•The study examined protective and risk factors of intentions to quit vaping and quit attempts among adolescents, using a structural equation modeling approach.•Protective factors of intentions to ...quit vaping and quit attempts was risk perceptions of vaping.•Risk factors included e-cigarette marketing, vaping to deal with mental issues and for nicotine buzz, vaping frequency, nicotine dependence, grade level, and identifying as Hispanic or sexual minority.
Previous youth tobacco research has identified multiple factors relating to intentions to quit vaping and quit attempts among current e-cigarette users in adolescents. The pathways in the complex associations with vaping cessation behaviors remain unclear.
Using data from the 2022 National Youth Tobacco Survey (NYTS) (grades 6–12), structural equation models (SEMs) are developed to examine the associations of social environment, vaping risk perceptions, e-cigarette marketing, vaping characteristics, and demographics with two outcome measures – intentions to quit vaping and past year quit attempts among current e-cigarette users.
The national sample of current e-cigarette users (n = 2,701) consisted of 52.7 % females, 47.0 % non-Hispanic Whites, 80.1 % high school students, and 56.2 % heterosexual individuals. Among them, 70.2 % reported intentions to quit vaping and 66.3 % reported past year quit attempts. The protective factor for quit intentions was vaping risk perceptions (p < 0.001). Risk factors included e-cigarette marketing (p = 0.04), dual use of e-cigarettes and other tobacco products (p = 0.003), vaping due to feeling anxious or stressed (p = 0.01), vaping for nicotine buzz (p = 0.002), nicotine dependence (p = 0.02), identifying as Gay or Lesbian (p < 0.001), bisexual (p = 0.03), or Hispanic (p = 0.04). Similar associations were observed with quit attempts except that e-cigarette marketing, vaping due to feeling anxious or stressed, vaping dependence, and identifying as Hispanic were not significant. Besides, high vaping frequency (p < 0.001), grade level (p < 0.001) and not sure about sexual orientation (p = 0.01) were also negatively associated with quit attempts.
This study provided insights into factors influencing vaping cessation outcomes among adolescent current e-cigarette users. Developing tailored vaping cessation programs based on these findings could enhance quit success.
Background
Addiction is a significant problem among many Native American groups but has rarely been examined in urban populations. In particular, little is known about the context in which urban ...Native Americans first use substances. This study compares cases (people with a history of addiction) to controls (people without a history of addiction) on demographics, substance use history, context of first substance use, and polysubstance use. In addition, this appears to be the first study to overcome the lack of Native American professionals by employing and training lay community members to identify criteria of substance use disorders in survey participants. Employing community members helped foster trust that enabled the revelation of sensitive and often illegal activity. As a result, the investigators were able to recruit participants who likely would not have engaged with traditional researchers.
Methods
The trained Native American lay research assistants recruited community members and administered surveys. They first asked questions regarding the criteria for substance use disorders. Individuals who were determined to have met criteria for a substance use disorder in the past were classified as cases (
n
= 38) and those who never met such criteria were classified as controls (
n
= 42). They then asked demographic, substance use, and polysubstance use questions. Lastly, eight cases and eight controls were randomly selected for a second interview by a licensed drug and alcohol counselor (LDAC) who conducted a blinded assessment regarding the presence or absence of a history of a substance use disorder.
Results
Both groups reported a relatively young age of first substance use (age 16 years for cases and age 15 years for controls). Alcohol was the first substance most commonly used in both groups. Controls reported first benzodiazepine use at a younger age than cases but no other significant differences were found. Both groups reported first obtaining their first drug from family, friends, or at home (rather than a party, bar, or store). Most commonly, the location of their first use of drugs occurred at a friend’s home, a party, a bar, or school rather than at their own home. Cases were marginally more likely to report that their first drug use occurred with a friend rather than with a family member when compared with controls. The majority of both groups reported that their first drug use occurred with other Native Americans rather than with non-Native Americans. Polysubstance use was common in both groups (43–45%). There were no significant differences between the groups regarding polysubstance use. The LDAC arrived at the same determination as the trained research assistants on all eight cases and eight controls.
Alcohol intent (the susceptibility to initiating alcohol use) and alcohol sips (the initiation of alcohol) in youth are a multifactorial puzzle with many components. This research aims to examine the ...connection between genetic and environmental factors across sex, race and ethnicity.
Data was obtained from the twin hub of the Adolescent Brain Cognitive Development (ABCD) study at baseline (2016-2018). Variance component models were conducted to dissect the additive genetic (A), common (C) and unique environmental (E) effects on alcohol traits. The proportion of the total alcohol phenotypic variation attributable to additive genetic factors is reported as heritability (h2).
