Glutathione depletion and dihydroorotate dehydrogenase inhibition actuated ferroptosis-augment to surmount triple-negative breast cancer.

Ferroptosis is a promising therapeutic approach for combating malignant cancers, but its effectiveness is limited in clinical due to the adaptability and self-repair abilities of cancer cells. Mitochondria, as the pivotal player in ferroptosis, exhibit tremendous therapeutic potential by targeting the intramitochondrial anti-ferroptotic pathway mediated by dihydroorotate dehydrogenase (DHODH). In this study, an albumin-based nanomedicine was developed to induce augmented ferroptosis in triple-negative breast cancer (TNBC) by depleting glutathione (GSH) and inhibiting DHODH activity. The nanomedicine (ATO/SRF@BSA) was developed by loading sorafenib (SRF) and atovaquone (ATO) into bovine serum albumin (BSA). SRF is an FDA-approved ferroptosis inducer and ATO is the only drug used in clinical that targets mitochondria. By combining the effects of SRF and ATO, ATO/SRF@BSA promoted the accumulation of lipid peroxides within mitochondria by inhibiting the glutathione peroxidase 4 (GPX4)-GSH pathway and downregulating the DHODH-coenzyme Q (CoQH2) defense mechanism, triggers a burst of lipid peroxides. Simultaneously, ATO/SRF@BSA suppressed cancer cell self-repair and enhanced cell death by inhibiting the synthesis of adenosine triphosphate (ATP) and pyrimidine nucleotides. Furthermore, the anti-cancer results showed that ATO/SRF@BSA exhibited tumor-specific killing efficacy, significantly improved the tumor hypoxic microenvironment, and lessened the toxic side effects of SRF. This work presents an efficient and easily achievable strategy for TNBC treatment, which may hold promise for clinical applications.

The application of 5E rehabilitation management mode in the nursing of patients with aortic dissection complicated by obstructive sleep apnea.

OBJECTIVE: This study was designed to explore the effect of 5E rehabilitation mode (encouragement, education, exercise, employment, and evaluation) in patients with aortic dissection (AD) complicated by obstructive sleep apnea (OSA). METHODS: Patients with Stanford type B AD (TBAD) complicated by OSA were admitted to Guangdong Provincial People's Hospital from January 2019 to December 2020. They were randomly divided into an experimental group and a control group. After discharge, patients in the control group were given routine nursing and follow-up education, whereas patients in the experimental group were given 5E rehabilitation management mode-based nursing and follow-up education. Upon the nursing intervention, the differences in polysomnography (PSG) parameters, medication adherence, quality of life, blood pressure, and heart rate of patients between the two groups were compared. Logistic regression analysis was performed to evaluate the risk factors for the occurrence of adverse aortic events. RESULTS: A total of 89 patients were enrolled, 49 in the experimental group and 40 in the control group. After the intervention, the control of heart rate, systolic blood pressure, medication adherence, PSG parameters, and quality of life scores in the experimental group were significantly better than those in the control group (P<0.05). The incidence of adverse aortic events including aortic rupture and progressive aortic dilation in the experimental group was significantly lower than that in the control group (P < 0.05). Logistic regression analysis revealed that acute TBAD [odds ratio (OR) = 15.069; 95%confidence interval (CI), 1.738-130.652; P=0.014], history of chronic kidney disease (OR=10.342; 95%CI, 1.056-101.287; P=0.045), and apnea hypopnea index (AHI) ≥ 30 (OR=2.880; 95%CI, 1.081-9.51; P=0.036) were adverse factors affecting adverse aortic events; while 5E rehabilitation management mode (OR=0.063; 95%CI, 0.008-0.513; P=0.010) was a favorable factor for occurrence of adverse aortic events. CONCLUSION: The findings suggest that continuous nursing based on information carrier 5E rehabilitation management significantly enhanced medication adherence, improved patients' overall quality of life, and decreased the incidence of adverse aortic events in patients TBAD patients and OSA.

Tumor microenvironment-initiated lipid redox cycling for efficient triple-negative breast cancer therapy.

