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In recent years, post-secondary students' mental health has become an important public health concern. However, studies examining protective factors of mental health among students and during challenging times are limited. Guided by the strength-based Resilience Portfolio Model and following a group of undergraduates (N = 1004) throughout the 2020/2021 academic year, this study examined multiple domains of resilience internal assets and external resources and simultaneously tested multiple protective mechanisms for student mental health using structural equation modelling. Results provided support for insulating effects: both internal assets such as emotion regulation and external recourses such as social network supportiveness and cultural fit in university (i.e., perceived congruity between students' personal and cultural selves and their university environment) were associated with reducing academic stress which in turn promoted student mental health at the end of the academic year. There was also support for additive effects: greater cultural fit in university was also directly related to better end-of-year student mental health. As cultural fit in university was associated both directly and indirectly with student mental health, creating an inclusive university community may help reduce student academic stress, lower student psychological distress and improve student subjective well-being., (© 2024 The Author(s). Stress and Health published by John Wiley & Sons Ltd.)

Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of the seminal challenges in treating and studying addiction in human populations is the high prevalence of co-morbid conditions, including an increased risk of contracting a human immunodeficiency virus (HIV) infection. Of the ~15 million people who inject drugs globally, 17% are persons with HIV. Conversely, HIV is a risk factor for SUD because chronic pain syndromes, often encountered in persons with HIV, can lead to an increased use of opioid pain medications that in turn can increase the risk for opioid addiction. We hypothesize that SUD and HIV exert shared effects on brain cell types, including adaptations related to neuroplasticity, neurodegeneration, and neuroinflammation. Basic research is needed to refine our understanding of these affected cell types and adaptations. Studying the effects of SUD in the context of HIV at the single-cell level represents a compelling strategy to understand the reciprocal interactions among both conditions, made feasible by the availability of large, extensively-phenotyped human brain tissue collections that have been amassed by the Neuro-HIV research community. In addition, sophisticated animal models that have been developed for both conditions provide a means to precisely evaluate specific exposures and stages of disease. We propose that single-cell genomics is a uniquely powerful technology to characterize the effects of SUD and HIV in the brain, integrating data from human cohorts and animal models. We have formed the Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium to carry out this strategy., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Photooxidative damage is heavily influenced by the presence of bioactive agents. Conversely, bioactive agents influence the local environment, which in turn is perturbed by photooxidative damage. These sorts of processes give rise to a version of the "chicken-and-egg" quandary. In this Perspective, we probe this issue by referring to photooxidative damage in one direction as the light-dark (L-D) sequence and in a second direction as the dark-light (D-L) sequence with a reversed cause and effect. The L-D sequence can lead to the downstream production of reactive molecular species (RMS) in the dark, whereas the D-L sequence can be a pre-irradiation period, such as an additive to limit cellular iron levels to enhance biosynthesized amounts of a protoporphyrin sensitizer. A third direction comes from L-D or D-L sequences, or both simultaneously, which can also be useful for optimizing photodynamics. Photodynamic optimization will benefit from understanding and quantitating unidirectional L-D and D-L pathways, and bidirectional L-D/D-L pathways, for improved control over photooxidative damage. Photooxidative damage, which occurs during anticancer photodynamic therapy (PDT), will be shown to involve RMS. Such RMS include persulfoxides (R 2 S + OO - ), NO 2 • , peroxynitrate (O 2 NOO - ), OOSCN - , SO 3 •- , selenocyanogen [(SeCN) 2 ], the triselenocyanate anion [(SeCN) 3 - ], I • , I 2 •- , I 3 - , and HOOI, as well as additives to destabilize membranes (e.g., caspofungin and saponin A16), inhibit DNA synthesis (5-fluorouracil), or sequester iron (desferrioxamine). In view of the success that additive natural products and repurposed drugs have had in PDT, a Perspective of additive types is expected to reveal mechanistic details for enhanced photooxidation reactions in general. Indeed, strategies for how to potentiate photooxidations with additives remain highly underexplored.

The Gambling Craving Scale (GACS) is a multifaceted measure of gambling craving. Initial validation work by Young and Wohl (2009) in university student samples showed that the GACS had a three-factor structure capturing dimensions of Desire, Anticipation, and Relief. Despite its potential clinical utility as a measure of craving, the GACS has yet to be validated in people seeking treatment for gambling problems. Accordingly, we examined the psychometric properties in a sample of people (N = 209; M age  = 37.66; 62.2% female) participating in a randomized controlled trial testing a novel online treatment for problem gambling. We predicted the GACS would have a three-factor structure. In addition, we also examined measurement invariance across sex and problem gambling risk status. Finally, we assessed concurrent validity of the factors with other measures of problem gambling severity and involvement. Exploratory structural equation modeling findings supported a three-factor structure that was invariant across the groups tested. Each of the Desire, Anticipation, and Relief subscales were significant positive predictors of problem gambling severity and symptoms, and some form of gambling behaviour. Findings show the GACS is a promising scale to assess multidimensional craving experiences among people in treatment for gambling problems., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Undergraduates frequently engage in risky drinking (i.e., drinking alcohol in ways that may result in problems). The reasoned action approach identifies injunctive norms (i.e., perceptions that others approve of risky drinking) as central in predicting engagement in risky drinking. However, research linking injunctive norms and risky drinking is equivocal, possibly because of extensive variability in the operationalization of injunctive norms across studies. This study describes the development and validation of the Perceived Approval of Risky Drinking Inventory (PARDI), designed according to best practice guidelines in questionnaire development., Method: Undergraduate students ( N = 1,313) participated in one of the three phases of data collection, including focus group interviews for item generation ( n = 31), self-report questionnaires for scale refinement ( n = 407), and self-report questionnaires for scale validation ( n = 875)., Results: Exploratory and confirmatory factor analyses supported a 20-item four-factor solution (Heavy Drinking, Drinking-Related Problems, Coping-Related Drinking, and Sexual-Risk Taking) across the three assessed referent groups (friends, parents, and typical students), all of which present satisfactory estimates of scale score and composite reliability. The results also provided preliminary support for the convergent validity of scores obtained on the PARDI, as demonstrated through correlations with other measures of perceived norms, alcohol use, alcohol-related problems, and coping-motivated drinking. Finally, the results supported the generalizability of the PARDI factor structure by demonstrating its measurement invariance across gender and drinking status (i.e., alcohol use and problems)., Conclusions: The PARDI represents a reliable, valid, yet nuanced measure of injunctive norms that can be used to support further theory development and intervention. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Patients may use crowdfunding to solicit donations, typically from multiple small donors using internet-based means, to offset the financial toxicity of cancer care., Objective: To describe crowdfunding campaigns by gynecologic cancer patients and to compare campaign characteristics and needs expressed between patients with cervical, uterine, and ovarian cancer., Study Design: We queried the public crowdfunding forum GoFundMe.com for "cervical cancer," "uterine cancer," and "ovarian cancer." The first 200 consecutive posts for each cancer type fundraising within the United States were analyzed. Data on campaign goals and needs expressed were manually extracted. Descriptive statistics and bivariate analyses were performed., Results: Among the 600 fundraising pages, the median campaign goal was $10,000 [IQR $5000-$23,000]. Campaigns raised a median of 28.6% of their goal with only 8.7% of campaigns reaching their goal after a median of 54 days online. On average, ovarian cancer campaigns had higher monetary goals, more donors, and larger donation amounts than cervical cancer campaigns and raised more money than both cervical and uterine cancer campaigns. Campaigns were fundraising to support medical costs (80-85%) followed by lost wages (36-56%) or living expenses (27-41%). Cervical cancer campaigns reported need for non-medical costs more frequently than uterine or ovarian cancer campaigns. States without Medicaid expansions (31% of the national population) were over-represented among cervical cancer and uterine cancer, but not ovarian cancer campaigns., Conclusions: Crowdfunding pages reveal patients fundraising for out-of-pocket costs in the thousands of dollars and a wide range of unmet financial needs based on cancer type., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal name] and was not involved in the editorial review or the decision to publish this article. The authors have no conflicts of interest related to this work. This paper was presented as an oral presentation at the Western Association of Gynecologic Oncology in June 2023 in Monterey, CA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling revealed that DPn neurons innervate the parabrachial nucleus (PBn). Spatial and single-nuclei transcriptomics resolved a population of PBn-projecting pyramidal neurons in the DPn that express μ-opioid receptors (μORs). Disrupting μOR signaling in the DPn switched oxycodone from rewarding to aversive and exacerbated the severity of opioid withdrawal. These findings identify the DPn as a key substrate for the abuse liability of opioids.