The sample (n = 1,772) included an approximately equal male-female distribution. The 886 same-sex twin pairs were 60.4% dizygotic (DZ), 39.6% monozygotic (MZ), 65.4% non-Hispanic Whites, 13.9% non-Hispanic Blacks, 10.8% of Hispanics with a mean age of 121.2 months. Overall, genetic predisposition was moderate for alcohol intent (h2 = 28%, p = .006) and low for alcohol initiation (h2 = 4%, p = 0.83). Hispanics (h2 = 53%, p < .0001) and Blacks (h2 = 48%, p < .0001) demonstrated higher alcohol intent due to additive genetic factors than Whites (h2 = 34%, p < .0001). Common environmental factors explained more variation in alcohol sips in females (c2 = 63%, p = .001) than in males (c2 = 55%, p = .003). Unique environmental factors largely attributed to alcohol intent, while common environmental factors explained the substantial variation in alcohol initiation.
Sex and racial/ethnic disparities in genetic and environmental risk factors for susceptibility to alcohol initiation can lead to significant health disparities. Certain populations may be at greater risk for alcohol use due to their genetic and ecological factors at an early age.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
WNT4, a member of the Wnt family of ligands, is critical for the development of the female reproductive tract. Analysis of Wnt4 expression in the adult uterus during pregnancy indicates that ...it may play a role in the regulation of endometrial stromal cell proliferation, survival, and differentiation, which is required to support the developing embryo. To investigate the role of Wnt4 in adult uterine physiology, conditional ablation of Wnt4 using the PRC” mouse model was accomplished. Ablation of Wnt4 rendered female mice subfertile due to a defect in embryo implantation and subsequent defects in endometrial stromal cell survival, differentiation, and responsiveness to progesterone signaling. In addition to altered stromal cell function, the uteri of PITe/+ Wnt4f/f (Wnt4d/d) mice displayed altered epithelial differentiation characterized by a reduction in the number of uterine glands and the emergence of a p63‐positive basal cell layer beneath the columnar luminal epithelial cells. The altered epithelial cell phenotype was further escalated by chronic estrogen treatment, which caused squamous cell metaplasia of the uterine epithelium in the Wnt4d/d mice. Thus, WNT4 is a critical regulator not only of proper postnatal uterine development, but also embryo implantation and decidualization.—Franco, H. L., Dai, D., Lee, K. Y., Rubel, C. S., Roop, D., Boerboom, D., Jeong, J.‐W., Lydon, J.‐P., Bagchi, I. C., Bagchi, M. K., DeMayo, F. J. WNT4 is a key regulator of normal postnatal uterine development and progesterone signaling during embryo implantation and decidualization in the mouse. FASEB J. 25, 1176–1187 (2011). www.fasebj.org
Mice lacking p63, a single gene that encodes a group of transcription factors that either contain (TA) or lack (ΔN) a transactivation domain, fail to develop stratified epithelia as well as ...epithelial appendages and limbs. ΔNp63 isoforms are predominantly expressed during late embryonic and postnatal epidermal development, however, the function of these proteins remains elusive. Using an epidermal-specific inducible knockdown mouse model, we demonstrate that ΔNp63 proteins are essential for maintaining basement membrane integrity and terminal differentiation of keratinocytes. Furthermore, we have identified two ΔNp63α target genes that mediate these processes. We propose that ΔNp63α initially induces expression of the extracellular matrix component Fras1, which is required for maintaining the integrity of the epidermal-dermal interface at the basement membrane. Subsequently, induction of IκB kinase-α by ΔNp63α initiates epidermal terminal differentiation resulting in the formation of the spinous layer. Our data provide insights into the role of ΔNp63α in epidermal morphogenesis and homeostasis, and may contribute to our understanding of the pathogenic mechanisms underlying disorders caused by p63 mutations.
Because consumer reviews leverage the wisdom of the crowd, the way in which they are aggregated is a central decision faced by platforms. We explore this “rating aggregation problem” and offer a ...structural approach to solving it, allowing for (1) reviewers to vary in stringency and accuracy, (2) reviewers to be influenced by existing reviews, and (3) product quality to change over time. Applying this to restaurant reviews from Yelp.com, we construct an adjusted average rating and show that even a simple algorithm can lead to large information efficiency gains relative to the arithmetic average.
E-cigarette use increased from 2017 to 2019 and then declined in 2020 among U.S. adults. It is important to understand whether the decline differed by smoking status and sociodemographic groups and ...whether daily e-cigarette use has subsequently changed. This study estimated e-cigarette use prevalence in 2019 and 2020 by analyzing the pooled National Health Interview Survey (n = 63,565) in 2022. Multivariable logistics regressions were performed to examine biannual change in current and daily e-cigarette use, overall and stratified by cigarette smoking status, sociodemographic factors, and subjective depression frequency. Among US adults, change in current e-cigarette use during 2019–2020 differed by smoking status (cigarette smoking status × year, p =.01) and race/ethnicity (race/ethnicity × year, p =.03). Current e-cigarette use prevalence decreased among current cigarette smokers (11.7 % to 8.0 %, p = 0.0001) but not among former or never smokers, and among Non-Hispanic White adults (5.1 % to 4.2 %, p = 0.04) and Non-Hispanic Black adults (3.4 % to 1.6 %, p = 0.0003) but not among other racial and ethnic groups. Current e-cigarette use also declined among those 25–64 years old but not among young adults 18–24 years old. Daily e-cigarette use did not significantly change during 2019–2020 in the overall sample (2.3 % to 2.0 %, p = 0.10), but declined among adults who were Non-Hispanic Black (2.4 % to 0.9 %, p = 0.0007), aged 35–44 years, and lived below the federal poverty level. Adults with monthly depressive episodes (vs without) continued to have a higher prevalence of current (7.0 % vs 3.0 %) and daily e-cigarette use (3.6 % vs 1.6 %) in 2020. Continuous monitoring of cross-population differences in adult e-cigarette use is warranted.