The use of overwhelming reactive oxygen species (ROS) attack has shown great potential for treating aggressive malignancies; however, targeting this process for further applications is greatly hindered by inefficiency and low selectivity. Here, a novel strategy for ROS explosion induced by tumor microenvironment-initiated lipid redox cycling was proposed, which was developed by using soybean phosphatidylcholine (SPC) to encapsulate lactate oxidase (LOX) and sorafenib (SRF) self-assembled nanoparticles (NPs), named LOX/SRF@Lip. SPC is not only the delivery carrier but an unsaturated lipid supplement for ROS explosion. And LOX catalyzes excessive intratumoral lactate to promote the accumulation of large amounts of H2O2. Then, H2O2 reacts with excessive endogenous iron ions to generate amounts of hydroxyl radical for the initiation of SPC peroxidation. Once started, the reaction will proceed via propagation to form new lipid peroxides (LPO), resulting to devastating LPO explosion and widespread oxidative damage in tumor cells. Furthermore, SRF makes contribution to mass LPO accumulation by inhibiting LPO elimination. Compared to normal tissue, tumor tissue has higher levels of lactate and iron ions. Therefore, LOX/SRF@Lip shows low toxicity in normal tissues, but generates efficient inhibition on tumor proliferation and metastasis, enabling excellent and safe tumor-specific therapy. This work offers new ideas on how to magnify anticancer effect of ROS through rational nanosystem design and tumor-specific microenvironment utilization.

Mental Health of Healthcare Workers during COVID-19 Pandemic in Taiwan: The First Wave Outbreak Occurred 1 Year Later Than in Other Countries.

We probed the psychological influence exerted on traumatic stress endured by healthcare workers (HCWs) and the coping behaviors adopted during the first wave of COVID-19 in Taiwan, which occurred one year later than in other countries. Clinical HCWs from two branches of a hospital network in Taichung, Taiwan, were recruited for this cross-sectional study. The participants were administered a questionnaire on sociodemographic and work-related characteristics, perceived influence exerted by COVID-19, coping behaviors in relation to COVID-19, and Impact of Event Scale-Revised scores. We obtained 769 valid questionnaires. A chi-square test, generalized linear modeling, and multivariate stepwise regression analyses were performed. Although the first wave of COVID-19 occurred one year later in Taiwan than in other countries, the traumatic stress experienced by Taiwanese HCWs was noted to be comparable to that of those in other countries. Factors for increased traumatic stress included caring for more patients with COVID-19, fair or poor self-rated mental health, higher perceived influence of COVID-19, vulnerable household income, and more negative coping behaviors. Positive coping behaviors such as exposure reduction and protection measures decreased traumatic stress. Accordingly, managers should strengthen protective measures, enhance COVID-19-related training, and provide psychological support and counseling for high-risk employees.

Effect of anodization on friction behavior of ß­titanium orthodontic archwires.

PURPOSE: To evaluate the effects of anodization on the friction behavior of beta-titanium (ß-Ti) orthodontic archwires in conventional or self-ligating brackets in vitro. METHODS: ß­Ti archwires (0.018â€¯× 0.025 inch) pre- and postanodization were tested in combination with 0.022-inch stainless steel conventional and self-ligating brackets. The surface composition and oxide thickness of the ß­Ti archwires pre- and postanodization were measured using Auger electron spectroscopy (AES) and transmission electron microscopy (TEM). Detailed surface topography and roughness were assessed using atomic force microscopy (AFM). Surface topographies of the ß­Ti archwires pre- and postanodization were examined using scanning electron microscopy (SEM). Friction was measured using a universal testing machine; the data were statistically analyzed. RESULTS: Postanodization, the identified titanium oxide layer on the surface of the ß­Ti archwires increased in thickness from 10 to 100 nm; at the same time, the values for surface roughness were significantly reduced by half (p < 0.001). The archwire surfaces post anodization were harder and had fewer scratches after the friction test. Anodization significantly reduced 23.77% of the static (p < 0.01) and 25.61% of the kinetic (p < 0.001) friction of the ß­Ti archwires in conventional brackets, while it significantly reduced 85.71% of the static and 84.38% of the kinetic friction (p < 0.01) in self-ligating brackets. CONCLUSION: Anodization reduced the ß­Ti archwire friction, which was particularly more effective in combination with self-ligating brackets. The friction reduction via anodization could be attributed to the increased thickness, surface hardness, and decreased surface roughness of the titanium oxide layer.

