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Objectives The objective of the present work to encapsulate the resveratrol (RES) inside the chitosan-based microsponges, employing the systematic optimization by 33 Box-Behnken design for the colonic targeting.Significance Enhanced therapeutic efficacy of RES-loaded microsponges and matrix tablets, vis-a-vis pureRES for ulcerative colitis.Methods RES-loaded microsponges were prepared employing the systematic optimization by 33 Box-Behnken design for the colonic targeting. The best-optimizedRES-loaded microsponge was compressed in the form of a tablet, employing pectin as a matrix-forming material. The encapsulation of RES inside microsponge was confirmed by XRD, DSC and FT-IR. Further, both RES-loaded microsponges and matrix tablets were evaluated for in vitro release kinetics and further evaluated for in vivo ulcerative colitis animal model.Results Optimization experiments was obtained as the high value of r2 (particle size = 0.9999; %EE = 0.9652; %CDR = 0.9469) inferred excellent goodness of fit. SEM revealed nearly spherical and porous nature of RES-loaded microsponges. The in vitro release kinetic showed zero-order release for RES-loaded microsponges and Korsmeyer-Peppas model for matrix tablets. The pharmacodynamic studies, in ulcerative colitis rat model, indicated better therapeutic efficacy of drug-loaded microsponges and matrix tablets, vis-a-vis pure RES. Thus, the present study advocates the potential of RES based microsponges delivered by pectin based matrix tablet, in the treatment of various colonic disorders.Conclusion The present study proved that RES-loaded microsponges and matrix tablets based on chitosan and pectin can be the ideal delivery system for colonic delivery of RES.Through autoethnographic analysis, I present my personal illness story as a case study in patient consent. In doing so, I explore the complexities that emerge at the intersection of gender and health, including issues of autonomy and choice. Specifically, I reflect on the ideological and systemic factors that contribute to a paradox of consent versus noncompliance in US healthcare contexts. Within this paradoxical binary, control is both persistent and illusive, which is a condition fueled by individualism, paternalistic antagonism, and medical colonization. As an alternative, I offer two viable options for facilitating patients' agency in gendered health contexts, even under marginalizing conditions.Chronic pain is long-lasting nociceptive state, impairing the patient's quality of life. Existing analgesics are generally not effective in the treatment of chronic pain, some of which such as opioids have the risk of tolerance/dependence, overdose death with higher daily opioid doses for increasing analgesic effect. Opioid use disorders have already reached an epidemic level in the United States, therefore, non-opioid analgesic approach and/or use of non-pharmacologic interventions will be employed with increasing frequency. Viral vector mediated gene therapy is promising in clinical trials in the nervous system diseases. Glutamic acid decarboxylase (GAD) enzyme, a key enzyme in biosynthesis of GABA, plays an important role in analgesic mechanism. In the literature review, we used PubMed and BioRxiv to search the studies, and the eligible criteria include (1) manuscript written in English, (2) use of viral vectors expressing GAD67 or GAD65, and (3) preclinical pain models. We identified 13 eligible original research papers, in which the pain models include nerve injury, HIV-related pain, painful diabetic neuropathy, and formalin test. GAD expressed by the viral vectors from all of the reports produced antinociceptive effects. Restoring GABA systems is a promising therapeutic strategy for chronic pain, which provides evidence for the clinical trial of gene therapy for pain in the near future.Although there has been increasing attention on a dyadic perspective of illness, contemporary dyadic research methods are still rarely utilized in cardiovascular disease. The focus of this paper is to describe the advantages of two types of multilevel dyadic models (the matched pairs model and the lesser known incongruence model). Data exemplars in a sample of heart failure family dyads are used to illustrate the distinct advantages of these two related multilevel dyadic models with particular emphasis on alignment with research questions. The more commonly known matched pairs model examines separate outcomes for each member of the dyad, controlling for the interdependent nature of the data. By re-parameterizing this model into a univariate dyadic outcomes model, researchers can address distinct, and sometimes more appropriate, research questions (e.g. incongruent appraisals of the illness experience). This paper promotes greater application of these methods in cardiovascular research to further understanding of the dyadic experience and more appropriately target interventions.Introduction Fetal growth restriction (FGR), viz., birth weight less then 10th percentile is a common pregnancy complication which increases the risk of adverse fetal and newborn outcomes. The placenta is the key organ for fetal growth as it controls oxygen and nutrient availability. This study aims to elucidate the mechanisms of and identify putative placental biomarkers for FGR using high-resolution metabolomics.Methods Placenta samples from 19 FGR cases and 30 controls were analyzed using proton magnetic resonance (1H NMR) spectroscopy and direct flow injection mass spectrometry with reverse-phase liquid-chromatography mass spectrometry (DI-LC-MS/MS). Significant concentration differences (p-value less then .05) in 179 of the 220 metabolites were measured.Results Of the 179 metabolites, 176 (98.3%) had reduced placental levels in FGR cases. The best performing metabolite model 3-hydroxybutyrate, glycine and PCaaC420 achieved an AUC (95% CI) = 0.912 (0.814-1.000) with a sensitivity of 86.7% and specificity of 84.2% for FGR detection. Metabolite set enrichment analysis (MSEA) revealed significant (p  less then  .05) perturbation of multiple placental metabolite pathways including urea metabolism, ammonia recycling, porphyrin metabolism, bile acid biosynthesis, galactose metabolism and perturbed protein biosynthesis.Conclusion The placental metabolic pathway analysis revealed abnormalities that are consistent with fetal hepatic dysfunction in FGR. SodiumLlactate Near global reduction of metabolite concentrations was found in the placenta from FGR cases and metabolites demonstrated excellent diagnostic accuracy for FGR detection.
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