Heavy drinking and smoking have been found to be among the leading causes of morbidity and mortality within Indigenous youth in North America. The focus of this study was to examine the relative roles of cultural identity, parent-child communication about the harms of substance use (SU), and perception about peers' opinions on heavy drinking and cigarette smoking among Indigenous youth. Strong Indigenous cultural identity, parent-child communication about SU, and affiliation with peers who do not use and/or who disapprove of substance use were all expected to reduce risk for heavy drinking and smoking. Substance use beliefs were hypothesized to mediate these effects. Youth ( N   =  117; M age   =  14.07; grades 6-11) from two Indigenous communities in Quebec completed self-reports. Consistent with the hypotheses, strong cultural identity predicted increased negative beliefs about substance use, which predicted reduced drinking and smoking. Similarly, affiliating with peers who did not use alcohol predicted decreased positive beliefs about alcohol use, which predicted reduced drinking. Affiliating with peers who did not smoke cigarettes predicted reduced cigarette smoking. Parental influences were not supported in this model. Intervention strategies may benefit from targeting cultural identity, peer groups, and substance use beliefs among Indigenous youth., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Negative affect (depression/anxiety) and alcohol use among Indigenous youth in Canada remain a concern for many communities. Disparate rates of these struggles are understood to be a potential outcome of colonization and subsequent intergenerational trauma experienced by individuals, families, and communities. Using a longitudinal design, we examined change in alcohol use and negative affect, and reciprocal associations, among a group of Indigenous adolescents. Indigenous youth (N = 117; 50% male; M age =12.46-16.28; grades 6-10) from a remote First Nation in northern Quebec completed annual self-reported assessments on negative affect (depression/anxiety) and alcohol use. A Latent Curve Model with Structured Residuals (LCM-SR) was used to distinguish between- and within-person associations of negative affect and alcohol use. Growth models did not support change in depression/anxiety, but reports of drinking increased linearly. At the between-person level, girls reported higher initial levels of depression/anxiety and drinking; depression/anxiety were not associated with drinking. At the within-person level, drinking prospectively predicted increases in depression/anxiety but depression/anxiety did not prospectively predict drinking. When Indigenous adolescents reported drinking more alcohol than usual at one wave of assessment, they reported higher levels of negative affect than expected (given their average levels of depression/anxiety) at the following assessment. Our findings suggest that when Indigenous youth present for treatment reporting alcohol use, they should also be screened for negative affect (depression/anxiety). Conversely, if an Indigenous adolescent presents for treatment reporting negative affect, they should also be screened for alcohol use., (© 2024. The Author(s).)

Background: Simultaneous alcohol and cannabis use is common, but observational studies examining negative consequences of simultaneous use have rarely considered dose-related interactions between alcohol and cannabis. This study examined interactions between quantities of cannabis and alcohol consumed in predicting negative consequences on simultaneous use days., Methods: Young adults (N = 151; 64% female; 62% White) reporting recent simultaneous use and at least weekly alcohol and cannabis use completed 21 daily, smartphone-based surveys assessing previous day quantities of cannabis and alcohol used, types of cannabis used (flower, concentrates, edibles), and negative substance-related consequences. Multilevel models examined: (1) whether negative consequences differed within-person across simultaneous use days and single-substance use days; and (2) whether quantities of alcohol and cannabis consumed on simultaneous use days interacted, within-person, to predict negative consequences. We focused on quantities of cannabis flower (grams) in primary analyses and explored quantities of other forms of cannabis (concentrates, edibles) in supplementary analyses., Results: Participants reported fewer negative consequences on alcohol-only (243 observations) and cannabis-only (713 observations) days than they did on simultaneous use days (429 observations). On simultaneous use days involving cannabis flower use (313 observations across 81 participants), the within-person association between number of standard drinks and negative consequences was weaker on days during which larger (vs. smaller) amounts of cannabis flower were consumed. Inspection of simple slopes revealed that decreased alcohol use was associated with less of a decline in negative consequences when combined with relatively greater amounts of cannabis flower., Conclusions: Although simultaneous use was associated with more negative consequences than alcohol-only and cannabis-only use, negative consequences on simultaneous use days varied as a function of the interaction between alcohol and cannabis quantities. As findings suggest that using larger amounts of cannabis may attenuate declines in negative consequences associated with lighter drinking, interventions for higher-risk simultaneous use patterns may benefit from a focus on quantities of both alcohol and cannabis., (© 2024 The Authors. Alcohol, Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.)

Herein, we report that readily accessible azoxy-triazenes can serve as nitrogen atom sources under visible light excitation for the phthalimido-protected aziridination of alkenes. This approach eliminates the need for external oxidants, precious transition metals, and photocatalysts, marking a departure from conventional methods. The versatility of this transformation extends to the selective aziridination of both activated and unactivated multisubstituted alkenes of varying electronic profiles. Notably, this process avoids the formation of competing C-H insertion products. The described protocol is operationally simple, scalable, and adaptable to photoflow conditions. Mechanistic studies support the idea that the photofragmentation of azoxy-triazenes results in the generation of a free singlet nitrene. Furthermore, a mild photoredox-catalyzed N-N cleavage of the protecting group to furnish the free aziridines is reported. Our findings contribute to the advancement of sustainable and practical methodologies for the synthesis of nitrogen-containing compounds, showcasing the potential for broader applications in synthetic chemistry.