Survival and pretreatment prognostic factors for extensive-stage small cell lung cancer: A comprehensive analysis of 358 patients.

BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) is deemed as a fatal malignancy with a poor prognosis. Although immunotherapy has gradually played an important role in the treatment of ES-SCLC since 2018, ES-SCLC treatment data and patient outcome before 2018, when chemotherapy served as a fundamental therapeutic strategy, is still meaningful as a summary of the situation regarding previous medical treatment and is a baseline for comparative data. In addition, the prognostic factors of ES-SCLC have failed to reach a consensus until now. Therefore, this study aimed to evaluate survival and identify the prognostic factors in an ES-SCLC population. METHODS: We retrospectively collected the detailed medical records of 358 patients with ES-SCLC from January 1, 2011 to December 31, 2018 in a Chinese top-level cancer hospital. The prognostic factors were evaluated by Cox univariate and multivariate analysis. RESULTS: The median overall survival (OS) of ES-SCLC patients (N = 358) was 14.0 months, the one- and two-year OS rates were 56.2% and 21.7%, respectively. Moreover, we identified two demographic characters (age ≥ 70, smoking index ≥ 400), one tumor burden factor (bone multimetastasis), two tumor biomarkers (cyfra211, CA125) and two laboratory indexes (decreased Na, PLR < 76) as independent prognostic factors for OS in this patient population. Progression-free survival (PFS) data of 238 patients was obtained for further analysis, and the median PFS was 6.2 months, and six-month and one-year PFS rates were 51.7% and 14.3%, respectively. Elevated cyfra211, decreased Hb and Na were identified as independent prognostic factors for PFS. CONCLUSIONS: This study provides real-world evidence of the survival and prognosis of ES-SCLC patients which will enable better evaluation and clinical decision-making in the future.

Causes of nursing staff burnout: Exploring the effects of emotional exhaustion, work-family conflict, and supervisor support.

AIM: Nursing staff burnout threatens not only nurses' health but also the safety and health of their patients. Organizations should be aware of how work-related conflict can affect this burnout. This study examined the effect of supervisor support and work-family conflict on resource loss and burnout. METHODS: A cross-sectional method and quantitative approach were adopted. A total of 300 questionnaires were distributed to clinical nursing staff in two regional teaching hospitals, and 239 valid questionnaires were returned. RESULTS: Work-family conflict had a mediating effect on the relationship between supervisor support and emotional exhaustion. Emotional exhaustion fully mediated the relationships between depersonalization, work-family conflict, and reduced professional efficacy. CONCLUSION: The mediating effect of emotional exhaustion in work-family conflict results from depersonalization and reduced professional efficacy, whereas work-family conflict mediated the effect of supervisor support on emotional exhaustion. The findings indicate that the medical industry should implement supervisor support strategies to reduce nursing staff work-family conflict and improve interventions for emotional exhaustion.

Tobacco Industry Marketing Exposure and Commercial Tobacco Product Use Disparities among American Indians and Alaska Natives.

Background: Non-Hispanic American Indians and Alaska Natives (NH AI/AN) have the highest commercial tobacco use (CTU) among U.S. racial/ethnic groups. Tobacco marketing is a risk factor, however few studies examine it among NH AI/AN. Objective: We identified prevalence of tobacco industry marketing exposure and correlates of CTU among NH AI/AN compared to other racial/ethnic groups. Methods: Data were from wave 1 (2013-2014; N = 32,320) of the Population Assessment of Tobacco and Health Study, analyzing self-reported exposure to tobacco ads from stores, tobacco package displays, direct mail and email marketing. Correlates of CTU were identified and interactions between racial/ethnic groups and tobacco marketing were assessed. Results: NH AI/AN (n = 955) had a higher prevalence of exposure to retail tobacco ads (64.5% vs 59.3%; p < 0.05), mail (20.2% vs.14.3%; p < 0.001) and email (17.0% vs.10.6%; p < 0.001) marketing than NH Whites (n = 19,297). Adjusting for tobacco use and related risk factors, exposure to email marketing remained higher among NH AI/AN than NH Whites. Interactions between racial/ethnic groups and marketing exposures on CTU were nonsignificant. CTU was higher among NH AI/AN than NH Whites and among adults who reported exposure to tobacco ads, mail, and email marketing. Conclusions/importance: There is higher tobacco marketing exposure in stores and via mail for NH AI/AN. Email marketing exposure was higher, even after controlling for tobacco-related risk factors. The tobacco industry may be targeting NH AI/AN through emails, which include coupons and other marketing promotions. Culturally relevant strategies that counter-act tobacco industry direct marketing tactics are needed to reduce disparities in this population.

