Assessment of the Calibration of Periodontal Diagnosis and Treatment Planning Among Dental Students at Three Dental Schools

Calibration in diagnosis and treatment planning is difficult to achieve due to variations that exist in clinical interpretation. To determine if dental faculty members are consistent in teaching how to diagnose and treat periodontal disease, variations among dental students can be evaluated. A previous study reported high variability in diagnoses and treatment plans of periodontal cases at Indiana University School of Dentistry. This study aimed to build on that one by extending the research to two additional schools: Marquette University School of Dentistry and West Virginia University School of Dentistry. Diagnosis and treatment planning by 40 third- and fourth-year dental students were assessed at each of the schools. Students were asked to select the diagnosis and treatment plans on a questionnaire pertaining to 11 cases. Their responses were compared using chi-square tests, and multirater kappa statistics were used to assess agreement between classes and between schools. Logistic regression models were used to evaluate the effects of school, class year, prior experience, and GPA/class rank on correct responses. One case had a statistically significant difference in responses between third- and fourth-year dental students. Kappas for school agreement and class agreement were low. The students from Indiana University had higher diagnosis and treatment agreements than the Marquette University students, and the Marquette students fared better than the West Virginia University students. This study can help restructure future periodontal courses for a better understanding of periodontal diagnosis and treatment planning

Kinetics of Carbamylcholine Binding to Membrane-Bound Acetylcholine Receptor Monitored by Fluorescence Changes of a Covalently Bound Probe

The fluorescent probe 5-(iodoacetamido)salicylic acid has been used to alkylate acetylcholine receptor enriched membrane fragments from Torpedo californica following their reduction with low concentrations of dithiothreitol. This modification did not affect the equilibrium binding of carbamylcholine to the receptor. The fluorescence of bound 5-(iodoacetamido)salicylic acid was enhanced when the labeled membrane fragments were mixed with carbamylcholine. This increase in fluorescence was abolished by preincubation of the membrane fragments with excess ɑ-bungarotoxin and was therefore specific for the acetylcholine receptor. Estimates of dissociation constants obtained from centrifugation experiments with radioactive ligand and from fluorescence titration data were in good agreement, showing that the observed fluorescence enhancement was an accurate reflection of receptor- carbamylcholine complex formation. The kinetics of carbamylcholine binding to labeled membrane fragments have been investigated over a wide range of ligand concentrations by using stopped-flow fluorescence techniques. The kinetic signal was complicated, and four distinct exponential phases were observed. A kinetic mechanism has been proposed to account for this behavior

Upregulation of RASSF1A in Colon Cancer by Suppression of Angiogenesis Signaling and Akt Activation

Background/Aims: Silencing of tumor suppressor genes (TSGs) and promotion of angiogenesis are associated with tumor development and metastasis. However, little is known if angiogenic molecules directly control TSGs and vice versa. Methods: A regulatory link between angiogenesis and down regulation of TSGs was evaluated using an anti-cancer agent, andrographolide (AGP) in cancer cells, mouse xenograft tissues and patient derived organoids through gene/protein expression, gene silencing, and immunohistochemical analyses. Results: AGP treatment demonstrated significant expression of RASSF1A and PTEN TSGs in colon cancer and other cancer cells, mouse tissues and organoids. Depletion of RASSF1A with siRNA limited cyclin D1 and BAX expression. SiRNA depletion of PTEN, upstream regulator of RASSF1A resulted in a 50% reduction in RASSF1A expression. Histopathological analysis of the AGP treated tumor sections showed significant reduction in vessel size, microvascular density and tumor mitotic index suggesting suppression of angiogenesis. This was corroborated by protein analysis demonstrating significant reductions in angiogenesis signaling pathway molecules VEGF165, FOXM1, and pAkt, but significant elevation of the endogenous angiogenesis inhibitor Tsp-2. Treatment of cells with exogenous VEGF prevented the suppression of angiogenesis signaling by AGP, resulting in sustained expression of pAkt, an upstream down-regulator of RASSF1A. RASSF1A expression remained low in VEGF treated cells despite the addition of AGP. Conclusion: Our results demonstrate for the first time that AGP induces RASSF1A expression in colon cancer cells and is dependent on angiogenesis signaling events. Therefore, our research may facilitate novel therapeutic options for advanced colon cancer therapy

Dasatinib inhibits the growth of molecularly heterogeneous myeloid leukemias.

