Inhibition effect of copper-bearing metals on arterial neointimal hyperplasia via the AKT/Nrf2/ARE pathway in vitro and in vivo.

In-stent restenosis can be caused by the activation, proliferation and migration of vascular smooth muscle cells (VSMCs), which affects long-term efficacy of interventional therapy. Copper (Cu) has been proved to accelerate the endothelialization and reduce thrombosis formation, but little is known about its inhibition effect on the excessive proliferation of VSMCs. In this study, 316L-Cu stainless steel and L605-Cu cobalt-based alloy with varying Cu content were fabricated and their effects on surface property, blood compatibility and VSMCs were studied in vitro and in vivo. CCK-8 assay and EdU assay indicated that the Cu-bearing metals had obvious inhibitory effect on proliferation of VSMCs. Blood clotting and hemolysis tests showed that the Cu-bearing metals had good blood compatibility. The inhibition effect of the Cu-bearing metals on migration of cells was detected by Transwell assay. Further studies showed that Cu-bearing metals significantly decreased the mRNA expressions of bFGF, PDGF-B, HGF, Nrf2, GCLC, GCLM, NQO1 and HO1. The phosphorylation of AKT and Nrf2 protein expressions in VSMCs were significantly decreased by Cu-bearing metals. Furthermore, it was also found that SC79 and TBHQ treatments could recover the protein expressions of phospho-AKT and Nrf2, and their downstream proteins as well. Moreover, 316L-Cu stent proved its inhibitory action on the proliferation of VSMCs in vivo. In sum, the results demonstrated that the Cu-bearing metals possessed apparent inhibitory effect on proliferation and migration of VSMCs via regulating the AKT/Nrf2/ARE pathway, showing the Cu-bearing metals as promising stent materials for long-term efficacy of implantation.

Prediction of Human Liver Microsome Clearance with Chirality-Focused Graph Neural Networks.

In drug candidate design, clearance is one of the most crucial pharmacokinetic parameters to consider. Recent advancements in machine learning techniques coupled with the growing accumulation of drug data have paved the way for the construction of computational models to predict drug clearance. However, concerns persist regarding the reliability of data collected from public sources, and a majority of current in silico quantitative structure-property relationship models tend to neglect the influence of molecular chirality. In this study, we meticulously examined human liver microsome (HLM) data from public databases and constructed two distinct data sets with varying HLM data quantity and quality. Two baseline models (RF and DNN) and three chirality-focused GNNs (DMPNN, TetraDMPNN, and ChIRo) were proposed, and their performance on HLM data was evaluated and compared with each other. The TetraDMPNN model, which leverages chirality from 2D structure, exhibited the best performance with a test R2 of 0.639 and a test root-mean-squared error of 0.429. The applicability domain of the model was also defined by using a molecular similarity-based method. Our research indicates that graph neural networks capable of capturing molecular chirality have significant potential for practical application and can deliver superior performance.

Youth Suicide Prevention Programming among the Mississippi Band of Choctaw Indians: Effects of the Lifelines Student Curriculum.

Suicide continues to be a leading cause of mortality for young people. Given persistent intersecting forms of disadvantage, Native American adolescents are especially vulnerable to mental health adversities and other suicide risk factors. The Mississippi Band of Choctaw Indians (MBCI) implemented the Choctaw Youth Resilience Initiative (CYRI), a five-year SAMHSA-funded project that began in 2019. This study uses Choctaw student pre-test/post-test survey data to examine the effectiveness of the Hazelden Lifelines Suicide Prevention Training curriculum for youth. A lagged post-test design was used, whereby post-surveys were administered at least one month after program completion. Several intriguing results were observed. First, the lagged post-test model was subject to some pre-to-post attrition, although such attrition was comparable to a standard pre/post design. Second, analyses of completed surveys using means indicated various beneficial effects associated with the Lifelines curriculum implementation. The greatest benefit of the program was a significant change in student perceptions concerning school readiness in response to a suicidal event. Some opportunities for program improvement were also observed. Our study sheds new light on suicide prevention training programs that can be adapted according to Native American youth culture. Program implementation and evaluation implications are discussed in light of these findings.

Expanding the Question-Persuade-Refer (QPR) Evidence Base: Youth Suicide Prevention among the Mississippi Band of Choctaw Indians.