Pro-tobacco marketing and anti-tobacco campaigns aimed at vulnerable populations: A review of the literature.

INTRODUCTION: We reviewed research literature on pro-tobacco marketing and anti-tobacco campaigns targeting eight vulnerable populations to determine key findings and research gaps. Results can inform tobacco policy and control efforts and the design of public education campaigns for these groups. METHODS: Five journal databases in medicine, communication, and science, were used to identify 8875 peer-reviewed, original articles in English, published in the period 2004-2018. There were 144 articles that met inclusion criteria on pro-tobacco marketing or anti-tobacco campaigns aimed at eight US groups: women of reproductive age, racial/ethnic minority groups (African American, Hispanic/Latino, Asian/Pacific Islander and American Indian/Alaska Native), Lesbian/Gay/Bisexual/Transgender (LGBT) populations, groups with low socioeconomic status, rural/inner city residents, military/veterans, and people with mental health or medical co-morbidities. We summarized the number of articles for each population, type of tobacco, and pro-tobacco or anti-tobacco focus. Narrative summaries were organized by population and by pro-tobacco or anti-tobacco focus, with key strategies and gaps by group. RESULTS: There were more studies on pro-tobacco marketing rather than anti-tobacco campaigns, and on cigarettes rather than other tobacco products. Major gaps included studies on Asian Americans, American Indian/Alaska Natives, pregnant women, LGBT populations, and those with mental health or medical co-morbidities. Gaps related to tobacco products were found for hookah, snus, and pipe/roll-your-own tobacco in the pro-tobacco studies, and for all products except cigarettes in anti-tobacco studies. Common tobacco industry methods used were tailoring of product and package design and messages that were used to reach and appeal to different sociodemographic groups. Studies varied by research design making it difficult to compare results. CONCLUSIONS: We found major research gaps for specific groups and tobacco products. Public education campaigns need a stronger foundation in empirical studies focused on these populations. Research and practice would benefit from studies that permit comparisons across studies.

Cigarette Constituent Health Communications for Smokers: Impact of Chemical, Imagery, and Source.

INTRODUCTION: Communication campaigns are incorporating tobacco constituent messaging to reach smokers, yet there is a dearth of research on how such messages should be constructed or will be received by smokers. METHODS: In a 2 × 2 × 2 experiment, we manipulated three cigarette constituent message components: (1) the toxic constituent of tobacco (arsenic vs. lead) with a corresponding health effect, (2) the presence or absence of an evocative image, and (3) the source of the message (FDA vs. no source). We recruited smokers (N = 1669, 55.4% women) via an online platform and randomized them to one of the eight message conditions. Participants viewed the message and rated its believability and perceived effectiveness, the credibility of the message source, and action expectancies (ie, likelihood of seeking additional information and help with quitting as a result of seeing the message). RESULTS: We found significant main effects of image, constituent, and source on outcomes. The use of arsenic as the constituent, the presence of an evocative image, and the FDA as the source increased the believability, source credibility, and perceived effectiveness of the tobacco constituent health message. CONCLUSIONS: Multiple elements of a constituent message, including type of constituent, imagery, and message source, impact their reception among smokers. Specifically, communication campaigns targeting smokers that utilize arsenic as the tobacco constituent, visual imagery, and the FDA logo may be particularly effective in changing key outcomes that are associated with subsequent attitude and behavioral changes. IMPLICATIONS: This article describes how components of communication campaigns about cigarette constituents are perceived. Multiple elements of a tobacco constituent message, including type of constituent, image, and message source may influence the reception of messages among current smokers. Communication campaigns targeting smokers that utilize arsenic as the tobacco constituent, visual imagery, and the FDA logo may be particularly effective in changing key outcomes among smokers. The effects of such campaigns should be examined, as well as the mechanisms through which such campaigns affect change.

