Diels-Alder Cycloadditions of Oxacyclic Allenes and α-Pyrones.

Reactions of α-pyrones with oxacyclic allenes in Diels-Alder trappings are described. We investigate regioselectivity trends and perform competition experiments to assess the influence of structural and electronic features on relative reaction rates. We also demonstrate the stereospecific trapping of an oxacyclic allene, which proceeds in high optical yield. This study provides insight into strained cyclic allene reactivity, as well as new synthetic tools for the rapid construction of complex, heterocyclic scaffolds.

Psychological readiness for injury recovery: evaluating psychometric properties of the IPRRS and assessing group differences in injured physically active individuals.

Objectives: The primary purpose of the study was to assess the one-factor and two-factor structure of the Injury Psychological Readiness to Return to Sport Scale (IPRRS) in an injured physically active population using confirmatory factor analysis (CFA) procedures and assess group (ie, sex, age, injury type, athlete status) and longitudinal differences using structural equation modelling (eg, invariance testing). Methods: The non-experimental study included a sample of 629 physically active individuals who suffered a musculoskeletal injury who sought treatment at an outpatient integrated sport medicine and rehabilitation therapy clinic. Participants filled out a questionnaire packet at three time points. Data analysis included a CFA and multigroup and longitudinal invariance. Results: Sample mean age was 26.3 years, with females comprising 49.5%. Chronic injuries represented 29.6% of the sample and 35.0% were classified as competitive athletes. A six-item, one-factor model was confirmed in the sample with factor loadings ranging from 0.67 to 0.86. Multigroup and longitudinal invariance were established. Multigroup invariance demonstrated null differences between sex and injury type, and statistical differences between age and athlete status subgroups. Longitudinal invariance demonstrated a statistically significant increase in psychological readiness over time. Conclusions: The findings support the use of the IPRRS as a tool to measure aspects of psychological readiness. Clinicians and researchers can use the IPRRS to assess interventions in future research.

Higher prevalence of sacbrood virus in Apis mellifera (Hymenoptera: Apidae) colonies after pollinating highbush blueberries.

Highbush blueberry pollination depends on managed honey bees (Apis mellifera) L. for adequate fruit sets; however, beekeepers have raised concerns about the poor health of colonies after pollinating this crop. Postulated causes include agrochemical exposure, nutritional deficits, and interactions with parasites and pathogens, particularly Melisococcus plutonius [(ex. White) Bailey and Collins, Lactobacillales: Enterococcaceae], the causal agent of European foulbrood disease, but other pathogens could be involved. To broadly investigate common honey bee pathogens in relation to blueberry pollination, we sampled adult honey bees from colonies at time points corresponding to before (t1), during (t2), at the end (t3), and after (t4) highbush blueberry pollination in British Columbia, Canada, across 2 years (2020 and 2021). Nine viruses, as well as M. plutonius, Vairimorpha ceranae, and V. apis [Tokarev et al., Microsporidia: Nosematidae; formerly Nosema ceranae (Fries et al.) and N. apis (Zander)], were detected by PCR and compared among colonies located near and far from blueberry fields. We found a significant interactive effect of time and blueberry proximity on the multivariate pathogen community, mainly due to differences at t4 (corresponding to ~6 wk after the beginning of the pollination period). Post hoc comparisons of pathogens in near and far groups at t4 showed that detections of sacbrood virus (SBV), which was significantly higher in the near group, not M. plutonius, was the primary driver. Further research is needed to determine if the association of SBV with highbush blueberry pollination is contributing to the health decline that beekeepers observe after pollinating this crop.

Honey bee stressor networks are complex and dependent on crop and region.

