Direct effects of adipocyte lipolysis on AMPK through intracellular long-chain acyl-CoA signaling.

Long-chain acyl-CoAs (LC-acyl-CoAs) are important intermediary metabolites and are also thought to function as intracellular signaling molecules; however, the direct effects of LC-acyl-CoAs have been difficult to determine in real-time and dissociate from Protein Kinase A (PKA) signaling. Here, we examined the direct role of lipolysis in generating intracellular LC-acyl-CoAs and activating AMPK in white adipocytes by pharmacological activation of ABHD5 (also known as CGI-58), a lipase co-activator. Activation of lipolysis in 3T3-L1 adipocytes independent of PKA with synthetic ABHD5 ligands, resulted in greater activation of AMPK compared to receptor-mediated activation with isoproterenol, a ß-adrenergic receptor agonist. Importantly, the effect of pharmacological activation of ABHD5 on AMPK activation was blocked by inhibiting ATGL, the rate-limiting enzyme for triacylglycerol hydrolysis. Utilizing a novel FRET sensor to detect intracellular LC-acyl-CoAs, we demonstrate that stimulation of lipolysis in 3T3-L1 adipocytes increased the production of LC-acyl-CoAs, an effect which was blocked by inhibition of ATGL. Moreover, ATGL inhibition blocked AMPKß1 S108 phosphorylation, a site required for allosteric regulation. Increasing intracellular LC-acyl-CoAs by removal of BSA in the media and pharmacological inhibition of DGAT1 and 2 resulted in greater activation of AMPK. Finally, inhibiting LC-acyl-CoA generation reduced activation of AMPK; however, did not lower energy charge. Overall, results demonstrate that lipolysis in white adipocytes directly results in allosteric activation of AMPK through the generation of LC-acyl-CoAs.

Overdose deaths involving synthetic opioids: Racial/ethnic and educational disparities in the eastern and western US.

BACKGROUND: This study examined racial/ethnic and educational disparities in US synthetic opioid overdose mortality East and West of the Mississippi River. METHODS: Using restricted-access 2018-2021 mortality data from the Centers for Disease Control and Prevention and population estimates from the American Community Survey, age-standardized rate ratios (SRRs) and 95% Confidence Intervals (CIs) were used to compare rates of synthetic opioid mortality by race/ethnicity and educational attainment level in the regions East and West of the Mississippi River. RESULTS: Racial/ethnic disparities in synthetic opioid mortality rates, relative to the Non-Hispanic (NH) White population, were observed in the NH Black (SRR, 1.5 [95% CI, 1.5-1.6]) and NH American Indian/Alaska Native (SRR, 2.1 [95% CI, 1.9-2.2]) populations in the West, and the Puerto Rican (SRR, 1.3 [95% CI, 1.3-1.3]) and NH American Indian/Alaska Native (SRR, 1.5 [95% CI, 1.4-1.6]) populations in the East. Relative to those with a Bachelor's degree or higher: in the West, the synthetic opioid mortality rate was more than seven times as high for those with a high school diploma only (SRR 7.7 [95% CI, 7.4-8.0]), and in the East, approximately thirteen times as high for those with a high school diploma only (SRR, 13.0 [95% CI, 12.7-13.3]) or less than a high school diploma (SRR, 13.3 [95% CI, 13.0-13.7]). CONCLUSION: Disparities in rates of synthetic opioid mortality differ in the eastern and western US, supporting tailored responses within each region.

The Moderating Role of Race and Ethnicity in the Association Between Cognitive Performance and Functional Abilities in Later Life.

This study examined ethnic/racial influences on the relationship of cognitive performance and functional abilities of 2,713 older individuals from the National Health and Nutrition Examination Survey (NHANES). Functional domains included activities of daily living (ADL), instrumental ADL, and leisure and social activities. In adjusted logistic regression models, low cognitive performance as assessed by the Digit Symbol Substitution Test was found significantly associated with functional limitation in each domain. However, moderation analysis revealed that being Hispanic and non-Hispanic Black may weaken this association demonstrating protective effects of underrepresented ethnic/racial status. Future studies should investigate perceived discrimination and resilience.

