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Breast cancer stem cells (CSCs) have been hypothesized to be the driving force behind tumorigenesis and metastasis. In this study, we evaluated the relationships between CSC expressions in primary breast cancers and corresponding metastatic sentinel and nonsentinel lymph nodes (SLNs and NSLNs). The clinical implications of these relationships were also investigated. CSC expressions were evaluated in 167 breast cancer specimens and associated lymph node biopsies (when present). We used double immunohistochemistry of CD44/CD24 and single immunohistochemistry of ALDH-1 on paraffin-embedded breast tissue, SLN, and NSLN specimens. Seven cases had metastatic NSLNs without SLN involvement--so-called "skip metastasis." Fifty cases of SLNs (29.9%) and 33 cases of NSLNs (25.7%) had metastases. In the breast cancers, metastatic SLNs, and NSLNs, the expression rates of CD44+/CD24- were 47.9%, 26.1%, and 34.6 %, respectively, while the expression rates of ALDH-1+ were 42.5%, 36.4%, and 33.3%, respectively. Significant relationships were not observed between CSC expressions in breast cancer and metastatic SLNs or NSLNs. The presence of skip metastasis correlated with negative ALDH-1 in breast cancer (P = .04), as well as several clinicopathologic factors: age >50 years (P = .004), negative lymphovascular tumor emboli (P = .02), and high Ki-67 expression (P = .04). Axillary lymph node metastasis showed no significant relationship with any CSC marker. However, CD44+/CD24- and ALDH-1 expressions of metastatic SLNs correlated with CSCs of primary breast cancers. In summary, skip metastasis correlated with negative expression of ALDH-1 in primary breast cancers, which could be promising as a means of assessing the risk of skip metastasis. [ABSTRACT FROM AUTHOR]

Purpose: Identifying patients' agendas is important; however, the extent of Korean medical students'agenda-setting abilities is unknown. The study aim was to investigate the patterns of Korean medical students'agenda solicitation. Methods: A total of 94 third-year medical students participated. One scenario involving a female patient with abdominal pain was created. Students were video-recorded as they interviewed the patient. To analyze whether students identify patients' reasons for visiting, a checklist was developed based on a modified version of the Calgary-Cambridge Guide to the Medical Interview: Communication Process checklist. The duration of the patient's initial statement of concerns was measured in seconds. The total number of patient concerns expressed before interruption and the types of interruption effected by the medical students were determined. Results: The medical students did not explore the patients' concerns and did not negotiate an agenda. Interruption of the patient's opening statement occurred in 4.62±2.20 seconds. The most common type of initial interruption was a recompleter (79.8%). Closed-ended questions were the most common question type in the second and third interruptions. Conclusion: Agenda setting should be emphasized in the communication skills curriculum of medical students. The Korean Clinical Skills Exam must assess medical students' ability to set an agenda. [ABSTRACT FROM AUTHOR]

Tissue injury may create a specific microenvironment for inducing the systemic participation of stromal-like cells in the repair process. Here we show that substance P is an injury-inducible factor that acts early in the wound healing process to induce CD29+ stromal-like cell mobilization. Likewise, mobilization of such cells also occurs in uninjured mice, rats and rabbits if substance P is intravenously injected. Upon further characterization these substance P–mobilized CD29+ cells were found to be similar to stromal cells from a number of connective tissues, including bone marrow (that is, bone marrow stromal cells, or BMSCs). Both substance P injection and transfusion of autologously derived substance P–mobilized CD29+ cells from uninjured rabbits accelerated wound healing in an alkali burn model. Also, epithelial engraftment of the transfused cells into the injured tissue occurred during the wound healing. Finally, using human BMSCs as a test population, we show that substance P stimulates transmigration, cell proliferation, activation of the extracellular signal–related kinases (Erk) 1 and 2 and nuclear translocation of β-catenin in vitro. This finding highlights a previously undescribed function of substance P as a systemically acting messenger of injury and a mobilizer of CD29+ stromal-like cells to participate in wound healing. [ABSTRACT FROM AUTHOR]