Youth suicide risks have been on the rise or persistently elevated for decades, and Native American communities are especially vulnerable. This study provides a promising framework for suicide prevention among underserved populations in the U.S., especially Native American communities in states lacking strong suicide prevention supports. Our investigation reports the evaluation results of the Question-Persuade-Refer (QPR) gatekeeper training program, a key component of the SAMHSA-funded Choctaw Youth Resilience Initiative (CYRI) implemented by the Mississippi Band of Choctaw Indians (MBCI). QPR trains adult gatekeepers to identify youth at risk of suicide and refer them to certified mental health service providers. Standardized QPR pre-test and post-test training surveys were administered at in-person trainings delivered to youth-serving MBCI organization leaders and staff. Statistical analyses of all survey items indicate that QPR gatekeeper trainings significantly enhanced the knowledge of prevention practices and risk identification skills for the MBCI trainees. The robust evidence of positive changes revealed in this study suggests that QPR can be an effective suicide prevention program for underserved minority communities, especially Native American populations in rural states where suicide is a persistent and leading cause of mortality.

Constructing Innovative Covalent and Noncovalent Compound Libraries: Insights from 3D Protein-Ligand Interactions.

Noncovalent interactions between small-molecule drugs and protein targets assume a pivotal role in drug design. Moreover, the design of covalent inhibitors, forming covalent bonds with amino acid residues, requires rational reactivity for their covalent warheads, presenting a key challenge as well. Understanding the intricacies of these interactions provides a more comprehensive understanding of molecular binding mechanisms, thereby guiding the rational design of potent inhibitors. In this study, we adopted the fragment-based drug design approach, introducing a novel methodology to extract noncovalent and covalent fragments according to distinct three-dimensional (3D) interaction modes from noncovalent and covalent compound libraries. Additionally, we systematically replaced existing ligands with rational fragment substitutions, based on the spatial orientation of fragments in 3D space. Furthermore, we adopted a molecular generation approach to create innovative covalent inhibitors. This process resulted in the recombination of a noncovalent compound library and several covalent compound libraries, constructed by two commonly encountered covalent amino acids: cysteine and serine. We utilized noncovalent ligands in KLIFS and covalent ligands in CovBinderInPDB as examples to recombine noncovalent and covalent libraries. These recombined compound libraries cover a substantial portion of the chemical space present in the original compound libraries and exhibit superior performance in terms of molecular scaffold diversity compared to the original compound libraries and other 11 commercial libraries. We also recombined BTK-focused libraries, and 23 compounds within our libraries have been validated by former researchers to possess potential biological activity. The establishment of these compound libraries provides valuable resources for virtual screening of covalent and noncovalent drugs targeting similar molecular targets.

In silico construction of a focused fragment library facilitating exploration of chemical space.

Fragment-based drug design (FBDD) has emerged as a captivating subject in the realm of computer-aided drug design, enabling the generation of novel molecules through the rearrangement of ring systems within known compounds. The construction of focused fragment library plays a pivotal role in FBDD, necessitating the compilation of all potential bioactive ring systems capable of interacting with a specific target. In our study, we propose a workflow for the development of a focused fragment library and combinatorial compound library. The fragment library comprises seed fragments and collected fragments. The extraction of seed fragments is guided by receptor information, serving as a prerequisite for establishing a focused libraries. Conversely, collected fragments are obtained using the feature graph method, which offers a simplified representation of fragments and strikes a balance between diversity and similarity when categorizing different fragments. The utilization of feature graph facilitates the rational partitioning of chemical space at fragment level, enabling the exploration of desired chemical space and enhancing the efficiency of screening compound library. Analysis demonstrates that our workflow enables the enumeration of a greater number of entirely new potential compounds, thereby aiding in the rational design of drugs.

RPBP: Deep Retrosynthesis Reaction Prediction Based on Byproducts.