Tobacco Advertisement Liking, Vulnerability Factors, and Tobacco Use Among Young Adults.

INTRODUCTION: Young adulthood (aged 18-24) is a crucial period in the development of long-term tobacco use patterns. Tobacco advertising and promotion lead to the initiation and continuation of smoking among young adults. We examined whether vulnerability factors moderated the association between tobacco advertisement liking and tobacco use in the United States. METHODS: Analyses were conducted among 9109 US young adults in the nationally representative Population Assessment of Tobacco and Health (PATH) Study wave 1 (2013-14). Participants viewed 20 randomly selected sets of tobacco advertisements (five each for cigarettes, e-cigarettes, cigars, and smokeless tobacco) and indicated whether they liked each ad. The outcome variables were past 30-day cigarette, e-cigarette, cigar, and smokeless tobacco use. Covariates included tobacco advertisement liking, age, sex, race or ethnicity, sexual orientation, education, poverty level, military service, and internalizing and externalizing mental health symptoms. RESULTS: Liking tobacco advertisements was associated with tobacco use, and this association was particularly strong among those with lower educational attainment (cigarettes, cigars) and living below the poverty level (e-cigarettes, smokeless tobacco). CONCLUSIONS: The association between tobacco advertisement liking and tobacco use was stronger among young adults with lower educational attainment and those living below the poverty level. Policies that restrict advertising exposure and promote counter-marketing messages in this population could reduce their risk. IMPLICATIONS: This study shows that liking tobacco advertisements is associated with current tobacco use among young adults, with stronger associations for vulnerable young adults (ie, lower education levels and living below the poverty level). Findings suggest a need for counter-marketing messages, policies that restrict advertising exposure, and educational interventions such as health and media literacy interventions to address the negative influences of tobacco advertisements, especially among young adults with a high school education or less and those living below the poverty level.

Juggling Two Balls-Smoking (Re)Normalization and Harm Reduction: E-Cigarettes-Facts and Misconceptions in Taiwan.

The increasing popularity of e-cigarettes, especially among adolescents, has alarmed health advocates and government officials, dominating the tobacco control narrative in the past few years. According to the Global Youth Tobacco Survey, the percentage of Taiwanese teenagers reporting use of e-cigarettes in the past 30 days rose from 2.01% (95% confidence interval [CI] = 1.82% to 2.23%) in 2014 to 3.54% (95% CI = 3.30% to 3.80%) in 2017. However, during the same period, prevalence of cigarettes declined from 11.51% (95% CI = 9.84% to 13.42%) to 8.26% (95% CI = 7.80% to 8.76%) among senior high school students, and from 5.00% (95% CI = 4.36% to 5.74%) to 2.66% (95% CI = 2.38% to 2.96%) among junior high school students, with figures for both groups reaching historical lows. This trend is similar to population-level trends observed in both the United Kingdom and the United States, but only future long-term studies will be able to clarify if it is consistent or not with the fears that e-cigarette may act as a "gateway" to cigarette smoking renormalization.

Adolescent tobacco coupon receipt, vulnerability characteristics and subsequent tobacco use: analysis of PATH Study, Waves 1 and 2.

