Investigation of the SH3BP2 Gene Mutation in Cherubism

Cherubism is a rare developmental lesion of the jaw that is generally inherited as an autosomal dominant trait. Recent studies have revealed point mutations in the SH3BP2 gene in cherubism patients. In this study, we examined a 6-year-old Korean boy and his family. We found a Pro418Arg mutation in the SH3BP2 gene of the patient and his mother. A father and his 30-month-old younger brother had no mutations. Immunohistochemically, the multinucleated giant cells proved positive for CD68 and tartrate-resistant acid phosphatase (TRAP). Numerous spindle-shaped stromal cells expressed a ligand for receptor activator of nuclear factor kB (RANKL), but not in multinucleated giant cells. These results provide evidence that RANKL plays a critical role in the differentiation of osteoclast precursor cells to multinucleated giant cells in cherubism. Additionally, genetic analysis may be a useful method for differentiation of cherubism.</p

Suppression of STAT3 and HIF-1 Alpha Mediates Anti-Angiogenic Activity of Betulinic Acid in Hypoxic PC-3 Prostate Cancer Cells

Background: Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that regulates various cellular processes such as cell survival, angiogenesis and proliferation. In the present study, we examined that betulinic acid (BA), a triterpene from the bark of white birch, had the inhibitory effects on hypoxia-mediated activation of STAT3 in androgen independent human prostate cancer PC-3 cells. Methodology/Principal Findings: BA inhibited the protein expression and the transcriptional activities of hypoxia-inducible factor-1a (HIF-1a) under hypoxic condition. Consistently, BA blocked hypoxia-induced phosphorylation, DNA binding activity and nuclear accumulation of STAT3. In addition, BA significantly reduced cellular and secreted levels of vascular endothelial growth factor (VEGF), a critical angiogenic factor and a target gene of STAT3 induced under hypoxia. Furthermore, BA prevented in vitro capillary tube formation in human umbilical vein endothelial cells (HUVECs) maintained in conditioned medium of hypoxic PC-3 cells, implying anti-angiogenic activity of BA under hypoxic condition. Of note, chromatin immunoprecipitation (ChiP) assay revealed that BA inhibited binding of HIF-1a and STAT3 to VEGF promoter. Furthermore, silencing STAT3 using siRNA transfection effectively enhanced the reduced VEGF production induced by BA treatment under hypoxia. Conclusions/Significance: Taken together, our results suggest that BA has anti-angiogenic activity by disturbing th

Does Objective Structured Clinical Examinations Score Reflect the Clinical Reasoning Ability of Medical Students?

Abstract:BackgroundClinical reasoning ability is an important factor in a physician's competence and thus should be taught and tested in medical schools. Medical schools generally use objective structured clinical examinations (OSCE) to measure the clinical competency of medical students. However, it is unknown whether OSCE can also evaluate clinical reasoning ability. In this study, the authors investigated whether OSCE scores reflected students' clinical reasoning abilities.MethodsSixty-five fourth-year medical students participated in this study. Medical students completed the OSCE with 4 cases using standardized patients. For assessment of clinical reasoning, students were asked to list differential diagnoses and the findings that were compatible or not compatible with each diagnosis. The OSCE score (score of patient encounter), diagnostic accuracy score, clinical reasoning score, clinical knowledge score and grade point average (GPA) were obtained for each student, and correlation analysis was performed.ResultsClinical reasoning score was significantly correlated with diagnostic accuracy and GPA (correlation coefficient = 0.258 and 0.380; P = 0.038 and 0.002, respectively) but not with OSCE score or clinical knowledge score (correlation coefficient = 0.137 and 0.242; P = 0.276 and 0.052, respectively). Total OSCE score was not significantly correlated with clinical knowledge test score, clinical reasoning score, diagnostic accuracy score or GPA.ConclusionsOSCE score from patient encounters did not reflect the clinical reasoning abilities of the medical students in this study. The evaluation of medical students' clinical reasoning abilities through OSCE should be strengthened

Altered resting-state connectivity in subjects at ultra-high risk for psychosis: an fMRI study

<p>Abstract</p> <p>Background</p> <p>Individuals at ultra-high risk (UHR) for psychosis have self-disturbances and deficits in social cognition and functioning. Midline default network areas, including the medial prefrontal cortex and posterior cingulate cortex, are implicated in self-referential and social cognitive tasks. Thus, the neural substrates within the default mode network (DMN) have the potential to mediate self-referential and social cognitive information processing in UHR subjects.</p> <p>Methods</p> <p>This study utilized functional magnetic resonance imaging (fMRI) to investigate resting-state DMN and task-related network (TRN) functional connectivity in 19 UHR subjects and 20 matched healthy controls. The bilateral posterior cingulate cortex was selected as a seed region, and the intrinsic organization for all subjects was reconstructed on the basis of fMRI time series correlation.</p> <p>Results</p> <p>Default mode areas included the posterior/anterior cingulate cortices, the medial prefrontal cortex, the lateral parietal cortex, and the inferior temporal region. Task-related network areas included the dorsolateral prefrontal cortex, supplementary motor area, the inferior parietal lobule, and middle temporal cortex. Compared to healthy controls, UHR subjects exhibit hyperconnectivity within the default network regions and reduced anti-correlations (or negative correlations nearer to zero) between the posterior cingulate cortex and task-related areas.</p> <p>Conclusions</p> <p>These findings suggest that abnormal resting-state network activity may be related with the clinical features of UHR subjects. Neurodevelopmental and anatomical alterations of cortical midline structure might underlie altered intrinsic networks in UHR subjects.</p

Establishment, Regeneration, and Succession of Korean Red Pine (Pinus densiflora S. et Z.) Forest in Korea

Seed production of Korean red pine (Pinus densiflora Siebold & Zucc.) was ranging from 25 to 27 seeds/m2 with a viability averaging between 42 and 44%. Seed dispersal reaches about 80 m. Germination rate of seed varied from 19 to 90%, and survival rate of seedling varied from 0 to 30% depending on moisture condition in field experiment. Survivorship curve of the pine population showed type III. Species composition of the pine forest was characterized by possessing plants with resistant capacity to water deficit such as Rhododendron micranthum, Vaccinium hirtum var. koreanum, Spodiopogon sibiricus, and Lespedeza cyrtobotrya. Ecological longevity of the pine was about 140 years based on mean age of gap makers. Natural maintenance of the pine forest depended on disturbance regime, which is dominated by endogenous factor. Natural regeneration of the pine forest is possible only in a very restricted site such as ridgetop with thin and infertile soil condition. Therefore, active and systematic management is required for artificial regeneration of the forest as is known in silivicultural method. Pine gall midge damage accelerated succession of the pine forest to the deciduous broadleaved forest dominated by oak except on the ridgetop where the forest can be maintained naturally