Retrosynthesis prediction is crucial in organic synthesis and drug discovery, aiding chemists in designing efficient synthetic routes for target molecules. Data-driven deep retrosynthesis prediction has gained importance due to new algorithms and enhanced computing power. Although existing models show certain predictive power on the USPTO-50K benchmark data set, no one considers the effects of byproducts during the prediction process, which may be due to the lack of byproduct information in the benchmark data set. Here, we propose a novel two-stage retrosynthesis reaction prediction framework based on byproducts called RPBP. First, RPBP predicts the byproduct involved in the reaction based on the product molecule. Then, it handles an end-to-end prediction problem based on the prediction of reactants by product and byproduct. Unlike other methods that first identify the potential reaction center and then predict reactant molecules, RPBP considers additional information from byproducts, such as reaction reagents, conditions, and sites. Interestingly, adding byproducts reduces model learning complexity in natural language processing (NLP). Our RPBP model achieves 54.7% and 66.6% top-1 retrosynthesis prediction accuracy when the reaction class is unknown and known, respectively. It outperforms existing methods for known-class reactions, thanks to the rich chemical information in byproducts. The prediction of four kinase drugs from the literature demonstrates the model's practicality and potential to accelerate drug discovery.

Just Plain Hot: Examining Summer Daily High Heat Indices and Community-Level Social Vulnerability on Emergency Medical Services On-Scene Responses in San Antonio, Texas, 2015-2018.

Introduction Increased summer heat has a deleterious effect on people's health and the healthcare system. Emergency Medical Services (EMS) are at the healthcare system frontline, responsive to the community and environmental conditions. The present study examined how EMS on-scene response is affected by community-level social vulnerability and heat. Methods The Centers for Disease Control and Prevention's Social Vulnerability Index, heat and humidity data from the National Weather Service, and City of San Antonio EMS data were collected. Data were analyzed using negative binomial regression models with time-stratified case-crossover design to observe independent and interactive effects of heat and social vulnerability on EMS on-scene response over four constricted calendar years. Results Results indicated that community-based social vulnerability and heat, independently and interactively, are associated with increased EMS on-scene responses. Conclusion Even when examining normal summertime heat conditions, there is evidence of the relationships between geographic and environmental conditions and the healthcare system.

The association between physical activity and subjective well-being among adolescents in southwest China by parental absence: a moderated mediation model.

OBJECTIVES: Built on the Positive Youth Development (PYD) framework, this study examined how physical activity affected the subjective well-being of adolescents in the multi-ethnic area of southwest China. The mediating role of school connectedness as an external development asset and the moderating role of resilience as an internal development asset were specified and tested within the framework of sport-based PYD. METHODS: A cross-sectional survey of 3143 adolescents (47.2% boys with mean age = 12.88 and SD = 1.68) was conducted in 2020. A structural equation model (SEM) was developed to estimate the direct effect of physical activity, the mediating effect of school connectedness, and the moderating effect of resilience on adolescents' subjective well-being. Multi-group comparison was made to investigate differences and similarities across three parental absence subgroups: (1) both parents present, (2) one parent absent, and (3) both parents absent. RESULTS: As surmised, physical activity, school connectedness, and resilience all positively and significantly affected adolescents' subjective well-being. SEM analyses revealed that school connectedness mediated the effect of physical activity on subjective well-being. Moreover, resilience moderated both the direct and indirect effects of physical activity (through school connectedness) on subjective well-being. Finally, the multi-group comparison revealed a moderating effect of parental absence on the moderated mediation model. LIMITATIONS: This study is a cross-sectional survey, so inference of causal associations among the study variables is impossible. CONCLUSIONS: Healthy lifestyle behaviors, school-supportive settings, and positive individual development assets can enhance the subjective well-being of adolescents in southwest China, especially those whose parents were absent. Physical activity interventions informed by the PYD framework should be incorporated into public health programs designed to foster the physical and mental health of left-behind adolescents in southwest China.

The association between tea consumption and blood pressure in the adult population in Southwest China.

