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People with limited English proficiency in the United States have suffered disproportionate negative health outcomes during the COVID-19 pandemic. Effective communications are critical tools in addressing inequities insofar as they can motivate adoption of protective behaviors and reduce incidence of disease; however, little is known about experiences of communities with limited English proficiency receiving relevant information during COVID-19 or other outbreaks. To address this gap and provide inputs for communication strategies, we completed a study based on 2 novel and nationally representative surveys conducted between June and August 2020 among Spanish and Chinese speakers with limited English proficiency (n = 764 and n = 355, respectively). Results first showed that Spanish and Chinese speakers did not consistently receive information about protective behaviors from key public health and government institutions early in the pandemic. Second, for such information, Spanish and Chinese speakers used a diverse set of information resources that included family and friends, social media, and traditional media from both inside and outside the United States. Third, Spanish and Chinese speakers faced challenges getting COVID-19 information, including receiving media messages that felt discriminatory toward Latinx or Chinese people. Together, these findings suggest gaps in effectively reaching Spanish and Chinese speakers. Data highlight the important role of bilingual materials to support sharing of information between Spanish or Chinese speakers and English speakers within their social networks, and the need for digital news content for traditional and social media. Finally, efforts are needed to address discriminatory messaging in media and to actively counter it in public health communications.

INTRODUCTION: Differences in healthcare utilization and medical expenditures associated with perinatal depression are estimated. METHODS: Using the MarketScan Multi-State Medicaid Database, the analytic cohort included individuals aged 15–44 years who had an inpatient live birth delivery hospitalization between January 1, 2017 and December 31, 2018. Multivariable negative binomial regression models were used to estimate the differences in utilization associated with perinatal depression, and multivariable generalized linear models were used to estimate the differences in expenditures associated with perinatal depression. Analyses were conducted in 2021. RESULTS: The cohort included 330,593 individuals. Nearly 17% had perinatal depression. Compared with individuals without perinatal depression individuals with perinatal depression had a larger number of inpatient admissions (0.19, 95% CI=0.18, 0.20), total inpatient days (0.95, 95% CI=0.92, 0.97), outpatient visits (14.02, 95% CI=13.81, 14.22), emergency department visits (1.70, 95% CI=1.66, 1.74), and weeks of drug therapy covered by a prescription (28.70, 95% CI=28.12, 29.28) and larger total expenditures ($5,078, 95% CI=$4,816, $5,340). Non-Hispanic Black individuals had larger differences in utilization and expenditures for inpatient services and outpatient visits but smaller differences in utilization for pharmaceutical services associated with perinatal depression than non-Hispanic White individuals. Hispanic individuals had larger differences in utilization for outpatient visits but smaller differences in utilization for pharmaceutical services associated with perinatal depression than non-Hispanic White individuals. CONCLUSIONS: Individuals with perinatal depression had more healthcare utilization and medical expenditures than individuals without perinatal depression, and differences varied by race/ethnicity. The findings highlight the need to ensure comprehensive and equitable mental health care to address perinatal depression.

Objectives: Some older drivers choose to avoid certain situations where they do not feel confident driving. Little is known about the process by which older drivers may use avoidance in transitioning to non-driving. Methods: We analyzed 2015 ConsumerStyles data for 1198 drivers aged 60+. Driving patterns were examined by sociodemographic and driving characteristics. Avoidance classes were characterized by latent class analysis. Results: Among drivers 60+, 79% reported driving 3+ days/week and 84% reported good to excellent health. We identified four driving avoidance classes (low, mild, moderate, and high). High- (versus low-) avoidance drivers were more likely female, 75+, not White/non-Hispanic, and to have income

Unintentional and violence-related injury fatalities, including suicide, homicide, overdoses, motor vehicle crashes, and falls, were among the 10 leading causes of death for all age groups in the United States in 2019.* There were 246,041 injury deaths in 2019 (unintentional injury was the most frequent cause of death after heart disease and cancer) with an economic cost of $2.2 trillion (1). Extending a national analysis (1), CDC examined state-level economic costs of fatal injuries based on medical care costs and the value of statistical life assigned to 2019 injury records from the CDC's Web-based Injury Statistics Query and Reporting System (WISQARS).† West Virginia had the highest per capita cost ($11,274) from fatal injury, more than twice that of New York, the state with the lowest cost ($4,538). The five areas with the highest per capita total fatal injury costs were West Virginia, New Mexico, Alaska, District of Columbia (DC), and Louisiana; costs were lowest in New York, California, Minnesota, Nebraska, and Texas. All U.S. states face substantial avoidable costs from injury deaths. Individual persons, families, organizations, communities, and policymakers can use targeted proven strategies to prevent injuries and violence. Resources for best practices for preventing injuries and violence are available online from the CDC's National Center for Injury Prevention and Control.§.

Dietary polyphenols can be utilized to treat obesity and chronic disorders linked to it. Dietary polyphenols can inhibit pre-adipocyte proliferation, adipocyte differentiation, and triglyceride accumulation; meanwhile, polyphenols can also stimulate lipolysis and fatty acid β-oxidation, but the molecular mechanisms of anti-obesity are still unclear. The mechanistic target of rapamycin (mTOR) is a protein kinase that regulates cell growth, survival, metabolism, and immunity. mTOR signaling is also thought to play a key role in the development of metabolic diseases such as obesity. Recent studies showed that dietary polyphenols could target mTOR to reduce obesity. In this review, we systematically summarized the research progress of polyphenols in preventing obesity through the mTOR signaling pathway. Mechanistically, polyphenols can target multiple signaling pathways and gut microbiota to regulate the mTOR signaling pathway to exert anti-obesity effects. The main mechanisms include: modulating lipid metabolism, adipogenesis, inflammation, etc. Dietary polyphenols exerting an anti-obesity effect by targeting mTOR signaling will broaden our understanding of the anti-obesity mechanisms of polyphenols and provide valuable insights for researchers in this novel field.

Approximately 47,000 persons in the United States died from an opioid-involved overdose in 2018 (1), and 2.0 million persons met the diagnostic criteria for an opioid use disorder in 2017 (2). The economic cost of the U.S. opioid epidemic in 2017 was estimated at $1,021 billion, including cost of opioid use disorder estimated at $471 billion and cost of fatal opioid overdose estimated at $550 billion (3). CDC used national-level cost estimates to estimate the state-level economic cost of opioid use disorder and fatal opioid overdose during 2017. Cases and costs of state-level opioid use disorder and fatal opioid overdose and per capita costs were calculated for each of the 38 states and the District of Columbia (DC) that met drug specificity requirements for mortality data (4). Combined costs of opioid use disorder and fatal opioid overdose (combined costs) varied substantially, ranging from $985 million in Wyoming to $72,583 million in Ohio. Per capita combined costs also varied considerably, ranging from $1,204 in Hawaii to $7,247 in West Virginia. States with high per capita combined costs were mainly in two regions: the Ohio Valley and New England. Federal and state public health agencies can use these data to help guide decisions regarding research, prevention and response activities, and resource allocation.

