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BACKGROUND & AIMS: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. METHODS: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. RESULTS: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002). CONCLUSIONS: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. IMPACT AND IMPLICATIONS: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

PURPOSE: Mental health inequalities continue to persist among American Indian/Alaska Native (AI/AN) people. However, few studies have examined the association of social networks and depression and anxiety among urban emerging AI/AN adults. METHODS: This study analyzes the association of social network characteristics with depression and anxiety among a sample of urban AI/AN emerging adults. A second set of regression models tested the same associations but controlling for respondent sexual and gender minority (SGM) status. Data were from a sample of 150 AI/AN emerging adults residing in urban areas from 20 different states (86% female; mean age 21.8; 48.0% SGM) who participated in a randomized controlled trial analyzing the effects of culturally grounded interventions on alcohol and other drug use and cultural connectedness. RESULTS: Participants with a higher proportion of network members who were around the same age reported significantly less anxiety. Those who had a higher proportion of network members who they sometimes/often argue/fight with were more likely to report greater depression and anxiety. Participants with higher proportions of social network members who have ever lived on a reservation/Rancheria/tribal land/tribal village reported significantly less depression. However, participants with higher proportions of social network members who lived 50 miles away or more reported significantly more depression. Controlling for SGM status, results were largely similar. DISCUSSION: Results highlight the role of social connections on the mental well-being of urban AI/AN emerging adults.

American Indian/Alaska Native (AI/AN) communities are disproportionately affected by the opioid epidemic. AI/AN emerging adults (ages 18-25) in urban areas are at particularly high risk, with the overdose death rate among urban-dwelling AI/AN people 1.4 times higher than rural-dwelling AI/AN people. Despite these challenges, there are no evidence-based culturally tailored prevention or intervention programs to address opioid, alcohol and other drug use among urban AI/AN emerging adults. This study focused on understanding AI/AN emerging adults experiences with two culturally tailored programs addressing opioid, cannabis, and alcohol use as part of the randomized controlled trial for Traditions and Connections for Urban Native Americans (TACUNA) in order to enhance feasibility of this intervention. Using a convergent mixed methods design at 3-month follow-up, we collected satisfaction and experience ratings and written narratives (total n = 162; intervention n = 77; control n = 85) from a sample of urban-dwelling AI/AN emerging adults who participated in both programs. We analyzed data through simultaneous examination of qualitative and quantitative data. The quantitative ratings show that both programs were rated highly. The qualitative data contextualized these ratings, illustrating pathways through which specific components were perceived to cause desired or observed behavioral change in participants. Among the elements that mattered most to these participants were the convenience of the virtual format, having a comfortable and safe space to share personal stories, and learning new information about their social networks. Negative comments focused on workshop length and inconvenient scheduling. This is one of the first studies to explore participant satisfaction and experience with culturally tailored substance use programming among a historically marginalized and understudied population. It is important to consider the voices of urban-dwelling AI/AN people in program development because hidden factors, such as limited financial resources, limited time, and misalignment with cultural values may prevent existing programs from being feasible.

Emerging adulthood shapes personal, professional, and overall well-being through identity exploration. This study addresses a gap in the minority identity literature by investigating how urban AI/AN emerging adults think about their identity and discussing challenges and protective factors associated with exploring their identity holistically. This mixed-methods study created a sampling framework based on discrimination experiences, cultural identity, social network support, mental health, and problematic substance use. We recruited 20 urban AI/AN emerging adults for interviews. We sought to gain deeper insights into their experiences and discussions surrounding identity formation and exploration. We provide descriptives for demographic characteristics and conducted a thematic analysis of the qualitative data from the interviews. Four themes emerged: a) being an urban AI/AN emerging adult means recognizing that ones identity is multifaceted; b) a multifaceted identity comes with tension of living in multiple worlds; c) the trajectory of ones identity grows over time to a deeper desire to connect with Native American culture; and d) understanding ones Native American background affects ones professional trajectory. Findings underscore the importance of developing programs to support well-being and identity development through cultural connection for urban AI/AN emerging adults.

