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Biomedical subjects

Thuan Nguyen

Publications and source records attributed to Thuan Nguyen.

6 recordsLinked to original sources

Comparing problem-based learning with case-based learning: effects of a major curricular shift at two institutions.

PURPOSE: Problem-based learning (PBL) is now used at many medical schools to promote lifelong learning, open inquiry, teamwork, and critical thinking. PBL has not been compared with other forms of discussion-based small-group learning. Case-based learning (CBL) uses a guided inquiry method and provides more structure during small-group sessions. In this study, we compared faculty and medical students' perceptions of traditional PBL with CBL after a curricular shift at two institutions. METHOD: Over periods of three years, the medical schools at the University of California, Los Angeles (UCLA) and the University of California, Davis (UCD) changed first-, second-, and third-year Doctoring courses from PBL to CBL formats. Ten months after the shift (2001 at UCLA and 2004 at UCD), students and faculty who had participated in both curricula completed a 24-item questionnaire about their PBL and CBL perceptions and the perceived advantages of each format RESULTS: A total of 286 students (86%-97%) and 31 faculty (92%-100%) completed questionnaires. CBL was preferred by students (255; 89%) and faculty (26; 84%) across schools and learner levels. The few students preferring PBL (11%) felt it encouraged self-directed learning (26%) and valued its greater opportunities for participation (32%). From logistic regression, students preferred CBL because of fewer unfocused tangents (59%, odds ration [OR] 4.10, P = .01), less busy-work (80%, OR 3.97, P = .01), and more opportunities for clinical skills application (52%, OR 25.6, P = .002). CONCLUSIONS: Learners and faculty at two major academic medical centers overwhelmingly preferred CBL (guided inquiry) over PBL (open inquiry). Given the dense medical curriculum and need for efficient use of student and faculty time, CBL offers an alternative model to traditional PBL small-group teaching. This study could not assess which method produces better practicing physicians.

Academic Medical Centers↗

Lysine-spermine conjugates: hydrophobic polyamine amides as potent lipopolysaccharide sequestrants.

Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane constituents of Gram-negative bacteria. Lipopolysaccharides play a key role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient. Therapeutic options aimed at limiting downstream systemic inflammatory processes by targeting lipopolysaccharide do not exist at the present time. We have defined the pharmacophore necessary for small molecules to specifically bind and neutralize LPS and, using animal models of sepsis, have shown that the sequestration of circulatory LPS by small molecules is a therapeutically viable strategy. In this paper, the interactions of a focused library of lysine-spermine conjugates with lipopolysaccharide (LPS) have been characterized. Lysine-spermine conjugates with the epsilon-amino terminus of the lysinyl moiety derivatized with long-chain aliphatic hydrophobic substituents in acyl or alkyl linkage bind and neutralize bacterial lipopolysaccharides, and may be of use in the prevention or treatment of endotoxic shock states.

Amides↗

Functionalized dendrimers as endotoxin sponges.

Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane constituents of Gram-negative bacteria, and play a key role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient. We had previously defined the pharmacophore necessary for small molecules to specifically bind and neutralize LPS and, using animal models of sepsis, have shown that the sequestration of circulatory LPS by small molecules is a therapeutically viable strategy. Polyamidoamine dendrimers, with the surface amines substoichiometrically derivatized with alkyl groups bind LPS with high affinity, neutralize LPS-induced inflammatory responses in vitro, and afford protection in a murine model of endotoxic shock. Dendrimers represent a new class of potentially useful compounds for the therapy of Gram-negative sepsis.

Animals↗

Multiplex cytokine profiling of initial therapeutic response in patients with chronic hepatitis C virus infection.

Currently available prognostic tools are inadequate to discern the molecular basis of the heterogenic response in hepatitis C virus (HCV)-infected patients treated with the current standard of therapy. The expression and biological function of immune mediators have been shown to be critical in all phases of the immune response to HCV infection and likely therefore influence host response. Herein, a biometric multiplex serum cytokine assay was utilized to characterize the immunomodulatory effects of host response in 10 HCV patients. Serum levels of 17 cytokines were compared before and after 1 month of treatment and against controls. Overall serum cytokine levels were significantly higher in patients (P < 0.05) than controls. Additionally, viral titers decreased in all patients after 1 month of therapy, as did overall serum cytokine levels in the cohort (P < 0.05). To assess relationships between changes in cytokine levels and changes in viral titer, the cohort was divided into three statistically distinct subgroups based on changes in viral titers. Specific sets of cytokines decreased in each group: decreases in CCL4, interleukin (IL)-2, CXCL8, and IL-1beta correlated with the greatest drops in viral titer, decreases in IL-5, granulocyte colony stimulating factor (G-CSF), and CCL4 correlated with moderate drops in viral titer, and only CCL2 correlated with the lowest drops in viral titer. Interestingly, decreases in CCL4 levels correlated with decreases in viral titers in all patients. CCL4 controls leukocyte influx and thus propagates inflammation. In conclusion, these data raise the possibility that characteristic changes in host response modulate the therapeutic response, demonstrating the prognostic power of serum cytokine profiling in chronic HCV.

Adult↗

Helix-loop-helix proteins regulate pre-TCR and TCR signaling through modulation of Rel/NF-kappaB activities.

E2A and HEB are basic helix-loop-helix transcription factors essential for T cell development. Complete inhibition of their activities through transgenic overexpression of their inhibitors Id1 and Tal1 leads to a dramatic loss of thymocytes. Here, we suggest that bHLH proteins play important roles in establishing thresholds for pre-TCR and TCR signaling. Inhibition of their function allows double-negative cells to differentiate without a functional pre-TCR, while anti-CD3 stimulation downregulates bHLH activities. We also find that the transcription factor NF-kappaB becomes activated in transgenic thymocytes. Further activation of NF-kappaB exacerbates the loss of thymocytes, whereas inhibition of NF-kappaB leads to the rescue of double-positive thymocytes. Therefore, we propose that E2A and HEB negatively regulate pre-TCR and TCR signaling and their removal causes hyperactivation and apoptosis of thymocytes.

Animals↗