Honey bees play a major role in crop pollination but have experienced declining health throughout most of the globe. Despite decades of research on key honey bee stressors (e.g., parasitic Varroa destructor mites and viruses), researchers cannot fully explain or predict colony mortality, potentially because it is caused by exposure to multiple interacting stressors in the field. Understanding which honey bee stressors co-occur and have the potential to interact is therefore of profound importance. Here, we used the emerging field of systems theory to characterize the stressor networks found in honey bee colonies after they were placed in fields containing economically valuable crops across Canada. Honey bee stressor networks were often highly complex, with hundreds of potential interactions between stressors. Their placement in crops for the pollination season generally exposed colonies to more complex stressor networks, with an average of 23 stressors and 307 interactions. We discovered that the most influential stressors in a network-those that substantively impacted network architecture-are not currently addressed by beekeepers. Finally, the stressor networks showed substantial divergence among crop systems from different regions, which is consistent with the knowledge that some crops (e.g., highbush blueberry) are traditionally riskier to honey bees than others. Our approach sheds light on the stressor networks that honey bees encounter in the field and underscores the importance of considering interactions among stressors. Clearly, addressing and managing these issues will require solutions that are tailored to specific crops and regions and their associated stressor networks.

Mindfulness induction and executive function after high-intensity interval training with and without mindful recovery intervals.

OBJECTIVES: Determine the effect of incorporating mindfulness-based activities into the recovery intervals of high-intensity interval training (HIIT) on mindfulness induction and subsequent executive function performance. DESIGNS: A within-subject crossover trial. METHODS: Forty adults participated in two experimental conditions, including a 30-min bout of HIIT involving mindfulness recovery intervals (Mindful) and a 30-min bout of HIIT without mindfulness recovery intervals (Non-mindful), on two separate days in counterbalanced order. Before and after each condition, participants completed the flanker task, switch-flanker task, and n-back task to measure inhibitory control, cognitive flexibility, and working memory, respectively. RESULTS: A higher level of mindfulness state was observed following the Mindful condition than the Non-mindful condition. Dispositional mindfulness was positively correlated with the level of the mindful state only during the Mindful condition but not the Non-mindful condition. The switch-flanker response accuracy was improved from the pretest to posttest during the Non-mindful condition but remained unchanged over time during the Mindful condition. Time-related improvements in the flanker and n-back task outcomes were observed for both the Mindful and Non-mindful conditions and did not differ between conditions. CONCLUSION: Although incorporating mindfulness-based activities during the recovery intervals of HIIT successfully led to greater state-related mindfulness, such a heightened mindful state did not correspond with additional modulation in inhibitory control and working memory performance while attenuating HIIT-related positive changes in task performance requiring cognitive flexibility.

Acute effects of mindful interval exercise on cognitive performance in a higher education setting.

Interval exercise (IE) has been shown to have acute facilitating effects on cognition; however, the existing literature has been limited to laboratory settings and has focused on manipulating the parameters of exercise bouts during IE. This study included two classroom-based experiments to (1) investigate the effect of an acute bout of IE delivering mindfulness activity during its recovery intervals (mindful IE) on cognitive performance, and (2) compare cognitive performance following acute bouts of mindful IE with non-mindful IE. Experiment 1: Using a class-based within-subject crossover design, 59 participants completed the Stroop, d2, and trail-making tests to measure inhibitory control, attention, and cognitive flexibility, after a 30-min non-exercise or mindful IE session on separate counterbalanced days. Experiment 2: Using a similar design, 70 participants were assigned to two groups to receive a non-exercise and an IE session with (mindful) or without (non-mindful) mindfulness-based recovery intervals on separate counterbalanced days. Results from Experiment 1 showed superior d2 performance following the mindful IE than the non-exercise session. Although Experiment 2 found exercise-related decreases in commission error rate during the d2 test in both groups, the non-mindful group showed additional decreases in omission and total error rates. Further, higher scores on the nonreactivity facet of dispositional mindfulness were correlated with larger decreases in omission and total error rates during the d2 test for the mindful IE group. No exercise-related effect was found for outcomes of the Stroop and trail-making tests in both experiments. These findings in the selective improvements in d2 test performance are the first to suggest the feasibility of integrating mindfulness activity into the recovery intervals of IE for enhanced cognitive performance that may depend on individual differences in dispositional mindfulness.

Clinical and biological heterogeneity of multisystem inflammatory syndrome in adults following SARS-CoV-2 infection: a case series.

