Rab8, Rab11, and Rab35 coordinate lumen and cilia formation during zebrafish left-right organizer development.

An essential process during Danio rerio's left-right organizer (Kupffer's Vesicle, KV) formation is the formation of a motile cilium by developing KV cells which extends into the KV lumen. Beating of motile cilia within the KV lumen directs fluid flow to establish the embryo's left-right axis. However, the timepoint at which KV cells start to form cilia and how cilia formation is coordinated with KV lumen formation have not been examined. We identified that nascent KV cells form cilia at their centrosomes at random intracellular positions that then move towards a forming apical membrane containing cystic fibrosis transmembrane conductance regulator (CFTR). Using optogenetic clustering approaches, we found that Rab35 positive membranes recruit Rab11 to modulate CFTR delivery to the apical membrane, which is required for lumen opening, and subsequent cilia extension into the lumen. Once the intracellular cilia reach the CFTR positive apical membrane, Arl13b-positive cilia extend and elongate in a Rab8 dependent manner into the forming lumen once the lumen reaches an area of 300 µm2. These studies demonstrate the need to acutely coordinate Rab8, Rab11, and Rab35-mediated membrane trafficking events to ensure appropriate timing in lumen and cilia formation during KV development.

Comparative feasibility and preliminary efficacy of CBT for insomnia among adults seeking and not seeking addiction treatment.

Two out of three adults seeking treatment for alcohol or other substance use disorders report co-occurring symptoms of insomnia. This study compared the feasibility, acceptability, and preliminary efficacy of cognitive behavioural therapy for insomnia (CBT-I) among adults seeking and not seeking treatment for substance use. Adults with alcohol or other substance use disorders (n = 22, 32% female, 82% White; Mage = 39.5) completed assessments at baseline, post-treatment, and at 6 week follow-up. Of those, 11 were and 11 were not enrolled in substance use treatment. All received CBT-I. Multiple imputation was used for missing data. Data were analysed using repeated measures analyses of variance. In the substance use treatment group, 6/11 completed post and 5/11 completed follow-up. In the non-treatment group, 9/11 completed post and 7/11 completed follow-up. Participants in both groups reported improvements in insomnia severity, sleep onset latency, and dysfunctional beliefs about sleep, with most effects evident at post and follow-up. There was a marginal group-by-time interaction in the change in frequency of substance use, with only participants not in substance use treatment reporting decreases at follow-up. Participants in substance use treatment reported significant reductions in substance-related problems and symptoms of post-traumatic stress disorder over time; however, they also reported more symptoms at baseline. CBT-I produces similar reductions in insomnia but is relatively less feasible among individuals in (versus not in) treatment for substance use disorder. This may be due to the more complex logistics of accessing CBT-I among those in treatment. We speculate that integrating CBT-I into treatment for addictions may improve feasibility in this population. clinicaltrials.gov NCT04198311.

An exploratory analysis of drinking motives and alcohol-related problems among Hispanic college students.

The increase in college enrollment for Hispanic college students warrants increased attention to their health and wellness. Given that a common threat to health and well-being in college students is alcohol use and that Hispanic college students are at elevated risk for alcohol-related problems, it is essential to investigate factors that might lead to heightened alcohol-related problems among this population. The present study is a secondary data analysis of an NIAAA-funded study investigating brief interventions for alcohol use among 583 heavy-drinking college students. Specifically, we examined the relationship between Hispanic student status and alcohol-related problems measured one month later. Additionally, we examined the indirect effects of Hispanic status on alcohol-related problems through drinking motives. Analyses revealed a significant association between Hispanic status and alcohol-related problems at baseline but no association between Hispanic status and problems at 1-month, controlling for baseline problems. An indirect effect of the prospective association between Hispanic student status and alcohol-related problems was evident for only one of the four drinking motives (coping). Our findings suggest that reducing coping motives for drinking among Hispanic college students may reduce alcohol-related problems.

Moral injury, mental health and behavioural health outcomes: A systematic review of the literature.