Effect of stem cell secretome in skin rejuvenation: a narrative review.

PURPOSE: Cutaneous aging is an inevitable biological process that develops over time due to cumulative cellular and molecular changes caused by exposure to intrinsic (chronological aging) and extrinsic (photo-aging) factors on the skin. Skin aging is characterized by a decline in the body's capability to sustain senescence, dermal cell apoptosis, and homeostasis. Stem cell secretions (secretome) are defined as the total set of dynamically overlapping paracrine soluble growth factors, cytokines, chemokines, angiogenic factors, extracellular matrix proteins, and antimicrobial peptides known to be responsible for tissue rejuvenation, regeneration, homeostasis, and immunomodulation. METHODS: In this review, we summarized the molecular and regulatory mechanism of the secretome in preventing the skin aging process, as well as its capacity in inducing skin rejuvenation. Furthermore, we illustrated secretome efficiency as an anti-aging therapeutic strategy based on in vitro and in vivo published studies. RESULTS: In all reviewed publications, the secretome has been proven to be the most effective treatment for aged skin, capable of reversing the aging process through the action of cytokines, growth factors, and collagen, which are its primary components. The reported mechanism of action involves modulating the signaling pathways of aging and replenishing the skin with collagen, fibronectin, and elastin, ultimately resulting in skin renewal and rejuvenation. CONCLUSION: In conclusion, compared to available treatments, the secretome shows great promise as an anti-aging therapy.

Acculturative Stress and Self-rated Health among Hispanic Emerging Adults: Examining the Moderating Effects of the Social Environment and Social Support.

Little is known about the impact of sociocultural stressors such as acculturative stress on self-rated health among Hispanics. We aimed to examine (a) associations between acculturative stress and self-rated health, and (b) the moderating effects of the community of settlement (i.e., Maricopa County, AZ and Miami-Dade County, FL) and social support on the association between acculturative stress and self-rated health. A hierarchical multiple regression model and moderation analyses were conducted using a cross-sectional sample of 200 Hispanic emerging adults from Arizona and Florida. Findings indicate that higher levels of pressure to acculturate are associated with lower levels of self-rated health. Community of settlement functioned as a moderator whereby pressure to acculturate was only associated with lower levels of self-rated health in Maricopa County. Lastly, a three-way interaction indicated that emotional social support mitigated the association between pressure to acculturate and self-rated health in Maricopa County. This study highlights the importance of accounting for community of settlement when examining associations between acculturative stress and health-related outcomes. A finding that may have implications for interventions is that social support may help to counteract the effects of acculturative stress.

Acculturation gap conflicts and self-rated health among Hispanic emerging adults.

INTRODUCTION: Emerging adulthood is a distinct and challenging developmental stage of life. It may be particularly stressful for Hispanic emerging adults due to various cultural stressors. However, there is little research on the impact of one particular cultural stressor, the acculturation gap. Therefore, this study aims to examine whether acculturation gap conflicts are associated with self-rated health. METHOD: Participants were recruited in Arizona and Florida, and 200 Hispanic emerging adults (ages 18-25) completed a cross-sectional survey. Data were analyzed using hierarchical multiple regression. RESULTS: Coefficients from a hierarchical multiple regression model indicated that higher levels of acculturation gap conflicts were associated with lower self-rated health after controlling for psychological stress and other demographic variables. DISCUSSION: This is the first study on acculturation gap conflicts and self-rated health among Hispanics. Findings from this study indicate that acculturation gap conflicts are associated with self-rated health and merit further investigation as they may have implications for health interventions targeting Hispanics. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Ethnic discrimination and psychological stress among Hispanic emerging adults: Examining the moderating effects of distress tolerance and optimism.