BACKGROUND: Dilated cardiomyopathy (DCM) is a major complication of, and leading cause of mortality in Duchenne muscular dystrophy (DMD). Its severity, age at onset, and rate of progression display wide variability, whose molecular bases have been scarcely elucidated. Potential DCM-modifying factors include glucocorticoid (GC) and cardiological treatments, DMD mutation type and location, and variants in other genes. METHODS AND RESULTS: We retrospectively collected 3138 echocardiographic measurements of left ventricular ejection fraction (EF), shortening fraction (SF), and end-diastolic volume (EDV) from 819 DMD participants, 541 from an Italian multicentric cohort and 278 from the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS). Using generalized estimating equation (GEE) models, we estimated the yearly rate of decrease of EF (-0.80%) and SF (-0.41%), while EDV increase was not significantly associated with age. Utilizing a multivariate generalized estimating equation (GEE) model we observed that mutations preserving the expression of the C-terminal Dp71 isoform of dystrophin were correlated with decreased EDV (-11.01 mL/m2, p = 0.03) while for dp116 were correlated with decreased EF (-4.14%, p =

There are few substance use treatment and prevention programs for AI/AN people that integrate culturally based practices with evidence-based treatment and prevention. The National Institutes of Healths (NIHs) Helping to End Addiction Long-term (HEAL) Prevention Cooperative supports two projects focused on AI/AN populations. One focuses on youth ages 15 to 20 years living within the Cherokee Nation reservation, a multicultural rural area in northeastern Oklahoma, and the second focuses on emerging adults ages 18 to 25 years living in diverse urban areas. We provide a brief overview of the two prevention trials and a case comparison across approaches using the framework of promising practices for intervention science with Indigenous communities (Whitesell et al., 2020) related to (1) integration of Indigenous and academic perspectives to respond to community needs, (2) community partnership and engagement, (3) alignment with Indigenous cultural values and practices, (4) capacity building and empowerment, (5) implementation within complex cultural contexts, and (6) tribal oversight. Overall, these two projects highlight the importance of long-standing relationships with community partners, engaging the community at all levels to ensure that programming is culturally and developmentally appropriate, and having tribal and elder oversight. These practices are key to establishing trust and building confidence in research in these communities and ensuring that research can benefit AI/AN people. These studies showcase how strong partnerships can advance health and support the conduct of rigorous science to help pinpoint optimal health solutions by identifying efficacious, culturally grounded intervention strategies. Although the sovereign status of tribes demands this type of partnership, this research serves as a model for all community research that has a goal of improving health.

Current literature lacks clear examples of how to engage with communities in the development of opioid misuse interventions for diverse populations and across various settings. The National Institutes of Health (NIH) Helping to End Addiction Long-term® Initiative (HEAL) Prevention Cooperative (HPC) research projects work collaboratively with communities to develop and adapt their opioid misuse interventions to increase both feasibility and sustainability. Ten HPC projects were selected to receive NIH funding and are required to have partnerships with communities where their intervention is being conducted. This paper applies the Centers for Disease Control and Prevention (CDC)-adapted Public Participation Framework to examine the levels of community engagement used by each of these 10 HPC projects (Clinical and Translational Science Awards Consortium Community Engagement Key Function Committee Task Force on the Principles of Community Engagement, 2015). Using this framework, this paper illustrates the range of community engagement approaches and levels that the HPC projects rely on to develop, adapt, and adopt opioid prevention interventions across diverse populations and settings. This paper also lays a foundation for future examinations of the role of community engagement in intervention implementation and effectiveness and the level of community engagement that is necessary to improve intervention effectiveness.

OBJECTIVES: Assess associations between social networks and urban American Indian/Alaska Native emerging adults alcohol, cannabis, and opioid use and intentions. METHOD: American Indian/Alaska Native participants ages 18-25 (N = 150; 86% female) were recruited across the United States from 12/20 to 10/21 via social media. Participants named up to 15 people whom they talked with most over the past 3 months and reported who (a) used alcohol and cannabis heavily or used other drugs (e.g., opioid use), (b) engaged in traditional practices, and (c) provided support. They also reported past 3-month alcohol, cannabis, and opioid use and intentions to use. RESULTS: Having a higher proportion of network members engaging in regular cannabis and heavy alcohol use (but not other drugs) was associated with more frequent cannabis use and stronger cannabis use intentions. Participants with higher proportions of members engaging in heavy alcohol use, regular cannabis use, or other drug use and who did not engage in traditional practices were more likely to report cannabis use and greater intentions to use cannabis and drink alcohol. In contrast, participants with higher proportions of network members engaging in traditional practices and who did not report heavy alcohol use, regular cannabis use, or other drug use were less likely to report intentions to use cannabis or drink alcohol. CONCLUSIONS: Findings emphasize what many studies have shown among various racial/ethnic groups-having network members who use substances increases the chance of use. Findings also highlight that traditional practices may be an important part of the prevention approach for this population. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