Importance: Multisystem inflammatory syndrome in adults (MIS-A) is a poorly understood complication of SARS-CoV-2 infection with significant morbidity and mortality. Objective: Identify clinical, immunological, and histopathologic features of MIS-A to improve understanding of the pathophysiology and approach to treatment. Design: Three cases of MIS-A following SARS-CoV-2 infection were clinically identified between October 2021 - March 2022 using the U.S. Centers for Disease Control and Prevention diagnostic criteria. Clinical, laboratory, imaging, and tissue data were assessed. Findings: All three patients developed acute onset cardiogenic shock and demonstrated elevated inflammatory biomarkers at the time of hospital admission that resolved over time. One case co-occurred with new onset Type 1 diabetes and sepsis. Retrospective analysis of myocardial tissue from one case identified SARS-CoV-2 RNA. All three patients fully recovered with standard of care interventions plus immunomodulatory therapy that included intravenous immunoglobulin, corticosteroids, and in two cases, anakinra. Conclusion: MIS-A is a severe post-acute sequela of COVID-19 characterized by systemic elevation of inflammatory biomarkers. In this series of three cases, we find that although clinical courses and co-existent diseases vary, even severe presentations have potential for full recovery with prompt recognition and treatment. In addition to cardiogenic shock, glucose intolerance, unmasking of autoimmune disease, and sepsis can be features of MIS-A, and SARS-CoV-2 myocarditis can lead to a similar clinical syndrome.

Total Synthesis of Atrachinenins A and B.

Inspired by a new biosynthetic hypothesis, we report a biomimetic total synthesis of atrachinenins A and B that explains their racemic nature. The synthesis exploits an intermolecular Diels-Alder reaction between a quinone meroterpenoid and E-ß-ocimene, followed by intramolecular (3 + 2) cycloaddition and a late-stage aerobic oxidation. Divergent transformations of a simple model system gave several complex polycyclic scaffolds, while also suggesting a structure revision for atrachinenin C.

Rate of transcription elongation and sequence-specific pausing by RNA polymerase I directly influence rRNA processing.

One of the first steps in ribosome biogenesis is transcription of the ribosomal DNA by RNA polymerase I (Pol I). Processing of the resultant rRNA begins cotranscriptionally, and perturbation of Pol I transcription elongation results in defective rRNA processing. Mechanistic insight regarding the link between transcription elongation and ribosome assembly is lacking because of limited in vivo methods to assay Pol I transcription. Here, we use native elongating transcript sequencing (NET-Seq) with a strain of Saccharomyces cerevisiae containing a point mutation in Pol I, rpa190-F1205H, which results in impaired rRNA processing and ribosome assembly. We previously demonstrated that this mutation caused a mild reduction in the transcription elongation rate of Pol I in vitro; however, transcription elongation by the mutant has not been characterized in vivo. Here, our findings demonstrate that the mutant Pol I has an increased pause propensity during processive transcription elongation both in vitro and in vivo. NET-Seq reveals that rpa190-F1205H Pol I displays alternative pause site preferences in vivo. Specifically, the mutant is sensitized to A/G residues in the RNA:DNA hybrid and at the last incorporated nucleotide position. Furthermore, both NET-Seq and EM analysis of Miller chromatin spreads reveal pileups of rpa190-F1205H Pol I throughout the ribosomal DNA, particularly at the 5' end of the 35S gene. This combination of in vitro and in vivo analyses of a Pol I mutant provides novel insights into Pol I elongation properties and indicates how these properties are crucial for efficient cotranscriptional rRNA processing and ribosome assembly.

A negative body image contextualization of the self-compassion scale.

Self-compassion, a style of responding to oneself in times of suffering, is typically measured as a general tendency for how one normally responds using the Self-Compassion Scale (SCS; Neff, 2003). A contextualized adaptation to the SCS could provide a new understanding of how one responds to suffering by providing a standard frame of reference, is more likely to be more predictive of context outcomes, and reduces intraindividual variance (Baird & Lucas, 2011). How a contextualized assessment of self-compassion compares to the original assessment using parallel measures is unknown. The purpose of this study was to explore the use of a modified SCS adapted for the context of responding to the experience of negative body image (BI-SCS). There were 468 participants who completed the SCS and then wrote about a specific negative body image experience (to prime a negative body image experience) before they completed a modified SCS and related constructs. Confirmatory Factor Analysis supported a bi-factor structure consistent with SCS. Correlations with body image outcomes were stronger for the majority of BI-SCS scores compared to the SCS. Unique explained variance of the BI-SCS supported incremental validity. Results show promising initial evidence supporting the use of the BI-SCS for body-related outcomes.