“Dating Matters®” is a CDC-developed comprehensive, multi-component teen dating violence (TDV) prevention model, made available to the public in 2019. A longitudinal, multi-site demonstration project found that the model significantly reduced TDV during middle school relative to an evidence-based, single-program intervention (Safe Dates; Niolon et al., 2019 ), when implemented across 46 middle schools in four high-risk urban areas with predominantly Black (55%) and Hispanic (28%) youth participants. Research on the costs of implementing TDV prevention strategies is limited, despite recognition within the field of prevention science that such data are critical to widespread dissemination. The current study adds to the available literature on the cost of dating violence prevention by estimating the budgetary impact from the payer perspective of implementing the comprehensive Dating Matters model, compared to Safe Dates, at four sites over four school years to inform prevention planning in communities. Total costs of implementing Dating Matters were relatively stable within sites over time but varied greatly between sites ( M = $175,452 per year; range = $130,149 to $227,604). The mean per-student cost of Dating Matters was $145.40 but also ranged widely ($20.66 to $324.65) across sites and years. Variation was largely driven by staffing costs and number of students served. As expected, total and per-student costs were substantially lower at all sites for the Safe Dates program ( M = $12,148; range = $2,848 to $17,840; $44.81 per student) compared to Dating Matters. This study provides an estimate from the payer perspective to demonstrate the budgetary impact of Dating Matters. These estimates can help inform implementation decisions and planning by potential funders, communities, and organizations as they seek to support and implement effective TDV prevention strategies. It also adds substantially to understanding of the additional costs associated with a move from single-program interventions to community-wide initiatives.

Black/African American (Black) versus White persons are unequally burdened by human immunodeficiency virus (HIV) in the United States. Structural factors can influence social determinants of health, key components in reducing HIV-related health inequality by race. This analysis examined HIV care outcomes among Black and White persons with diagnosed HIV (PWDH) in relation to three structural factors: racial redlining, Medicaid expansion, and Ryan White HIV/AIDS Program (RWHAP) use. Using National HIV Surveillance System, U.S. Census, and Home Mortgage Disclosure Act data, we examined linkage to HIV care and viral suppression (i.e., viral load 200 copies/mL) in relation to the structural factors among 12,996 Black and White PWDH with HIV diagnosed in 2017/alive at year-end 2018, aged ≥ 18 years, and residing in 38 U.S. jurisdictions with complete laboratory data, geocoding, and census tract-level redlining indexes. Compared to White PWDH, a lower proportion of Black PWDH were linked to HIV care within 1 month after diagnosis and were virally suppressed in 2018. Redlining was not associated with the HIV care outcomes. A higher prevalence of PWDH residing (v. not residing) in states with Medicaid expansion were linked to HIV care ≤ 1 month after diagnosis. A higher prevalence of those residing (v. not residing) in states with 50% of PWDH in RWHAP had viral suppression. Direct exposure to redlining was not associated with poor HIV care outcomes. Structural factors that reduce the financial burden of HIV care and improve care access like Medicaid expansion and RWHAP might improve HIV care outcomes of PWDH.

Food-derived bioactive peptides are considered as the important sources of natural bioactive ingredients. Approximately 3094 peptides were identified by nESI-LC–MS/MS in the hydrolyzed yak milk residue. Peptide KALNEINQF (T10) is the strongest antioxidant peptide. The damage model of H2O2-induced human umbilical vein endothelial cells (HUVECs) was used to evaluate the antioxidant effect. After treatment with 25, 50, or 100 μg/mL T10 peptide, T10 obviously decreased H2O2-induced damage and increased the cell survival. Comparing with the H2O2-induced damage group, superoxide dismutase (SOD) activities were significantly increased 1.03, 1.1, and 1.33 times, and glutathione reductase (GR) activities were significantly increased 1.11, 1.30, and 1.43 times, respectively. Malondialdehyde (MDA) also reduced 1.41, 1.54, and 1.72 times, respectively. T10 inhibited H2O2-induced apoptosis in HUVECs, and protein expressions of the apoptosis-related genes bcl-2 and bax were increased and decreased by 1.95 and 1.44 times, respectively, suggesting T10 decreases apoptosis of the mitochondria-dependent pathway. Comparing with the H2O2-induced damage group, the RNA expressions of Nrf2, HO-1, and NQO1 were significantly increased by 2.00, 2.11, and 1.94 times; the protein expressions of p-Nrf2, HO-1, and NQO1 were significantly increased by 2.67, 1.73, and 1.04 times; and Keap1 was downregulated by 3.9 and 1.32 times, respectively. T10 also regulated the Nrf2 pathway and expressions of related genes (Keap1, HO-1, and NQO1), and blocking the Nrf2 pathway in the model decreased the protective effect of T10. Taken together, T10 peptide isolated from yak milk residue has a protective effect against H2O2-induced damage in HUVECs and the molecular mechanisms are involved in the regulation of Nrf2 signaling pathway and cell apoptosis.

In the present study, the anti-inflammatory function of Phellinus linteus polysaccharide (PLP) was investigated in animal and cell inflammation models, and the anti-inflammatory mechanism of PLP was also explored. Sixty 8-week ICR mice were randomly divided into 3 groups, and DSS group and DSS + PLP group mice received 2.0% DSS and PLP was orally administered at 500 mg/kg/day. Our data showed that PLP administration obviously improved the health status of mice and inhibited DSS-induced pathological alterations and significantly reduced inflammatory cytokine expressions in the colonic tissues. In lipopolysaccharide-induced inflammation cell model, PLP supplement also significantly reduced inflammatory cytokine expressions and inhibited MAPK pathway as well as the translocations of NF-κB and AP-1. Meanwhile, PLP supplement regulated PPARα and PPARγ phosphorylation and blocked MAPK activation. Taken together, PLP exhibits anti-inflammatory function and its molecular mechanism may be involved in MAPK and PPAR signal pathways, which reduce the expressions of inflammatory cytokines.

Key Points Question How much does substance use disorder cost each year in US hospitals? Findings In this economic evaluation of 124 573 175 hospital emergency department encounters and 33 648 910 hospital inpatient encounters, the annual medical cost associated with substance use disorder in US emergency departments and inpatient settings exceeded $13 billion in 2017. Meaning These findings suggest that costs associated with substance use disorder are high; costs of treatment and prevention could potentially be offset by reducing the direct medical cost of substance use disorder., This economic evaluation investigates the annual estimated medical cost of substance use disorder in US emergency departments and inpatient settings., Importance A persistently high US drug overdose death toll and increasing health care use associated with substance use disorder (SUD) create urgency for comprehensive estimates of attributable direct costs, which can assist in identifying cost-effective ways to prevent SUD and help people to receive effective treatment. Objective To estimate the annual attributable medical cost of SUD in US hospitals from the health care payer perspective. Design, Setting, and Participants This economic evaluation of observational data used multivariable regression analysis and mathematical modeling of hospital encounter costs, controlling for patient demographic, clinical, and insurance characteristics, and compared encounters with and without secondary SUD diagnosis to statistically identify the total attributable cost of SUD. Nationally representative hospital emergency department (ED) and inpatient encounters from the 2017 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample and National Inpatient Sample were studied. Statistical analysis was performed from March to June 2020. Exposures International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) principal or secondary SUD diagnosis on the hospital discharge record according to the Clinical Classifications Software categories (disorders related to alcohol, cannabis, hallucinogens, inhalants, opioids, sedatives, stimulants, and other substances). Main Outcomes and Measures Annual attributable SUD medical cost in hospitals overall and by substance type (eg, alcohol). The number of encounters (ED and inpatient) with SUD diagnosis (principal or secondary) and the mean cost attributable to SUD per encounter by substance type are also reported. Results This study examined a total of 124 573 175 hospital ED encounters and 33 648 910 hospital inpatient encounters from the 2017 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample and National Inpatient Sample. Total annual estimated attributable SUD medical cost in hospitals was $13.2 billion. By substance type, the cost ranged from $4 million for inhalant-related disorders to $7.6 billion for alcohol-related disorders. Conclusions and Relevance This study’s results suggest that the cost of effective prevention and treatment may be substantially offset by a reduction in the high direct medical cost of SUD hospital care. The findings of this study may inform the treatment of patients with SUD during hospitalization, which presents a critical opportunity to engage patients who are at high risk for overdose. Aligning incentives such that prevention cost savings accrue to payers and practitioners that are otherwise responsible for SUD-related medical costs in hospitals and other health care settings may encourage prevention investment.