Hispanic emerging adults are often exposed to ethnic discrimination, yet little is known about coping resources that may mitigate the effects of ethnic discrimination on psychological stress in this rapidly growing population. As such, this study aims to examine (1) the associations of ethnic discrimination, distress tolerance, and optimism with psychological stress and (2) the moderating effects of distress tolerance and optimism on the association between ethnic discrimination and psychological stress. Data were drawn from a cross-sectional study of 200 Hispanic adults ages 18-25, recruited from two urban counties in Arizona and Florida. Hierarchical multiple regression and moderation analyses were utilized to examine these associations and moderated effects. Findings indicated that higher optimism was associated with lower psychological stress. Conversely, higher ethnic discrimination was associated with higher psychological stress. Moderation analyses indicated that both distress tolerance and optimism moderated the association between ethnic discrimination and psychological stress. These study findings add to the limited literature on ethnic discrimination among Hispanic emerging adults and suggest that distress tolerance may be a key intrapersonal factor that can protect Hispanic emerging adults against the psychological stress often resulting from ethnic discrimination.

State-specific Prevalence and Factors Associated With Current Marijuana, ENDS, and Cigarette use Among US Adults With Asthma.

Background: The use of marijuana (MJ), combustible cigarettes (hereafter cigarettes), and electronic nicotine delivery systems (ENDS) is widespread among United States (US) adults and linked to worsening respiratory symptoms, especially among adults with asthma. This study examined state-specific prevalence and factors associated with MJ, ENDS, and cigarette use among US adults with asthma. Methods: We analyzed data of 41 974 adults aged ≥18 years having self-reported current asthma from the 2018 Behavioral Risk Factor Surveillance System (BRFSS). We reported weighted prevalence to account for complex survey design and performed multivariable logistic regression models to examine factors associated with current use of MJ, ENDS, and cigarettes. Results: Overall prevalence of current MJ, ENDS, and cigarette use among adults with asthma was 14.5%, 6.6%, and 27.2%, respectively. Our results showed the US states and territories with highest and lowest use prevalence for MJ (California: 23.6% vs Guam: 3.2%), ENDS (Indiana: 12.8% vs North Dakota: 4.0%), and cigarettes (West Virginia: 42.1% vs Guam: 12.3%). Both MJ and ENDS users were more likely to be male, younger, and live in an urban area, but MJ users were more likely and ENDS users less likely to be Non-Hispanic (NH) American Indian/Alaskan Native. Cigarette users were more likely to be older, have at least 1 health condition, and were less likely to be NH Black or Hispanic and college-educated. Conclusion: Many US adults with asthma use MJ, ENDS, and cigarettes. Our findings provide insights for clinicians about the urgent need for effective interventions to reduce tobacco and MJ use among adults with asthma.

Physicians' perceptions and preferences for implementing venous thromboembolism (VTE) clinical practice guidelines: a qualitative study using the Theoretical Domains Framework (TDF).

BACKGROUND: Venous thromboembolism is a primary cause of morbidity and mortality in hospitalised patients. Clinical practice guidelines were developed to prevent venous thromboembolism events. This study adopted the Theoretical Domains Framework to explore the beliefs and perceptions of physicians adoption of clinical practice guidelines for the uptake of venous thromboembolism prevention guidelines. METHODS: Semi-structured interviews were conducted with a stratified purposive sample of internal medicine physicians in an acute hospital. The interview topic guide was developed using the Theoretical Domains Framework to identify the factors perceived to influence the practice. Two researchers coded the interview transcripts using thematic content analysis. Emerging relevant themes were mapped to TDF domains. RESULTS: A total of sixteen medical physicians were interviewed over a six-month period. Nine theoretical domains derived from thirty-three belief statements were identified as relevant to the target behaviour; knowledge (education about the importance of VTE guidelines); beliefs about capabilities (with practice VTE tool easier to implement); beliefs about consequences (positive consequences in reducing the development of VTE, length of stay, financial burden and support physician decision) and (negative consequence risk of bleeding); reinforcement (recognition and continuous reminders); goals (patient safety goal); environmental context and resources (workload and availability of medications were barriers, VTE coordinator and electronic medical record were enablers); social influences (senior physicians and patient/family influence the VTE practice); behavioural regulation (monitoring and mandatory hospital policy); and nature of the behaviour. CONCLUSIONS: Using the Theoretical Domains Framework, factors thought to influence the implementation of VTE clinical practice guidelines were identified which can be used to design theoretically based interventions by targeting specific psychological constructs and linking them to behaviour change techniques to change the clinical practice of physicians.