OBJECTIVES: Prior research on the effect of tea consumption on blood pressure (BP) generated inconsistent findings. The objective of this study was to explore the effects of different types of tea consumption on BP. METHODS: We included 76,673 participants aged 30-79 from the baseline data of the China Multi-Ethnic Cohort (CMEC) study. Binary logistic regression was used to analyze the influences of different types of tea consumption on the risk of hypertensive BP. Moreover, multiple linear regression was used to examine the association between tea drinking and BP. RESULTS: Tea consumption was associated with a reduced risk of hypertensive BP by 10% (AOR: 0.90, 95%CI: 0.86-0.94). While dark tea was related to a 1.79-5.31 mmHg reduction in systolic blood pressure (SBP) and a 0.47-1.02 mmHg reduction in diastolic blood pressure (DBP), sweet tea, regardless of the duration, frequency, or amount of consumption, significantly was associated with a reduced SBP by 3.19-7.18 mmHg. Green tea also was associated with a reduced SBP by 1.21-2.98 mmHg. Although scented tea was related to reduced SBP by 1.26-2.48 mmHg, the greatest effect came from the long duration (> 40 years:ß=-2.17 mmHg, 95%CI=-3.47 mmHg --0.87 mmHg), low frequency (1-2 d/w: ß = -2.48 mmHg, 95%CI=-3.76 mmHg--1.20 mmHg), and low amount (≤ 2 g/d: ß=-2.21 mmHg, 95%CI=-3.01 mmHg--1.40 mmHg). Additionally, scented tea was correlated to a decrease in DBP at the frequency of 1-2 d/w (ß=-0.84 mmHg, 95%CI=-1.65 mmHg--0.02 mmHg). Drinking black tea only was associated with lowered SBP. The protective effect of black tea on SBP was characterized by the long-duration (> 15 years, -2.63--5.76 mmHg), high frequency (6-7 d/w, -2.43 mmHg), and medium amount (2.1-4.0 g/d, -3.06 mmHg). CONCLUSION: Tea consumption was associated with lower SBP and a reduced risk of hypertensive BP. The antihypertensive effect varies across types of tea consumed.

Racial Differences in Breastfeeding on the Mississippi Gulf Coast: Making Sense of a Promotion-Prevalence Paradox with Cross-Sectional Data.

Breastfeeding is less prevalent among African American women than their white peers. Moreover, breastfeeding rates in the South lag behind those in other regions of the U.S. Consequently, various efforts have been undertaken to promote breastfeeding among groups for which this practice is less common. This study examines African American and white racial disparities concerning (1) exposure to breastfeeding promotional information and (2) reported prevalence of breastfeeding in primary social networks. The survey combines a randomly selected sample of adults representative of the population and a non-random oversample of African Americans in a predominantly rural tri-county area on the Mississippi Gulf Coast. An initial wave of 2019 Mississippi REACH Social Climate Survey data collected under the auspices of the CDC-funded REACH program (Mississippi's Healthy Families, Mothers, and Babies Initiative; 2018-2023) is used to examine racial disparities in these two key outcomes for Mississippians in Hancock, Harrison, and Jackson counties. The results show that African American respondents are more likely to be exposed to breastfeeding promotional messages than their white counterparts. However, the reported prevalence of breastfeeding in African American respondents' primary social networks is significantly lower than that indicated by their white peers. These paradoxical results underscore the limitations of promotional efforts alone to foster breastfeeding. While breastfeeding promotion is important, the reduction of racial disparities in this practice likely requires a multi-pronged effort that involves structural breastfeeding supports (e.g., lactation spaces, peer networking groups, and pro-breastfeeding employment policies and workplaces). This study provides a promising model of innovative methodological approaches to the study of breastfeeding while underscoring the complex nature of racial disparities in lactation prevalence.

Antibacterial and anti-inflammatory activities of chitosan/copper complex coating on medical catheters: In vitro and in vivo.

Copper ions (Cu) grafted chitosan coating was prepared using the pneumatic spraying method on the silicone rubber surface. Coating's surface properties, morphology, composition, Cu releasing behavior, antibacterial, and anti-inflammatory activities are investigated and discussed. Surface properties, composition, and morphology were investigated by scanning electron microscopy (SEM) and contact angle measurements. The antibacterial activity has been tested with Escherichia coli and Staphylococcus aureus suspensions in vitro. Besides, the morphology of the biofilm was inspected with a field emission SEM. To evaluate the anti-inflammatory activity and biosafety of the coating in vivo, the optimized coating samples and control groups were implanted subcutaneously into the back of mice. The bacterial environment model was established by injection of the bacterial suspension. The morphology and bacterial adhered on the surface of catheters and the surrounding tissues were analyzed after 5 days of implantation. As in vitro results, the number of adhered bacterial on the surface of the silicon rubber surface was decreased, and the anti-inflammatory rate was increased by the intensify of the Cu content in chitosan coating. As for in vivo results, after 5 days of implantation, there was no evident inflammation in the surrounding tissues of all catheters in all without the S. aureus injected group. In the injected chitosan/Cu coated group; the inflammation, the number of the adhered bacteria were observed less than other injected samples without Cu; no inflammation were noticeable. Results indicate that the Cu-modified chitosan coating can confer excellent antibacterial and anti-inflammatory activity as applied on medical catheters.

