Eccomi pronto : implementation of a Socio-Emotional Development curriculum in a South Korean elementary school

‘Eccomi Pronto’ (EP), an elementary school socio-emotional learning curriculum that was originally developed and evaluated in Italy was translated in Korean and implemented and evaluated in 4th grade classrooms of a primary school in South Korea. Qualitative data from teachers indicated that EP improved the self-reflection and selfdirection of students, resulted in pedagogically useful insights into the psychological functioning of students, and enhanced the quality of teacher-student interaction. However, statistically significant changes in students’ engaged, academic behavior (as measured by an 8-item survey) were not noted. Teachers reported that the core of the EP curriculum was appropriate for the South Korean educational context. Teachers also recommended modifications in the follow-up learning activities to make these activities more consistent with South Korean education practices.peer-reviewe

Effects of Activin and TGFβ on p21 in Colon Cancer

Activin and TGFβ share SMAD signaling and colon cancers can inactivate either pathway alone or simultaneously. The differential effects of activin and TGFβ signaling in colon cancer have not been previously dissected. A key downstream target of TGFβ signaling is the cdk2 inhibitor p21 (p21cip1/waf1). Here, we evaluate activin-specific effects on p21 regulation and resulting functions. We find that TGFβ is a more potent inducer of growth suppression, while activin is a more potent inducer of apoptosis. Further, growth suppression and apoptosis by both ligands are dependent on SMAD4. However, activin downregulates p21 protein in a SMAD4-independent fashion in conjunction with increased ubiquitination and proteasomal degradation to enhance migration, while TGFβ upregulates p21 in a SMAD4-dependent fashion to affect growth arrest. Activin-induced growth suppression and cell death are dependent on p21, while activin-induced migration is counteracted by p21. Further, primary colon cancers show differential p21 expression consistent with their ACVR2/TGFBR2 receptor status. In summary, we report p21 as a differentially affected activin/TGFβ target and mediator of ligand-specific functions in colon cancer, which may be exploited for future risk stratification and therapeutic intervention

A EVOLUÇÃO DA PROTEÇÃO JURÍDICA DO ANIMAL NO DIREITO CIVIL BRASILEIRO

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Assessing Attitudes toward Nicotine Replacement Therapy for Adolescent Smoking Cessation

The objective was to ascertain attitudes toward nicotine replacement therapy for adolescent tobacco cessation. The authors created a 17-item survey consisting of demographics, quantitative, and qualitative items which was distributed to middle and high school students in North Central Florida. The authors assessed associations and conducted discriminant analyses to compare results by age. One-hundred ninety-eight students completed the survey (57.6% female, 61.6% white). When asked to select the best way to help teens stop using tobacco, combination of methods was most frequently selected (31.6%), followed by “Cold Turkey” (19.5%), e-cigarettes (16.8%), NRT (14.7%), Counseling (10.5%), and Alternative Therapies (6.8%). Qualitative data from students revealed misconceptions toward tobacco use, but an overall awareness that tobacco is a harmful. High school students were more likely than middle school students to agree that nicotine is harmful and e-cigarettes or chewing tobacco are less harmful than traditional cigarettes. Discriminant analyses were inconclusive. These data highlight misconceptions regarding tobacco use and nicotine that might play a role in attitudes toward NRT for adolescent tobacco cessation. Whereas high school students might be more likely to agree nicotine is harmful, their decreased perception of harm of alternative tobacco products such as e-cigarettes or chewing tobacco could be problematic. Further research in this area remains a priority

Activin and TGFβ use diverging mitogenic signaling in advanced colon cancer.

BackgroundUnderstanding cell signaling pathways that contribute to metastatic colon cancer is critical to risk stratification in the era of personalized therapeutics. Here, we dissect the unique involvement of mitogenic pathways in a TGFβ or activin-induced metastatic phenotype of colon cancer.MethodMitogenic signaling/growth factor receptor status and p21 localization were correlated in primary colon cancers and intestinal tumors from either AOM/DSS treated ACVR2A (activin receptor 2) -/- or wild type mice. Colon cancer cell lines (+/- SMAD4) were interrogated for ligand-induced PI3K and MEK/ERK pathway activation and downstream protein/phospho-isoform expression/association after knockdown and pharmacologic inhibition of pathway members. EMT was assessed using epithelial/mesenchymal markers and migration assays.ResultsIn primary colon cancers, loss of nuclear p21 correlated with upstream activation of activin/PI3K while nuclear p21 expression was associated with TGFβ/MEK/ERK pathway activation. Activin, but not TGFβ, led to PI3K activation via interaction of ACVR1B and p85 independent of SMAD4, resulting in p21 downregulation. In contrast, TGFβ increased p21 via MEK/ERK pathway through a SMAD4-dependent mechanism. While activin induced EMT via PI3K, TGFβ induced EMT via MEK/ERK activation. In vivo, loss of ACVR2A resulted in loss of pAkt, consistent with activin-dependent PI3K signaling.ConclusionAlthough activin and TGFβ share growth suppressive SMAD signaling in colon cancer, they diverge in their SMAD4-independent pro-migratory signaling utilizing distinct mitogenic signaling pathways that affect EMT. p21 localization in colon cancer may determine a dominant activin versus TGFβ ligand signaling phenotype warranting further validation as a therapeutic biomarker prior to targeting TGFβ family receptors

Benchmarking urine storage and collection conditions for evaluating the female urinary microbiome.

