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AIM To design and evaluate psychometrics of adolescent self-report and parent proxy-report questionnaires assessing readiness for independent self-care in adolescents with type 1 diabetes (RISQ-T and RISQ-P). METHODS 178 adolescents with type 1 diabetes (ages 13-17&nbsp;years) and their parents completed the 20-item RISQ-T and 15-item RISQ-P, along with diabetes-specific measures of parent involvement, self-efficacy, burden, and treatment adherence. Evaluation of psychometric properties included calculation of internal consistency, adolescent and parent agreement, test-retest reliability, concurrent and predictive validity. RESULTS The RISQ-T (α&nbsp;=&nbsp;0.78) and RISQ-P (α&nbsp;=&nbsp;0.77) demonstrated sound internal consistency. Higher RISQ-T and RISQ-P scores (indicating more adolescent readiness for independent self-care) showed significant associations with less parent involvement in diabetes care (adolescent r&nbsp;=&nbsp;-0.34; parent r&nbsp;=&nbsp;-0.47; p&nbsp; less then &nbsp;.0001), greater adolescent diabetes self-efficacy (adolescent r&nbsp;=&nbsp;0.32; parent r&nbsp;=&nbsp;0.54; p&nbsp; less then &nbsp;.0001), less parent-endorsed diabetes-related burden (parent r&nbsp;=&nbsp;-0.30; p&nbsp; less then &nbsp;.0001), and greater treatment adherence (adolescent r&nbsp;=&nbsp;0.26, p&nbsp;=&nbsp;.0004; parent r&nbsp;=&nbsp;0.31, p&nbsp; less then &nbsp;.0001). Adolescent and parent scores were significantly correlated (r&nbsp;=&nbsp;0.35; p&nbsp; less then &nbsp;.0001); test-retest reliability was reasonable (ICC RISQ-T r&nbsp;=&nbsp;0.66; RISQ-P r&nbsp;=&nbsp;0.71). Higher baseline RISQ-P scores significantly predicted reduced family involvement after six months (β&nbsp;=&nbsp;-0.14, p&nbsp;=&nbsp;.02). CONCLUSIONS RISQ-T and RISQ-P demonstrate sound psychometric properties. Surveys may help inform diabetes teams of the level of support needed to facilitate shift to independent self-management. AIM To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of probiotics in pregnancy on the incidence of gestational diabetes (GDM) and fasting plasma glucose (FPG). METHODS A MEDLINE, EMBASE, Scopus and Cochrane search (up to May 30th, 2019) was performed to identify RCTs of comparison of probiotics with placebo/active comparators in pregnant women. Principal endpoints were the incidence of GDM and the change of FPG. Other maternal and fetal outcomes were secondary endpoints. Mantel-Haenszel Odds Ratio with 95% CI (MH-OR) was calculated for dichotomous outcomes, whereas standardized differences in means was calculated for continuous variables. (PROSPERO registration CRD42019139889). FINDINGS A total of 17 RCTs, all versus placebo, was identified. The overall quality of the trials was satisfactory. No effect of probiotics on incidence of GDM (MH-OR 0.77[0.51,1.16], p&nbsp;=&nbsp;0.21,I262%) was observed, with a small but significant reduction of FPG (mean difference -1.01 [-1.96, -0.06]mg/dl, p&nbsp;=&nbsp;0.02, I246%). Among secondary endpoints, a significant reduction of maternal insulin (both in women with or without diabetes) was observed in the probiotics group. INTERPRETATION Probiotics during pregnancy do not reduce the incidence of GDM, with a very little (statistically but not clinically significant) reduction of fasting plasma glucose. V.OBJECTIVE This study examines the relationships between three measures of asthma related self-efficacy and compares them by their relationships to quality of life, medication adherence, asthma control, asthma knowledge, and attitudes in adolescents. [https://www.selleckchem.com/pharmacological_epigenetics.html Epigenetic inhibitor] METHODS Participants included 371 urban adolescents (age 12-20 years) with asthma. Three self-efficacy measures included the Asthma Outcome Expectation-self-efficacy subscale (AOE-SE), Asthma Management Index-self-efficacy subscale (AMI-SE), and the Asthma Self-Efficacy scale (ASE). RESULTS The sample included 50% male, predominantly African American (78.4%) participants. All three measures of self-efficacy were positively correlated with each other (r= 0.46 to 0.54, p less then .001). After controlling for gender, age, race and health insurance type, all three self-efficacy measures predicted the symptom domain of quality of life, adherence, asthma control, and knowledge. Activity limitation was predicted by AMI-SE (B=0.19, p=0.008) and ASE (B=0.38, p less then 0.001) but not by AOE-SE, while emotional function associated only with ASE (B=0.37, p less then 0.001). Attitudes were positively associated with AOE-SE and ASE (B=1.83 and 2.87 respectively, p less then 0.001 for both), but not with AMI-SE. CONCLUSIONS Medication adherence and symptom control in adolescents were predicted by self-efficacy measured by the three measures, while these measures differed in their performance in predicting psychosocial outcomes. ASE appears the measure of choice in measuring adolescents' self-efficacy given its association with all outcome measures of the study. Further research is needed to investigate the generalized use of the self-efficacy measures in populations with varying demographic or asthma characteristics. Histone lysine methyltransferase 2 (KMT2) proteins form multimeric enzymatic complexes that methylate lysine 4 on histone H3 (H3K4) at transcription regulatory elements in the genome. A strong association of H3K4 methylation with active transcription has led to intense efforts to reveal the functional involvement of KMT2 complexes in transcriptional regulation. A number of biochemical and cellular studies have shown that KMT2 complexes regulate transcription of target genes via H3K4 methylation. However, in many cases, loss of KMT2 complex enzymatic activity fails to fully account for observed transcriptional defects. Accumulating evidence indicates that, in certain contexts, KMT2 complex-mediated transcriptional regulation can occur in an H3K4 methylation-independent manner. Here, we comprehensively review functions of