Subjective well-being among AIDS orphans in southwest China: the role of school connectedness, peer support, and resilience.

BACKGROUND: Few studies have explored the health and development of AIDS orphans using the positive youth development (PYD) framework. Grounded in this framework, the main objective of this study is to examine how internal assets (i.e., resilience) and external assets (i.e., school connectedness, peer support) affect subjective well-being among Yi AIDS orphans in the Liangshan Yi Autonomous Prefecture, Sichuan province, China. METHODS: A cross-sectional survey was conducted by interviewing 571 AIDS orphans and 979 non-orphans of Yi ethnic minority from 5th-10th grades. Structural equation models (SEM) were utilized to identify and estimate the direct and indirect effects of internal and external assets on subjective well-being. RESULTS: The average score of subjective well-being was significantly lower for AIDS orphans than for in non-orphans (P < 0.05). Resilience, school connectedness, peer support (number of friends, caring friends), and self-rated physical health had significant and positive direct effects on subjective well-being. In addition, the effects of school connectedness, and peer support on subjective well-being were mediated by resilience. CONCLUSIONS: Positive individual and school-related contextual assets can bolster subjective well-being among AIDS orphans. The design of health intervention programs for AIDS orphans should incorporate these positive development assets.

Depression and sleep disorders among AIDS orphans in an HIV/AIDS high-epidemic area in China.

BACKGROUND: The Liangshan Yi Autonomous Prefecture is home to the largest population of Yi ethnic minority within mainland China. Due to the high HIV/AIDS epidemic, many Yi children become AIDS orphans who lost one or both parents to AIDS-related causes. This study explored the prevalence and correlates of AIDS orphans' depressive symptom, sleep disorders and their comorbidity. METHODS: A cross-sectional survey was conducted to collect pertinent information from 467 AIDS orphans and 856 non-orphans of Yi ethnic minority. Depressive symptoms were screened by a two-item Patient Health Questionnaire (PHQ-2). The symptoms of insomnia were assessed by the Insomnia Severity Index (ISI), which was complemented by one item from the Pittsburgh Quality Sleep Index (PSQI) to measure the frequency of nightmare. RESULTS: The prevalence of depression (26.8% vs. 20.4%, P = 0.009) and comorbidity of depression, insomnia and nightmare (7.5% vs. 4.3%, P = 0.046) was significantly higher for AIDS orphans than for non-orphans. Risk factors such as ostracization and self-reported poor physical health had stronger effects on depressive symptoms and sleep disorders for AIDS orphans than for non-orphans. On the other hand, peer support, as an important protective factor, was significantly and negatively associated with depressive symptoms and sleep disorders for AIDS orphans. CONCLUSIONS: AIDS orphans of Yi ethnic minority reported higher levels of depressive symptoms and comorbidity of depression and sleep disorders than their non-orphan counterparts. These symptoms were exacerbated by ostracization and self-rated poor physical health but lowered by peer support.

Intimate Partner Violence Victimization and Depressive Symptoms in Sichuan, China: Are There Gender Variations?

An emerging body of research has linked intimate partner violence (IPV) victimization with negative mental health outcomes among women in postreform China. However, limited scholarly attention has been given to the independent effects of multiple types of IPV victimization on depressive symptoms among men and women. Little is known if these independent effects will vary by gender in China where research on the association between IPV victimization and mental health did not emerge until fairly recently. Given this research paucity, this study aims to (a) examine the independent effects of different types of lifetime IPV victimization among married men and women in Sichuan province on their self-reported past 30-day depressive symptoms and (b) explore possible gender variations in these effects. The data utilized in this study came from a subsample of married men (N = 1,083) and women (N = 1,185) from the Third Survey of Chinese Women's Social Status 2010, a representative sample of adults aged 18 to 64 in Sichuan province. Statistical analyses indicate that all types of lifetime IPV victimization are significantly and positively associated with past 30-day depressive symptoms for women, whereas for men lifetime experiences of general controlling behavior and sexual IPV were not statistically associated with depressive symptoms. Moreover, the effects of multiple types of IPV victimization on depressive symptoms do not significantly vary by gender. Bearing this gender-neutral pattern in mind, health professionals, governmental officials, and researchers are strongly encouraged to focus on both married men and women in their IPV and mental health intervention, prevention, and treatment endeavors in postreform China.