BACKGROUND: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) are reported. METHODS: Eligible adults had R/R B-ALL and received one infusion of brexu-cel (1×10⁶ CAR T cells/kg) following conditioning chemotherapy. The primary endpoint was the CR/CRi rate per central review. Post hoc subgroup analyses were exploratory with descriptive statistics provided. RESULTS: Phase 1 and 2 patients (N=78) were included with median follow-up of 29.7 months (range, 20.7-58.3). High CR/CRi rates were observed across all prior therapy subgroups examined: 1 prior line of therapy (87%, n=15) and ≥2 prior lines (70%, n=63); prior blinatumomab (63%, n=38) and no prior blinatumomab (83%, n=40); prior inotuzumab (59%, n=17) and no prior inotuzumab (77%, n=61); and prior alloSCT (76%, n=29) and no prior alloSCT (71%, n=49). The frequency of Grade ≥3 cytokine release syndrome, neurological events, and treatment-related Grade 5 adverse events were largely similar among prior therapy subgroups.Median duration of remission (DOR) in responders with (n=14) and without (n=43) subsequent alloSCT was 44.2 (95% CI, 8.1 to not estimable (NE)) and 18.6 months (95% CI, 9.4 to NE); median OS was 47.0 months (95% CI, 10.2 to NE) and not reached (95% CI, 23.2 to NE), respectively. Median DOR and OS were not reached in responders without prior or subsequent alloSCT (n=22). CONCLUSIONS: In ZUMA-3, adults with R/R B-ALL benefited from brexu-cel, regardless of prior therapies and subsequent alloSCT status, though survival appeared better in patients without certain prior therapies and in earlier lines of therapy. Additional studies are needed to determine the impact prior therapies and subsequent alloSCT have on outcomes of patients who receive brexu-cel.

Urban American Indian/Alaska Native (AI/AN) young adults and their families are often geographically or socially distant from tribal networks and traditional social support. Young adults can be especially vulnerable to cultural and social disconnection, so understanding how AI/AN family functioning can augment resilience and protect against risk is important. This research precedes a preventive substance use intervention study and explores urban Native family functioning, emphasizing the role of young adults by analyzing data from 13 focus groups with urban AI/AN young adults (n = 32), parents (n = 25), and health providers (n = 33). We found that young adults can and want to become agents of family resilience, playing active roles in minimizing risks and strengthening family functioning in both practical and traditional ways. Also, extended family and community networks played a vital role in shaping family dynamics to support resilience. These resilience pathways suggest potential targets for intervention.

Abstract Background Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH. Methods Biospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction. Results Resistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P

OBJECTIVES: Food insecurity contributes to racial/ethnic disparities in health. This is the first study to examine associations among food insecurity, sleep, and cardiometabolic outcomes in urban American Indian/Alaska Native (AI/AN) youth. DESIGN: Participants were 142 urban AI/AN youth (mean age = 14 years, 58% female). Food insecurity and self-reported sleep disturbance were measured using validated surveys. A multi-dimensional sleep health composite was derived using questionnaires (ie, satisfaction, alertness) and actigraphy-derived indices (ie, duration, efficiency, regularity, timing). Cardiometabolic measures included body mass index, blood pressure, glycosylated hemoglobin, waist circumference, cholesterol, and triglycerides. Covariates were sex, age, and single-parent household. RESULTS: Greater food insecurity was significantly associated with greater body mass index (b = 0.12, p = .015), higher systolic blood pressure (b = 0.93, p = .03), and greater sleep disturbance (b = 1.49, p < .001), and marginally associated with lower sleep health composite scores (b = -0.09, p = .08). There was a significant indirect path from greater food insecurity to greater waist circumference through poorer sleep health (0.11, 95% bootstrapping CI: [0.01, 0.30]). CONCLUSION: Food insecurity is an important correlate of sleep and cardiometabolic health among urban AI/AN youth and should be addressed to reduce emerging health risks during this important developmental period. Policies to reduce food insecurity and increase access to healthy foods as well as sleep interventions for these youth could help, as preliminary findings suggest that sleep health may mediate the negative impact of food insecurity on cardiometabolic risks.