Experiences of Ethnic Discrimination Among US Hispanics: Intersections of Language, Heritage, and Discrimination Setting.

BACKGROUND: Informed by Latino Critical Race Theory, the present study examined how intersections between English use/proficiency, Spanish use/proficiency, and heritage group shape the varying experiences of ethnic discrimination reported by US Hispanic adults. METHODS: The study utilized data from 7,037 Hispanic adults from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III. Multivariable binomial logistic regression modeled language use/proficiency, heritage, and demographic characteristics as predictors of past-year self-reported perceived ethnic discrimination, overall and in six different settings. RESULTS: Both English and Spanish use/proficiency were positively associated with increased adjusted odds of reporting ethnic discrimination overall, in public, or with respect to employment/education/ housing/courts/police; however, with respect to being called a racist name or receiving verbal/physical threats/assaults, a positive association was observed for English, yet not Spanish. Results also indicated a significant interaction between English use/proficiency and Spanish use/proficiency when predicting past-year ethnic discrimination overall or for any of the six types/settings examined, although the relationship between language use/proficiency and ethnic discrimination varied by Hispanic heritage group. CONCLUSION: Study findings emphasize that experiencing some form of ethnic discrimination is relatively common among US Hispanic adults, yet the prevalence and types or settings of ethnic discrimination vary widely on the basis of demographics, immigrant generation, heritage, and the interplay between English and Spanish use/proficiency.

Exposure to ethnic discrimination in social media and symptoms of anxiety and depression among Hispanic emerging adults: Examining the moderating role of gender.

METHOD: Two hundred Hispanic emerging adults from Arizona (n = 99) and Florida (n = 101) completed a cross-sectional survey, and data were analyzed using hierarchical multiple regression and moderation analyses. RESULTS: Higher social media discrimination was associated with higher symptoms of depression and generalized anxiety. Moderation analyses indicated that higher social media discrimination was only associated with symptoms of depression and generalized anxiety among men, but not women. CONCLUSION: This is likely the first study on social media discrimination and mental health among emerging adults; thus, expanding this emerging field of research to a distinct developmental period.

Neurogenesis After Stroke: A Therapeutic Perspective.

Stroke is a major cause of death and disability worldwide. Yet therapeutic strategies available to treat stroke are very limited. There is an urgent need to develop novel therapeutics that can effectively facilitate functional recovery. The injury that results from stroke is known to induce neurogenesis in penumbra of the infarct region. There is considerable interest in harnessing this response for therapeutic purposes. This review summarizes what is currently known about stroke-induced neurogenesis and the factors that have been identified to regulate it. Additionally, some key studies in this field have been highlighted and their implications on future of stroke therapy have been discussed. There is a complex interplay between neuroinflammation and neurogenesis that dictates stroke outcome and possibly recovery. This highlights the need for a better understanding of the neuroinflammatory process and how it affects neurogenesis, as well as the need to identify new mechanisms and potential modulators. Neuroinflammatory processes and their impact on post-stroke repair have therefore also been discussed.

Nicotine-naïve adolescents who live with tobacco products users, 2018 Florida Youth Tobacco Survey.

OBJECTIVE: We assessed the prevalence and factors associated with living with tobacco/nicotine product users among nicotine-naïve adolescents. METHODS: Data were from the 2018 Florida Youth Tobacco Survey that included 34,183 adolescents who were never-tobacco product users and provided information about living with tobacco/nicotine users. RESULTS: More than a quarter of adolescents lived with a tobacco/nicotine user. Girls were more likely than boys and middle-schoolers were more likely than high-schoolers to live with someone who uses cigarettes, cigars, and poly-tobacco. Compared to non-Hispanic Whites, Hispanics were less likely to live with someone who uses cigarettes, electronic nicotine delivery systems, cigars, and poly-tobacco. Adolescents who reported currently having asthma were more likely to report living with someone who smokes cigarettes, hookah, and poly tobacco. CONCLUSIONS: To reduce and ideally eliminate exposure to smoke/aerosol emitted from tobacco products in nicotine-naïve adolescents, individual and family-centered interventions, coupled with state-wide tobacco prevention strategies are warranted.

