Bullying at School, Cyberbullying, and Loneliness: National Representative Study of Adolescents in Denmark.

AIMS: The aim was to examine how loneliness was associated with bullying victimization at school and online. METHODS: We used data from the Danish arm of the international Health Behavior in School-aged Children (HBSC) study from 2022. The study population was a nationally representative sample of 11-15-year-olds who completed the internationally standardized HBSC questionnaire at school, n = 5382. Multilevel logistic regression was applied to study the associations between bullying victimization and loneliness. RESULTS: The prevalence of reporting loneliness often or very often was 9.0%; 6.3% of the sample experienced habitual bullying victimization at school, and 4.8% incurred cyberbullying. There was a strong and graded association between loneliness and bullying victimization at school and cyberbullying. The associations were significant for boys and girls, and the association between exposure to bullying at school and loneliness was steeper for boys than girls. The gradients were steeper for physical bullying than for cyberbullying. Students exposed to habitual bullying in both contexts had an adjusted OR (95% CI) of 11.21 (6.99-17.98) for loneliness. CONCLUSION: Exposure to bullying at school and cyberbullying are strongly associated with loneliness. It is important to reduce bullying at school and on the internet and to promote effective interventions to reduce continuing loneliness.

Do Patterns of Adolescent Participation in Arts, Culture and Entertainment Activities Predict Later Wellbeing? A Latent Class Analysis.

Participation in arts, culture, and entertainment (PACE) activities may promote adolescent wellbeing. However, little is known about how such activities cluster together, and previous research has used small samples, cross-sectional designs, focused on single activities, and/or has not considered the influence of socio-demographic factors on participation. Using latent class analysis, the aims of this study were to establish: (i) classes of adolescent PACE activities; (ii) associations between socio-demographic characteristics and PACE classification; and, (iii) whether PACE classification predicts later wellbeing. Longitudinal data from the #BeeWell study (N = 18,224 adolescents; mean age at T1 = 12 years 7 months (±3.56 months); 50.54% female) were analyzed. Four latent classes were established: the 'Dynamic Doers' (high, wide-ranging participation; 11.87%); the 'Mind and Body Crew' (reading, arts, videogames, sports/exercise; 39.81%); the 'Game and Gain Squad' (videogames and sports/exercise; 29.05%); and the 'Activity Free Adolescents' (uniformly low participation; 19.27%). Associations between socio-demographic characteristics and PACE classification were observed (e.g., socio-economic disadvantage increased the likelihood of Activity Free Adolescents classification, compared to Game and Gain Squad classification). Finally, PACE classification predicted later wellbeing (e.g., Dynamic Doers reported significantly higher wellbeing than Activity Free Adolescents). These findings are discussed in relation to the need to improve accessibility and appeal of arts, culture, and entertainment provision for adolescents as a means to optimize their wellbeing. PRE-REGISTRATION: The analysis plan for this study was pre-registered on the Open Science Framework and can be found here: https://osf.io/2jtpd.

Chiral Brønsted Acid Catalyzed Cascade Alcohol Deprotection and Enantioselective Cyclization.

The protection-deprotection sequence is vital to organic synthesis. Here, we describe a novel catalytic cascade where a chiral Brønsted acid selectively removes ether protecting groups and catalyzes intramolecular cyclization in one pot. We tested three model substrates from our previous work and investigated the rate of deprotection through gas chromatography (GC) studies. This work builds on our stereoselective synthesis of lactones by streamlining our synthesis. It also opens the door for additional investigations into other catalytic cascade reactions using chiral Brønsted acid catalysts.

Neighbourhood effects on loneliness among adolescents.