Despite a burgeoning of research on moral injury in the past decade, existing reviews have not explored the breadth of consequences and the multitude of pathways through which moral injury and potentially morally injurious experiences (PMIEs) influence mental and behavioural health outcomes. This study aimed to identify associations between moral injury on mental and behavioural health. Literature searches of psychological and medical databases were conducted through April 2020. Eligible studies measured moral injury or PMIEs, and health outcomes (e.g., depression, substance use and suicidality). Fifty-seven publications representing 49 separate samples were included. Studies examined the impact of moral injury on post-traumatic stress disorder (PTSD) (n = 43); depression (n = 32); anxiety (n = 15); suicide (n = 15); substance use (n = 14); and 'other' health outcomes, including pain, burnout, sleep disturbance and treatment-seeking behaviours (n = 11). The majority of studies found significant positive associations between moral injury-related constructs, mental health and behavioural health outcomes; however, the majority were also cross-sectional and focused on military samples. Proposed mediators included lack of social support, negative cognitions and meaning-making. Moderators included self-compassion, pre-deployment mental health education and mindfulness. Moral injury is associated with a variety of negative health outcomes. Research is needed to determine the mechanisms by which moral injury may influence these outcomes over time.

Insomnia treatment effects among young adult drinkers: Secondary outcomes of a randomized pilot trial.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) has moderate-to-large effects on insomnia among young adult drinkers, with preliminary data indicating that improvements in insomnia may have downstream effects on alcohol-related consequences. However, the mechanism(s) by which insomnia treatment may facilitate reductions in alcohol-related problems is unclear. Secondary outcome data from a randomized pilot trial were used to examine CBT-I effects on four proposed mediators of the insomnia/alcohol link: alcohol craving, delay discounting, negative affect, and difficulties with emotion regulation. METHODS: Young adults (ages 18 to 30 years) with insomnia who reported 1+ binge drinking episode (4/5+ drinks for women/men) in the past month were randomized to receive CBT-I (n = 28) or to a sleep hygiene control (n = 28). Outcomes were assessed at baseline, after 5 weeks of treatment, and at 1-month posttreatment. RESULTS: Relative to those in sleep hygiene, CBT-I participants reported greater decreases in alcohol craving (d = 0.33) at the end of treatment and greater 1-month posttreatment decreases in delay discounting of large rewards (d = 0.42). CBT-I did not have a significant effect on delay discounting of smaller rewards or momentary negative affect. There was also no significant treatment effect on difficulties with emotion regulation, although findings were confounded by a significant group difference at baseline in difficulties with emotion regulation. CONCLUSIONS: Treatment of insomnia may lead to improvements in alcohol craving and delay discounting of large rewards among young adult drinkers with insomnia. Additional research examining whether improvement in insomnia is a mechanism for improvement in addiction domains is warranted.

Positive associations between potentially morally injurious experiences and alcohol outcomes in college students: Results from a dominance analysis.

OBJECTIVE: A novel framework for understanding college students' alcohol use is moral injury-psychological distress that stems from events that violate moral beliefs. Considering the predominantly positive associations between moral injury and alcohol use in military samples, this relationship may extend to students. The purpose of this study was to examine the association between potentially morally injurious experiences (PMIEs), alcohol use, and related consequences. Furthermore, we aimed to determine the relative importance of PMIE subtypes on alcohol outcomes. METHOD: Participants included 604 college students (78% female; 38% Caucasian) with a mean age of 21 years (SD = 4.44). We hypothesized that (a) the composite PMIE score would be positively associated with alcohol consumption and consequences and (b) Commission with Agency would have the strongest association with alcohol outcomes, followed by Betrayal, Omission, Commission under Duress, posttraumatic stress (PTS) symptoms, and Witnessing. RESULTS: Analyses revealed that PMIEs were positively associated with alcohol-related consequences but not drinks per week when controlling for PTS symptoms. Moreover, the dominance analysis showed that Commission with Agency had the strongest association with consumption, followed by Betrayal, PTS symptoms, Commission under Duress, Witnessing, and Omission. PTS symptoms had the strongest association with alcohol-related consequences, followed by Commission with Agency, Commission under Duress, Omission, Betrayal, and Witnessing. CONCLUSIONS: These findings help distinguish moral injury constructs from PTS and highlight the importance of Commission with Agency in analyzing alcohol outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Shame-and-guilt-proneness, interpersonal sensitivity, and alcohol: Results from a moderated mediation.