Colon cancer commonly develops from long-term chronic inflammation in the intestine and seriously threatens human health. Natural polyphenols have been valued as a crucial regulator of nutrient metabolism and metabolic diseases, owing to their anti-inflammatory and antioxidant functions and the ability to maintain a balance between gut microbes and their hosts. Notably, experimental and clinical evidence has shown that natural polyphenols could act as a targeted modulator to play a key role in the prevention or treatment of colon cancer. Thus, in this review, we summarized recent advances in the possible regulatory mechanism and the potential application of natural polyphenols in colon cancer, which might be regarded as a novel platform for the colon cancer management.

Lung cancer is the world’s highest morbidity and mortality of malignant tumors, with lung adenocarcinoma (LUAD) as a major subtype. The competitive endogenous RNA (ceRNA) regulative network provides opportunities to understand the relationships among different molecules, as well as the regulative mechanisms among them in order to investigate the whole transcriptome landscape in cancer pathology. We designed this work to explore the role of a key oncogene, MYC, in the pathogenesis of LUAD, and this study aims to identify important long noncoding RNA (lncRNA)-microRNA (miRNA)- transcription factor (TF) interactions in non-small cell lung cancer (NSCLC) using a bioinformatics analysis. The Cancer Genome Atlas (TCGA) database, containing mRNA expression data of NSCLC, was used to determine the deferentially expressed genes (DEGs), and the ceRNA network was composed of WT1-AS, miR-206, and nicotinamide phosphoribosyltransferase (NAMPT) bashing on the MYC expression level. The Kaplan–Meier univariate survival analysis showed that these components may be closely related prognostic biomarkers and will become new ideas for NSCLC treatment. Moreover, the high expression of WT1-AS and NAMPT and low expression of miR-206 were associated with a shortened survival in NSCLC patients, which provided a survival advantage. In summary, the current study constructing a ceRNA-based WT1-AS/miR-206/NAMPT axis might be a novel important prognostic factor associated with the diagnosis and prognosis of LUAD.

Dietary fiber has a long history in the intervention study of hyperlipidemia. In this review, current understandings of structures, sources, and natures of various kinds of dietary fibers (DFs) were analyzed first. Available evidences for the use of different varieties of DFs in the lipid-lowering action both in vitro and in vivo were subsequently classified, including both soluble ones, such as glucans, pectins, and gums, and insoluble ones, including arabinooxylans and chitosans, in order to draw a primary conclusion of their dose and molecular weight relationship with lipid-lowering effect. Their potential mechanisms, especially the related molecular mechanism of protective action in the treatment and prevention of hyperlipidemia, were summarized at last. Five major mechanisms are believed to be responsible for the antihyperlipidemic benefits of DFs, including low levels of energy, bulking effect, viscosity, binding capacity, and fermentation thus ameliorating the symptoms of hyperlipidemia. From the molecular level, DFs could possibly affect the activities of HMG-CoA reductase, LDL receptors, CYP7A1, and MAPK signaling pathway as well as other lipid metabolism-related target genes. In summary, dietary fibers could be used as alternative supplements to exert certain lipid-lowering effects on humans. However, more clinical evidence is needed to strengthen this proposal and its fully underlying mechanism still requires more investigation.

Studies have shown that the peroxidation caused by oxygen free radicals is an important reason of vascular endothelial dysfunction and multiple diseases. In this study, active peptides (F2ds) were isolated from the fermentation product of rice dregs and its antioxidant effects were approved. Human umbilical vein endothelial cells (HUVECs) stimulated by H2O2 were used to evaluate the antioxidation effect and its molecular mechanism in the oxidative stress model. F2d protected H2O2-induced damage in HUVECs in a dosage-dependent manner. F2d can reduce the expression of Keap1, promote the expression of Nrf2, and activate the downstream target HO-1, NQO1, etc. It means F2d can modulate the Nrf2 signaling pathway. Using Nrf2 inhibitor ML385 to block the Nrf2 activation, the protective function of F2d is partially lost in the damage model. Our results indicated that F2d isolated from rice exerts antioxidant effects via the Nrf2 signaling pathway in H2O2-induced damage, and the work will benefit to develop functional foods.

Introduction: Falls among older adults are a significant health concern affecting more than a quarter of older adults (age 65+). Certain fall risk factors, such as medication use, increase fall risk among older adults (age 65+). Aim: The aim of this study is to examine the association between antidepressant-medication subclass use and self-reported falls in community-dwelling older adults. Methods: This analysis used the 2009–2013 Medicare Current Beneficiary Survey, a nationally representative panel survey. A total of 8,742 community-dwelling older adults, representing 40,639,884 older Medicare beneficiaries, were included. We compared self-reported falls and psychoactive medication use, including antidepressant subclasses. These data are controlled for demographic, functional, and health characteristics associated with increased fall risk. Descriptive analyses and multivariate logistic regression analyses were conducted using SAS 9.4 and Stata 15 software. Results: The most commonly used antidepressant subclass were selective serotonin reuptake inhibitors (SSRI) antidepressants (13.1%). After controlling for characteristics associated with increased fall risk (including depression and concurrent psychoactive medication use), the risk of falling among older adults increased by approximately 30% among those who used a SSRI or a serotonin-norepinephrine reuptake inhibitors (SNRI) compared to non-users. The adjusted risk ratio (aRR) for SSRI was 1.29 (95% CI = 1.13, 1.47) and for SNRI was 1.32 (95% CI = 1.07, 1.62). Conclusion: SSRI and SNRI are associated with increased risk of falling after adjusting for important confounders. Medication use is a modifiable fall risk factor in older adults and can be targeted to reduce risk of falls. Practical Applications: Use of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors increased the risk of falling in older adults by approximately 30%, even after controlling for demographic, functional, and health characteristics, including depression. Health care providers can work towards reducing fall risk among their older patients by minimizing the use of certain medications when potential risks outweigh the benefits.

Nano Ag has excellent antibacterial properties and is widely used in various antibacterial materials, such as antibacterial medicine and medical devices, food packaging materials and antibacterial textiles. Despite the many benefits of nano-Ag, more and more research indicates that it may have potential biotoxic effects. Studies have shown that people who ingest nanoparticles by mouth have the highest uptake in the intestinal tract, and that the colon area is the most vulnerable to damage and causes the disease. In this study, we examined the toxic effects of different concentrations of Ag-NPs on normal human colon cells (NCM460) and human colon cancer cells (HCT116). As the concentration of nanoparticles increased, the activity of the two colon cells decreased and intracellular reactive oxygen species (ROS) increased. RT-qPCR and Western-blot analyses showed that Ag NPs can promote the increase in P38 protein phosphorylation levels in two colon cells and promote the expression of P53 and Bax. The analysis also showed that Ag NPs can promote the down-regulation of Bcl-2, leading to an increased Bax / Bcl-2 ratio and activation of P21, further accelerating cell death .This study showed that a low concentration of nano Ag has no obvious toxic effect on colon cells, while nano Ag with concentrations higher than 15 &mu, g/mL will cause oxidative damage to colon cells.