The association between restrained eating and alcohol use remains poorly understood among undergraduates. Consistent with tension reduction theory, individuals with disordered eating may be motivated to drink alcohol to cope with negative emotionality. Perhaps what pushes them to drink despite restriction goals is impulsivity. The combined impact of drinking to cope and impulsivity on the theoretically complex link between restrained eating and alcohol outcomes has not been previously examined. The current study tested the moderating effect of drinking to cope and impulsivity on the association between restrained eating and alcohol use and problems. Undergraduates ( N  = 1,619) self-reported on eating disorder symptoms, alcohol use motives, impulsivity, and alcohol outcomes. A moderation model revealed that restrained eating predicted past 30-day alcohol use, but only for women high in both drinking to cope and impulsivity. These findings help characterize alcohol misuse risk among young adults who restrict their eating, thereby, results may inform interventions.

Due to the spread of resistance to front-line artemisinin derivatives worldwide, there is a need for new antimalarials. Tartrolon E (TrtE), a secondary metabolite of a symbiotic bacterium of marine bivalve mollusks, is a promising antimalarial because it inhibits the growth of sexual and asexual blood stages of Plasmodium falciparum at sub-nanomolar levels. The potency of TrtE warrants further investigation into its mechanism of action, cytotoxicity, and ease with which parasites may evolve resistance to it., Competing Interests: The authors declare no conflict of interest.

Objective: To identify correlations between disease recurrence and adherence to NCCN posttreatment surveillance guidelines in patients who develop recurrent uterine cancer., Methods: Retrospective analysis identified patients (n = 60) with recurrent uterine cancer and at least one surveillance visit with a gynecologic oncologist between 2011 and 2020. Adherence to NCCN guidelines and details of recurrence were recorded., Results: Recurrent uterine cancer was identified in 60 patients with an average time to recurrence (TTR) of 25 months. Of those, 39 (65%) were adherent to NCCN surveillance guidelines and 36 (60%) were symptomatic at the time of recurrence diagnosis. Asymptomatic recurrence was diagnosed by imaging in 11 (46%), physical exam in 7 (29%), and blood work in 6 (25%) patients. Patients who were adherent to NCCN guidelines were diagnosed with recurrence on average 11 months earlier (p = 0.0336). Adherence was an independent predictor of TTR for all patients regardless of symptoms. There was no significant effect of age, race, primary language, or stage of disease on adherence., Conclusion: Adherence to NCCN posttreatment surveillance guidelines for uterine cancer is independently associated with an earlier diagnosis of recurrence., Competing Interests: Declaration of Competing Interest Christopher M. Mayer, Reed M. O'Connor, Anthony T. Do, Victoria R. Cerda, Stephanie M. Wang, Marla E. Scott, Andrew J. Li, BJ Rimel, Michael R. Manuel, Kristin N. Taylor, and Kenneth H. Kim report no conflict of interest. BJ Rimel reports being a consultant for Deep6AI as well as participation on a Data Safety Monitoring Board or Advisor Board for Merck, GSK, AstraZeneca, and Immunogen., (Copyright © 2023. Published by Elsevier Inc.)

Study Objective: To compare rates of vaginal cuff dehiscence (VCD) in transgender patients with cisgender patients after minimally invasive hysterectomy (MIH)., Design: We performed a single-surgeon, retrospective cohort analysis comparing the rates of VCD in patients undergoing MIH for gender affirmation with other indications (benign, malignant, prophylactic) with our study surgeon between January, 2015, and December, 2021., Setting: Major, urban, academic tertiary care hospital in the United States., Patients: 166 patients met inclusion criteria with 49 of those patients undergoing MIH (29.5%) for gender affirmation. Of the remaining 117 patients, 92 (78.6%) underwent MIH for cancer, 15 (12.8%) for prophylaxis, and 10 (8.5%) for benign indications., Interventions: Not applicable., Measurements: We assessed included patients for baseline demographics, presence of risk factors for VCD, details of index hysterectomy, and details of cuff dehiscence events., Main Results: Transgender patients tended to be younger at the time of surgery, but demographics were otherwise similar between both groups. Most transgender patients (n = 36, 73.5%) had both ovaries removed at the time of hysterectomy, 100% were on testosterone therapy pre- and postoperatively, and none used supplementary estrogen. Three of the 49 transgender patients (6.1%) experienced postoperative dehiscence of the vaginal cuff compared with 2 of the 117 cisgender patients (1.7%). This failed to reach statistical significance; however, our descriptive analysis showed that all cases of dehiscence in the cisgender group had identifiable precipitating factors (i.e., trauma). By comparison, all cases of dehiscence in the transgender group were spontaneous with few identifiable risk factors., Conclusion: Transgender patients undergoing MIH may be at increased risk of VCD, although the rarity of this surgical complication precluded determination of statistical significance in our data set. We propose testosterone exposure as a possible risk factor for VCD, although we cannot exclude other factors, such as young age, as drivers of VCD in this population. Future studies of biospecimens are needed to evaluate for cellular differences in these patients., (Copyright © 2023 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: Evaluation of the influence of potential risk factors (RFs) on glycemic changes at 3 years postpartum., Methods: The glycemic status of 1400 women, in absence of a new pregnancy, was evaluated at 3 months (3 m) and 3 years (3 y) postpartum, after participation in the St. Carlos Gestational Study (2228 normoglycemic pregnant women followed from before gestational week 12 to delivery, from 2015-2017). Abnormal glucose regulation (AGR) was defined as fasting serum glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7% and/or 2 h 75 g OGTT glucose ≥ 140 mg/dL. In total, 12 modifiable and 3 unmodifiable RFs were analyzed., Results: 3 m postpartum, 110/1400 (7.9%) women had AGR; 3 y postpartum, 137 (9.8%) women exhibited AGR (110 with 3 m normal glucose tolerance [NGT]); 1263 (90.2%) had NGT (83 with 3 m AGR). More women with gestational diabetes mellitus (GDM) progressed to AGR at 3 y (OR: 1.60 [1.33-1.92]) than women without GDM. Yet, most women with 3 m and/or 3 y AGR had no GDM history. Having ≥2 unmodifiable RFs was associated with increased risk for progression to AGR (OR: 1.90 [1.28-2.83]) at 3 y postpartum. Having >5/12 modifiable RFs was associated with increased progression from NGT to AGR (OR: 1.40 [1.00-2.09]) and AGR persistence (OR: 2.57 [1.05-6.31]). Pregestational BMI ≥ 25 kg/m 2 (OR: 0.59 [0.41-0.85]), postdelivery weight gain (OR: 0.53 [0.29-0.94]), and waist circumference > 89.5 cm (OR: 0.54 [0.36-0.79]) reduced the likelihood of NGT persisting at 3 y., Conclusions: 3-month and/or 3-year postpartum AGR can be detected if sought in women with no prior GDM. Modifiable and unmodifiable RF predictors of AGR at 3 y postpartum were identified. Universal screening for glycemic alterations should be considered in all women following delivery, regardless of prior GDM. These findings could be useful to design personalized strategies in women with risk factors for 3 y AGR.