BACKGROUND: Shame-proneness has been consistently associated with more problematic alcohol outcomes, and guilt-proneness has been associated with fewer. The aim of this study was to determine if the associations of shame-and-guilt-proneness with alcohol outcomes vary as a function of interpersonal sensitivity. METHOD: A longitudinal study examined shame-proneness and guilt-proneness as predictors of alcohol consumption and related problems one month later. This research was conducted at a large public university in the United States. RESULTS: Participants (N=414) were heavy-drinking college students (51% female) with a mean age of 21.76 (SD=2.02) who consumed an average of 12.13 (SD=8.81) standard drinks per week. Shame-proneness, but not guilt-proneness, was directly associated with increased drinking and indirectly associated with increased problems. The indirect effects of shame on problems through drinking were stronger at higher levels of interpersonal sensitivity. CONCLUSIONS: Results suggest that shame-proneness may increase alcohol consumption and subsequent problems among those high in interpersonal sensitivity. Alcohol may be used as a means to withdraw from social threats that are amplified by interpersonal sensitivity.

Longitudinal associations between descriptive and injunctive norms on college drinking.

Perceived norms of drinking prevalence (descriptive norms) and approval (injunctive norms) are among the most robust predictors of college student drinking, but the dynamic fluctuations of these relationships over time are less understood. We examined longitudinal associations of descriptive and injunctive norms on alcohol consumption, disaggregating within-person fluctuations from between-person associations. Participants were 593 heavy drinking college students who completed measures of perceived descriptive and injunctive norms and drinking at baseline, one month, three months, six months, and 12 months. Longitudinal multilevel model analyses revealed that, at the between-person level, only descriptive norms predicted drinking. In contrast, both descriptive and injunctive norms at the within-person level predicted weekly drinking. The findings are the first to examine between- and within-person effects of descriptive and injunctive norms simultaneously on drinking and suggest that future college drinking interventions using normative influence would benefit from recognizing and incorporating within-person fluctuations in perceived norms.

Perceived belonging on campus predicts depression among heavy drinkers: A test of three moderators.

Objective: An association exists between perceived belonging and depression among college students. Because a student's sense of belongingness may vary as a function of their social identity, three identities - ethnicity, first-generation college student status, and sex - were investigated as potential moderators of this relationship. Participants: One hundred eighty-seven heavy-drinking college students (63% female; 52% non-Latinx White; M = 20 years of age) were assessed. Methods: Three hierarchical linear regressions were conducted to test whether belonging at baseline predicted depression at six months and whether each identity variable moderated this association. Results: Analyses yielded significant main effects between belonging and depression. Hispanic nor first-generation status interacted with belonging in predicting depression. Sex interacted with belonging where higher belongingness was associated with lower levels of depression only among female students. Conclusion: Mental health providers should consider asking female students about their perceptions of belonging on college campuses to understand their vulnerability to depression.

Gender, acculturation, and alcohol-related consequences among college students of color.

OBJECTIVE: The present study examined if identification with mainstream American culture (acculturation) and heritage culture (enculturation) are differentially associated with blackouts and other drinking consequences among male and female college students of color. PARTICIPANTS: Participants were college students (N = 150) who self-identified as a racial/ethnic minority and endorsed blackouts in the past year. METHODS: Regression models were used to examine gender-by-acculturation/enculturation interaction effects on alcohol-induced blackout and other alcohol-related consequences. RESULTS: While acculturation was not significantly associated with either drinking outcome, enculturation showed a significant relationship with blackout frequency. Gender moderated this relationship; greater enculturation was associated with increased blackout frequency among male but not female students. CONCLUSIONS: The present findings suggest the importance of considering the interplay between enculturation and gender in understanding alcohol use among college students of color. Men who endorse high levels of enculturation may be at an increased risk of experiencing negative drinking-related consequences.

Motives for and Barriers to Research Participation Among Racially and Ethnically Diverse Veterans.

