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Physical activity (PA) service provision in the post-secondary context is recognized as important for promoting student mental health. Nonetheless, most evidence is of poor quality and lacks critical information regarding how the PA programs are designed, delivered, and made accessible to students. This study will examine PA program effectiveness for student mental health and social well-being, as well as implementation processes to offer insight for future research and program scale-up. Post-secondary students who are physically inactive and experiencing poor mental health will be recruited. A 3-arm parallel Randomized Controlled Trial, using a hybrid effectiveness-implementation design, will be conducted using a collaborative implementation approach. The effects of 6-week supervised one-on-one and group PA, compared to a waitlist control will be examined, with outcomes assessed at baseline (T1), 6-weeks (T2), and 1-month follow-up (T3). Primary outcomes will include immediate post-program changes (T1-T2) in mental health indices, including anxiety, depression, psychological distress, and well-being. Secondary outcomes will include changes from baseline to follow-up (T1-T3) and maintenance effects from post-intervention to follow-up (T2-T3) in mental health indices, as well as changes in social well-being indices (i.e., social connectedness, social support), and PA behavior. A process evaluation will be conducted to explore contextual influences (i.e., fidelity, adherence, reach, acceptability) on the conduct of implementation across PA program delivery styles. Effectiveness data will be analyzed using linear mixed effects modeling. Process evaluation outcomes will be analyzed using a mixed methods evaluation. A knowledge mobilization plan to enhance dissemination of the findings to the intended audiences (i.e., sport and recreation professionals, mental health professionals, students, researchers) has been developed. ClinicalTrials.gov NCT06350877.

The present thesis provided a detailed examination of the self-concept variables associated with eating disturbance. Two distinct self-concept variables, namely, the content and evaluative dimensions of self, were evaluated in relation to global measures of bulimia nervosa. These self-concept dimensions were further examined in relation to the eating pathology and general maladjustment features of bulimia, including the behavioural, motivational, and cognitive-affective components of eating disturbance. Study 1 examined the actual and ideal self-concept content dimensions and the self-certainty and attribute importance evaluative self-dimensions, across the domains of body image, depressive personality, sociability, and social roles. Individuals reporting higher levels of bulimia described themselves as fatter, more depressive and less sociable, and they viewed themselves more negatively in comparison to their peers. Higher levels of bulimic symptomatology were also associated with greater actual-ideal self-discrepancies for the body image, depressive personality and sociability domains. Greater self-uncertainty was also evident among individuals with more bulimia, with this relationship evident only for social comparison ratings. More negative self-views of highly important self-attributes had implications for the cognitive-affective components of eating disturbance. Study 2 provided a more detailed examination of the relationship between bulimia and the content (actual, ideal and feared selves) and evaluative (self-certainty and attribute importance) self-concept dimensions. These self-concept variables were evaluated across primary (body image, self-control, depressive personality) and secondary (sociability, dominance, orderliness, social roles) adjective domains. Results indicated that more negative actual self-views for the primary adjective domains were more predictive of global bulimia and measures of eating pathology; whereas negative actual self-views for the secondary adjective domains were more predictive of general maladjustment. Individuals with higher levels of bulimia also reported a greater discrepancy between their actual and ideal selves and a greater congruence between their actual and feared selves, with this being most evident across the primary adjective domains. Highly certain negative self-views and more negative actual self-views of highly important self-attributes had implications for the cognitive-affective features of bulimia. The present findings were discussed in relation to cognitive-behavioural models of bulimia, as well as social cognitive theories of the self-concept. Implications for assessment and treatment were also presented. Finally, limitations of the present research were discussed and future research directions were recommended.

