glucose intolerant, and obese. Four groups of mice (standard diet, Western, and Western plus 1% or 3% wt/wt naringenin) were fed ad libitum for 4 weeks. VLDL production and parameters of insulin and glucose tolerance were determined. RESULTS: We report that naringenin treatment of Ldlr(-/-) mice fed a Western diet corrected VLDL overproduction, ameliorated hepatic steatosis, and attenuated dyslipidemia without affecting caloric intake or fat absorption. Naringenin 1) increased hepatic fatty acid oxidation through a peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha/PPARalpha-mediated transcription program; 2) prevented sterol regulatory element-binding protein 1c-mediated lipogenesis in both liver and muscle by reducing fasting hyperinsulinemia; 3) decreased hepatic cholesterol and cholesterol ester synthesis; 4) reduced both VLDL-derived and endogenously synthesized fatty acids, preventing muscle triglyceride accumulation; and 5) improved overall insulin sensitivity and glucose tolerance. CONCLUSIONS: Thus, naringenin, through its correction of many of the metabolic disturbances linked to insulin resistance, represents a promising therapeutic approach for metabolic syndrome.

Inhibition of apoB secretion from HepG2 cells by insulin is amplified by naringenin, independent of the insulin receptor.

Hepatic overproduction of apolipoprotein B (apoB)-containing lipoproteins is characteristic of the dyslipidemia associated with insulin resistance. Recently, we demonstrated that the flavonoid naringenin, like insulin, decreased apoB secretion from HepG2 cells by activation of both the phosphoinositide-3-kinase (PI3-K) pathway and the mitogen-activated protein kinase/extracellular-regulated kinase (MAPK(erk)) pathway. In the present study, we determined whether naringenin-induced signaling required the insulin receptor (IR) and sensitized the cell to the effects of insulin, and whether the kinetics of apoB assembly and secretion in cells exposed to naringenin were similar to those of insulin. Immunoblot analysis revealed that insulin stimulated maximal phosphorylation of IR and IR substrate-1 after 10 min, whereas naringenin did not affect either at any time point up to 60 min. The combination of naringenin and submaximal concentrations of insulin potentiated extracellular-regulated kinase 1/2 activation and enhanced upregulation of the LDL receptor, downregulation of microsomal triglyceride transfer protein expression, and inhibition of apoB-100 secretion. Multicompartmental modeling of apoB pulse-chase studies revealed that attenuation of secreted radiolabeled apoB in naringenin- or insulin-treated cells was similar under lipoprotein-deficient or oleate-stimulated conditions. Naringenin and insulin both stimulated intracellular apoB degradation via a kinetically defined rapid pathway. Therefore, naringenin, like insulin, inhibits apoB secretion through activation of both PI3-K and MAPK(erk) signaling, resulting in similar kinetics of apoB secretion. However, the mechanism for naringenin-induced signaling is independent of the IR. Naringenin represents a possible strategy for reduction of hepatic apoB secretion, particularly in the setting of insulin resistance.

Orchestrating key personnel to increase colorectal cancer awareness at the worksite.

Colorectal cancer is the second leading cause of deaths due to cancer for both men and women in the United States. Screening promotes the early detection of colorectal cancer and reduces the morbidity and mortality rates. Worksite wellness programs are an effective way to promote colorectal cancer prevention and screening awareness and compliance with the American Cancer Society's screening guidelines, and they provide several advantages from the perspectives of the employees, employers, and nurses. This article explains how to orchestrate key personnel to increase colorectal cancer awareness in the worksite. A review of evidence-based literature is utilized to maximize the effectiveness of these worksite education sessions. The goals for the worksite employees are to resolve their individual barriers through education, to commit to colorectal cancer screening and prevention, and to feel a sense of obligation to follow through on their plans.