OBJECTIVES: We examine adolescent receipt of tobacco coupons and subsequent tobacco use. METHODS: Data were from the Population Assessment of Tobacco and Health (PATH) Study (2013-2015). We identified correlates of coupon receipt at Wave 1 (youth sample age 12-17 ; n = 13 651) including demographics, additional vulnerability factors that may place youth at risk of tobacco use and correlates of coupon receipt by channel. We examined associations of Wave 1 coupon receipt with Wave 2 tobacco use using weighted multivariable models. RESULTS: Overall, 7.6% of US youth received tobacco coupons in the 6 months before Wave 1. Coupon recipients were more likely to be women, living outside urban areas, living with a tobacco user, current and former (vs never) tobacco users, having high internalising mental health symptoms and having a favourite tobacco advertisement. Coupons were received primarily through direct mail (56%), product packs (28%) and online (25%). Never tobacco users at Wave 1 who received coupons were more likely to be ever users at Wave 2 (adjusted OR (aOR)=1.42; 95% CI 1.06 to 1.91). Coupon recipients were more likely to use a new tobacco product between waves (aOR=1.67; 95% CI 1.18 to 2.36) and report past 30-day tobacco use at Wave 2 (aOR=1.81; 95% CI 1.31 to 2.49). CONCLUSIONS: One in 13 US youth (7.6%) received coupons. Vulnerable youth had the greatest odds of coupon receipt. Coupon recipients had greater odds of tobacco use among never users, trying a new tobacco product and current use. Coupon bans, limits on youth coupon exposure, stronger age verification, pack inserts or restricting coupon redemption may help reduce tobacco use among adolescents, particularly for those at greatest risk.

Believability of Cigarette Warnings About Addiction: National Experiments of Adolescents and Adults.

Introduction: We conducted two experiments to examine the believability of three addiction-focused cigarette warnings and the influence of message source on believability among adolescents and adults in the United States. Methods: Experimental data were collected using national phone surveys of adolescents (age 13-17; n = 1125; response rate, 66%) and adults (age 18+; n = 5014; response rate, 42%). We assessed the believability of three cigarette warnings about addiction attributed to four message sources (Food and Drug Administration [FDA], Surgeon General, Centers for Disease Control and Prevention [CDC], no source). Results: The majority of adolescents and adults reported the three cigarette warnings were very believable (49%-81% for adolescents; 47%-76% for adults). We found four to five times higher odds of adolescents believing a warning that cigarettes are addictive (warning 1) or that nicotine was an addictive chemical (warning 2) compared to a warning that differentiated the addictive risks of menthol versus traditional cigarettes (warning 3), warning 1 adjusted odds ratio (aOR): 4.53, 95% confidence interval (CI): 3.10, 6.63; warning 2 aOR: 3.87, 95% CI: 2.70, 5.50. Similarly, we found three to five times higher odds of adults (including current smokers) believing the same warnings, warning 1 aOR: 3.74, 95% CI: 2.82, 4.95; warning 2 aOR: 3.24, 95% CI: 2.45, 4.28. Message source had no overall impact on the believability of warnings for either population. Conclusions: Our findings support the implementation of FDA's required warnings that cigarettes are addictive and that nicotine is an addictive chemical. These believable warnings may deter adolescents from initiating smoking and encourage adults to quit smoking. Implications: This article describes, for the first time, the believability of different cigarette warnings about addiction. We now know that the majority of adolescents and adults believe cigarette warnings that highlight cigarettes as addictive and that nicotine is an addictive chemical in tobacco. However, a warning that highlighted the relative risk of addiction for menthol cigarettes compared to traditional cigarettes was not as believable among either population. Our findings support the implementation of FDA's required warnings that cigarettes are addictive and that nicotine is an addictive chemical that may deter adolescents from initiating smoking and encourage adults to quit smoking.

Which types of anti-smoking television advertisements work better in Taiwan?

Research in high income countries suggests that anti-smoking television advertisements with emotionally evocative graphic messages or personal testimonials that depict serious consequences from smoking are the most effective. Research to determine the most effective smoking cessation messages for low- and middle-income countries is needed to inform campaign development in these countries. Fifty-four male Taiwanese smokers, aged 18-34, rated advertisements and participated in a focus group to evaluate eight antismoking television advertisements with contrasting messaging strategies. Participants individually evaluated advertisements, after which they participated in a semi-structured focus group discussion (10 groups, 2-9 smokers per group). One week after this session, participants were called to assess advertisement recall. Both quantitative and qualitative data indicated that highly emotional testimonial ads that featured a graphic portrayal of personal suffering from the consequences of smoking and visceral graphic ads were more effective. The ad on tobacco industry denormalization that focuses on the responsibility of the industry for smoking-related harms was considered ineffective because smokers perceived it as having little personal relevance. Humorous advertisements were evaluated as the least effective because they lacked strong emotional content linked to smoking consequences. Qualitative results suggest that advertisement characteristics are more important than the demographic characteristics of people featured in advertisements. Study findings provide preliminary evidence that testimonial ads that involve graphic and emotionally evocative portrayals of smoking-attributed diseases and visceral graphic ads may have the greater potential to motivate Taiwanese smokers to quit smoking.