Herein, we report a protocol for the anaerobic oxidation of alcohols, amines, aldehydes, and imines promoted by photoexcited nitroarenes. Mechanistic studies support the idea that photoexcited nitroarenes undergo double hydrogen atom transfer (HAT) steps with alcohols and amines to provide the respective ketone and imine products. In the presence of aldehydes and imines, successive HAT and oxygen atom transfer (OAT) events occur to yield carboxylic acids and amides, respectively. This transformation is amenable to a continuous-photoflow setup, which led to reduced reaction times.

Objective: Alcohol use and related problems increase during adolescence and peak in early adulthood. Tension reduction theories suggest that those high in anxiety sensitivity (AS) may be at risk for misusing alcohol for its anxiolytic effects. Cognitive theories point to drinking motives and alcohol expectancies as explanatory mechanisms of this risk pathway. This study examined AS risk for prospective alcohol misuse, as explained by an unfolding cognitive process, among those transitioning out of Collège d'enseignement général et professionnel (CEGEP, i.e., junior college equivalent in Quebec, Canada). We hypothesized that there would be trait-like (average levels over time), positive associations between AS, coping motives, tension-reduction alcohol expectancies, and alcohol use and problems, and that AS would lead to state-like (occasion-specific, reciprocal associations) bidirectional and positive associations between alcohol cognitions and outcomes., Method: Final-year CEGEP students ( N = 193) completed three online questionnaires at 6-month intervals assessing AS, drinking motives (coping, enhancement), alcohol expectancies (tension reduction, sociability/liquid courage), and alcohol use/problems. State-trait modeling was used for hypothesis testing., Results: Consistent with hypotheses, at the "trait" level, drinking motives and alcohol expectancies were positively associated, and drinking motives and sociability/liquid courage expectancies were positively associated with alcohol problems. At the "state" level, AS positively predicted coping motives and alcohol use, tension-reduction expectancies positively predicted coping motives, and coping motives and sociability/liquid courage expectancies positively predicted alcohol use., Conclusions: Results suggest that AS is a risk factor for coping-motivated drinking, and that there is interplay between cognitions that may help understand emerging adult alcohol risk pathways. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The role of singlet oxygen potentially mediating increased conformational flexibility of a disulfide was investigated. Density functional theory (DFT) calculations indicate that the singlet oxygenation of 1,2-dimethyldisulfane produces a peroxy intermediate. This intermediate adopts a structure with a longer S-S bond distance and a more planar torsional angle θ (C-S-S-C) compared with the nonoxygenated 1,2-dimethyldisulfane. The lengthened S-S bond enables a facile rotation about the torsional angle in the semicircle region 0° < θ < 210°, that is ~5 kcal mol -1 lower in energy than the disulfane. The peroxy intermediate bears n O  → σ S-S and n O  → σ* S-S interactions that stabilize the S-O bond but destabilize the S-S bond, which contrasts with stabilizing n S  → σ* S-S hyperconjugative effects in the disulfane S-S bond. Subsequent departure of O 2 from the disulfane peroxy intermediate is reminiscent of peroxy intermediates which also expel O 2 , yet facilitate cis-trans isomerizations of stilbenes, hexadienes, cyanines, and carotenes. "Non-oxidative" 1 O 2 interactions with a variety of bond types are currently underappreciated. We hope to raise awareness of how these interactions can help elucidate the origins of molecular twisting., (© 2022 American Society for Photobiology.)

Background: Gray's original Reinforcement Sensitivity Theory (RST) posits that an oversensitive behavioral inhibition system (BIS) may increase risk for negative-reinforcement-motivated drinking, given its role in anxiety. However, existing data provides mixed support for the BIS-alcohol use association. The inconsistent evidence is not surprising, as the revised RST predicts that the behavioral approach system (BAS) should moderate the effect of the BIS on alcohol use. A strong BAS is thought to bring attention to the negatively reinforcing effects of alcohol, leading to problem drinking among those with a strong BIS. While emerging results support this interaction, we still have much to learn about the mechanisms underlying this effect on alcohol use. Accordingly, we examined motives for alcohol use as mediators of the joint associations of the BIS and the BAS on drinking behaviors. Specifically, our central hypothesis was that individuals with a strong BIS and a strong BAS would endorse increased negative reinforcement motives for drinking (coping and conformity motives), which in turn would predict heavy drinking and alcohol problems. Method: Participants ( N =346; 195 women) completed study measures as part of the baseline assessment for a larger study. Results: Overall, results partially supported the hypotheses. Mediated moderation analyses showed that the indirect effect of the BIS on alcohol problems, through coping and conformity motives, was strongest at high levels of the BAS. This effect was not supported for alcohol use. Conclusions: Our findings suggest that clinical interventions should target coping and conformity reasons for drinking among anxious, reward responsive, young adults.

New therapeutic agents for cryptosporidiosis are a critical medical need. The marine organic compound, tartrolon E (trtE), is highly effective against multiple apicomplexan parasites, including Cryptosporidium . Understanding the mechanism of action of trtE is required to advance in the drug development pipeline. Here, we validate using Nluc C. parvum parasites for the study of trtE and pinpoint the life stage targeted by trtE. Results show that trtE kills Nluc and wild type C. parvum with equal efficiency, confirming the use of the Nluc C. parvum to study this compound. Results revealed that trtE kills the parasite within an hour of treatment and while the compound has no effect on viability of sporozoites, trtE does inhibit establishment of infection. Targeting treatment at particular life cycle stages demonstrated that trtE is effective against asexual of the parasite but has reduced efficacy against mature sexual stages. Gene expression analysis shows that trtE inhibits the early sexual stage of the parasite. Results from these studies will aid the development of trtE as a therapeutic for cryptosporidiosis.

Rates of obesity and obesity-associated diseases have increased dramatically in countries with developed economies. Substance use disorders (SUDs) are characterized by the persistent use of the substance despite negative consequences. It has been hypothesized that overconsumption of palatable energy dense food can elicit SUD-like maladaptive behaviors that contribute to persistent caloric intake beyond homeostatic need even in the face of negative consequences. Palatable food and drugs of abuse act on many of the same motivation-related circuits in the brain, and can induce, at least superficially, similar molecular, cellular, and physiological adaptations on these circuits. As such, applying knowledge about the neurobiological mechanisms of SUDs may serve as useful heuristic to better understand the persistent overconsumption of palatable food that contributes to obesity. However, many important differences exist between the actions of drugs of abuse and palatable food in the brain. This warrants caution when attributing weight gain and obesity to the manifestation of a putative SUD-related behavioral disorder. Here, we describe similarities and differences between compulsive drug use in SUDs and overconsumption in obesity and consider the merit of the concept of "food addiction"., (Copyright © 2022. Published by Elsevier Inc.)