BACKGROUND: Loneliness is a growing public health concern, but little is known about how place affects loneliness, especially during adolescence. This is the first study to examine the influence of neighbourhoods on loneliness in early-to-mid adolescence. METHODS: Baseline data from the #BeeWell cohort study in Greater Manchester (England), including 36 141 adolescents (aged 12-15 years) across 1590 neighbourhoods, were linked to neighbourhood characteristics using administrative data at the level of lower super output areas and analysed using multilevel regression. RESULTS: Neighbourhood differences explained 1.18% of the variation in loneliness. Ethnic, gender and sexual orientation inequalities in loneliness varied across neighbourhoods. Several neighbourhood characteristics predicted loneliness at the individual level, including skills deprivation among children and young people, lower population density and perceptions of the local area (feeling safe; trust in local people; feeling supported by local people; seeing neighbours as helpful; the availability of good places to spend free time). Finally, a longer distance from home to school was associated with significantly higher loneliness. CONCLUSIONS: Neighbourhoods account for a small but significant proportion of the variation in adolescent loneliness, with some neighbourhood characteristics predicting loneliness at the individual level, and loneliness disparities for some groups differing across neighbourhoods.

Adolescent loneliness across the world and its relation to school climate, national culture and academic performance.

BACKGROUND: Loneliness during adolescence has adverse consequences for mental health, education and employment outcomes. Yet, we know little about common correlates of loneliness among adolescents, making intervention work difficult. AIMS: In this study, we (1) explore individual-, school- and country-level correlates of loneliness to help identify potential intervention targets, and (2) examine the influence of loneliness on academic performance. SAMPLE: A total of 518,210 students aged 15 years from 75 countries provided self-reported loneliness data. RESULTS: Using multilevel modelling, we found individual-, school- and country-level correlates of self-reported school-based loneliness, and showed that loneliness negatively influenced academic performance. CONCLUSIONS: Based on the findings, interventions that focus on enhancing social and emotional skills, increasing trust between teachers and students and changing school climate to be more inclusive are likely to be the most effective for adolescents; they should also be culturally sensitive.

Stereoselective Desymmetrizations of Dinitriles to Synthesize Lactones.

Nitriles are important organic functional groups, allowing for installation of nitrogen in organic synthesis. The Pinner reaction transforms nitriles into esters via the imidate group, but in general has previously necessitated harsh acid conditions. This work builds on the utility of the Pinner reaction through a stereoselective desymmetrization of dinitriles to form γ- and δ-lactones in good yields and diastereoselectivites.

Dual-Factor Mental Health from Childhood to Early Adolescence and Associated Factors: A Latent Transition Analysis.

The dual-factor model of mental health indicates the importance of simultaneously assessing symptoms and subjective wellbeing, but there is limited understanding of how dual-factor mental health changes during the transition from childhood to early adolescence and factors associated with change. The current study investigated dual-factor mental health over a 2-year period from when children were 8-9 years old to 10-11 years old (N = 2402; 48% female), using latent transition analysis. Further analyses determined whether sex and peer support were associated with initial mental health status or specific transitions during this period. Following class enumeration procedures, a 5-class model was selected at both timepoints. Classes were: (1) complete mental health, (2) vulnerable, (3) emotional symptoms but content, (4) conduct problems but content, and (5) troubled. Half of the sample changed mental health status during the study period. Sex and peer support were associated with specific mental health statuses and subsequent transitions. The findings have implications for mental health screening practice and identifying those in need of targeted interventions.

Exploring the Frequency, Intensity, and Duration of Loneliness: A Latent Class Analysis of Data from the BBC Loneliness Experiment.

Almost all measures of loneliness have been developed without discussing how to best conceptualize and assess the severity of loneliness. In the current study, we adapted the four-item UCLA, so that it continued to measure frequency of loneliness, but also assessed intensity and duration, providing a measure of other aspects of loneliness severity. Using data from participants resident in the UK who completed the BBC Loneliness Experiment (N = 36,767; F = 69.6%) and Latent Class Profile Analyses, we identified four groups of people who scored high on loneliness on at least one of the three severity measures. Duration of loneliness often over months or years seemed to be particularly important in distinguishing groups. Further, group membership was predicted by important demographic and psychological variables. We discuss the findings in terms of implications for research and practice. We highlight the need to explore these profiles longitudinally to investigate how membership predicts later mental and physical health, and well-being.

The Application of Latent Class Analysis for Investigating Population Child Mental Health: A Systematic Review.