Cancer is a serious public health problem in the world and a major disease affecting human health. Dietary polyphenols have shown good potential in the treatment of various cancers. It is worth noting that cancer cells usually exhibit metabolic abnormalities of high glucose intake and inefficient utilization. AMPK is the key molecule in the regulation of energy metabolism and is closely related with obesity and diabetes. Recent studies indicate that AMPK also plays an important role in cancer prevention and regulating cancer-related genes and pathways, and dietary polyphenols can significantly regulate AMPK activity. In this review, we systemically summarized the progress of dietary polyphenols preventing carcinogenesis via AMPK pathway. From the view point of interfering energy metabolism, the anti-cancer effects of dietary polyphenols were explained. AMPK pathway modulated by different dietary polyphenols affects pathways and target genes were summarized. Dietary polyphenols exert anti-cancer effect through the target molecules regulated by AMPK, which broadens our understanding of polyphenols anti-cancer mechanisms and provides value reference for the investigators of the novel field. This article is protected by copyright. All rights reserved.

Objectives: Policies that increase household income, such as the earned income tax credit (EITC), have shown reductions on risk factors for child maltreatment (ie, poverty, maternal stress, depression), but evidence is lacking on whether the EITC actually reduces child maltreatment. We examined whether states’ EITCs are associated with state rates of hospital admissions for abusive head trauma among children aged Methods: We conducted difference-in-difference analyses (ie, pre- and postdifferences in intervention vs control groups) of annual rates of states’ hospital admissions attributed to abusive head trauma among children aged Results: A refundable EITC was associated with a decrease of 3.1 abusive head trauma admissions per 100 000 population in children aged Conclusions: Our findings with others suggest that policies such as the EITC that increase household income may prevent serious abusive head trauma.

Problem Motor-vehicle crashes were the second leading cause of injury death for adults aged 65–84 years in 2014. Some older drivers choose to self-regulate their driving to maintain mobility while reducing driving risk, yet the process remains poorly understood. Methods Data from 729 older adults (aged ≥ 60 years) who joined an older adult ride service program between April 1, 2010 and November 8, 2013 were analyzed to define and describe classes of driving self-regulation. Latent class analysis was employed to characterize older adult driving self-regulation classes using driving frequency and avoidance of seven driving situations. Logistic regression was used to explore associations between characteristics affecting mobility and self-regulation class. Results Three classes were identified (low, medium, and high self-regulation). High self-regulating participants reported the highest proportion of always avoiding seven risky driving situations and the lowest driving frequency followed by medium and low self-regulators. Those who were female, aged 80 years or older, visually impaired, assistive device users, and those with special health needs were more likely to be high self-regulating compared with low self-regulating. Conclusions and practical applications Avoidance of certain driving situations and weekly driving frequency are valid indicators for describing driving self-regulation classes in older adults. Understanding the unique characteristics and mobility limitations of each class can guide optimal transportation strategies for older adults.

Octacosanol has multiple biological functions. In this study, the anti-inflammatory effect and molecular mechanism of octacosanol were evaluated by using dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice and lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells. The colitis mouse model was induced by 3.0% DSS in 8-week ICR mice and octacosanol orally administered with 100 mg/kg/day. The results showed that octacosanol significantly improved the health status of mice and reduced DSS-induced pathological damage in the colonic tissues. Octacosanol obviously inhibited the mRNA and protein expression levels of pro-inflammatory factors of colonic tissues. In vitro, octacosanol administration significantly reduced the expression of mRNA or protein of pro-inflammatory cytokines and the phosphorylation of c-Jun N-terminal kinase and p38, and it also partly prevented LPS-induced translocations of NF-κB and AP-1. Octacosanol has anti-inflammatory effect, and its molecular mechanism may be involved in downregulating the expression of inflammatory factors and blocking of MAPK/NF-κB/AP-1 signaling pathway.

Injury-associated deaths have substantial economic consequences in the United States. The total estimated lifetime medical and work-loss costs associated with fatal injuries in 2013 were $214 billion (1). In 2014, unintentional injury, suicide, and homicide (the fourth, tenth, and seventeenth leading causes of death, respectively) accounted for 194,635 deaths in the United States (2). In 2014, a total of 199,756 fatal injuries occurred in the United States, and the associated lifetime medical and work-loss costs were $227 billion (3). This report examines the state-level economic burdens of fatal injuries by extending a previous national-level study (1). Numbers and rates of fatal injuries, lifetime costs, and lifetime costs per capita were calculated for each of the 50 states and the District of Columbia (DC) and for four injury intent categories (all intents, unintentional, suicide, and homicide). During 2014, injury mortality rates and economic burdens varied widely among the states and DC. Among fatal injuries of all intents, the mortality rate and lifetime costs per capita ranged from 101.9 per 100,000 and $1,233, respectively (New Mexico) to 40.2 per 100,000 and $491 (New York). States can engage more effectively and efficiently in injury prevention if they are aware of the economic burden of injuries, identify areas for immediate improvement, and devote necessary resources to those areas.

During 2000-2016, the suicide rate among the U.S. working age population (persons aged 16-64 years) increased 34%, from 12.9 per 100,000 population to 17.3 (https://www.cdc.gov/injury/wisqars). To better understand suicide among different occupational groups and inform suicide prevention efforts, CDC analyzed suicide deaths by Standard Occupational Classification (SOC) major groups for decedents aged 16-64 years from the 17 states participating in both the 2012 and 2015 National Violent Death Reporting System (NVDRS) (https://www.cdc.gov/violenceprevention/nvdrs). The occupational group with the highest male suicide rate in 2012 and 2015 was Construction and Extraction (43.6 and 53.2 per 100,000 civilian noninstitutionalized working persons, respectively), whereas the group with the highest female suicide rate was Arts, Design, Entertainment, Sports, and Media (11.7 [2012] and 15.6 [2015]). The largest suicide rate increase among males from 2012 to 2015 (47%) occurred in the Arts, Design, Entertainment, Sports, and Media occupational group (26.9 to 39.7) and among females, in the Food Preparation and Serving Related group, from 6.1 to 9.4 (54%). CDC's technical package of strategies to prevent suicide is a resource for communities, including workplace settings (1).

Background Falls are a common and serious health issue among older Americans. A common fall risk factor is the use of psychoactive medications. There is limited recent information on the national prevalence of psychoactive medication use among older Americans. Objectives To estimate the prevalence of psychoactive medication use among community-dwelling older Americans and compare it with previous estimates from 1996. Methods The data source was the 2013 Cost and Use Data files combining Medicare claims data and survey data from the Medicare Current Beneficiary Survey, an in-person nationally representative survey of Medicare beneficiaries. Participants were included if they were 65 years of age and older, lived in the community, and had a complete year of prescription use data. Medication use was examined for 7 classes of psychoactive medications categorized by the 2015 American Geriatric Society Beers criteria as increasing fall risk. These include opioids, benzodiazepines, selective serotonin reuptake inhibitors, anticonvulsants, nonbenzodiazepine sedative hypnotics, antipsychotics, and tricyclic antidepressants. Data on participant demographic factors were also collected. Results Among the 6959 community-dwelling older adults studied, representing 33,268,104 community-dwelling Medicare beneficiaries, 53.3% used at least 1 psychoactive medication linked to falls in 2013. The most frequently used medication classes were opioids (34.9%), benzodiazepines (15.4%), selective serotonin reuptake inhibitors (14.3%), and anticonvulsants (13.3%). These estimates are considerably higher for all classes except tricyclic antidepressants than previous reports from 1996 that used the same data source. Among most psychoactive medication classes observed, women had higher usage than men. Conclusion More than half of all older Americans used at least 1 psychoactive medication in 2013. Health care providers, including pharmacists, play a vital role in managing older adults’ exposure to psychoactive medications. Medication management can optimize health and reduce older adult falls.