PURPOSE: Dasatinib is a dual Src/Abl inhibitor recently approved for Bcr-Abl+ leukemias with resistance or intolerance to prior therapy. Because Src kinases contribute to multiple blood cell functions by triggering a variety of signaling pathways, we hypothesized that their molecular targeting might lead to growth inhibition in acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: We studied growth factor-dependent and growth factor-independent leukemic cell lines, including three cell lines expressing mutants of receptor tyrosine kinases (Flt3 or c-Kit) as well as primary AML blasts for responsiveness to dasatinib. RESULTS: Dasatinib resulted in the inhibition of Src family kinases in all cell lines and blast cells at approximately 1 x 10(-9) mol/L. It also inhibited mutant Flt3 or Kit tyrosine phosphorylation at approximately 1 x 10(-6) mol/L. Mo7e cells expressing the activating mutation (codon 816) of c-Kit were most sensitive to growth inhibition with a GI(50) of 5 x 10(-9) mol/L. Primary AML blast cells exhibited a growth inhibition of \u3c1 x\u3e10(-6) mol/L. Cell lines that showed growth inhibition at approximately 1 x 10(-6) mol/L showed a G(1) cell cycle arrest and correlated with accumulation of p21 and p27 protein. The addition of rapamycin or cytotoxic agents enhanced growth inhibition. Dasatinib also caused the apoptosis of Mo7e cells expressing oncogenic Kit. CONCLUSIONS: Although all of the precise targets for dasatinib are not known, this multikinase inhibitor causes either growth arrest or apoptosis in molecularly heterogeneous AML. The addition of cytotoxic or targeted agents can enhance its effects

Genoviz Software Development Kit: Java tool kit for building genomics visualization applications

<p>Abstract</p> <p>Background</p> <p>Visualization software can expose previously undiscovered patterns in genomic data and advance biological science.</p> <p>Results</p> <p>The Genoviz Software Development Kit (SDK) is an open source, Java-based framework designed for rapid assembly of visualization software applications for genomics. The Genoviz SDK framework provides a mechanism for incorporating adaptive, dynamic zooming into applications, a desirable feature of genome viewers. Visualization capabilities of the Genoviz SDK include automated layout of features along genetic or genomic axes; support for user interactions with graphical elements (Glyphs) in a map; a variety of Glyph sub-classes that promote experimentation with new ways of representing data in graphical formats; and support for adaptive, semantic zooming, whereby objects change their appearance depending on zoom level and zooming rate adapts to the current scale. Freely available demonstration and production quality applications, including the Integrated Genome Browser, illustrate Genoviz SDK capabilities.</p> <p>Conclusion</p> <p>Separation between graphics components and genomic data models makes it easy for developers to add visualization capability to pre-existing applications or build new applications using third-party data models. Source code, documentation, sample applications, and tutorials are available at <url>http://genoviz.sourceforge.net/</url>.</p

Ad Libitum Choline Intake in Healthy Individuals Meets or Exceeds the Proposed Adequate Intake Level

Choline is an essential nutrient for humans that is used to synthesize membrane phospholipids and the neurotransmitter acetylcholine. Betaine, a metabolite of choline, functions as a methylgroup donor in the conversion of homocysteine to methionine, and is important for renal function. Accurate analysis of choline intake was previously not possible because the choline content of most foods was not known. Using new and recently published data on the concentrations of choline in common foods, we measured the choline content of diets consumed ad libitum by healthy adult volunteers housed in a clinical research center and compared these with estimates of choline intake derived from 3-d food records kept by subjects immediately before study enrollment. Mean choline intake in this subject population met or slightly exceeded the current Adequate Intake (AI) of 7 mg/(kg · d) set by the Institute of Medicine. Men and women consumed similar amounts of choline per day (8.4 and. 6.7 mg/kg, respectively; P = 0.11). Choline intakes estimated from the 3-d food records were significantly lower than this (when expressed as mg/kg, or as total mg, but not when normalized to energy intake), suggesting underreporting of food intake. Intake of betaine, which may spare choline utilization as a methylgroup donor, was 5.3 mg/(kg · d) in men and 4.7 mg/(kg · d) in women. Intake of folate, vitamin B-12, and methionine + cysteine, were similar and sufficient in all subjects. The current recommended AI for choline seems to be a good approximation of the actual intake of this nutrient