Can brain impermeable BACE1 inhibitors serve as anti-CAA medicine?

BACKGROUND: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of ß-amyloid peptides (Aß) in and surrounding the wall of microvasculature in the central nervous system, together with parenchymal amyloid plaques collectively referred to as cerebral amyloidosis, which occurs in the brain commonly among the elderly and more frequently in patients with Alzheimer's disease (AD). CAA is associated with vascular injury and may cause devastating neurological outcomes. No therapeutic approach is available for this lesion to date. MAIN BODY: ß-Secretase 1 (BACE1) is the enzyme initiating Aß production. Brain permeable BACE1 inhibitors targeting primarily at the parenchymal plaque pathology are currently evaluated in clinical trials. This article presents findings in support of a role of BACE1 elevation in the development of CAA, in addition to plaque pathogenesis. The rationale, feasibility, benefit and strategic issues for developing BACE1 inhibitors against CAA are discussed. Brain impermeable compounds are considered preferable as they might exhibit sufficient anti-CAA efficacy without causing significant neuronal/synaptic side effects. CONCLUSION: Early pharmacological intervention to the pathogenesis of CAA is expected to provide significant protection for cerebral vascular health and hence brain health. Brain impermeable BACE1 inhibitors should be optimized and tested as potential anti-CAA therapeutics.

Trends and Correlates of Hookah Use Among High School Students in North Carolina.

OBJECTIVES Although youth cigarette smoking has declined in the United States, use of alternative tobacco products, such as hookah, has increased. This study assesses changes in prevalence of use from 2011 to 2013, and examines factors associated with current hookah use among North Carolina high school students in 2013.METHODS Data came from the North Carolina Youth Tobacco Survey in 2011 (n = 4,791) and 2013 (n = 4,092). STATA (StataCorp LLC) logistic regression survey procedures account for the complex survey design and sampling weights.RESULTS Prevalence of reported current hookah use significantly increased from 3.6% (95% CI: 2.8-4.5) in 2011 to 6.1% (95% CI: 4.9-7.5) in 2013 while reported lifetime hookah use increased from 9.8% (95% CI: 8.0-12.0) in 2011 to 12.6% (95% CI: 11.0-14.4) in 2013. Correlates of current hookah use included having a weekly disposable income over $50 (adjusted odds ratio (AOR) = 2.05, 95% CI: 1.25-3.35), currently smoking cigarettes (AOR = 4.57, 95% CI: 1.80-11.62), and living with hookah users (AOR = 6.45, 95% CI: 3.21-12.93). Participant self-reports of "liking" or positively commenting on tobacco products on social media were associated with current hookah use (AOR = 1.83, 95% CI: 1.84-4.52). Frequent exposure to online tobacco advertisements (AOR = 1.61, 95% CI: 1.13-2.28) were also associated with current hookah use.CONCLUSIONS Comprehensive product specific communication and policy interventions are needed to educate youth about the dangers of hookah use and reduce social acceptability among youth. To decrease hookah use in North Carolina, policymakers should consider restoring funding for comprehensive tobacco prevention and control programs, and equalizing tobacco tax rates for all tobacco product types.

Perceptions and Experiences with Flavored Non-Menthol Tobacco Products: A Systematic Review of Qualitative Studies.