The association between sleep duration, napping, and stroke stratified by self-health status among Chinese people over 65 years old from the China health and retirement longitudinal study.

PURPOSE: Stroke is a major cause of death in China. This study aimed to investigate the association between sleep duration (nighttime sleep and daytime napping) and stroke in elderly Chinese individuals with self-reported health status. METHODS: A total of 4785 Chinese adults over 65 years from the 2011 China Health and Retirement Longitudinal Study (CHARLS) were included. Binary logistic regression was used to estimate odds ratios and 95% confidence intervals of the association between sleep duration and stroke stratified by self-reported health status. RESULTS: A significant association between short sleep duration (< 7 h per day) and the risk of stroke (aOR = 2.05; 95% CI 1.31-3.19), after controlling for sociodemographic characteristics, lifestyle factors, health status, and comorbidities. There was no significant association between short and long sleep duration and stroke in the individuals who reported good general health status. However, in individuals who reported poor health status, short sleep duration (aOR = 2.11; 95% CI 1.30-3.44) and long sleep duration (aOR = 1.86; 95% CI 1.08-3.21) were significantly associated with increased risk of stroke, compared with normal sleep duration (7-8 h per day). Disability was significantly associated with stroke in both self-reported good and poor health groups. Rural residence was significantly associated with a lower risk of stroke among individuals who reported poor health status. CONCLUSIONS: Both short and long sleep duration were significantly associated with stroke among individuals who reported poor health. Stroke prevention should be focused on elderly individuals who believe that they have health problems.

Influence of Tobacco Marketing on Nepalese Adolescents: Cigarette Use and Susceptibility to Cigarette Use.

BACKGROUND: Tobacco advertising, promotion, and sponsorship (TAPS) are common tactics of the tobacco industry to encourage adolescents to use tobacco products. OBJECTIVE: The objective of the study is to assess the influence of TAPS on cigarette use and susceptibility to cigarette use among Nepalese adolescents. MATERIALS AND METHODS: Data (n=2,878) were drawn from the Global Youth Tobacco Survey for Nepal (GYTS, 2011). Channel-specific and cumulative TAPS exposure were the primary exposures of the study. Six multivariate logistic regression analyses were performed to examine current and ever cigarette use outcome with exposure to TAPS. Six binary logistic regression analyses were applied to determine the susceptibility to cigarette use when exposed to TAPS. RESULTS: Channel-specific TAPS analyses show that indirect TAPS increases the odds of all the three outcomes; current cigarette use (OR=1.68, 95% CI=1.10-2.58), ever cigarette use (OR=1.81, 95% CI=1.23-2.65) and susceptibility to cigarette use (OR=1.65, 95% CI=1.25-2.19) after adjusting for the covariates. Television (TV) and movies exposure decreases the odds of susceptibility to cigarette use (OR=0.55, 95% CI=0.31-0.97). Cumulative TAPS analyses show that exposure to 5 sources of TAPS increases the odds of current cigarette use (OR=2.53, 95% CI=1.21-5.29). Being male increases the odds of all the three outcomes; current (OR=3.52, 95% CI=2.11-5.87), ever (OR=2.51, 95% CI=1.69-3.73) and susceptibility to cigarette use (OR=1.31, 95% CI=1.01-1.69). Social influence is likely to increase current (OR=6.47, 95% CI=2.50-16.74), ever (OR=1.79, 95% CI=1.10-2.93) and susceptibility to cigarette use (OR=1.66, 95% CI=1.25-2.21). CONCLUSION: Indirect TAPS exposure increased the current, ever, and susceptibility to cigarette use among Nepalese adolescents. Overall, the current use of cigarettes followed a dose-response relationship with TAPS exposure. The result implies a requirement of active surveillance of tobacco products and future research on adolescent-focused tobacco marketing in Nepal.

Neuroinflammation and fibrosis in stroke: The good, the bad and the ugly.