Peripheral blood leucocyte telomere length is associated with progression of interstitial lung disease in systemic sclerosis.

BACKGROUND: Peripheral blood leucocyte telomere length (PBL-TL) is associated with outcomes in patients with idiopathic pulmonary fibrosis. Whether PBL-TL is associated with progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is unknown. METHODS: A retrospective observational cohort study was performed using prospectively collected data from 213 patients with SSc followed at the University of California San Francisco (UCSF) Scleroderma Center. PBL-TL was measured by quantitative PCR of DNA isolated from peripheral blood. Associations between PBL-TL and pulmonary function test trends in patients with SSc-ILD were assessed by longitudinal analysis using Generalised Linear Mixed Models. Findings were validated in a cohort of 61 patients with SSc-ILD enrolled in the Stanford University Scleroderma Center database. RESULTS: Patients with UCSF SSc with ILD were found to have shorter PBL-TL compared with those without ILD (6554±671 base pairs (bp) vs 6782±698 bp, p=0.01). Shorter PBL-TL was associated with the presence of ILD (adjusted OR 2.1 per 1000 bp TL decrease, 95% CI [1.25 to 3.70], p=0.006). PBL-TL was shorter in patients with SSc-ILD lacking SSc-specific autoantibodies compared with seropositive subjects (6237±647 bp vs 6651±653 bp, p=0.004). Shorter PBL-TL was associated with increased risk for lung function deterioration with an average of 67 mL greater loss in per year for every 1000 bp decrease in PBL-TL in the combined SSc-ILD cohorts (longitudinal analysis, adjusted model: 95% CI -104 mL to -33 mL, p<0.001). CONCLUSIONS: These findings suggest that telomere dysfunction may be associated with SSc-ILD progression and that PBL-TL measurement may be useful for stratifying risk for SSc-ILD progression.

Nascent Transcript Folding Plays a Major Role in Determining RNA Polymerase Elongation Rates.

Transcription elongation rates influence RNA processing, but sequence-specific regulation is poorly understood. We addressed this in vivo, analyzing RNAPI in S. cerevisiae. Mapping RNAPI by Miller chromatin spreads or UV crosslinking revealed 5' enrichment and strikingly uneven local polymerase occupancy along the rDNA, indicating substantial variation in transcription speed. Two features of the nascent transcript correlated with RNAPI distribution: folding energy and GC content in the transcription bubble. In vitro experiments confirmed that strong RNA structures close to the polymerase promote forward translocation and limit backtracking, whereas high GC in the transcription bubble slows elongation. A mathematical model for RNAPI elongation confirmed the importance of nascent RNA folding in transcription. RNAPI from S. pombe was similarly sensitive to transcript folding, as were S. cerevisiae RNAPII and RNAPIII. For RNAPII, unstructured RNA, which favors slowed elongation, was associated with faster cotranscriptional splicing and proximal splice site use, indicating regulatory significance for transcript folding.

Examining the effects of mindfulness-based yoga instruction on positive embodiment and affective responses.

Empirical evidence provides support for the inclusion of yoga as part of eating disorder prevention efforts through its positive impact on positive embodiment and experience of positive core affect. However, there is a need to identify the specific instructional strategies that will more consistently support positive embodiment and positive affect. We examined the effect of teaching a single yoga class using mindfulness-based instruction compared to appearance-based and neutral instruction alternatives on embodiment (i.e., state body surveillance, state body appreciation, pleasure during yoga) and changes in affect from before to after class. Female participants (N = 62; M age = 23.89, SD = 6.86) were randomly assigned to a yoga class that emphasized: being mindfully present in one's body, changing one's appearance, or just getting into yoga poses. ANOVAs revealed significantly higher body surveillance (ηp 2 =.10) and lower forecasted pleasure (ηp 2 =.21) in the appearance class compared to the other two classes. Participants in the mindfulness class experienced greater improvement in affect (ηp 2 =.08) from before to after class and higher remembered pleasure during the yoga class (ηp 2 =.19) compared to those in the appearance class. Emphasizing changes to appearance in yoga instruction may place participants at risk for less positive affect and less positive experiences of embodiment compared to mindfulness-based or even neutral yoga instruction.