Museus são locais com potencial de promoção de emoções e criação de lembranças a partir das experiências que eles proporcionam. Nesse sentido, este artigo busca saber por que as pessoas visitam museus de ciência. O objetivo da pesquisa é conhecer a diversidade do público e facilitar a compreensão de seus interesses e motivações para essa prática cultural. A coleta de dados se deu por meio de um questionário impresso e autoaplicado, preenchido por visitantes adultos, acima de trinta anos, no decorrer das visitas a cinco museus de ciência, situados na região metropolitana do Rio de Janeiro. Com base nos conceitos de capital cultural, de ciência, interesse e motivação, a abordagem analítica aplicada foi qualiquantitativa, com auxílio do método do discurso do sujeito coletivo. Os achados trazem contribuições para o campo de estudos de público e lazer cultural. Emergem dos discursos o processo de aquisição, ampliação e transmissão dessas formas de capital para filhos, família e amigos, durante a interação com exposições e atividades educacionais e de divulgação oferecidas pelos museus de ciência. Essa compreensão pode contribuir para a elaboração de estratégias para atrair, reter e fidelizar seu público de visitação espontânea

ABSTRACT BACKGROUND: Deep penetrating endometriosis (DE) can affect abdominal and pelvic organs like the bowel and bladder, requiring treatment to alleviate symptoms. AIMS: To study and investigate clinical and surgical outcomes in patients diagnosed with DE involving the intestines, aiming to analyze the effectiveness of surgical treatments. METHODS: All cases treated from January 2021 to July 2023 were included, focusing on patients aged 18 years or older with the disease affecting the intestines. Patients without intestinal involvement and those with less than six months of post-surgery follow-up were excluded. Intestinal involvement was defined as direct invasion of the intestinal wall or requiring adhesion lysis for complete resection. Primary outcomes were adhesion lysis, rectal shaving, disc excision (no-colectomy group), and segmental resection (colectomy group) along with surgical complications like anastomotic leak and fistulas, monitored for up to 30 days. RESULTS: Out of 169 patients with DE surgically treated, 76 met the inclusion criteria. No colectomy treatment was selected for 50 (65.7%) patients, while 26 (34.2%) underwent rectosigmoidectomy (RTS). Diarrhea during menstruation was the most prevalent symptom in the RTS group (19.2 vs. 6%, p

This paper considers a twelve-year period (2008-2019) and examines to what extent conference presentations and journal publications from three leading literacy and language professional organizations addressed the topic of climate change. Despite it being perhaps the most significant "mega-problem" of the 21st century (Martin, 2007), findings from this study demonstrate that climate change was largely invisible across the thousands of presentations and publications in this data set. It is time literacy and language educators and corresponding professional associations reckon with this troubling reality.

OBJECTIVE: Sleep is a multi-dimensional health behavior associated with elevated risk of substance use. This is the first study to utilize a latent class approach to characterize sleep health across multiple dimensions and across time from late adolescence to emerging adulthood, and to examine associations with alcohol and cannabis use trajectories. METHODS: The sample included 2995 emerging adults (mean ages = 18 to 24 years across six waves of data collection; 54% female) who provided data on sleep dimensions (quality, duration, and social jetlag) and frequency and consequences of alcohol and cannabis use. Longitudinal latent class analysis (LLCA) models characterized participants according to the three sleep dimensions. Latent growth models examined trajectories of frequency and consequences of alcohol or cannabis use over time among emergent sleep classes, with and without controlling for covariates. RESULTS: LLCA models identified four sleep classes: good sleepers (n = 451; 15.2%); untroubled poor sleepers (n = 1024; 34.2%); troubled, moderately good sleepers (n = 1056; 35.3%); and suboptimal sleepers (n = 460; 15.4%). Good sleepers reported significantly lower levels of alcohol or cannabis use and consequences, and less of an increase in alcohol consequences as compared to suboptimal sleepers. CONCLUSIONS: Persistent poor sleep health was associated with higher levels of alcohol and cannabis use and consequences, and greater increases in alcohol-related consequences during the transition from late adolescence to emerging adulthood. Findings have important clinical implications, highlighting that addressing multi-dimensional sleep health may be an important, novel target of intervention to reduce substance use frequency and consequences.