Signaling sickness: the role of recalled sickness behavior and psychosocial factors in shaping communication style.

BACKGROUND AND OBJECTIVES: Active infection results in several outward signs in humans, including visible symptoms, changes in behavior and possible alterations in skin color and gait. A potential adaptive function of these indicators is to signal distress and elicit care from close others. We hypothesized that sickness behavior, a suite of stereotypical changes in mood and behavior, also serves to communicate health status to others. We further hypothesized that such outward signals/cues of health status would vary based on context and sociocultural norms. METHODOLOGY: We explored self-reported, recalled sickness behavior, communication style, demographics and theoretically relevant cultural factors in a large national US sample (n = 1259) using multinomial probit regressions. RESULTS: In accordance with predictions, relatively few participants were willing to talk or complain about sickness to strangers. Self-reported, recalled sickness behavior was associated with some communication styles but attention received from others was more consistently associated with potential signaling. Several cultural factors, including stoicism and traditional machismo, were also associated with different sickness signaling styles. CONCLUSIONS AND IMPLICATIONS: These preliminary, self-reported data lend some tentative support to the sickness behavior signaling hypothesis, though experimental or observational support is needed. The role of cultural norms in shaping how such signals are transmitted and received also deserves further attention as they may have important implications for disease transmission. LAY SUMMARY: Evolutionary medicine hypothesizes that signs and symptoms of infectious disease-including sickness behavior-have adaptive functions, one of which might be to reliably signal one's health status to others. Our results suggest that evolved signals like these are likely shaped by cultural factors.

Association between depression and HIV treatment outcomes in a US military population with HIV infection.

BACKGROUND: Depression is common among HIV-infected individuals and may contribute to suboptimal adherence to antiretroviral therapy (ART) and subsequent inability to attain viral load (VL) suppression. We evaluated associations between depression, self-reported adherence, and longitudinal HIV treatment outcomes in US Military HIV Natural History Study (NHS) participants with and without depression. METHODS: Male NHS participants with available ICD-9 data for mental health diagnoses, Center for Epidemiological Studies Depression (CES-D) measures, and self-reported adherence (SRA) were included. ART use was defined as ART initiation between 2006 and 2010, with follow-up through 2015. SRA was defined as taking 95% of ART doses and continuous ART was defined as longitudinal ART use with gaps < 30 days. Continuous VL suppression was defined as maintaining VLs < 200 c/mL on ART. To analyse the association between depression and HIV treatment outcomes, latent class analysis was used to create classes of depression trajectories: low depression (LD), recent onset depression (ROD) and high Depression (HD). RESULTS: Participants had a mean age of 32 (± 8.3) years at HIV diagnosis, and similar proportions were Caucasian (44.3%) or African American (40.8%). Overall, older participants at HIV diagnosis had greater odds of having 95% self-reported adherence (OR 1.06, 95% CI 1.02-1.12), and African Americans had lower odds (OR 0.41, 95% CI 0.22-0.76) compared to Caucasians (OR 1.49, 95% CI 0.52-4.28). However, there was no difference in SRA by depression trajectory. Participants with HD had an increased odds of taking ART continuously (OR 1.75, 95% CI 0.99-3.09), and those with ROD had significantly higher odds of virologic failure (OR 0.58, 95% CI 0.38-0.91). CONCLUSIONS: Although there was no observed association between depression and SRA, participants with ROD had lower odds of attaining the HIV treatment goal of VL suppression. Continued efforts to identify and aggressively manage mental health disorders is important to success along the HIV care continuum.

A latent profile analysis of the link between sociocultural factors and health-related risk-taking among U.S. adults.