Existing research on perfectionism and binge eating suggests that socially prescribed, self-oriented, and other-oriented perfectionism (Socially Prescribed Perfectionism, SPP; Self-Oriented Perfectionism, SOP; and Other-Oriented Perfectionism, OOP) are differentially related to binge eating. However, previous studies have largely utilized cross-sectional methodology. The present study used a 20-day daily diary methodology to examine associations between daily levels of perfectionistic dimensions and next-day binge eating behaviors with a nonclinical sample of emerging adults ( N = 263). Zero-inflated negative binomial regression models indicated that daily SPP (but not SOP or OOP) predicted a greater intensity of next-day binge eating behaviors in the count portion of the model; however, daily levels of perfectionistic dimensions did not predict the presence/absence of next-day binge eating behaviors in the zero-inflated portion of the model. Additionally, analyses examining the reverse causal direction (i.e., binge eating behaviors predicting higher next-day perfectionism) failed to provide evidence that the occurrence or intensity of binge eating behaviors predicts next-day levels of SPP, SOP, or OOP. Overall, at a daily level, SPP appears to be a vulnerability factor for binge eating behaviors. It may be helpful for clinicians to target state-levels of SPP to reduce harmful binge eating behaviors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cryptosporidium sp. are apicomplexan parasites that cause significant morbidity and possible mortality in humans and valuable livestock. There are no drugs on the market that are effective in the population most severely affected by this parasite. This study is the first high-throughput screen for potent anti- Cryptosporidium natural products sourced from a unique marine compound library. The Harbor Branch Oceanographic Institute at Florida Atlantic University has a collection of diverse marine organisms some of which have been subjected to medium pressure liquid chromatography to create an enriched fraction library. Numerous active compounds have been discovered from this library, but it has not been tested against Cryptosporidium parvum . A high-throughput in vitro growth inhibition assay was used to test 3764 fractions in the library, leading to the identification of 23 fractions that potently inhibited the growth of Cryptosporidium parvum . Bioassay guided fractionation of active fractions from a deep-sea sponge, Leiodermatium sp., resulted in the purification of leiodolide A, the major active compound in the organism. Leiodolide A displayed specific anti- Cryptosporidium activity at a half maximal effective concentration of 103.5 nM with selectivity indexes (SI) of 45.1, 11.9, 19.6 and 14.3 for human ileocecal colorectal adenocarcinoma cells (HCT-8), human hepatocellular carcinoma cells (Hep G2), human neuroblastoma cells (SH-SY5Y) and green monkey kidney cells (Vero), respectively. The unique structure of leiodolide A provides a valuable drug scaffold on which to develop new anti- Cryptosporidium compounds and supports the importance of screening natural product libraries for new chemical scaffolds.

Animals with a chronic infection of the parasite Toxoplasma gondii are protected against lethal secondary infection with other pathogens. Our group previously determined that soluble T. gondii antigens (STAg) can mimic this protection and be used as a treatment against several lethal pathogens. Because treatments are limited for the parasite Cryptosporidium parvum, we tested STAg as a C. parvum therapeutic. We determined that STAg treatment reduced C. parvum Iowa II oocyst shedding in gamma interferon knockout (IFN-γ-KO) mice. Murine intestinal sections were then sequenced to define the IFN-γ-independent transcriptomic response to C. parvum infection. Gene Ontology and transcript abundance comparisons showed host immune response and metabolism changes. Transcripts for type I interferon-responsive genes were more abundant in C. parvum-infected mice treated with STAg. Comparisons between phosphate-buffered saline (PBS) and STAg treatments showed no significant differences in C. parvum gene expression. C. parvum transcript abundance was highest in the ileum and mucin-like glycoproteins and the GDP-fucose transporter were among the most abundant. These results will assist the field in determining both host- and parasite-directed future therapeutic targets.

Since the onset of the COVID-19 pandemic, researchers around the world have made efforts to assess its impact on youth mental health; however, the breadth of this topic has impeded a clear assessment of pandemic outcomes. This study aimed to address this gap by reviewing changes in youth (age ≤ 25) mental health, psychological wellbeing, substance use, and the use or delivery of relevant services during the pandemic. PubMed and Embase were searched in May 2021 to conduct a rapid review of the literature. The results encompass 156 primary publications and are reported using a narrative synthesis. Studies of mental health (n = 122) and psychological wellbeing (n = 28) generally indicated poor outcomes in many settings. Publications regarding substance use (n = 41) noted overall declines or unchanged patterns. Studies of service delivery (n = 12) indicated a generally positive reception for helplines and telehealth, although some youth experienced difficulties accessing services. The findings indicate negative impacts of the pandemic on youth mental health, with mixed results for substance use. Services must support marginalized youth who lack access to telehealth., Supplementary Information: The online version contains supplementary material available at 10.1007/s40894-022-00185-6., Competing Interests: Conflict of interestThe authors report no conflict of interests., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022.)

Many young adults struggle with comorbid alcohol misuse and emotional problems (i.e., depression and anxiety). However, there is currently a paucity of evidence-based, integrated, accessible treatment options for individuals with these comorbidities. The main goal of this study was to examine efficacy of a novel online, minimally guided, integrated program for comorbid alcohol misuse and emotional problems in young adults. Method: The study was an open-label two-arm RCT. Participants ( N =  222, M age  = 24.6, 67.6% female) were randomized to one of two conditions: the Take Care of Me program (an 8-week, online integrated treatment condition consisting of 12 modules), or an online psychoeducational control condition. Intervention modules incorporated content based on principles of cognitive behavioral therapy and motivational interviewing. Participants completed assessment data at baseline, at the end of treatment (i.e., 8 weeks), and at follow-up (i.e., 24 weeks). Data were analyzed using generalized linear mixed models. Results: We observed that participants in the treatment condition showed larger reductions in depression, hazardous drinking, as well as increases in psychological quality of life and confidence at the end of treatment. We did not find group differences on total alcohol use at follow-up, but participants in the treatment group reduced their hazardous drinking and improved their quality of life at 24-week follow-up. Conclusions: Our study provides promising initial evidence for the first iteration of the comorbid alcohol misuse and emotional problems online program., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier Ltd.)