PURPOSE: The aim was to assess the associations of antibullying U.S. state statutes that enumerate sexual orientation with exposure to bullying and other stressors and with suicidal ideation and suicide attempts in sexual minority and non sexual minority youth. METHODS: We analyzed data from the 2015 national school-based Youth Risk Behavior Survey, representative of 9th through 12th grade students attending public and private schools in the United States. We reviewed each state’s antibullying statutes and classified them on enumeration. RESULTS: Antibullying state laws that enumerate sexual orientation were associated with lower risk for suicide attempts and serious attempts requiring medical attention and lower risk for forced sexual intercourse. They were also associated with feeling safe at school or on the way to or from school. Results did not differ by sexual orientation. CONCLUSIONS: Enumeration of sexual orientation was associated with reduced stressors and suicide attempts, but it is insufficient to remove significant disparities based on sexual orientation. Additional policies and practices are required to address persistent sexual orientation disparities in exposure to bullying and suicidal behavior.

Background The United States (U.S.) is experiencing an ongoing opioid crisis. Economic burden estimates that describe the impact of the crisis are needed when considering federal and state resources devoted to addressing overdoses. In this study, we estimate the societal costs for opioid use disorder and fatal overdose from all opioids in 2017. Methods We estimated costs of fatal overdose from all opioids and opioid use disorder based on the incidence of overdose deaths and the prevalence of past-year opioid use disorder for 2017. Incidence of fatal opioid overdose was obtained from the National Vital Statistics System; prevalence of past-year opioid use disorder was estimated from the National Survey of Drug Use and Health. Costs were estimated for health care, criminal justice and lost productivity. Costs for the reduced quality of life for opioid use disorder and life lost due to fatal opioid overdose were valued using U.S. Department of Health and Human Services guidelines for valuing reductions in morbidity and mortality. Results Costs for opioid use disorder and fatal opioid overdose in 2017 were estimated to be $1.02 trillion. The majority of the economic burden is due to reduced quality of life from opioid use disorder and the value of life lost due to fatal opioid overdose. Conclusions These estimates can assist decision makers in understanding the magnitude of opioid use disorder and fatal overdose. Knowing the magnitude and distribution of the economic burden can inform public policy, clinical practice, research, and prevention and response activities.

Paediatric abusive head trauma (AHT) is a leading cause of fatal child maltreatment among young children. Current prevention efforts have not been consistently effective. Policies such as paid parental leave could potentially prevent AHT, given its impacts on risk factors for child maltreatment. To explore associations between California's 2004 paid family leave (PFL) policy and hospital admissions for AHT, we used difference-in-difference analyses of 1995–2011 US state-level data before and after the policy in California and seven comparison states. Compared with seven states with no PFL policies, California's 2004 PFL showed a significant decrease in AHT admissions in both

Evidence supports addressing medication management.

Injury-associated deaths have substantial economic consequences. In 2013, unintentional injury was the fourth leading cause of death, suicide was the tenth, and homicide was the sixteenth; these three causes accounted for approximately 187,000 deaths in the United States. To assess the economic impact of fatal injuries, CDC analyzed death data from the National Vital Statistics System for 2013, along with cost of injury data using the Web-Based Injury Statistics Query and Reporting System. This report updates a previous study that analyzed death data from the year 2000, and employs recently revised methodology for determining the costs of injury outcomes, which uses the most current economic data and incorporates improvements for estimating medical costs associated with injury. Number of deaths, crude and age-specific death rates, and total lifetime work-loss costs and medical costs were calculated for fatal injuries by sex, age group, intent (intentional versus unintentional), and mechanism of injury. During 2013, the rate of fatal injury was 61.0 per 100,000 population, with combined medical and work-loss costs exceeding $214 billion. Costs from fatal injuries represent approximately one third of the total $671 billion medical and work-loss costs associated with all injuries in 2013. The magnitude of the economic burden associated with injury-associated deaths underscores the need for effective prevention. The number of injury-associated deaths in the United States during 2013 was obtained from National Vital Statistics System, and lifetime costs were obtained from the Web-based Injury Statistics Query and Reporting System database. Injury death rates were calculated using the U.S. Census Bureau's bridged race population estimates for 2013. Lifetime cost estimates, which include lifetime work-loss and medical costs, were computed from average costs of earnings and treating injuries in 2010, adjusted to 2013 prices. For each death record, lifetime work-loss cost was assigned according to the sex and age of the decedent. The sex- and age-specific probability of surviving to a given age was multiplied by the mean earnings of persons of that sex and age using U.S. Census Bureau earnings data, assuming that no one would live beyond age 102 years. Lifetime medical costs were assigned by injury diagnosis and mechanism, place of death, and decedent's age. Medical costs were derived from various sources that measure the cost of transport, examination by a coroner or medical examiner, and health care in multiple settings, including emergency departments, hospitals, and nursing homes. Work-loss costs were developed using earnings data from the U.S. Census Bureau's Current Population Survey and life expectancy data from CDC's National Center for Health Statistics. Number of deaths, rates and total lifetime medical and work-loss costs were examined for 2013, stratified by sex, age, and intent of injury. The distribution of costs by mechanism and intent of injury was also examined for the five highest-cost mechanisms, stratified by intent. The total estimated lifetime medical and work-loss costs associated with fatal injuries in 2013 was $214 billion. Males accounted for approximately 78% of these costs and for 67% of injury deaths. Approximately two thirds of injury deaths were unintentional, and these deaths also represented a majority of the cost ($129.7 billion [61%]). Approximately one fifth of injury-related deaths were suicides, and the cost of these deaths ($50.8 billion) accounted for about 24% of all injury death costs. Approximately 8% of injury-related deaths were homicides, and the associated costs ($26.4 billion) accounted for about 12% of the medical and work-loss costs for all injury deaths. Male victims represented 82% of the costs for suicide ($41.7 billion) and 86% of the costs for homicide ($22.5 billion). Overall, rates of fatal injury increased with age; however, this pattern differed by injury intent, with higher homicide rates among young persons and higher suicide rates among middle-aged adults. The costs associated with fatal injury were concentrated among adolescents and young adults aged 15–24 years and adults aged 25–64 years. The lowest costs and the lowest proportion of costs were associated with injury deaths in persons aged ≥65 years. These differences are also reflected in the mean cost of injury death by intent (Figure 1). The mean medical and work-loss cost of any injury death in 2013 was slightly more than $1.1 million, ranging from just below $1 million for unintentional injuries, to in excess of $1.6 million for homicides; the cost per suicide was $1.2 million. Among all injury deaths, drug poisonings accounted for 26% of the costs associated with fatal injuries, followed by transportation-related deaths (23%), firearm-related deaths (22%), deaths from suffocation (9%), and deaths resulting from falls (5%). Considerable differences were observed in the proportional distribution of costs accounted for by each mechanism among unintentional deaths, homicides, and suicides. Firearm-related fatal injuries accounted for 75% of the homicide-associated costs and 48% of the suicide-associated costs. Other leading mechanisms contributing to suicide costs were suffocation (including hanging) (29%) and drug poisoning (12%). Costs associated with unintentional injury deaths were primarily related to transportation-related deaths (37%) and drug poisonings (38%).... Language: en