BACKGROUND: Coupling social network visualizations with Motivational Interviewing in substance use interventions has been shown to be acceptable and feasible in several pilot tests, and has been associated with changes in participants substance use and social networks. The objective of this study was to assess acceptability and feasibility of an adaptation of this behavior change approach into a culturally centered behavior change intervention for American Indian/Alaska Native (AI/AN) emerging adults living in urban areas. AI/AN populations experience high rates of health disparities and substance use. Although 70% of AI/AN people live outside of tribal lands, there are few culturally tailored health interventions for these AI/AN populations. Social networks can both increase and discourage substance use. Leveraging healthy social networks and increasing protective factors among urban AI/AN emerging adults may help increase resilience. METHODS: We conducted thirteen focus groups with 91 male and female participants (32 urban AI/AN emerging adults ages 18-25, 26 parents, and 33 providers) and one pilot test of the three workshop sessions with 15 AI/AN emerging adults. Focus group participants provided feedback on a proposed workshop-based intervention curriculum that combined group Motivational Interviewing (MI) and social network visualizations. Pilot workshop participants viewed their own social networks during group MI sessions focused on substance use and traditional practices and discussed their reactions to viewing and discussing their networks during these sessions. We used a combination of open coding of focus group and workshop session transcripts to identify themes across the group sessions and content analysis of comments entered into an online social network interview platform to assess the extent that participants had an intuitive understanding of the information conveyed through network diagrams. RESULTS: Focus group and pilot test participants reacted positively to the intervention content and approach and provided constructive feedback on components that should be changed. Themes that emerged included feasibility, acceptability, relevance, understandability, and usefulness of viewing personal network visualizations and discussing social networks during group MI workshops. Workshop participants demonstrated an intuitive understanding of network concepts (network composition and structure) when viewing their diagrams for the first time. CONCLUSIONS: Social network visualizations are a promising tool for increasing awareness of social challenges and sources of resilience for urban AI/AN emerging adults. Coupled with Motivational Interviewing in a group context, social network visualizations may enhance discussions of network influences on substance use and engagement in traditional practices. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04617938. Registered October 26, 2020.

Genetic modifiers of Duchenne muscular dystrophy (DMD) are variants located in genes different from the disease-causing gene DMD, but associated with differences in disease onset, progression, or response to treatment. Modifiers described so far have been tested mainly for associations with ambulatory function, while their effect on upper limb function, which is especially relevant for quality of life and independence in non-ambulatory patients, is unknown. We tested genotypes at several known modifier loci (SPP1, LTBP4, CD40, ACTN3) for association with Performance Upper Limb version 1.2 score in an Italian multicenter cohort, and with Brooke scale score in the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS), using generalized estimating equation (GEE) models of longitudinally collected data, with age and glucocorticoid treatment as covariates. CD40 rs1883832, previously linked to earlier loss of ambulation, emerged as a modifier of upper limb function, negatively affecting shoulder and distal domains of PUL (p = 0.023 and 0.018, respectively) in the Italian cohort, as well as of Brooke score (p = 0.018) in the CINRG-DNHS. These findings will be useful for the design and interpretation of clinical trials in DMD, especially for non-ambulatory populations.

While scientific consensus about human-caused climate change has been clear for decades, denial of this science "and" denial about the need for timely, responsive action continue in the United States and around the world. The "Climate Denial Inquiry Model" can help educators grapple with the complex components of this denial with critical literacy+ and eco-civic practices of deliberation, reflexivity, and counter-narration to help investigate climate denial texts, stories, contexts, and philosophies. This charts a pathway toward ecojustice-centered stories-to-live by.

BACKGROUND: COVID-19 has profoundly affected sleep, although little research has focused on high-risk populations for poor sleep health, including American Indian/Alaska Native (AI/AN) adolescents. METHODS: This is the first longitudinal study to examine changes in sleep with surveys completed before the pandemic and during the early months of COVID-19 in a sample of urban AI/AN adolescents (N = 118; mean age = 14 years at baseline; 63% female). We use a mixed-methods approach to explore how COVID-19 affected urban AI/AN adolescents sleep, daily routines, and interactions with family and culture. Quantitative analysis examined whether pandemic-related sleep changes were significant and potential moderators of COVID-19s effect on sleep, including family and community cohesion and engagement in traditional practices. RESULTS: : Findings demonstrate changes in sleep, including increases in sleep duration, delays in bedtimes and waketimes, and increases in sleep-wake disturbances (ps