Background: Latent class analysis (LCA) can be used to identify subgroups of children with similar patterns of mental health symptoms and/or strengths. The method is becoming more commonly used in child mental health research, but there are reservations about the replicability, reliability, and validity of findings. Objective: A systematic literature review was conducted to investigate the extent to which LCA has been used to study population mental health in children, and whether replicable, reliable and valid findings have been demonstrated. Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A search of literature, published between January 1998 and December 2017, was carried out using MEDLINE, EMBASE, PsycInfo, Scopus, ERIC, ASSIA, and Google Scholar. A total of 2,748 studies were initially identified, of which 23 were eligible for review. The review examined the methods which studies had used to choose the number of mental health classes, the classes that they found, and whether there was evidence for the validity and reliability of the classes. Results: Reviewed studies used LCA to investigate both disparate mental health symptoms, and those associated with specific disorders. The corpus of studies using similar indicators was small. Differences in the criteria used to select the final LCA model were found between studies. All studies found meaningful or useful subgroups, but there were differences in the extent to which the validity and reliability of classes were explicitly demonstrated. Conclusions : LCA is a useful tool for studying and classifying child mental health at the population level. Recommendations are made to improve the application and reporting of LCA and to increase confidence in findings in the future, including use of a range of indices and criteria when enumerating classes, clear reporting of methods for replicability, and making efforts to establish the validity and reliability of identified classes.

Chiral Brønsted Acid Catalyzed Kinetic Resolutions.

The synthesis of enantioenriched small molecules is an ongoing goal of organic chemists. This focus review explores the use of kinetic resolutions catalyzed by chiral Brønsted acids. Methods include classic kinetic resolutions and dynamic kinetic resolutions. The small molecules obtained are potentially valuable intermediates in the synthesis of biologically important compounds.

Solenopsin A and analogs exhibit ceramide-like biological activity.

BACKGROUND: (-)-Solenopsin A is a piperidine alkaloid that is a component of the venom of the fire ant Solenopsis invicta. Previously, we have demonstrated that solenopsin exhibit anti-angiogenic activity and downregulate phosphoinositol-3 kinase (PI3K) in the p53 deficient renal cell carcinoma cell line 786-O. Solenopsin has structural similarities to ceramide, a major endogenous regulator of cell signaling and cancer therapy induced apoptosis. METHODS: Different analogs of solenopsin were synthesized in order to explore structure-activity relationships. The anti-proliferative effect of solenopsin and analogs was tested on six different cell lines, including three tumor cell lines, two normal cutaneous cell lines, and one immortalized hyperproliferative cell line. FRET-based reporters were used to study the affect of solenopsin and analogs on Akt activity and PDK1 activation and sucrose density gradient fractionation was performed to examine recruitment of PTEN to membrane rafts. Western-blotting was used to evaluate the affect of solenopsin and analogs on the Akt and the MAPK 44/42 pathways in three different tumor cell lines. Measurement of cellular oxygen consumption rate together with autophagy staining was performed to study mitochondrial function. Finally, the affect of solenopsin and analogs on ROS production was investigated. RESULTS: In this paper we demonstrate that solenopsin analogs with potent anti-proliferative effects can be synthesized from inexpensive dimethylpyridines. To determine whether solenopsin and analogs act as ceramide analogs, we examined the effect of solenopsin and analogs on two stereotypic sites of ceramide activity, namely at lipid rafts and mitochondria. We found that native solenopsin, (-)-solenopsin A, inhibits functional Akt activity and PDK1 activation in lipid rafts in a similar fashion as ceramide. Both cis and trans analogs of solenopsin reduce mitochondrial oxygen consumption, increase reactive oxygen, and kill tumor cells with elevated levels of Akt phosphorylation. However, only solenopsin induces mitophagy, like ceramide. CONCLUSIONS: The requirements for ceramide induced mitophagy and inhibition of Akt activity and PDK1 activation in lipid rafts are under strict stereochemical control. The naturally occurring (-)-solenopsin A mimic some of the functions of ceramide and may be therapeutically useful in the treatment of hyperproliferative and malignant disorders of the skin, even in the presence of elevated levels of Akt.

Nonenzymatic enantioselective synthesis of all-carbon quaternary centers through desymmetrization.