Comparatively little is known about how new instrumental actions are encoded in the brain. Using whole-brain c-Fos mapping, we show that neural activity is increased in the anterior dorsolateral striatum (aDLS) of mice that successfully learn a new lever-press response to earn food rewards. Post-learning chemogenetic inhibition of aDLS disrupts consolidation of the new instrumental response. Similarly, post-learning infusion of the protein synthesis inhibitor anisomycin into the aDLS disrupts consolidation of the new response. Activity of D1 receptor-expressing medium spiny neurons (D1-MSNs) increases and D2-MSNs activity decreases in the aDLS during consolidation. Chemogenetic inhibition of D1-MSNs in aDLS disrupts the consolidation process whereas D2-MSN inhibition strengthens consolidation but blocks the expression of previously learned habit-like responses. These findings suggest that D1-MSNs in the aDLS encode new instrumental actions whereas D2-MSNs oppose this new learning and instead promote expression of habitual actions., (© 2021. The Author(s).)

Dioxetane intermediates readily decompose to chemiluminescent triplet carbonyls, giving rise to what has been paradoxically called photochemistry in the dark. In this issue of Photochemistry and Photobiology, Bechara et al. report on mechanistic advances in such a reaction. With the use of horseradish peroxidase for isobutyraldehyde-derived triplet acetone, light emission from acetone and singlet oxygen can be quenched. The experiments reveal that the reaction depends on oxygen and the amino acid. The analysis reveals that free tryptophan is a target of this form of "carbonyl stress," with the efficient formation of mono-, bi- and tricyclic compounds (N-formylkynurenine, indoline, 1λ 2 -indole and 3H-indoles)., (© 2021 American Society for Photobiology.)

New treatments for the diseases caused by apicomplexans are needed. Recently, we determined that tartrolon E (trtE), a secondary metabolite derived from a shipworm symbiotic bacterium, has broad-spectrum anti-apicomplexan parasite activity. TrtE inhibits apicomplexans at nM concentrations in vitro, including Cryptosporidium parvum, Toxoplasma gondii, Sarcocystis neurona, Plasmodium falciparum, Babesia spp. and Theileria equi. To investigate the mechanism of action of trtE against apicomplexan parasites, we examined changes in the transcriptome of trtE-treated T. gondii parasites. RNA-Seq data revealed that the gene, TGGT1&#95;272370, which is broadly conserved in the coccidia, is significantly upregulated within 4 h of treatment. Using bioinformatics and proteome data available on ToxoDB, we determined that the protein product of this tartrolon E responsive gene (trg) has multiple transmembrane domains, a phosphorylation site, and localizes to the plasma membrane. Deletion of trg in a luciferase-expressing T. gondii strain by CRISPR/Cas9 resulted in a 68% increase in parasite resistance to trtE treatment, supporting a role for the trg protein product in the response of T. gondii to trtE treatment. Trg is conserved in the coccidia, but not in more distantly related apicomplexans, indicating that this response to trtE may be unique to the coccidians, and other mechanisms may be operating in other trtE-sensitive apicomplexans. Uncovering the mechanisms by which trtE inhibits apicomplexans may identify shared pathways critical to apicomplexan parasite survival and advance the search for new treatments., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cryptosporidium is a waterborne gastrointestinal parasite that causes outbreaks of diarrheal disease worldwide. Despite the impact of this parasite on human health there are no effective drugs or vaccines. Transcriptomic data can provide insights into host-parasite interactions that lead to identification of targets for therapeutic interventions. However, for Cryptosporidium, interpreting transcriptomes has been challenging, in part due to the presence of multiple life cycle stages, the lack of appropriate host cells and the inability to culture the parasite through its complete life cycle. The recent improvements in cell culture and the ability to tag and isolate specific life cycle stages will radically improve transcriptomic data and advance our understanding of Cryptosporidium host-parasite interactions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Apicomplexan parasites cause severe disease in both humans and their domesticated animals. Since these parasites readily develop drug resistance, development of new, effective drugs to treat infection caused by these parasites is an ongoing challenge for the medical and veterinary communities. We hypothesized that invertebrate-bacterial symbioses might be a rich source of anti-apicomplexan compounds because invertebrates are susceptible to infections with gregarines, parasites that are ancestral to all apicomplexans. We chose to explore the therapeutic potential of shipworm symbiotic bacteria as they are bona fide symbionts, are easily grown in axenic culture and have genomes rich in secondary metabolite loci [1,2]. Two strains of the shipworm symbiotic bacterium, Teredinibacter turnerae, were screened for activity against Toxoplasma gondii and one strain, T7901, exhibited activity against intracellular stages of the parasite. Bioassay-guided fractionation identified tartrolon E (trtE) as the source of the activity. TrtE has an EC50 of 3 nM against T. gondii, acts directly on the parasite itself and kills the parasites after two hours of treatment. TrtE exhibits nanomolar to picomolar level activity against Cryptosporidium, Plasmodium, Babesia, Theileria, and Sarcocystis; parasites representing all branches of the apicomplexan phylogenetic tree. The compound also proved effective against Cryptosporidium parvum infection in neonatal mice, indicating that trtE may be a potential lead compound for preclinical development. Identification of a promising new compound after such limited screening strongly encourages further mining of invertebrate symbionts for new anti-parasitic therapeutics., Competing Interests: The authors have declared that no competing interests exist.

Vulnerability to relapse during periods of attempted abstinence from cocaine use is hypothesized to result from the rewiring of brain reward circuitries, particularly ventral tegmental area (VTA) dopamine neurons. How cocaine exposures act on midbrain dopamine neurons to precipitate addiction-relevant changes in gene expression is unclear. We found that histone H3 glutamine 5 dopaminylation (H3Q5dop) plays a critical role in cocaine-induced transcriptional plasticity in the midbrain. Rats undergoing withdrawal from cocaine showed an accumulation of H3Q5dop in the VTA. By reducing H3Q5dop in the VTA during withdrawal, we reversed cocaine-mediated gene expression changes, attenuated dopamine release in the nucleus accumbens, and reduced cocaine-seeking behavior. These findings establish a neurotransmission-independent role for nuclear dopamine in relapse-related transcriptional plasticity in the VTA., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Development of an effective vaccine against cryptosporidiosis is a medical and veterinary priority. However, many putative Cryptosporidium vaccine candidates such as surface and apical complex antigens are posttranslationally modified with O- and N-linked glycans. This presents a significant challenge to understanding the functions of these antigens and the immune responses to them. Isolation of large amounts of native antigen from Cryptosporidium oocysts is expensive and is only feasible for C. parvum antigens. Here, we describe a method of producing recombinant, functional Cryptosporidium glycoprotein antigens in Toxoplasma gondii. These functional recombinant proteins can be used to investigate the role of glycotopes in Cryptosporidium immune responses and parasite-host cell interactions.