Acknowledgement of ethnic group membership has been found to be an important aspect of an individual's evaluation of self-worth. Traditional measures of self-esteem that do not contain questions on ethnicity reflect only a portion of a global sense of self. It is proposed that a measure of ethnic self-esteem would reflect a different portion of this structure, one that may be a central dimension of a person's overall sense of self. There is a paucity of information on reliability and validity of the measures used in research on ethnic attitudes and identity. In addition, especially little research has been conducted with Chinese Americans. This study investigated the hypothesis that the construct of ethnic self-esteem involves three components reflecting the processes of acquisition, internalization and evaluation. Evidence for the validity and reliability of measures of these components was examined as an initial investigation to explore the construct and better understand its salient characteristics. Eighty Chinese American first grade children were interviewed twice, with four months intervening. All children received the same battery of questions in identical order. Measures of Self-esteem; Chinese and American Cultural Exposure; Chinese and American Ethnic Self-esteem, Internalization and Evaluation; and General Knowledge were administered. Data regarding child's place of birth, parents' occupation and teacher background were also collected. With few exceptions, the pattern of correlations of the components of Chinese Ethnic Self-esteem exhibited positive relationships. As predicted, correlations between the components of Chinese and American Ethnic Self-esteem were either negative or not significantly different from zero. Chinese Ethnic Self-esteem was found distinct from General Self-esteem. Factor analysis did not confirm the hypothesized three component structure of Chinese Ethnic Self-esteem. Factors obtained better represented the facets of content rather than the facets of process. An exploratory analysis of classroom regression slopes suggested the possibility of an instructional treatment effect on Chinese Ethnic Self-esteem.

The Art Studios is a program established in 1992 to provide support for those in the Vancouver-Richmond area of British Columbia with a \"major mental health diagnosis. \" The program offers art classes, open studio for independent work, and a traveling art show supported by the Vancouver Coastal Health Authority. Sandra Yuen MacKay first attended the Art Studios as a student in 2002.

The preparation of 3-hydroxyfuran reported by Hodgson and Davies could not be verified. 2-bromo-3-hydroxyfuran was not obtained in the initial step which involved the treatment of 2-furoic acid with bromine in water. Only a mixture of various bromo-2-furoic acids were isolated. In addition, a small amount of material was obtained and found to be β-bromo-Δ α/β-crotonolactone. (4-bromo-2-oxo-2,5-dihydrofuran; 4-bromo-2-hydroxyfuran). Both α-bromo- and β-bromo-Δα/β-crotonolactones have been reported as early as 1894 by Hill and Cornelison, but the structures assigned to the isomers appeared to be incorrect. The two isomers were synthesized by the usual methods and their relative structures established conclusively by means of known derivatives, infrared, ultraviolet and nuclear magnetic resonance spectroscopy. The structures are the converse of the earlier assignments. The third isomer, γ-bromo-Δα/β-crotonolactone was also synthesized by a new method.

Marjolijn Ligtenberg and Suet Leung and colleagues report the identification of germline deletions in TACSTD1 , a gene directly upstream of MSH2 , in families with Lynch syndrome. The deletions result in transcriptional read-through of TACSTD1 into MSH2 , and methylation and silencing of the MSH2 allele. Lynch syndrome patients are susceptible to colorectal and endometrial cancers owing to inactivating germline mutations in mismatch repair genes, including MSH2 (ref. 1 ). Here we describe patients from Dutch and Chinese families with MSH2-deficient tumors carrying heterozygous germline deletions of the last exons of TACSTD1 , a gene directly upstream of MSH2 encoding Ep-CAM. Due to these deletions, transcription of TACSTD1 extends into MSH2 . The MSH2 promoter in cis with the deletion is methylated in Ep-CAM positive but not in Ep-CAM negative normal tissues, thus revealing a correlation between activity of the mutated TACSTD1 allele and epigenetic inactivation of the corresponding MSH2 allele. Gene silencing by transcriptional read-through of a neighboring gene in either sense, as demonstrated here, or antisense direction 2 , could represent a general mutational mechanism. Depending on the expression pattern of the neighboring gene that lacks its normal polyadenylation signal, this may cause either generalized or mosaic patterns of epigenetic inactivation.