BACKGROUND: Research suggests that health/safety behaviors (e.g., drinking heavily) and medical behaviors (e.g., donating blood) may be perceived as inherently risky, and further suggests there is substantial variation in the likelihood of engaging in a particular health-related risk behavior across people. Research examining demographic and sociocultural factors related to both health/safety and medical risk-taking is highly limited. Importantly, with very few exceptions the literature examining health risks characterized by potentially hazardous health behaviors (e.g, heavy alcohol use, driving without a seatbelt) is kept separate from the literature examining health risks characterized by potentially beneficial medical behaviors (e.g., donating blood, taking medication). In the interest of health promotion, it is critical for researchers to identify - and describe - individuals who are less inclined to engage in health-harming behaviors while at the same time being more inclined to engage in health-benefiting behaviors. Identifying such a subtype of individuals was the guiding aim for this study. METHOD: A national sample of adults in the United States responded to a survey on sociocultural and demographic correlates of health behaviors. Health-related risk-taking indicators were measured using the items from the health/safety and medical subscales of the DOSPERT-M. Subtypes of risk-takers were identified using latent profile analysis (LPA). Follow-up analyses to describe subtype demographic characteristics were conducted. RESULTS: LPA identified four subtypes of risk-takers, including a subtype (n = 565, 45% of the sample; labeled "divergent") that was comprised of individuals who highly endorsed medical risk-taking (e.g., taking medicine, giving blood) and minimally endorsed health/safety risk-taking (e.g., drinking heavily, unprotected sex). Subsequent analyses suggested that, among other findings, divergent profile members were likely to be married, endorse familial interdependence, and orient toward masculinity rather than femininity. CONCLUSION: By examining potentially modifiable factors related to individuals' inclinations to engage in health protective behaviors, this study is an important step toward improving current health behavior interventions among U.S. adults.

RPL41 sensitizes retinoblastoma cells to chemotherapeutic drugs via ATF4 degradation.

Retinoblastoma is the most common intraocular cancer with metastatic potential affecting infants and children. Although chemotherapy is available for retinoblastoma, side effects and drug resistance are frequent. Rpl41, encoding ribosomal protein L41 (RPL41), has been identified as a tumor suppressor gene, and its targeted degradation of activating transcription factor 4 (ATF4) produces an antitumor effect. The goal of the present study is to provide experimental evidence for the clinical application of a small peptide regimen in combination with chemotherapy for the treatment of retinoblastoma and to investigate the mechanism of their combined cytotoxicity. It was observed that treatment with the RPL41 peptide alone decreased the viability, migration, and invasion of retinoblastoma Y79 and Weri-Rb1 cells, in addition to promoting cell apoptosis and cell cycle arrest. Furthermore, RPL41 protein levels showed a significantly decreased trend in retinoblastoma specimens, whereas ATF4 protein levels tended to be increased. Mechanistically, ATF4 degradation as a result of RPL41 peptide treatment was observed in retinoblastoma Y79 and Weri-Rb1 cells. Most important, low-dose administration of the RPL41 peptide significantly enhanced the antitumor effect of carboplatin, and further analysis confirmed their synergistic effect as anti-retinoblastoma therapy, indicating that RPL41 sensitized Y79 and Weri-Rb1 retinoblastoma cells to carboplatin. Thus, our data provide a preclinical rationale for the exploration of the RPL41 peptide as a potential adjuvant to carboplatin treatment in retinoblastoma.

Substance abuse and HIV/STD prevention at a Hispanic-serving institution in South Texas: A study of racial/ethnic and gender heterogeneity and intersectionality.

The purpose of this study is to examine racial/ethnic and gender variations and intersectionality in the knowledge, attitudes, intentions, and behaviors pertaining to substance abuse (SA) and human immunodeficiency virus (HIV)/sexually transmitted disease (STD) prevention among racial/ethnic minority college students (ages 18-24) in South Texas. A total of 535 minority students completed a baseline survey between 2014 and 2016 (N = 535). Results revealed statistically significant (ranging from p < .05 to p < .001) racial/ethnic and gender variations in SA and HIV/STD prevention-related knowledge, attitudes, intentions, and behaviors. However, the significant interaction effects (i.e., intersectionality) were observed only for two of the nine composite variables. That is, although male minority students exhibited lower levels of awareness of sexual risks and safe sex negotiation skills than female minority students, Hispanic male students appeared to fare better in both awareness of sexual risks (p < .01) and safe sex negotiation skills (p < .05) compared to students of other racial/ethnic origin. Implications for prevention and intervention work involving minority college students are discussed.