The roles of self-compassion, body surveillance, and body appreciation in predicting intrinsic motivation for physical activity: Cross-sectional associations, and prospective changes within a yoga context.

Engaging in physical activity for the immediate internal experiences it brings (e.g., pleasure, satisfaction) is critical for long-term exercise adherence. Investigations of how factors such as body image contribute to intrinsic motivation for physical activity are needed. The present study examined body surveillance and body appreciation as mediators of the relationship between self-compassion and intrinsic motivation for physical activity cross-sectionally and prospectively. One sample of college women completed measures of study variables at one time point (Sample 1; N = 269, Mage = 19.96) and a second sample did so during Weeks 1, 8, and 16 while participating in a 16-week yoga course (Sample 2; N = 323, Mage = 20.31). In Sample 1, latent variable structural equation modeling supported body appreciation as a mediator between self-compassion and intrinsic motivation for physical activity. In Sample 2, latent growth curve analyses revealed that change in self-compassion predicted changes in body surveillance and body appreciation in expected directions. Further, change in body appreciation positively predicted change in intrinsic motivation. Targeting self-compassion and body appreciation may help support women's intrinsic motivation for physical activity.

Improving Adolescent Depression Screening in Pediatric Primary Care.

OBJECTIVE: Depression among adolescents is a leading public health problem. Although screening for adolescent depression in primary care is strongly recommended, screening rates remain low. Effective quality improvement (QI) initiatives can facilitate change. This study aims to assess the impact of a QI learning collaborative on adolescent depression screening and initial plans of care in primary care. METHODS: Seventeen pediatric-serving practices in Vermont participated in a QI learning collaborative aimed at improving practitioner knowledge and office systems around adolescent depression screening. Monthly medical record reviews provided monitoring of adolescent depression screening and initial plans of care over 7 months for QI. Randomly sampled annual medical record review data allowed comparison of screening and initial plans of care after the QI learning collaborative between participating and 21 control practices. RESULTS: As practices improved their office systems around adolescent depression screening and initial plans of care, data showed marked improvement in depression screening at all 17 practices, from 34% to 97% over 7 months. Adolescents at participating practices had 3.5 times greater odds (95% confidence interval [CI], 1.14-10.98, P = .03) of being screened for depression and 37.5 times greater odds (95% CI, 7.67-183.48, P < .0005) of being screened with a validated tool than adolescents at control practices, accounting for patient characteristics. CONCLUSIONS: There were significant within practice increases in adolescent depression screening after a QI learning collaborative, as well as in comparison with control practices 1 year later.

The difference is more than floating: factors affecting breast cancer survivors' decisions to join and maintain participation in dragon boat teams and support groups.

Purpose: Peer support can be helpful in rehabilitation from breast cancer, but participation in peer support groups is low. Groups that provide support opportunities in physical activity contexts are an attractive alternative for some survivors. This study examined survivors' reasons for joining and maintaining participation on a dragon boat team, along with perceptions of barriers and attractions to traditional peer support groups. Materials and methods: Seventeen breast cancer survivors were interviewed on five occasions over their first two seasons of a newly formed dragon boating team to explore their perceptions of peer support groups and dragon boating. Data were inductively analyzed using thematic analysis. Results: Categories surrounding physical, psychological, social and community features were identified with several themes emerging within each. Advantages of dragon boating included opportunities to get a combination of physical, psychosocial and community benefits; health improvement and behavior change; and obtaining social support without the focus being on cancer. Peer support groups were identified as having advantages for forming relationships and avoiding barriers associated with physical activity. Conclusions: While neither type of program meets all needs, practical considerations are identified for incorporating advantages of both programs to improve participation. Implications for rehabilitation Further understanding of perceptions, and attractions and challenges to taking part in group programs will inform development of accessible programs that target multiple rehabilitation needs. Physical activity can provide a positive, alternative focus that takes the emphasis off of cancer, which is more accessible to some survivors. Physical activity also provides opportunities to build relationships around a common, positive goal, which can be a foundation for providing support for coping with cancer.