KMT2 complexes in gene expression, focusing on what we currently know about the molecular mechanisms by which the KMT2 complexes regulate transcription. We also discuss how aberrant transcriptional regulation by KMT2 complexes contributes to different human diseases, such as cancer. V.The performances of poly(lactic-co-glycolic acid) drug delivery systems are affected by the molecular interactions established between the drug and the polymer matrix as well as by the physical state of the drug embedded. Indeed, the drug may induce polymer plasticization with a drastic change in the release kinetics and medicinal product performances. The aim of this study was to better understand the interactions between poly(lactic-co-glycolic acid) and ketoprofen, the latter known to plasticize hydrophilic and hydrophobic polymers. Ketoprofen interacts with poly(lactic-co-glycolic acid) exerting a maximum plasticizing effect at weight fractions around 0.25. Higher ketoprofen amounts form heterogeneous mixtures with the non-soluble molecules dispersed in the matrix as crystals or amorphous domains, depending on the preparation method. Unexpectedly, the amorphous ketoprofen dispersed in the poly(lactic-co-glycolic acid) matrix is remarkably stable. H-bonding seems responsible for the glass transition temperature reduction and the limited solubility. Brillouin spectroscopy and molecular dynamics simulation data suggest that ketoprofen solubility increases with temperature and non-polar interactions are responsible for this phenomenon. We induced changes in the tumor microenvironment (TME) through the synergistic actions of two drugs used in breast cancer therapy. The anti-fibrotic drug silibinin (SLB) targets tumor-associated fibroblasts and exerts immune-mediated anti-cancer effects. IPI-549, an efficient and highly selective phosphoinositide-3-kinase-gamma (PI3Kγ) inhibitor, was applied to alter the balance of immunosuppressive cells by inhibiting PI3Kγ molecules; it also promotes anti-tumor immunity. We developed nanoparticle formulations to encapsulate both drugs into the targeting carrier aminoethyl anisamide-polyethylene glycol-polycaprolactone (AEAA-PEG-PCL) respectively. The drugs were intravenously delivered in mice and resulted in an increase in anti-tumor efficacy and apoptotic tumor tissue compared with either IPI-549 or SLB alone in 4T1 breast cancer cell-derived tumors. Furthermore, a significant reduction in regulatory T (Treg) cells and myeloid suppressor cells (MDSCs) was observed. A normalized TME structure was also observed, including angiogenesis suppression, antifibrotic effects and the inhibition of collagen formation in the tumor tissue, significantly enhancing the anti-tumor effects. In summary, this combination strategy may offer an alternative treatment for breast cancer. The current first line therapy for oral mucositis pain control is unsatisfactory as it results in only a short duration of modest pain relief. Developing mucoadhesive in situ forming formulations to prolong pain relief is challenging due to their complex physicochemical properties and the unique requirements for oral mucosa application. The objective of this study is to develop a mucoadhesive in situ forming gel to deliver a novel drug molecule, Bupivacaine γ-linoleate (Bup-γL), for prolonged and more potent oral mucositis pain control. The formulation is sprayable at room temperature, and forms a mucoadhesive gel on contact with the oral mucosa. The pain would be managed by forming an adhesive protective layer from irritating agents (such as bacteria, food, etc.), and also by anesthetizing the nerve cells with Bup-γL. Pluronic® F127 and F68 were used to achieve in situ forming properties. Either Carbopol® or Noveon® was included as a mucoadhesion enhancer. Formulation preparation methods were extensively investigated. The physicochemical properties of the gels were characterized, including gelation behavior, ex vivo mucoadhesion, rheological properties, in vitro drug release and sprayability. The polymer mixing sequence was determined to have a profound impact on the preparation time of blank formulations. A final drug content in a range of 6.21-6.51&nbsp;mg/mL was obtained using the optimized method. The gelation temperature was significantly reduced by the addition of hydrophobic Bup-γL. Both Carbopol® and Noveon® significantly improved mucoadhesion without compromising the other main properties of the system (such as gelation temperature and drug content). Drug release from the formulation showed pH sensitive responses where lower pH favored faster drug release due to the ionization of Bup-γL. This study offers a promising strategy to achieve prolonged oral mucositis pain control. Moreover, a promising platform for the mucoadhesive in situ gels that allows high loading of hydrophobic drugs has been developed. Interactions of paclitaxel (PTX) with models mimicking biological interfaces (lipid membranes and serum albumin, HSA) were investigated to test the hypothesis that the set of in vitro assays proposed can be used to predict some aspects of drug pharmacokinetics (PK). PTX membrane partitioning was studied by derivative spectrophotometry; PTX effect on membrane biophysics was evaluated by dynamic light scattering, fluorescence anisotropy, atomic force microscopy and synchrotron small/wide-angle X-ray scattering; PTX distribution/molecular orientation in membranes was assessed by steady-state/time-resolved fluorescence and computer simulations. PTX binding to HSA was studied by fluorescence quenching, derivative spectrophotometry and dynamic/electrophoretic light scattering. PTX high membrane partitioning is consistent with its efficacy crossing cellular membranes and its off-target distribution. PTX is closely located in the membrane phospholipids headgroups, also interacting with the hydrophobic chains, and causes a major distortion of the alignment of the membrane phospholipids, which, together with its fluidizing effect, justifies some of its cellular toxic effects.