To evaluate the effects of a large population-based patient empowerment programme (PEP) on clinical outcomes and health service utilization rates in type 2 diabetes mellitus (T2DM) patients in the ...primary care setting.
A stratified random sample of 1,141 patients with T2DM enrolled to PEP between March and September 2010 were selected from general outpatient clinics (GOPC) across Hong Kong and compared with an equal number of T2DM patients who had not participated in the PEP (non-PEP group) matched by age, sex and HbA1C level group.
Clinical outcomes of HbA1c, SBP, DBP and LDL-C levels, and health service utilization rates including numbers of visits to GOPC, specialist outpatient clinics (SOPC), emergency department (ED) and inpatient admissions, were measured at baseline and at 12-month post-recruitment. The effects of PEP on clinical outcomes and health service utilization rates were assessed by the difference-in-difference estimation, using the generalized estimating equation models.
Compared with non-PEP group, PEP group achieved additional improvements in clinical outcomes over the 12-month period. A significantly greater percentage of patients in the PEP group attained HbA1C≤7% or LDL-C≤2.6 mmol/L at 12-month follow-up compared with the non-PEP group. PEP group had a mean 0.813 fewer GOPC visits in comparison with the non-PEP group.
PEP was effective in improving the clinical outcomes and reduced the general outpatient clinic utilization rate over a 12-month period. Empowering T2DM patients on self-management of their disease can enhance the quality of diabetes care in primary care.
ClinicalTrials.gov NCT01935349.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gene therapies have potential to improve outcomes of severe diseases after only a single administration. Novel therapies are continually being developed using knowledge gained from prior successes, a ...concept known as scientific spillover. Gene therapy advancement requires extensive development at each stage: preclinical work to create and evaluate vehicles for delivery of the therapy, design of clinical development programs, and establishment of a large-scale manufacturing process. Pioneering gene therapies are generating spillover as investigators confront myriad issues specific to this treatment modality. These include frameworks for construct engineering, dose evaluation, patient selection, outcome assessment, and safety monitoring. Consequently, the benefits of these therapies extend beyond offering knowledge for treating any one disease to establishing new platforms and paradigms that will accelerate advancement of future gene therapies. This impact is even more profound in rare diseases, where developing therapies in isolation may not be possible. This review describes some instances of scientific spillover in healthcare, and specifically gene therapy, using delandistrogene moxeparvovec (SRP-9001), a gene therapy recently approved by the US Food and Drug Administration for the treatment of ambulatory pediatric patients aged 4–5 years with Duchenne muscular dystrophy with a confirmed mutation in the DMD gene, as a case study.
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Rodino-Klapac and colleagues describe how knowledge gained from development and production of a gene therapy reaches beyond the therapy and its indication by helping accelerate further gene therapy advancements, a concept known as scientific spillover. An example of this is delandistrogene moxeparvovec, a novel gene therapy for Duchenne muscular dystrophy.
The loss of loricrin, a major component of the cornified envelope, results in a delay of epidermal barrier formation. Therefore, the living layers of the epidermis are aberrantly exposed to ...late-stage amniotic fluid, which may serve as the signal to upregulate genes that functionally compensate for the loss of loricrin. Consistent with this hypothesis, metabolomic studies revealed marked changes in amniotic fluid between E14.5 and E16.5 days postcoitum. In addition, we discovered that the Nrf2/Keap1 pathway detects these compositional changes and directly upregulates the expression of genes involved in the compensatory response, thus ensuring postnatal survival. In support of this finding, we demonstrate that genetically blocking the Nrf2 pathway abolishes the compensatory response and that preemptively activating Nrf2 pharmacologically rescues the delay in barrier formation in utero. Our findings reveal that the functions of Nrf2 and the composition of amniotic fluid have coevolved to ensure the formation of a functional barrier.
► Nrf2-activating metabolites are present in late-stage amniotic fluid ► Sprr2d and Sprr2h are direct downstream targets of Nrf2 in the epidermis ► Blocking the Nrf2 pathway in the loricrin null mouse results in postnatal lethality ► Pharmacological activation of Nrf2 in utero rescues the delay in barrier formation
Mutations in epidermal differentiation genes often cause a developmental delay in epidermal barrier formation, which must be resolved before birth to ensure survival. Huebner et al. discover that aberrant in utero exposure of keratinocytes to late-stage amniotic fluid activates the Nrf2/Keap1 pathway, and this compensatory mechanism rescues barrier formation.
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