Hyperlipidemia occurs very often in modern society along with a high calorie intake and is regarded as one of the greatest risk factors for the prevalence of cardiac vascular disease (CVD). In this study, we investigated the anti-hyperlipidemic effect of the rice bran polysaccharides (RBP) and its mechanism in a high fat diet animal model. 60 ICR mice were randomly divided into 3 groups, which included Control, HFD (high fat diet) and HFD + RBP, and each group included 20 mice. The control group was fed with a standard diet while the other two groups were fed with HFD. In addition, the HFD + RBP group was fed with 500 mg kg-1 of rice bran polysaccharides by intragastric administration while the other two groups were intragastrically administered with water. The results showed that RBP treatment for 10 weeks obviously decreased the body weight, liver weight and adipose tissues of mice; and it decreased the levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-c) in the plasma. H&E staining of the liver tissues showed that RBP treatment decreased the size of fat droplets compared with the HFD group. Microarray analysis revealed that RBP treatment results in 80 genes being up-regulated while 72 genes were down-regulated in the tissues of liver. IPA software analysis suggested that NF-κB may play a vital role in the lipid-lowering effect of RBP. Real-time quantitative PCR confirmed that the mRNA levels of PPAR-α, PPAR-γ, PPAR-δ, SREBP-1C, FASN, ACC, SIRT and CD36, which are related to lipid metabolism, were significantly regulated by RBP supplementation compared to HFD. The western blot analysis further confirmed these altered expressions after RBP treatment. Taken together, these results suggest that the oral administration of RBP exerts lipid-lowering in high fat diet mice via regulating the lipid metabolism-related gene expression.

In Western countries and China, the dietary habit of high calories usually results in hyperlipidemia, which is closely associated with cardiovascular diseases. In the study, we investigated the antihyperlipidemic effect of oryzanol and its molecular mechanism in the high fat diet (HFD) mouse model. In total, 60 ICR mice were randomly divided into control group, HFD group, and HFD+Ory group. The mice from the HFD+Ory group were additionally fed with 100 mg/kg of oryzanol by intragastric administration. Our data indicated that oryzanol treatment for 10 weeks significantly reduced bodyweight, liver weight, and adipose tissues weight of the mice; lowered the contents of total cholesterol (TC), triglycerides (TG), and low density lipoprotein-cholesterol (LDL-C); and elevated high density lipoprotein-cholesterol (HDL-C) in the plasma of HFD mice. Compared with the HFD group, HE staining showed that oryzanol treatment decreased the size of fat droplets of liver tissues and the size of adipocytes. Gene chip data found that oryzanol administration caused 32 genes to increase expressions while 60 genes had reduced expressions in the liver tissues of HFD mice. IPA software was used to analyze the protein interaction network and found that transcript factor NF-κB located in the central role of network, meaning NF-κB may have important function in the lipid-lowering effect of oryzanol. Western blotting and RT-qPCR confirmed that lipid metabolism-related gene expressions were obviously regulated by oryzanol administration. Oryzanol also inhibited expressions of inflammatory factor in the liver tissues of HDF mice. Taken together, our data indicate that oryzanol treatment can regulate lipid metabolism-related gene expressions and inhibit HDF-caused obesity in mice.

Objectives. We examined (1) whether sexual minority youths (SMYs) are at increased risk for physical dating violence victimization (PDVV) compared with non-SMYs, (2) whether bisexual youths have greater risk of PDVV than lesbian or gay youths, (3) whether youths who have had sexual contact with both sexes are more susceptible to PDVV than youths with same sex–only sexual contact, and (4) patterns of PDVV among SMYs across demographic groups. Methods. Using 2 measures of sexual orientation, sexual identity and sexual behavior, and compiling data from 9 urban areas that administered the Youth Risk Behavior Surveys from 2001 to 2011, we conducted logistic regression analyses to calculate odds of PDVV among SMYs across demographic sub-samples. Results. SMYs have significantly increased odds of PDVV compared with non-SMYs. Bisexual youths do not have significantly higher odds of PDVV than gay or lesbian youths, but youths who had sexual contact with both-sexes possess significantly higher odds of PDVV than youths with same sex–only sexual contact. These patterns hold for most gender, grade, and racial/ethnic subgroups. Conclusions. Overall, SMYs have greater odds of PDVV versus non-SMYs. Among SMYs, youths who had sexual contact with both sexes have greater odds of PDVV than youths with same sex–only sexual contact. Prevention programs that consider sexual orientation, support tolerance, and teach coping and conflict resolution skills could reduce PDVV among SMYs.

Prostate cancer is one of the most common malignancies affecting men worldwide, with bone being the most common site of metastasis in patients that progress beyond organ confinement. Bone metastases are virtually incurable and result in significant disease morbidity and mortality. Bone provides a unique microenvironment whose local interactions with tumor cells offer novel targets for therapeutic interventions. Several attractive molecules or pathways have been identified as new potential therapeutic targets for bone metastases caused by metastatic castration-resistant prostate cancer. In this review, we present the recent advances in molecular targeted therapies for prostate cancer bone metastasis focusing on therapies that target the bone cells and the bone microenvironment. The therapies covered in this review include agents that inhibit bone resorption, agents that stimulate bone formation, and agents that target the bone matrix. Suggestions to devise more effective molecular targeted therapies are proposed. Hopefully, with better understanding of the biology of the disease and the development of more robust targeted therapies, the survival and quality of life of the affected individuals could be significantly improved.

Objectives. We examined the associations between 2 measures of sexual orientation and 4 suicide risk outcomes (SROs) from pooled local Youth Risk Behavior Surveys. Methods. We aggregated data from 5 local Youth Risk Behavior Surveys from 2001 to 2009. We defined sexual minority youths (SMYs) by sexual identity (lesbian, gay, bisexual) and sex of sexual contacts (same- or both-sex contacts). Survey logistic regression analyses controlled for a wide range of suicide risk factors and sample design effects. Results. Compared with non-SMYs, all SMYs had increased odds of suicide ideation; bisexual youths, gay males, and both-sex contact females had greater odds of suicide planning; all SMYs, except same-sex contact males, had increased odds of suicide attempts; and lesbians, bisexuals, and both-sex contact youths had increased odds of medically serious attempts. Unsure males had increased odds of suicide ideation compared with heterosexual males. Not having sexual contact was protective of most SROs among females and of medically serious attempts among males. Conclusions. Regardless of sexual orientation measure used, most SMY subgroups had increased odds of all SROs. However, many factors are associated with SROs.

TGFβ1 is very important in the synthesis and degradation of extracellular matrix, and also in the mediation of human lung fibroblasts proliferation, and miR-29 plays an important role in this process. To explore the interactions of miR-29 family members and TGFβ1, the effects of transforming growth factor TGFβ1 on the expression of miR-29 and whether miR-29 is involved in pro-survival signaling pathways mediated by TGFβ1 were examined in human lung fibroblasts. Treatment of the human embryonic lung fibroblast cell line IMR90 with TGFβ1 caused a decrease in expression of miR-29a/b/c by real-time PCR analysis. TGFβ1 stimulation increased cell proliferation, colony formation and up-regulated expression of COL1A1; transfecting with miR-29a/b/c mimics reverse TGFβ1-induced phenotype changes in IMR90 cells. Western blot analyses showed that TGFβ1 treatment unchanged total protein expression levels of PI3K or AKT, but the expression levels of p-PI3K, p-AKT, and COL1A1 were increased; and miR-19a/b/c mimics interfering blocked phosphorylation of PI3K or AKT and decreased expression of COL1A1 after TGFβ1 treatment. The results indicate that TGFβ1 beta uses the PI3k-Akt pathway in these embryonic fibroblasts and miR29 blocks this activation pathway. It indicates a novel biological function of the PI3K-Akt pathway in IMR90. Elevated expression of miR-29 may play an important role in the pathogenesis of diseases related to fibrogenic reactions in human lung fibroblasts.