INTRODUCTION: Veterans in general-and especially those who identify as Veterans of color-are underrepresented in health-related treatment research. This contributes to health inequity by hindering the development of evidence-based treatment recommendations for people of color. This project utilized culturally centered research procedures to identify health-related research priorities and examine motives for and barriers to research participation in a diverse sample of Veterans. MATERIALS AND METHODS: Veterans (N = 330, 32% female; 36% Black, 28% White, 15% Latinx, 12% Asian, 4% Multiracial) reported their experiences with and perspectives on health-related research online from remote locations. Linear regression was used to test associations between discrimination and motives/barriers for research. All procedures were approved by the Institutional Review Board (#2033562). RESULTS: Participants identified psychological concerns, particularly PTSD, as research priorities for Veterans in their communities, but also prioritized physical problems (e.g., brain injury) and social concerns (e.g., homelessness, access to care). Perceptions of, motives for, and barriers to research were similar across racial/ethnic groups. The most common motive was contributing to research that seems important, and the most common barrier was not knowing about research opportunities. Every-day experiences with discrimination (e.g., people acting as if they are afraid of you because of your race/ethnicity) were associated with more barriers to research among Black participants. CONCLUSIONS: Experiences of racial/ethnic discrimination are associated with different research-related outcomes across racial/ethnic groups. Efforts to engage diverse populations should prioritize access to (not willingness to participate in) health-related research.

Daily associations between modifiable sleep behaviors and nighttime sleep among young adult drinkers with insomnia.

STUDY OBJECTIVES: Empirical evidence linking individual sleep hygiene practices to subsequent sleep parameters is limited, particularly at the daily level. This study compared the strength of daily, within-person associations between these modifiable sleep behaviors and nighttime sleep in young adult drinkers with insomnia. METHODS: Young adults (ages 18-30 years; n = 56) who met diagnostic criteria for insomnia and reported past-month binge drinking wore wrist actigraphy and completed online sleep diaries for 8.5 days (standard deviation = 2.3; 477 reports). Diaries assessed engagement in 11 sleep hygiene recommendations. Multilevel models tested daily associations between sleep behaviors and 3 outcomes: sleep quality, self-reported sleep efficiency, and actigraphy-measured sleep efficiency. RESULTS: Participants self-reported better sleep quality/efficiency on days that they slept in a comfortable environment, limited naps to 30 minutes, and maintained a consistent wake time. They self-reported worse sleep quality and efficiency on nights that they avoided alcohol use before bedtime. No sleep behaviors were significantly associated with actigraphy-measured sleep efficiency after correcting for inflation in type I error. CONCLUSIONS: The sleep hygiene recommendations most strongly associated with sleep at the daily level were consistent with stimulus control. Creating a comfortable sleep environment also emerged as an important correlate of daily sleep. Heavy drinkers with insomnia may perceive better sleep if they drink before bedtime; however, this finding may be unique to this population. CITATION: Miller MB, Curtis AF, Hall NA, et al. Daily associations between modifiable sleep behaviors and nighttime sleep among young adult drinkers with insomnia. J Clin Sleep Med. 2022;18(3):703-712.

A centriole's subdistal appendages: contributions to cell division, ciliogenesis and differentiation.

The centrosome is a highly conserved structure composed of two centrioles surrounded by pericentriolar material. The mother, and inherently older, centriole has distal and subdistal appendages, whereas the daughter centriole is devoid of these appendage structures. Both appendages have been primarily linked to functions in cilia formation. However, subdistal appendages present with a variety of potential functions that include spindle placement, chromosome alignment, the final stage of cell division (abscission) and potentially cell differentiation. Subdistal appendages are particularly interesting in that they do not always display a conserved ninefold symmetry in appendage organization on the mother centriole across eukaryotic species, unlike distal appendages. In this review, we aim to differentiate both the morphology and role of the distal and subdistal appendages, with a particular focus on subdistal appendages.

Sleep and alcohol use among young adult drinkers with Insomnia: A daily process model.