Standardized conditions for collection, preservation and storage of urine for microbiome research have not been established. We aimed to identify the effects of the use of preservative AssayAssure® (AA), and the effects of storage time and temperatures on reproducibility of urine microbiome results. We sequenced the V3-4 segment of the 16S rRNA gene to characterize the bacterial community in the urine of a cohort of women. Each woman provided a single voided urine sample, which was divided into aliquots and stored with and without AA, at three different temperatures (room temperature [RT], 4 °C, or -20 °C), and for various time periods up to 4 days. There were significant microbiome differences in urine specimens stored with and without AA at all temperatures, but the most significant differences were observed in alpha diversity (estimated number of taxa) at RT. Specimens preserved at 4 °C and -20 °C for up to 4 days with or without AA had no significant alpha diversity differences. However, significant alpha diversity differences were observed in samples stored without AA at RT. Generally, there was greater microbiome preservation with AA than without AA at all time points and temperatures, although not all results were statistically significant. Addition of AA preservative, shorter storage times, and colder temperatures are most favorable for urinary microbiome reproducibility

Assessing Attitudes toward Nicotine Replacement Therapy for Adolescent Smoking Cessation

The objective was to ascertain attitudes toward nicotine replacement therapy for adolescent tobacco cessation. The authors created a 17-item survey consisting of demographics, quantitative, and qualitative items which was distributed to middle and high school students in North Central Florida. The authors assessed associations and conducted discriminant analyses to compare results by age. One-hundred ninety-eight students completed the survey (57.6% female, 61.6% white). When asked to select the best way to help teens stop using tobacco, combination of methods was most frequently selected (31.6%), followed by “Cold Turkey” (19.5%), e-cigarettes (16.8%), NRT (14.7%), Counseling (10.5%), and Alternative Therapies (6.8%). Qualitative data from students revealed misconceptions toward tobacco use, but an overall awareness that tobacco is a harmful. High school students were more likely than middle school students to agree that nicotine is harmful and e-cigarettes or chewing tobacco are less harmful than traditional cigarettes. Discriminant analyses were inconclusive. These data highlight misconceptions regarding tobacco use and nicotine that might play a role in attitudes toward NRT for adolescent tobacco cessation. Whereas high school students might be more likely to agree nicotine is harmful, their decreased perception of harm of alternative tobacco products such as e-cigarettes or chewing tobacco could be problematic. Further research in this area remains a priority

Calnexin Is Necessary for T Cell Transmigration into the Central Nervous System

In multiple sclerosis (MS), a demyelinating inflammatory disease of the CNS, and its animal model (experimental autoimmune encephalomyelitis; EAE), circulating immune cells gain access to the CNS across the blood-brain barrier to cause inflammation, myelin destruction, and neuronal damage. Here, we discovered that calnexin, an ER chaperone, is highly abundant in human brain endothelial cells of MS patients. Conversely, mice lacking calnexin exhibited resistance to EAE induction, no evidence of immune cell infiltration into the CNS, and no induction of inflammation markers within the CNS. Furthermore, calnexin deficiency in mice did not alter the development or function of the immune system. Instead, the loss of calnexin led to a defect in brain endothelial cell function that resulted in reduced T cell trafficking across the blood-brain barrier. These findings identify calnexin in brain endothelial cells as a potentially novel target for developing strategies aimed at managing or preventing the pathogenic cascade that drives neuroinflammation and destruction of the myelin sheath in MS

Optimizing Vancomycin Dosing in Chronic Kidney Disease by Deriving and Implementing a Web-Based Tool Using a Population Pharmacokinetics Analysis.

Background: Chronic kidney disease (CKD) patients requiring intravenous vancomycin bear considerable risks of adverse outcomes both from the infection and vancomycin therapy itself, necessitating especially precise dosing to avoid sub- and supratherapeutic vancomycin exposure. Methods: In this retrospective study, we performed a population pharmacokinetic analysis to construct a vancomycin dose prediction model for CKD patients who do not require renal replacement therapy. The model was externally validated on an independent cohort of patients to assess its prediction accuracy. The pharmacokinetic parameter estimates and the equations were productized into a Web application (VancApp) subsequently implemented in routine care. The association between VancApp-based dosing and time-to-target concentration attainment, 30-day mortality, and nephrotoxicity were assessed postimplementation. Results: The model constructed from an initial cohort (n = 80) revealed a population clearance and volume of distribution of 1.30 L/h and 1.23 L/kg, respectively. External model validation (n = 112) demonstrated a mean absolute prediction error of 1.25 mg/L. Following 4 months of clinical implementation of VancApp as an optional alternative to usual care [VancApp (n = 22) vs. usual care (n = 21)], patients who had received VancApp-based dosing took a shorter time to reach target concentrations (median: 66 vs. 102 h, p = 0.187) and had fewer 30-day mortalities (14% vs. 24%, p = 0.457) compared to usual care. While statistical significance was not achieved, the clinical significance of these findings appear promising. Conclusion: Clinical implementation of a population pharmacokinetic model for vancomycin in CKD can potentially improve dosing precision in CKD and could serve as a practical means to improve vital clinical outcomes