OBJECTIVES:We investigated the relationship between parental incarceration history and young adult physical and mental health outcomes using Wave 1 and Wave 4 data from the National Longitudinal Study of Adolescent Health.METHODS:Dependent variables included self-reported fair/poor health and health diagnoses. The independent variable was parental incarceration history. Cross-tabulations and logistic regression models were run.RESULTS:Positive, significant associations were found between parental incarceration and 8 of 16 health problems (depression, posttraumatic stress disorder, anxiety, cholesterol, asthma, migraines, HIV/AIDS, and fair/poor health) in adjusted logistic regression models. Those who reported paternal incarceration had increased odds of 8 mental and physical health problems, whereas those who reported maternal incarceration had increased odds of depression. For paternal incarceration, with the exception of HIV/AIDS, larger associations were found for mental health (odds ratios range 1.43–1.72) as compared with physical health (odds ratios range 1.26–1.31) problems. The association between paternal incarceration and HIV/AIDs should be interpreted with caution because of the low sample prevalence of HIV/AIDs.CONCLUSIONS:This study suggests exposure to parental incarceration in childhood is associated with health problems in young adulthood. Extant literature suggests underlying mechanisms that link parental incarceration history to poor outcomes in offspring may include the lack of safe, stable, nurturing relationships and exposure to violence. To prevent poor health in offspring of the incarcerated, additional studies are needed to (1) confirm the aforementioned associations and (2) assess whether adverse experiences and violence exposure in childhood mediate the relationship between parental incarceration history and offspring health problems.

Importance:It is important to understand the magnitude and distribution of the economic burden of prescription opioid overdose, abuse, and dependence to inform clinical practice, research, and other decision makers. Decision makers choosing approaches to address this epidemic need cost information t

State prescription drug monitoring programs are promising tools to rein in the epidemic of prescription opioid overdose. We used data from a national survey to assess the effects of the programs on the prescribing of opioid analgesics and other pain medication in ambulatory care settings at the point of care in twenty-four states from 2001 to 2010. We found that implementation of a prescription drug monitoring program was associated with more than a 30 percent reduction in the rate of prescribing of Schedule II opioids. This reduction was seen immediately following the launch of the program and was maintained in the second and third years afterward. Effects on overall opioid prescribing and prescribing of nonopioid analgesics were limited. Increased utilization of these programs and the adoption of new policies and practices governing their use may have contributed to sustained effectiveness. Future studies are needed to evaluate the comparative effectiveness of these policies.

RAS proteins act as molecular switches between several homeostatic inputs and signal transduction pathways that regulate important cellular processes including cell growth, differentiation and survival. Activating mutations change the function of normal proto-oncogenic RAS proteins to oncogenic RAS proteins that trigger a wide range of downstream effectors altering expression of transcription factors that together stimulate cell proliferation and modulate apoptosis and differentiation. RAS genes are amongst the most frequently mutated genes in human cancers, in particular KRAS is mutated in 40-50% of colorectal cancers. Mutation of this gene has a significant impact on treatment management and patients' survival, particularly in relation to anti-EGFR therapy, which is only effective in KRAS wild-type cases. Here, we discuss the regulation of KRAS signalling in the colorectum, some of the post-transcriptional and post-translational modifications that control its activity, the mutations and other DNA alterations that are found in this tumour type and the implications that they have for disease progression and current drug treatments.

Objectives. We examined the associations of overall and age-specific suicide rates with business cycles from 1928 to 2007 in the United States. Methods. We conducted a graphical analysis of changes in suicide rates during business cycles, used nonparametric analyses to test associations between business cycles and suicide rates, and calculated correlations between the national unemployment rate and suicide rates. Results. Graphical analyses showed that the overall suicide rate generally rose during recessions and fell during expansions. Age-specific suicide rates responded differently to recessions and expansions. Nonparametric tests indicated that the overall suicide rate and the suicide rates of the groups aged 25 to 34 years, 35 to 44 years, 45 to 54 years, and 55 to 64 years rose during contractions and fell during expansions. Suicide rates of the groups aged 15 to 24 years, 65 to 74 years, and 75 years and older did not exhibit this behavior. Correlation results were concordant with all nonparametric results except for the group aged 65 to 74 years. Conclusions. Business cycles may affect suicide rates, although different age groups responded differently. Our findings suggest that public health responses are a necessary component of suicide prevention during recessions.

Grifolin, a secondary metabolite isolated from the fresh fruiting bodies of the mushroom Albatrellus confluens, has been shown to inhibit the growth of some cancer cell lines in vitro by induction of apoptosis in previous studies of our group. However, the mechanisms of action are not completely understood. An apoptosis-related gene expression profiling analysis provided a clue that death-associated protein kinase 1 (dapk1) gene was upregulated at least twofold in response to grifolin treatment in nasopharyngeal carcinoma cell CNE1. Here, we further investigated the role of DAPK1 in apoptotic effect induced by grifolin. We observed that protein as well as mRNA level of DAPK1 was induced by grifolin in a dose-dependent manner in nasopharyngeal carcinoma cell CNE1. We found that grifolin increased both Ser392 and Ser20 phosphorylation levels of transcription factor p53 protein, which could promote its transcriptional activity. Moreover, induced by grifolin, the recruitment of p53 to dapk1 gene promoter was confirmed to enhance markedly using EMSA and ChIP assays analysis. The involvement of DAPK1 in grifolin-induced apoptosis was supported by the studies that introducing siRNA targeting DAPK1 to CNE1 cells remarkably interfered grifolin-caused apoptotic effect as well as the activation of caspase-3. Grifolin induced upregulation of DAPK1 via p53 was also observed in tumour cells derived from human breast cancer and human colon cancer. The findings suggest that upregulation of DAPK1 via p53-DAPK1 pathway is an important mechanism of grifolin contributing to its ability to induce apoptotic effect. Since growing evidence found a significant loss of DAPK1 expression in a large variety of tumour types, grifolin may represent a promising candidate in the intervention of cancer via targeting DAPK1.

The principal Epstein-Barr virus (EBV) oncoprotein, latent membrane protein 1 (LMP1), has been suggested to contribute to the highly invasive nature of nasopharyngeal carcinoma (NPC). Signal transducer and activator of transcription 3 (STAT3) is a master transcriptional regulator in proliferation and apoptosis and is newly implicated in angiogenesis and invasiveness, which, in turn, are likely to contribute to the highly invasive character of NPC. The fundamental molecular mechanisms of LMP1-regulated STAT3 activation in NPC cell invasion have not been completely explored. Here, we showed that LMP1 signals the Janus kinase 3 (JAK3) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways upon the activation of STAT3 as well as STAT transactivation activity. LMP1 induces vascular endothelial growth factor (VEGF) expression via the JAK/STAT and mitogen-activated protein kinase (MAPK)/ERK signalling pathways. Induction of STAT3 by the human viral oncoprotein LMP1 may contribute to the invasion of NPC.