A key feature of circadian rhythms is the sleep/wake cycle. Sleep causes reduced responsiveness to the environment, which puts animals in a particularly vulnerable state; yet sleep has been conserved throughout evolution, indicating that it fulfils a vital purpose. A core function of sleep across species has not been identified, but substantial advances in sleep research have been made in recent years using the genetically tractable model organism, Drosophila melanogaster. This review describes the universality of sleep, the regulation of sleep, and current theories on the function of sleep, highlighting a historical and often overlooked theory called the Free Radical Flux Theory of Sleep. Additionally, we summarize our recent work with short-sleeping Drosophila mutants and other genetic and pharmacological tools for manipulating sleep which supports an antioxidant theory of sleep and demonstrates a bi-directional relationship between sleep and oxidative stress., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Objective: Trait negative urgency is consistently associated with alcohol problems, and cross-sectional findings have suggested a mediational role of impaired control over alcohol. Initial evidence also suggests that individual differences in self-reported sensitivity to alcohol's effects may moderate the association between urgency and alcohol outcomes. The aim of this study was to replicate and extend these findings using prospective data., Method: Young adult drinkers (N = 159, mean age = 18.87, SD = 1.16; 70.4% female) from Montreal, Quebec, Canada, completed an online survey at baseline and again 6 months later. Participants completed questionnaires measuring negative urgency, alcohol sensitivity, impaired control over alcohol, and hazardous drinking., Results: Moderated mediation analyses revealed that the prospective indirect association between negative urgency at baseline and hazardous drinking at follow-up (mediated via increased impaired control at follow-up) was significant only for young adults who reported relatively lower alcohol sensitivity at baseline., Conclusions: Using prospective data from a unique sample of young adults, the present study partially replicates prior cross-sectional findings suggesting that the indirect association between urgency and hazardous drinking via impaired control over alcohol is moderated by alcohol sensitivity.

In Drosophila , ~150 neurons expressing molecular clock proteins regulate circadian behavior. Sixteen of these neurons secrete the neuropeptide Pdf and have been called 'master pacemakers' because they are essential for circadian rhythms. A subset of Pdf + neurons (the morning oscillator) regulates morning activity and communicates with other non-Pdf + neurons, including a subset called the evening oscillator. It has been assumed that the molecular clock in Pdf + neurons is required for these functions. To test this, we developed and validated Gal4-UAS based CRISPR tools for cell-specific disruption of key molecular clock components, period and timeless . While loss of the molecular clock in both the morning and evening oscillators eliminates circadian locomotor activity, the molecular clock in either oscillator alone is sufficient to rescue circadian locomotor activity in the absence of the other. This suggests that clock neurons do not act in a hierarchy but as a distributed network to regulate circadian activity., Competing Interests: RD, RO, MP, MU, HK, MB, JC, MS No competing interests declared, (© 2019, Delventhal et al.)

Diabetes is far more prevalent in smokers than non-smokers, but the underlying mechanisms of vulnerability are unknown. Here we show that the diabetes-associated gene Tcf7l2 is densely expressed in the medial habenula (mHb) region of the rodent brain, where it regulates the function of nicotinic acetylcholine receptors. Inhibition of TCF7L2 signalling in the mHb increases nicotine intake in mice and rats. Nicotine increases levels of blood glucose by TCF7L2-dependent stimulation of the mHb. Virus-tracing experiments identify a polysynaptic connection from the mHb to the pancreas, and wild-type rats with a history of nicotine consumption show increased circulating levels of glucagon and insulin, and diabetes-like dysregulation of blood glucose homeostasis. By contrast, mutant Tcf7l2 rats are resistant to these actions of nicotine. Our findings suggest that TCF7L2 regulates the stimulatory actions of nicotine on a habenula-pancreas axis that links the addictive properties of nicotine to its diabetes-promoting actions.

Social anxiety (SA) is thought to relate to alcohol misuse. However, current evidence is inconsistent - especially in young adulthood. Recent non-experimental data show that trait impulsivity moderates the effect of SA on alcohol misuse. Specifically, this work suggests that concurrently elevated impulsivity may draw attention to the immediate, anxiolytic effects of drinking - thus promoting alcohol misuse among those high in SA. Otherwise, without elevated impulsivity, a socially anxious person may not drink due to focusing on alcohol's possible negative outcomes (e.g., embarrassing behaviours). The next step in this research is to examine if impulsivity impacts in-the-moment subjective craving among socially anxious individuals. This was the goal of the present experiment. After baseline measures, undergraduate participants (N = 110) completed the Trier Social Stress Test followed by an alcohol (versus neutral) cue exposure. Subjective craving ratings were collected at both baseline and post-cue exposure. Moderation analyses revealed that socially anxious individuals endorsed strong cravings following an alcohol (but not a neutral) cue exposure, but only if they also had elevated impulsivity. In-lab craving was positively correlated with retrospective reports of alcohol misuse. Our findings demonstrate that impulsivity contributes to SA-related risk for alcohol misuse., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Many Indigenous communities are concerned with substance use (SU) problems and eager to advance effective solutions for their prevention and treatment. Yet these communities also are concerned about the perpetuation of colonizing, disorder-focused, stigmatizing approaches to mental health, and social narratives related to SU problems. Foundational principles of community psychology-ecological perspectives, empowerment, sociocultural competence, community inclusion and partnership, and reflective practice-provide useful frameworks for informing ethical community-based research pertaining to SU problems conducted with and by Indigenous communities. These principles are explored and extended for Indigenous community contexts through themes generated from seven collaborative studies focused on understanding, preventing, and treating SU problems. These studies are generated from research teams working with Indigenous communities across the United States and Canada-inclusive of urban, rural, and reservation/reserve populations as well as adult and youth participants. Shared themes indicate that Indigenous SU research reflects community psychology principles, as an outgrowth of research agendas and processes that are increasingly guided by Indigenous communities. At the same time, this research challenges these principles in important ways pertaining to Indigenous-settler relations and Indigenous-specific considerations. We discuss these challenges and recommend greater synergy between community psychology and Indigenous research., (© 2019 Society for Community Research and Action.)

Background and Aims: Despite increases in female gambling, little research investigates female-specific factors affecting gambling behavior (GB). Although research suggests that some addictive behaviors may fluctuate across menstrual cycle phase (MCP), gambling requires further investigation. In two studies, we examined associations between MCP and three risky GBs: time spent gambling, money spent gambling, and the probability of consuming alcohol while gambling. Associations between MCP and negative affect were also examined in Study 2. We predicted that, consistent with self-medication theory, increases in negative affect (Study 2) and risky GBs (Studies 1 and 2) would occur premenstrually/menstrually relative to other phases., Methods: Data were obtained from 33 female gamblers using a retrospective timeline followback procedure (Study 1) and from 20 female gamblers using a prospective 32-day, daily diary method (Study 2). In Study 2, salivary progesterone levels verified self-reported MCP validity., Results: Findings revealed significant, but somewhat inconsistent, MCP effects on GBs across studies. The self-medication hypothesis was partially supported. Increases relative to another MCP(s) were found for alcohol consumption while gambling premenstrually, time spent gambling menstrually/premenstrually, money spent gambling menstrually, and negative affect premenstrually. Unexpectedly, findings more consistently indicated that GBs increased during ovulation, suggestive of enhanced reward sensitivity. Progesterone assays validated self-reported MCP (Study 2)., Discussion and Conclusions: The results suggest a role of ovarian hormones on negative affect and GBs in females. This research could lead to the identification of female-specific factors affecting gambling and the development of more effective interventions for females with, or at risk for, problematic gambling.