BACKGROUND: Previous studies examining associations between sleep and alcohol use have done so primarily at the aggregate (between-person) level and primarily among healthy young adults. This study aimed to examine reciprocal, within-person associations between sleep and alcohol use among young adult drinkers with insomnia. METHODS: Young adults who engaged in past-month binge drinking and met diagnostic criteria for insomnia (N = 56) wore wrist actigraphy and completed online daily diaries assessing sleep and drinking for an average of 8.52 days (SD = 2.31), resulting in 477 reports. Multilevel models were used to examine within- and between-person effects of sleep quality and efficiency on alcohol use and vice versa. Bedtime and waketime were included as secondary sleep parameters. RESULTS: Participants reported drinking on 231 days (48%). Participants did not report significantly different sleep quality on heavier-drinking days, nor did they demonstrate significant changes in actigraphy-measured sleep efficiency. However, they self-reported better sleep efficiency on heavier-drinking days (driven primarily by improvements in sleep onset latency), and they reported heavier drinking following days of better sleep efficiency (driven by improvements in total sleep time). Drinking was also associated with later bedtimes and waketimes. CONCLUSIONS: Young adult drinkers with insomnia report reciprocal associations between subjective sleep efficiency and alcohol use, but these results were not replicated using objective measures. Providers may need to challenge the belief that there is a positive association between alcohol use and sleep among young adults who drink and have insomnia.

Cognitive behavioral therapy for insomnia among young adults who are actively drinking: a randomized pilot trial.

STUDY OBJECTIVES: More than half of young adults at risk for alcohol-related harm report symptoms of insomnia. Insomnia symptoms, in turn, have been associated with alcohol-related problems. Yet one of the first-line treatments for insomnia (Cognitive Behavioral Therapy for Insomnia or CBT-I) has not been tested among individuals who are actively drinking. This study tested (1) the feasibility and short-term efficacy of CBT-I among binge-drinking young adults with insomnia and (2) improvement in insomnia as a predictor of improvement in alcohol use outcomes. METHODS: Young adults (ages 18-30 years, 75% female, 73% college students) who met criteria for Insomnia Disorder and reported 1+ binge drinking episode (4/5+ drinks for women/men) in the past month were randomly assigned to 5 weekly sessions of CBT-I (n = 28) or single-session sleep hygiene (SH, n = 28). All participants wore wrist actigraphy and completed daily sleep surveys for 7+ days at baseline, posttreatment, and 1-month follow-up. RESULTS: Of those randomized, 43 (77%) completed posttreatment (19 CBT-I, 24 SH) and 48 (86%) completed 1-month follow-up (23 CBT-I, 25 SH). CBT-I participants reported greater posttreatment decreases in insomnia severity than those in SH (56% vs. 32% reduction in symptoms). CBT-I did not have a direct effect on alcohol use outcomes; however, mediation models indicated that CBT-I influenced change in alcohol-related consequences indirectly through its influence on posttreatment insomnia severity. CONCLUSIONS: CBT-I is a viable intervention among individuals who are actively drinking. Research examining improvement in insomnia as a mechanism for improvement in alcohol-related consequences is warranted. TRIAL REGISTRATION: U.S. National Library of Medicine, https://clinicaltrials.gov/ct2/show/NCT03627832, registration #NCT03627832.

PLK1- and PLK4-Mediated Asymmetric Mitotic Centrosome Size and Positioning in the Early Zebrafish Embryo.

Factors that regulate mitotic spindle positioning remain unclear within the confines of extremely large embryonic cells, such as the early divisions of the vertebrate embryo, Danio rerio (zebrafish). We find that the mitotic centrosome, a structure that assembles the mitotic spindle [1], is notably large in the zebrafish embryo (246.44 ± 11.93 µm2 in a 126.86 ± 0.35 µm diameter cell) compared to a C. elegans embryo (5.78 ± 0.18 µm2 in a 55.83 ± 1.04 µm diameter cell). During embryonic cell divisions, cell size changes rapidly in both C. elegans and zebrafish [2, 3], where mitotic centrosome area scales more closely with changes in cell size compared to changes in spindle length. Embryonic zebrafish spindles contain asymmetrically sized mitotic centrosomes (2.14 ± 0.13-fold difference between the two), with the larger mitotic centrosome placed toward the embryo center in a polo-like kinase (PLK) 1- and PLK4-dependent manner. We propose a model in which uniquely large zebrafish embryonic centrosomes direct spindle placement within disproportionately large cells.