In 100 primary colorectal carcinomas, we demonstrate by array comparative genomic hybridization (aCGH) that 33% show DNA copy number (DCN) loss involving PARK2 , the gene encoding PARKIN, the E3 ubiquitin ligase whose deficiency is responsible for a form of autosomal recessive juvenile parkinsonism. PARK2 is located on chromosome 6 (at 6q25–27), a chromosome with one of the lowest overall frequencies of DNA copy number alterations recorded in colorectal cancers. The PARK2 deletions are mostly focal (31% ∼0.5 Mb on average), heterozygous, and show maximum incidence in exons 3 and 4. As PARK2 lies within FRA6E, a large common fragile site, it has been argued that the observed DCN losses in PARK2 in cancer may represent merely the result of enforced replication of locally vulnerable DNA. However, we show that deficiency in expression of PARK2 is significantly associated with adenomatous polyposis coli ( APC ) deficiency in human colorectal cancer. Evidence of some PARK2 mutations and promoter hypermethylation is described. PARK2 overexpression inhibits cell proliferation in vitro. Moreover, interbreeding of Park2 heterozygous knockout mice with Apc Min mice resulted in a dramatic acceleration of intestinal adenoma development and increased polyp multiplicity. We conclude that PARK2 is a tumor suppressor gene whose haploinsufficiency cooperates with mutant APC in colorectal carcinogenesis.

A large number of nonfatal injuries are treated in U.S. emergency departments (EDs) every year. CDC's National Center for Health Statistics estimates that approximately 29% of all ED visits in 2010 were for injuries. To assess the economic impact of ED-treated injuries, CDC examined injury data from the National Electronic Injury Surveillance System--All Injury Program (NEISS-AIP) for 2013, as well as injury-related lifetime medical and work-loss costs from the Web-Based Injury Statistics Query and Reporting System (WISQARS). NEISS-AIP collects data from a nationally representative sample of EDs, using specific guidelines for recording the primary diagnosis and mechanism of injury. Number of injuries, crude- and age-specific injury rates, and total lifetime work-loss costs and medical costs were calculated for ED-treated injuries, stratified by sex, age groups, and intent and mechanism of injury. ED-treated injuries were further classified as those that were subsequently hospitalized or treated and released. The rate of hospitalized injuries was 950.8 per 100,000, and the rate of treated and released injuries was 8,549.8 per 100,000. Combined medical and work-loss costs for all ED-treated injuries (both hospitalized and treated and released) were $456.9 billion, or approximately 68% of the total costs of $671 billion associated with all fatal and ED-treated injuries. The substantial economic burden associated with nonfatal injuries underscores the need for effective prevention strategies.

Suicide is the second leading cause of death among persons aged 10-24 years in the United States and accounted for 5,178 deaths in this age group in 2012. Firearm, suffocation (including hanging), and poisoning (including drug overdose) are the three most common mechanisms of suicide in the United States. Previous reports have noted that trends in suicide rates vary by mechanism and by age group in the United States, with increasing rates of suffocation suicides among young persons. To test whether this increase is continuing and to determine whether it varies by demographic subgroups among persons aged 10-24 years, CDC analyzed National Vital Statistics System mortality data for the period 1994-2012. Trends in suicide rates were examined by sex, age group, race/ethnicity, region of residence, and mechanism of suicide. Results of the analysis indicated that, during 1994-2012, suicide rates by suffocation increased, on average, by 6.7% and 2.2% annually for females and males, respectively. Increases in suffocation suicide rates occurred across demographic and geographic subgroups during this period. Clinicians, hotline staff and others who work with young persons need to be aware of current trends in suffocation suicides in this group so that they can accurately assess risk and educate families. Media coverage of suicide incidents and clusters should follow established guidelines to avoid exacerbating risk for "suicide contagion" among vulnerable young persons.* Suicide contagion is a process by which exposure to the suicide or suicidal behavior of one or more persons influences others who are already vulnerable and thinking about suicide to attempt or die by suicide. Early prevention strategies are needed to reduce the likelihood of young persons developing suicidal thoughts and behavior.

The incidence of inflammatory bowel disease (IBD) has increased considerably over the past few decades. In the present review, we discuss several disadvantages existing in the treatment of IBD and current understandings of the structures, sources, and natures of various kinds of non-starch polysaccharides (NSPs). Available evidences for the use of different sources of NSPs in IBD treatment both in vitro and in vivo are analyzed, including glucan from oat bran, mushroom, seaweed, pectin, gum, prebiotics, etc. Their potential mechanisms, especially their related molecular mechanism of protective action in the treatment and prevention of IBD, are also summarized, covering the anti-inflammation, immune-stimulating, and gut microbiota-modulating activities, as well as short-chain fatty acids (SCFAs) production, anti-oxidative stress accompanied with inflammation, the promotion of gastric epithelial cell proliferation and tissue healing, and the reduction of the absorption of toxins of NSPs, thus ameliorating the symptoms and reducing the reoccurrence rate of IBD. In summary, NSPs exhibit the potential to be promising agents for an adjuvant therapy and for the prevention of IBD. Further investigating of the crosstalk between immune cells, epithelial cells, and gut microorganisms in addition to evaluating the effects of different kinds and different molecular weights of NSPs will lead to well-designed clinical intervention trials and eventually improve the treatment and prevention of IBD.

This review provides up-to-date information on the anticancer properties of Monascus-fermented products. Topics covered include clinical evidence for the anticancer potential of Monascus metabolites, bioactive Monascus components with anticancer potential, mechanisms of the anticancer effects of Monascus metabolites, and existing problems as well as future perspectives. With the advancement of related fields, the development of novel anticancer Monascus food products and/or pharmaceuticals will be possible with the ultimate goal of decreasing the incidence and mortality of malignancies in humans.

Quercetin is one of flavonoids with cyto-protective activities. It has been demonstrated that quercetin inhibits oxidative stress in some animal models and specific cells, but the particular mechanism is known a little. In the present study, we found that quercetin could decrease the expression of Kruppel-like factor 4 (KLF4) induced by hydrogen peroxide (H 2 O 2 ) in human neuroblastoma SH-SY5Y cells, further increase the expression ratio of bcl-2 to bax, which were apoptotic-related target genes of KLF4, thus alleviate the apoptotic rate and caspase-3 enzyme activity of SH-5YSY cells; the overexpression or inhibition of KLF4 demonstrated the mediated role of KLF4 for the protective effect of quercetin on cell damage induced by H 2 O 2 . All results suggest a potential molecular mechanism of quercetin protecting against the oxidative damage, which may be applied in the treatment of oxidative related diseases, such as neurodegeneration diseases.

Disturbance of miRNA expression may play a key role in the initiation and progression of colorectal cancer (CRC). CRC should be viewed as a heterogeneous disease, but previous studies have only screened dysregulated miRNAs in CRC from a panel of 96, 145, 287 and 455 miRNAs, respectively. It is necessary to identify new aberrantly expressed miRNAs in rectal cancer. In this study tissue samples were derived from patients undergoing a surgical procedure to remove a portion of cancers. The expression profile of 904 miRNAs was analyzed using a miRCURY™ LNA Array from 6-paired rectal cancers and normal tissues. The expression levels of 4 miRNAs were compared by real-time PCR between colon and rectal cancer, and also the expression levels of metastatic miRNAs in different stages of rectal cancer were analyzed. We found that 67 miRNA precursors are upregulated in rectal cancer (p

Teen dating violence (TDV) is a preventable public health problem that has negative consequences for youth. Despite evidence that youth in urban communities with high crime and economic disadvantage may be at particularly high risk for TDV, little work has specifically addressed TDV in these communities. The Centers for Disease Control and Prevention (CDC) has developed a comprehensive approach to prevent TDV—Dating Matters™: Strategies to Promote Healthy Teen Relationships—that addresses gaps in research and practice. This Report from CDC describes the programmatic activities, implementation support, evaluation, and surveillance of the Dating Matters™ initiative, which will be implemented in four urban communities.