Although a few countries have banned flavored cigarettes (except menthol), flavors in most tobacco products remain unregulated across the globe. We conducted a systematic review of qualitative studies examining perceptions of and experiences with flavored non-menthol tobacco products. Of 20 studies on flavored tobacco products included in our qualitative systematic review, 10 examined hookah, six examined e-cigarettes, two examined little cigars and cigarillos (LCCs), and three examined other tobacco products, including cigarettes. The majority of studies, regardless of product type, reported positive perceptions of flavored tobacco products, particularly among young adults and adolescents. In six studies that assessed perceptions of harm (including hookah, LCCs, and other flavored tobacco products), participants believed flavored tobacco products to be less harmful than cigarettes. In studies that examined the role of flavors in experimentation and/or initiation (including three studies on e-cigarettes, one hookah study and one LCC study), participants mentioned flavors as specifically leading to their experimentation and/or initiation of flavored tobacco products. Given that many countries have not yet banned flavors in tobacco products, these findings add to existing research on why individuals use flavored tobacco products and how they perceive harm in flavored tobacco products, providing further support for banning non-menthol flavors in most tobacco products.

Impact of The Real Cost Campaign on Adolescents' Recall, Attitudes, and Risk Perceptions about Tobacco Use: A National Study.

The Food and Drug Administration's (FDA) The Real Cost campaign advertisements (ads) have targeted U.S. youth with messages designed to prevent and reduce tobacco use. This study examined exposure to The Real Cost campaign, including ad and slogan recall, and associations with attitudes and risk perceptions among U.S. adolescents. We analyzed data from a nationally representative sample of adolescents aged 13 to 17 years (n = 1125) surveyed by phone from October 2014 to June 2015. We assessed aided recall of and attitudes toward four campaign ads and the one slogan. Logistic regression models assessed whether aided recall of The Real Cost ads or slogan was associated with perceived likelihood of serious health consequences of cigarette smoking. Most (88%) adolescents reported seeing or hearing at least one of four ads for The Real Cost, and 54% recalled The Real Cost slogan. The majority of adolescents reported more negative attitudes toward tobacco products after seeing or hearing the ads. Recall of any The Real Cost ad was significantly associated with greater perceptions of serious health consequences of cigarette smoking (Adjusted Odd Ratios (AOR) = 5.58, 95% Confidence Interval (CI) = 1.20-25.90). The FDA's The Real Cost campaign has achieved very high reach and is associated with more negative attitudes toward tobacco products and greater risk perceptions of cigarette smoking among U.S. adolescents.

Effects of Framing Proximal Benefits of Quitting and Motivation to Quit as a Query on Communications About Tobacco Constituents.

INTRODUCTION: Little is known on how to communicate messages on tobacco constituents to tobacco users. This study manipulated three elements of a message in the context of a theory-based communication campaign about tobacco constituents: (1) latency of response efficacy (how soon expected health benefits would accrue), (2) self-efficacy (confidence about quitting), and (3) interrogative cue ("Ready to be tobacco-free?"). METHODS: Smokers (N = 1669, 55.4% women) were recruited via an online platform, and were randomized to a 3 (Latency of response efficacy) × 2 (Self-efficacy) × 2 (Interrogative cue) factorial design. The dependent variables were believability, credibility, perceived effectiveness of the communication message, and action expectancies (likelihood of seeking additional information and help with quitting). RESULTS: Latency of response efficacy influenced believability, perceived effectiveness, credibility, and action expectancies. In each case, scores were higher when specific health benefits were said to accrue within 1 month, as compared to general health benefits occurring in a few hours. The interrogative cue had a marginal positive effect on perceived effectiveness. The self-efficacy manipulation had no reliable effects, and there were no significant interactions among conditions. CONCLUSIONS: Smokers appear less persuaded by a communication message on constituents where general health benefits accrue immediately (within a few hours) than specific benefits over a longer timeframe (1 month). Additionally, smokers appeared to be more persuaded by messages with an interrogative cue. Such findings may help design more effective communication campaigns on tobacco constituents to smokers. IMPLICATIONS: This paper describes, for the first time, how components of tobacco constituent messages are perceived. We now know that smokers appear to be less persuaded by communication messages where general health benefits accrue immediately (within a few hours) than specific benefits over a longer timeframe (1 month). Additionally, including an interrogative cue ("Ready to be tobacco free?") may make messages more effective, whereas the self-efficacy manipulation designed to increase confidence about quitting had no effect. While messages were universally impactful across smoker subpopulations, everyday smokers and smokers with less trust in the government may be less receptive to communication campaigns.