The increase in senescent cells in tissues, including the brain, is a general feature of normal aging and age-related pathologies. Senescent cells exhibit a specific phenotype, which includes an altered nuclear morphology and transcriptomic changes. Astrocytes undergo senescence in vitro and in age-associated neurodegenerative diseases, but little is known about whether this process also occurs in physiological aging, as well as its functional implication. Here, we investigated astrocyte senescence in vitro, in old mouse brains, and in post-mortem human brain tissue of elderly. We identified a significant loss of lamin-B1, a major component of the nuclear lamina, as a hallmark of senescent astrocytes. We showed a severe reduction of lamin-B1 in the dentate gyrus of aged mice, including in hippocampal astrocytes, and in the granular cell layer of the hippocampus of post-mortem human tissue from non-demented elderly. The lamin-B1 reduction was associated with nuclear deformations, represented by an increased incidence of invaginated nuclei and loss of nuclear circularity in senescent astrocytes in vitro and in the aging human hippocampus. We also found differences in lamin-B1 levels and astrocyte nuclear morphology between the granular cell layer and polymorphic layer in the elderly human hippocampus, suggesting an intra-regional-dependent aging response of human astrocytes. Moreover, we described senescence-associated impaired neuritogenic and synaptogenic capacity of mouse astrocytes. Our findings show that reduction of lamin-B1 is a conserved feature of hippocampal cells aging, including astrocytes, and shed light on significant defects in nuclear lamina structure which may contribute to astrocyte dysfunctions during aging.

Abstract Background Sepsis and associated organ failures confer substantial morbidity and mortality. Xanthine oxidoreductase (XOR) is implicated in the development of tissue oxidative damage in a wide variety of respiratory and cardiovascular disorders including sepsis and sepsis-associated acute respiratory distress syndrome (ARDS). We examined whether single nucleotide polymorphisms (SNPs) in the XDH gene (encoding XOR) might influence susceptibility to and outcome in patients with sepsis. Methods We genotyped 28 tag SNPs in XDH gene in the CELEG cohort, including 621 European American (EA) and 353 African American (AA) sepsis patients. Serum XOR activity was measured in a subset of CELEG subjects. Additionally, we assessed the functional effects of XDH variants utilizing empirical data from different integrated software tools and datasets. Results Among AA patients, six intronic variants (rs206805, rs513311, rs185925, rs561525, rs2163059, rs13387204), in a region enriched with regulatory elements, were associated with risk of sepsis (P

Objectives: There are limited public health data on urban American Indian/Alaska Native (AI/AN) populations, particularly adolescents. The current study attempted to address gaps by providing descriptive information on experiences of urban AI/AN adolescents across northern, central, and southern California.Design: We describe demographics and several behavioral health and cultural domains, including: alcohol and other drug (AOD) use, risky sexual behavior, mental and physical health, discrimination experiences, involvement in traditional practices, and cultural pride and belonging. We recruited 185 urban AI/AN adolescents across northern, central, and southern California from 2014 to 2017 who completed a baseline survey as part of a randomized controlled intervention trial.Results: Average age was 15.6 years; 51% female; 59% of adolescents that indicated AI/AN descent also endorsed another race or ethnicity. Rates of AOD use in this urban AI/AN sample were similar to rates for Monitoring the Future. About one-third of adolescents reported ever having sexual intercourse, with 15% reporting using alcohol or drugs before sex. Most reported good mental and physical health. Most urban AI/AN adolescents participated in traditional practices, such as attending Pow Wows and learning their tribal history. Adolescents also reported discrimination experiences, including being a victim of racial slurs and discrimination by law enforcement.Conclusions: This study describes a select sample of California urban AI/AN adolescents across several behavioral health and cultural domains. Although these adolescents reported numerous discrimination experiences and other stressors, findings suggest that this sample of urban AI/AN teens may be particularly resilient with regard to behavioral health.

Although approximately 70% of American Indians/Alaska Natives (AI/ANs) reside in urban areas, our knowledge of risk and protective factors among AI/ANs seeking substance use treatment within urban areas is limited. We analyze substance and commercialized cigarette use, AI/AN cultural identity and involvement, physical health and cognitive functioning, and mental health symptoms among 63 AI/AN adults seeking substance use treatment within an urban area in California. Alcohol (37%), marijuana (27%), and methamphetamine (22%) were the most commonly reported substances. Sixty-two percent used commercialized tobacco use. The majority of AI/AN adults (78%) engaged in at least one traditional practice during the past month and endorsed high levels of spiritual connectedness. Those who engaged in traditional practices demonstrated significantly less depression (p = 0.007) and anxiety (p = 0.04). Medical and mental health issues were not prominent, although participants revealed high levels of cognitive impairment. Results highlight the importance of utilizing AI/AN traditional practices for AI/AN adults seeking substance use treatment within urban areas. Clinical Trials Registry Number NCT01356667.