The asymmetric desymmetrization of meso or prochiral compounds containing an all-carbon quaternary center is an attractive alternative to classical synthetic approaches aimed at the asymmetric formation of a new C-C bond. This review focuses on nonenzymatic desymmetrizations that utilize transition metal catalysts or organocatalysts to distinguish between enantiotopic groups to generate enantioenriched compounds containing all-carbon quaternary stereocenters.

Asymmetric Synthesis of Hydroxy Esters with Multiple Stereocenters via a Chiral Phosphoric Acid Catalyzed Kinetic Resolution.

The kinetic resolution of hydroxy tert-butyl esters through a Brønsted acid catalyzed lactonization is described. The resulting enantioenriched molecules have cyclic backbones and/or multiple stereocenters. DFT calculations explore how small changes in substrate structure can have a large impact on the selectivity of the process.

Enantioselective desymmetrization of diesters.

The desymmetrization of prochiral diesters with a chiral phosphoric acid catalyst to produce highly enantioenriched lactones in excellent yield is reported. The process is easily scaled and accommodates a variety of substitution patterns, many of which result in the generation of an enantioenriched all-carbon quaternary center. Manipulation of lactone product to useful small building blocks is also described.

Facile synthesis of versatile enantioenriched α-substituted hydroxy esters through a Brønsted acid catalyzed kinetic resolution.

An efficient synthesis of enantioenriched α-substituted γ-hydroxy esters via a kinetic resolution event is described. Bulky racemic esters in the presence of a chiral Brønsted acid selectively lactonize to yield a recoverable enantioenriched hydroxy ester and lactone. These esters are highly versatile building blocks that can readily be converted to synthetically useful materials.

Asymmetric, organocatalytic, three-step synthesis of gamma-hydroxy-(E)-alpha,beta-unsaturated sulfones and esters.

Efficient and enantiocontrolled synthesis of gamma-hydroxy-alpha,beta-unsaturated sulfones and esters are reported through the reaction of enantioenriched alpha-selenyl aldehydes with EWG-stabilized carbanions and then a one-pot selenide oxidation, in situ epoxide formation, and final in situ epoxide opening.

Malaria-infected mice are cured by oral administration of new artemisinin derivatives.

In four or five chemical steps from the 1,2,4-trioxane artemisinin, a new series of 23 trioxane dimers has been prepared. Eleven of these new trioxane dimers cure malaria-infected mice via oral dosing at 3 x 30 mg/kg. The clinically used trioxane drug sodium artesunate prolonged mouse average survival to 7.2 days with this oral dose regimen. In comparison, animals receiving no drug die typically on day 6-7 postinfection. At only 3 x 10 mg/kg oral dosing, seven dimers prolong the lifetime of malaria-infected mice to days 14-17, more than double the chemotherapeutic effect of sodium artesunate. Ten new trioxane dimers at only a single oral dose of 30 mg/kg prolong mouse average survival to days 8.7-13.7, and this effect is comparable to that of the fully synthetic trioxolane drug development candidate OZ277, which is in phase II clinical trials.

Low-calcemic, highly antiproliferative, 23-oxa ether analogs of the natural hormone 1 alpha,25-dihydroxyvitamin D3: design, synthesis, and preliminary biological evaluation.

Eight new side-chain allylic, benzylic, and propargylic ether analogs of the natural hormone calcitriol have been rationally designed and easily synthesized. Three of these 23-oxa ether analogs lacking the typical side-chain OH group are more antiproliferative in vitro and desirably less calcemic in vivo than the natural hormone. One of these three 23-oxa analogs has transcriptional potency almost as high as that of calcitriol, even though it binds to the human vitamin D receptor only about 1% as well as calcitriol.

Difluoromethyl analogs of the natural hormone 1alpha,25-dihydroxyvitamin D3: Design, synthesis, and preliminary biological evaluation.

Three new Vitamin D analogs 3-5 incorporating a -CHF(2) group as an -OH surrogate have been prepared. Two of these new analogs (3 and 5) are strongly antiproliferative toward murine keratinocytes and are approximately 50 times less calciuric in vivo than the natural hormone calcitriol. The transcriptional activity of the 25-CHF(2) analog 3 is higher than that of the 1-CHF(2) analog 4.