Non-invasive right ventricular load adaptability indices in patients with scleroderma-associated pulmonary arterial hypertension.

Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) is associated with worse outcome than idiopathic pulmonary arterial hypertension (IPAH), potentially due to worse right ventricular adaptation to load as suggested by pressure-volume loop analysis. The value of non-invasive load-adaptability metrics has not been fully explored in SSc-PAH. This study sought to assess whether patients with incident SSc-PAH have worse echocardiographic load-adaptability metrics than patients with IPAH. Twenty-two patients with incident SSc-PAH were matched 1:1 with IPAH based on pulmonary vascular resistance. Echocardiographic load-adaptability indices were divided into: surrogates of ventriculo-arterial coupling (e.g. right ventricular area change/end-systolic area), indices reflecting the proportionality of load adaptation (e.g. tricuspid regurgitation velocity-time integral normalized for average right ventricular radius), and simple ratios (e.g. tricuspid annular plane systolic excursion/right ventricular systolic pressure). The prognostic value of these indices for clinical worsening (i.e. death, transplant, or hospitalization for heart failure) at one year was explored. The two groups were comprised of patients of similar age, with similar cardiac index, pulmonary resistance, capacitance and NT-proBNP levels ( p > 0.10). There was no difference in baseline right ventricular dimension, function or load-adaptability indices. At one year, eight (36.4%) SSc-PAH patients had experienced clinical worsening (eight hospitalizations and two deaths) versus one hospitalization in the IPAH group. Load adaptation at one year in survivors was not worse in SSc-PAH ( p > 0.33). Patients with IPAH responded better to therapy than SSc-PAH in terms of reduction of right ventricular areas at one year ( p < 0.05). Right ventricular load-adaptability echocardiographic indices do not appear to capture the increased risk of negative outcomes at one year associated with SSc-PAH.

The Role of Caregivers in Physical Activity for Older Adults With Alzheimer's Disease.

This study examined the determinants of physical activity (PA) for older adults with Alzheimer's disease (AD) to learn more about how to promote PA in this population. Caregivers of older adults with AD (N = 99) provided information related to care recipient's PA, as well as addressed sociodemographics and perceptions about their care recipient's PA. Gender of care recipient was a significant predictor of PA (ß = .80, P < .05); men with AD participated in more PA than women with AD. Also, caregiver's outcome expectation for care recipient's PA also predicted more PA (ß = .82, P < .05). Caregiver's perceived benefits of PA (outcome expectation) for their care recipient partially mediated the relationship between self-efficacy for care recipient's PA and the reported levels of PA for the care recipient. This study demonstrated the importance of caregiver perceptions about care recipient's PA.

Enhancer SINEs Link Pol III to Pol II Transcription in Neurons.

Spatiotemporal regulation of gene expression depends on the cooperation of multiple mechanisms, including the functional interaction of promoters with distally located enhancers. Here, we show that, in cortical neurons, a subset of short interspersed nuclear elements (SINEs) located in the proximity of activity-regulated genes bears features of enhancers. Enhancer SINEs (eSINEs) recruit the Pol III cofactor complex TFIIIC in a stimulus-dependent manner and are transcribed by Pol III in response to neuronal depolarization. Characterization of an eSINE located in proximity to the Fos gene (FosRSINE1) indicated that the FosRSINE1-encoded transcript interacts with Pol II at the Fos promoter and mediates Fos relocation to Pol II factories, providing an unprecedented molecular link between Pol III and Pol II transcription. Strikingly, knockdown of the FosRSINE1 transcript induces defects of both cortical radial migration in vivo and activity-dependent dendritogenesis in vitro, demonstrating that FosRSINE1 acts as a strong enhancer of Fos expression in diverse physiological contexts.