RESUMEN
Mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), a mitochondrial microprotein, has been described as a novel regulator of glucose and lipid metabolism. In addition to its role as a metabolic regulator, MOTS-c prevents skeletal muscle atrophy in high fat-fed mice. Here, we examined the preventive effect of MOTS-c on skeletal muscle mass, using an immobilization-induced muscle atrophy model, and explored its underlying mechanisms. Male C57BL/6J mice (10 wk old) were randomly assigned to one of the three experimental groups: nonimmobilization control group (sterilized water injection), immobilization control group (sterilized water injection), and immobilization and MOTS-c-treated group (15 mg/kg/day MOTS-c injection). We used casting tape for the immobilization experiment. After 8 days of the experimental period, skeletal muscle samples were collected and used for Western blotting, RNA sequencing, and lipid and collagen assays. Immobilization reduced â¼15% of muscle mass, whereas MOTS-c treatment attenuated muscle loss, with only a 5% reduction. MOTS-c treatment also normalized phospho-AKT, phospho-FOXO1, and phospho-FOXO3a expression levels and reduced circulating inflammatory cytokines, such as interleukin-1b (IL-1ß), interleukin-6 (IL-6), chemokine C-X-C motif ligand 1 (CXCL1), and monocyte chemoattractant protein 1 (MCP-1), in immobilized mice. Unbiased RNA sequencing and its downstream analyses demonstrated that MOTS-c modified adipogenesis-modulating gene expression within the peroxisome proliferator-activated receptor (PPAR) pathway. Supporting this observation, muscle fatty acid levels were lower in the MOTS-c-treated group than in the casted control mice. These results suggest that MOTS-c treatment inhibits skeletal muscle lipid infiltration by regulating adipogenesis-related genes and prevents immobilization-induced muscle atrophy.NEW & NOTEWORTHY MOTS-c, a mitochondrial microprotein, attenuates immobilization-induced skeletal muscle atrophy. MOTS-c treatment improves systemic inflammation and skeletal muscle AKT/FOXOs signaling pathways. Furthermore, unbiased RNA sequencing and subsequent assays revealed that MOTS-c prevents lipid infiltration in skeletal muscle. Since lipid accumulation is one of the common pathologies among other skeletal muscle atrophies induced by aging, obesity, cancer cachexia, and denervation, MOTS-c treatment could be effective in other muscle atrophy models as well.
Asunto(s)
Micropéptidos , Proteínas Proto-Oncogénicas c-akt , Masculino , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones Endogámicos C57BL , Atrofia Muscular/etiología , Atrofia Muscular/prevención & control , Músculo Esquelético/metabolismo , Factores de Transcripción/metabolismo , Agua , LípidosRESUMEN
BACKGROUND: Opioid overdose deaths are of great concern to public health, with over one million lives lost since 1999. While many efforts have been made to mitigate these, Black communities continue to experience a greater burden of fatalities than their white counterparts. This study aims to explore why by working with Black community members in Indianapolis through semi-structured interviews. METHODS: Semi-structured one-on-one in-depth interviews were conducted in spring and summer of 2023 with Black residents (N = 23) of zip codes 46202, 46205, 46208, and 46218 in Indianapolis. Ten interview questions were used to facilitate conversations about opioid overdoses, recovery, fatality prevention tools such as calling 911 and naloxone, law enforcement, and racism. Data were analyzed using grounded theory and thematic analysis. RESULTS: Interviews revealed access barriers and intervention opportunities. Racism was present in both. Mental access barriers such as stigma, fear, and mistrust contributed to practical barriers such as knowledge of how to administer naloxone. Racism exacerbated mental barriers by adding the risk of race-based mistreatment to consequences related to association with substance use. Participants discussed the double stigma of substance use and being Black, fear of being searched in law enforcement encounters and what would happen if law enforcement found naloxone on them, and mistrust of law enforcement and institutions that provide medical intervention. Participants had favorable views of interventions that incorporated mutual aid and discussed ideas for future interventions that included this framework. CONCLUSIONS: Racism exacerbates Blacks' mental access barriers (i.e., help-seeking barriers), which, in turn, contribute to practical barriers, such as calling 911 and administering naloxone. Information and resources coming from people within marginalized communities tend to be trusted. Leveraging inter-community relationships may increase engagement in opioid overdose fatality prevention. Interventions and resources directed toward addressing opioid overdose fatalities in Black communities should use mutual aid frameworks to increase the utilization of the tools they provide.
Asunto(s)
Sobredosis de Droga , Sobredosis de Opiáceos , Trastornos Relacionados con Opioides , Trastornos Relacionados con Sustancias , Humanos , Antagonistas de Narcóticos/uso terapéutico , Sobredosis de Opiáceos/tratamiento farmacológico , Naloxona/uso terapéutico , Sobredosis de Droga/prevención & control , Sobredosis de Droga/tratamiento farmacológico , Trastornos Relacionados con Sustancias/tratamiento farmacológico , Analgésicos Opioides/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológicoRESUMEN
BACKGROUND: Dual use of combustible cigarettes and e-cigarettes is an emerging phenomenon among U.S. adults. Literature suggests two primary reasons for this emerging use (i.e., to help quit smoking and to stealth vape). This study investigated user profiles based on use intensity and the reasons for dual use. METHODS: A total of 1,151 U.S. adult dual users were drawn from the 2018-2019 Tobacco Use Supplement to the Current Population Survey. We divided them into four groups: daily dual users (n = 189), predominant smokers (n = 608), predominant vapers (n = 143), and non-daily dual users (n = 211). We performed weighted multivariable logistic regressions to identify factors associated with the two primary reasons for dual use. RESULTS: 3 in 10 of U.S. adult dual users used e-cigarettes to help quit smoking while 2 in 10 of U.S. adult dual users used e-cigarettes to stealth vape. Compared to daily dual users, predominant smokers [adjusted odds ratio (AOR) = 0.61, 95% CI = 0.23, 0.62] were less likely to use e-cigarettes to help quit smoking whereas predominant vapers (AOR = 1.80, 95% CI = 1.04, 3.13) were more likely to use e-cigarettes to help quit smoking and less likely to use e-cigarettes to stealth vape (AOR = 0.30, 95% CI = 0.10, 0.89). CONCLUSIONS: There was notable heterogeneity among the four groups of dual users. As the landscape of tobacco use is rapidly changing with an increasing popularity of e-cigarettes, reasons as well as behaviors of dual users need to be regularly monitored for effective tobacco control.
Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Cese del Hábito de Fumar , Productos de Tabaco , Vapeo , Adulto , Humanos , Vapeo/epidemiología , FumadoresRESUMEN
This study examined the associations of preferred flavorings and device type of ENDS with box or pack purchase behavior. We analyzed current adult ENDS users in the United States who reported purchase of their own ENDS. Logistic regression revealed an increased likelihood of box/pack purchase behavior among users of menthol or mint-flavored ENDS, disposable, pod-based devices, and those who purchase ENDS from the Internet. A moderation analysis showed that the magnitude of the association between menthol or mint-flavored ENDS use and box/pack purchase was stronger among disposable and pod-based device users compared to tank or mods (customizable devices) users. In a subsequent stratified analysis menthol or mint flavor users were more likely than non-flavor users to engage in box/pack purchase among disposable and pod-based device users, but not among tank or mods users. Regulating flavors and maximum unit sale quantities of ENDS by device could thwart ENDS box/pack purchase behavior.
Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Vapeo , Adulto , Aromatizantes , Humanos , Modelos Logísticos , Estados UnidosRESUMEN
OBJECTIVES: Prior studies that examined the role of electronic nicotine delivery systems (ENDS) use in smoking cessation have shown divergent conclusions. This study examined the time-course of ENDS-associated smoking abstinent behaviors among continuing cigarette smokers who were willing but unable to quit smoking. METHODS: Data were drawn from the four waves of the Population Assessment of Tobacco and Health Study. Of the 1684 smokers who tried to quit smoking completely at Wave 1, a total of 1094 who were continuing smokers until Wave 4 and were not lost to follow-ups comprised the sample. Using generalized linear mixed modeling, we fitted weighted negative binomial regression models to examine within-person associations of ENDS use with quit attempts and number of days abstinent from smoking. RESULTS: Quit attempt frequency and smoking abstinent days were highest at Wave 1, dropped at Wave 2, and then either increased a little or remained stagnant in later waves. ENDS use to quit smoking was associated with more frequent quit attempts (aIRR = 1.67, 95% CI = 1.42-1.95) and more abstinent days (aIRR = 3.28, 95% CI = 2.43-4.44), and the magnitude of such associations became stronger over time. ENDS use was associated with becoming a nondaily smoker among baseline daily smokers. CONCLUSIONS: ENDS use among continuing smokers may help increase the number of quit attempts and smoking abstinent days. Given that the study sample is continuing smokers who failed in complete smoking cessation, future research would be desirable that evaluates whether such abstinent behaviors sustain and manifest harm reduction with improved health outcomes. IMPLICATIONS: Smokers increasingly adopt electronic nicotine delivery systems (ENDS) to quit smoking. However, the association of ENDS use with smoking cessation efforts among continuing cigarette smokers who were willing but unable to quit smoking is largely unknown. This study found that quit attempts and smoking abstinent days increased with ENDS use to quit smoking by following up with population-representative continuing smokers. Additionally, this study assessed whether cigarette smokers' abstinent behaviors vary with their use of ENDS by estimating within-person associations with frequent assessments of both exposures and outcomes in a long-term perspective.
Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Cese del Hábito de Fumar , Productos de Tabaco , Adulto , Humanos , Fumadores , FumarRESUMEN
Intervention strategies to prevent adolescents from using electronic nicotine delivery systems (ENDS) should be based on robust predictors of ENDS use that may differ from predictors of conventional cigarette use. Literature points to the need for uncovering emerging predictors of ENDS use. This study identified emerging predictors of adolescent ENDS use using machine learning (ML) techniques. We analyzed nationally representative multi-wave longitudinal survey data (2013-2018) drawn from the Population Assessment of Tobacco and Health Study. A sample of adolescents (12-17 years) who never used any tobacco products at baseline and completed Wave 2 (n = 7958), Wave 3 (n = 6260) and Wave 4 (n = 4544) were analyzed. We developed a supervised ML prediction model using the penalized logistic regression to assess self-reported past-month ENDS use (i.e., current use) at Waves 2-4 based on the variables measured at the previous wave. We then extracted important predictors from each model. The penalized logistic regression models showed suitable capability to discriminate between ENDS uses and non-uses at each wave based on the area under the receiver operating characteristic curve and the area under the precision-recall curve. Interestingly, social media use emerged as an important variable in predicting adolescent ENDS use. ML models appear to be a promising method to identify unique population-level predictors for U.S. adolescent ENDS use behaviors. More research is warranted to investigate emerging predictors of ENDS use and experimentally examine the mechanism by which these emerging predictors affect ENDS use behavior across different spectrum of populations.