The plant metabolite montbretin A (MbA) and its precursor mini-MbA are potential new drugs for treating type 2 diabetes. These complex acylated flavonol glycosides only occur in small amounts in the corms of the ornamental plant montbretia (Crocosmia × crocosmiiflora). Our goal is to metabolically engineer Nicotiana benthamiana using montbretia genes to achieve increased production of mini-MbA and MbA. Two montbretia UDP-dependent glycosyltransferases (UGTs), CcUGT1 and CcUGT2, catalyze the formation of the first two pathway-specific intermediates in MbA biosynthesis, myricetin 3-O-rhamnoside and myricetin 3-O-glucosyl rhamnoside. In previous work, expression of these UGTs in N. benthamiana resulted in small amounts of kaempferol glycosides but not myricetin glycosides, suggesting that myricetin was limiting. Here, we investigated montbretia genes and enzymes of flavonol biosynthesis to enhance myricetin formation in N. benthamiana. We characterized two flavanone hydroxylases, a flavonol synthase, a flavonoid 3ʹ-hydroxylase (F3ʹH), and a flavonoid 3ʹ5ʹ-hydroxylase (F3ʹ5ʹH). Montbretia flavonol synthase converted dihydromyricetin into myricetin. Unexpectedly, montbretia F3ʹ5ʹH shared higher sequence relatedness with F3ʹHs in the CYP75B subfamily of cytochromes P450 than with those with known F3ʹ5ʹH activity. Transient expression of combinations of montbretia flavonol biosynthesis genes and a montbretia MYB transcription factor in N. benthamiana resulted in availability of myricetin for MbA biosynthesis. Transient coexpression of montbretia flavonol biosynthesis genes combined with CcUGT1 and CcUGT2 in N. benthamiana resulted in 2 mg g⁻¹ fresh weight of the MbA pathway-specific compound myricetin 3-O-glucosyl rhamnoside. Additional expression of the montbretia acyltransferase CcAT1 led to detectable levels of mini-MbA in N. benthamiana.

Abstract Purpose The diagnosis of adult GH deficiency (AGHD) is challenging and often requires confirmation with a GH stimulation test (GHST). The insulin tolerance test (ITT) is considered the reference standard GHST but is labor intensive, can cause severe hypoglycemia, and is contraindicated for certain patients. Macimorelin, an orally active GH secretagogue, could be used to diagnose AGHD by measuring stimulated GH levels after an oral dose. Materials and Methods The present multicenter, open-label, randomized, two-way crossover trial was designed to validate the efficacy and safety of single-dose oral macimorelin for AGHD diagnosis compared with the ITT. Subjects with high (n = 38), intermediate (n = 37), and low (n = 39) likelihood for AGHD and healthy, matched controls (n = 25) were included in the efficacy analysis. Results After the first test, 99% of macimorelin tests and 82% of ITTs were evaluable. Using GH cutoff levels of 2.8 ng/mL for macimorelin and 5.1 ng/mL for ITTs, the negative agreement was 95.38% (95% CI, 87% to 99%), the positive agreement was 74.32% (95% CI, 63% to 84%), sensitivity was 87%, and specificity was 96%. On retesting, the reproducibility was 97% for macimorelin (n = 33). In post hoc analyses, a GH cutoff of 5.1 ng/mL for both tests resulted in 94% (95% CI, 85% to 98%) negative agreement, 82% (95% CI, 72% to 90%) positive agreement, 92% sensitivity, and 96% specificity. No serious adverse events were reported for macimorelin. Conclusions Oral macimorelin is a simple, well-tolerated, reproducible, and safe diagnostic test for AGHD with accuracy comparable to that of the ITT. A GH cutoff of 5.1 ng/mL for the macimorelin test provides an excellent balance between sensitivity and specificity. The present multicenter, open-label, randomized, two-way crossover trial of macimorelin vs the ITT showed that macimorelin is a simple, well-tolerated, reproducible, and safe diagnostic test for AGHD.

Protein synthesis is frequently deregulated during tumorigenesis. However, the precise contexts of selective translational control and the regulators of such mechanisms in cancer is poorly understood. Here, we uncovered CNOT3, a subunit of the CCR4-NOT complex, as an essential modulator of translation in myeloid leukemia. Elevated CNOT3 expression correlates with unfavorable outcomes in patients with acute myeloid leukemia (AML). CNOT3 depletion induces differentiation and apoptosis and delayed leukemogenesis. Transcriptomic and proteomic profiling uncovers c-MYC as a critical downstream target which is translationally regulated by CNOT3. Global analysis of mRNA features demonstrates that CNOT3 selectively influences expression of target genes in a codon usage dependent manner. Furthermore, CNOT3 associates with the protein network largely consisting of ribosomal proteins and translation elongation factors in leukemia cells. Overall, our work elicits the direct requirement for translation efficiency in tumorigenesis and propose targeting the post-transcriptional circuitry via CNOT3 as a therapeutic vulnerability in AML. Here the authors uncovered CNOT3, a subunit of the CCR4-NOT complex, as an essential modulator of translation in leukemia. The work pointed to the potential of targeting the posttranscriptional circuitry via CNOT3 as a therapeutic vulnerability in acute myeloid leukemia.