The factors involved in gain or loss of virulence in Babesia bovis are unknown. Spherical body protein 2 truncated copy 11 (sbp2t11) transcripts in B. bovis were recently reported to be a marker of attenuation for B. bovis strains. Increased cytoadhesion of B. bovis-infected red blood cells (iRBC) to vascular endothelial cells is associated with severe disease outcomes and an indicator of parasite virulence. Here, we created a stable B. bovis transfected line over-expressing sbp2t11 to determine whether up-regulation of sbp2t11 is associated with changes in cytoadhesion. This line was designated sbp2t11up and five B. bovis clonal lines were derived from the sbp2t11up line by limiting dilution for characterisation. We compared the ability of iRBCs from the sbp2t11up line and its five derivative clonal lines to adhere to bovine brain endothelial cells, using an in vitro cytoadhesion assay. The same lines were selected for in vitro cytoadhesion and the levels of sbp2t11 transcripts in each selected line were quantified. Our results demonstrate that up-regulation of sbp2t11 is accompanied by a statistically significant reduction in cytoadhesion. Confirmed up-regulation of sbp2t11 in B. bovis concomitant with the reduction of iRBC in vitro cytoadhesion to bovine brain endothelial cell is consistent with our previous finding that up-regulation of sbp2t11 is an attenuation marker in B. bovis and suggests the involvement of sbp2t11 transcription in B. bovis virulence., (Copyright © 2018. Published by Elsevier Ltd.)

Rationale: Post-traumatic stress disorder (PTSD) is a devastating anxiety-related disorder which develops subsequent to a severe psychologically traumatic event. Only ~ 9% of people who experience such a trauma develop PTSD. It is clear that a number of factors, including genetics, influence whether an individual will develop PTSD subsequent to a trauma. The 129S1/SvImJ (S1) inbred mouse strain displays poor fear extinction and may be useful to model this specific aspect of PTSD. The metabotropic glutamate receptor 7 (mGlu 7 receptor) has previously been shown to be involved in cognitive processes and anxiety-like behaviour placing it in a key position to regulate fear extinction processes. We sought to compare mGlu 7 receptor mRNA levels in the S1 strain with those in the robustly extinguishing C57BL/6J (B6) inbred strain using in situ hybridisation (ISH) in three brain regions associated with fear extinction: the amygdala, hippocampus and prefrontal cortex (PFC)., Results: Compared to the B6 strain, S1 mice had increased mGlu 7 receptor mRNA levels in the lateral amygdala (LA) and basolateral amygdala (BLA) subdivisions. An increase was also seen in the hippocampal CA1 and CA3 subregions of S1 mice. No difference in mGlu 7 receptor levels were seen in the central nucleus (CeA) of the amygdala, dentate gyrus (DG) of the hippocampus or prefrontal cortex., Conclusions: These data show altered mGlu 7 receptor expression in key brain regions associated with fear extinction in two different inbred mouse strains which differ markedly in their fear extinction behaviour. Altered mGlu 7 receptor levels may contribute to the deficit fear extinction processes seen in fear extinction in the S1 strain.

Background: Alcohol misuse and emotional problems (ie, depression and anxiety) are highly comorbid among Canadian young adults. However, there is a lack of integrated, accessible, and evidence-based treatment options for these young adults., Objective: The main goal of this study is to develop and test the efficacy of an integrated, online self-help program designed to target both alcohol misuse and emotional problems., Methods: A two-arm randomized controlled trial design will be used to compare the efficacy of the online integrated treatment to a psychoeducational control group. A target sample of 214 participants will be recruited and randomly assigned to either condition. The integrated treatment will last 8 weeks, and participants will work through 12 modules. Modules will incorporate content based on principles of cognitive behavioral therapy and motivational interviewing. Participants in the control group will receive links to psychoeducational resources and will have access to the full treatment after follow-up. The primary outcome will be the number of Canadian standard drinks consumed in the week leading up the assessment. Secondary outcomes of interest include symptoms of depression, anxiety, alcohol-related problems, quality of life, and use of other drugs. Assessments will be completed at 3 time-points: at baseline, at the end of treatment (ie, 8 weeks), and at follow-up (ie, 24 weeks). Upon completion, data will be analyzed using generalized linear mixed models., Results: Data collection began in June 2018 and will continue until January 2020. Final study results will be submitted for publication by July 2020., Conclusions: Currently, there are no integrated treatments designed to target alcohol misuse and the range of emotional problems experienced by young adults. This research stands to provide an effective, accessible (ie, Web-based), and feasible option to treat the many struggling young adults in this country., Trial Registration: ClinicalTrials.gov ID NCT03406039; https://clinicaltrials.gov/ct2/show/NCT03406039 (Archived by WebCite at http://www.webcitation.org/72fDefnrh)., Registered Report Identifier: PRR1-10.2196/11298., (©Jona R Frohlich, Karli K Rapinda, Michael P Schaub, Andreas Wenger, Christian Baumgartner, Edward A Johnson, Roisin M O'Connor, Norah Vincent, Matthijs Blankers, David D Ebert, Heather Hadjistavropoulos, Corey S Mackenzie, Matthew T Keough. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 01.11.2018.)

Competing Interests: DLD has been involved in prior published reviews of youth mentoring programmes. However, these reviews did not address the effectiveness of CMC‐only e‐mentoring programmes, the focus of this review. RMO is the co‐author of practical guidance, published by the Early Intervention Foundation, on how to choose, commission, and evaluate mentoring services (O’Connor & Waddell, 2015); however, the guidance does not address the effectiveness e‐mentoring programmes, and has a specific focus on preventing gang and youth violence. LB is not aware of any potential conflicts of interest. All authors will strive to interpret the results without prejudice or bias.

Although sleep appears to be broadly conserved in animals, the physiological functions of sleep remain unclear. In this study, we sought to identify a physiological defect common to a diverse group of short-sleeping Drosophila mutants, which might provide insight into the function and regulation of sleep. We found that these short-sleeping mutants share a common phenotype of sensitivity to acute oxidative stress, exhibiting shorter survival times than controls. We further showed that increasing sleep in wild-type flies using genetic or pharmacological approaches increases survival after oxidative challenge. Moreover, reducing oxidative stress in the neurons of wild-type flies by overexpression of antioxidant genes reduces the amount of sleep. Together, these results support the hypothesis that a key function of sleep is to defend against oxidative stress and also point to a reciprocal role for reactive oxygen species (ROS) in neurons in the regulation of sleep., Competing Interests: The authors have declared that no competing interests exist.