Stroke is the leading cause of death and the main cause of disability in surviving patients. The detrimental interaction between immune cells, glial cells, and matrix components in stroke pathology results in persistent inflammation that progresses to fibrosis. A substantial effort is being directed toward understanding the exact neuroinflammatory events that take place as a result of stroke. The initiation of a potent cytokine response, along with immune cell activation and infiltration in the ischemic core, has massive acute deleterious effects, generally exacerbated by comorbid inflammatory conditions. There is secondary neuroinflammation that promotes further injury, resulting in cell death, but conversely plays a beneficial role, by promoting recovery. This highlights the need for a better understanding of the neuroinflammatory and fibrotic processes, as well as the need to identify new mechanisms and potential modulators. In this review, we summarize several aspects of stroke-induced inflammation, fibrosis, and include a discussion of cytokine inhibitors/inducers, immune cells, and fibro-inflammation signaling inhibitors in order to identify new pharmacological means of intervention.

Prevention of health care associated venous thromboembolism through implementing VTE prevention clinical practice guidelines in hospitalized medical patients: a systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in hospitalized patients. Numerous VTE prevention clinical practice guidelines are available but not consistently implemented. This systematic review explored effectiveness of implementing VTE prevention clinical practice guidelines on VTE risk assessment and appropriateness of prophylaxis in hospitalized adult medical patients and identified the interventions followed to improve the adherence to these guidelines. METHODS: Six electronic databases were searched for randomized controlled trials, clinical controlled trials, or pre/post evaluation studies up to January 2019. Studies identified were screened for eligibility by two reviewers independently. Data were extracted by two reviewers using a standardized form. Risk of bias was assessed using MINORS and the certainty of evidence for each outcome using the GRADE approach. RESULTS: Of the 3537 records identified, 36 were eligible; eight studies were included for qualitative synthesis and four for meta-analysis. The meta-analysis of the studies assessing the impact of implementing VTE clinical practice guidelines favored appropriate prophylaxis (RR 1.67, 95% CI 1.41 to 1.97, 552 patients). Potential risk of bias was assessed to be low for 28% of the studies. However, using GRADE, the certainty of the evidence of all outcomes was rated very low quality. CONCLUSIONS: The lack of randomized controlled trials in this area reduces the quality of the evidence available. The evidence from before-after studies suggests that the implementation of VTE clinical practice guidelines may increase the practice of VTE risk assessment and appropriate prophylaxis in hospitalized medical patients. TRIAL REGISTRATION: PROSPERO CRD42018085506.

Enhanced Hyaluronan Signaling and Autophagy Dysfunction by VPS35 D620N.

The motor features of Parkinson's disease (PD) result from the loss of dopaminergic (DA) neurons in the substantia nigra with autophagy dysfunction being closely linked to this disease. A PD-causing familial mutation in VPS35 (D620N) has been reported to inhibit autophagy. In order to identify signaling pathways responsible for this autophagy defect, we performed an unbiased screen using RNA sequencing (RNA-Seq) of wild-type or VPS35 D620N-expressing retinoic acid-differentiated SH-SY5Y cells. We report that VPS35 D620N-expressing cells exhibit transcriptome changes indicative of alterations in extracellular matrix (ECM)-receptor interaction as well as PI3K-AKT signaling, a pathway known to regulate autophagy. Hyaluronan (HA) is a major component of brain ECM and signals via the ECM receptors CD44, a top RNA-Seq hit, and HA-mediated motility receptor (HMMR) to the autophagy-regulating PI3K-AKT pathway. We find that high (>950 kDa), but not low (15-40 kDa), molecular weight HA treatment inhibits autophagy. In addition, VPS35 D620N facilitated enhanced HA-AKT signaling. Transcriptomic assessment and validation of protein levels identified the differential expression of CD44 and HMMR isoforms in VPS35 D620N mutant cells. We report that knockdown of HMMR or CD44 results in upregulated autophagy in cells expressing wild-type VPS35. However, only HMMR knockdown resulted in rescue of autophagy dysfunction by VPS35 D620N indicating a potential pathogenic role for this receptor and HA signaling in Parkinson's disease.