Costal cartilage has been proposed as an alternative donor of chondrocytes for articular-cartilage repair. In the present study we compared the initial cell yield of chondrocytes from rabbit costal cartilage and their cell expansion rates in monolayer culture with those of articular cartilage. Costal cartilage gave an approx. 2.6-fold higher cell yield than did articular cartilage. During in vitro culture, CCs (costal chondrocytes) grew faster and displayed approx. 3-fold more cell expansion up to P4 (passage 4) than did ACs (articular chondrocytes). In order to match the degree of dedifferentiation during serial cultivation with the cells' expansion rate, type II collagen expression and the emergence of fibroblastic morphology were monitored at each cell passage. Both ACs and CCs gradually lost their chondrocytic phenotype, changed to fibroblast-like cells and displayed a reduced expression of type II collagen. We then also evaluated the redifferentiation capacity of the expanded ACs and CCs by culturing them at high density in collagen gel. Almost fully dedifferentiated CCs at P4 were successfully redifferentiated into hyaline cartilage, which showed the expression of glycosaminoglycan and type II collagen as well as the formation of lacunae and a territorial matrix. In conclusion, costal cartilage may have advantages over articular cartilage as an alternative donor tissue for autologous chondrocytes on the basis of its higher cell yield, higher cell expansion and successful reversion into hyaline cartilage without ossification in vitro. However, although this experiment with a rabbit model gave a better insight into the problem than other experiments have done, it does not answer definitively the question as to which cells are most appropriate for articular cartilage repair in humans. [ABSTRACT FROM AUTHOR]

Background: The association of white matter (WM) abnormalities with clinical variables in schizophrenia (SCZ) is poorly understood. We investigated the clinical correlates of WM impairments using imaging data of 597 patients with SCZ and 490 healthy controls (HC). We focused on lifelong changes of WM (measured by Fractional Anisotropy [FA]) in SCZ and compared it to that of HC. We investigated how age, duration of illness, and medication influence WM trajectories, and examined how structural impairments are related to symptoms and cognition. Last, we tested for the role of sex in structure-function interactions. Methods: Diffusion-weighted images and clinical measurements were collected as part of 13 independent studies, and data was harmonized across all sites. We registered images to the IIT Human Brain Atlas and averaged FA for forceps major, forceps minor, cingulum, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus (SLF) and uncinate fasciculus. First, we modeled the FA age trajectory of each tract in HC and used it to regress out the effect of age in patients. The residuals in the FA values were utilized for further analyses. We conducted mediator regression analyses with FA as the dependent variable, sex as a covariate, and age and duration of illness as the independent variables. Next, patients were grouped based on Chlorpromazine equivalent dosage (CPZ) and CPZ group was added to the regression model. To examine the association between structure and function, a structural equation model (SEM) was used, with cognition as a mediator. Last, all analyses were repeated for males and females separately. Results: Regression analyses revealed a significant influence of duration of illness on the forceps major (T=3.24, p<.001), forceps minor (T=3.40, p<.001), and SLF (T=3.83, p<.0001). When adding both age and duration of illness, duration of illness mediated the influence of age on FA. Adding CPZ to the model displayed a significant effect of medication on forceps major (T=3.93, p<.0001). For SEM, FA of all tracts was used to represent structural impairment, and symptom scores were used to reflect functional impairment. All data paths were calculated with an asymptotically distribution-free model. The overall model fit was acceptable (RMSEA =.09) with a medium-strong effect of structural impairment on functional impairment (standardized estimate=.44). When separating sexes, males showed a significant association of duration of illness and FA. Females displayed a stronger influence of structural impairment on functional impairment (standardized estimate: males = .29, females =.52), and cognition had an impact on this relationship for females only. Discussion: The effect of duration of illness on specific WM tracts suggests a progressive, neurodegenerative pathology, which might contribute to the devastating effects of chronicity. Medication seems to have only a small, localized effect on corpus callosum WM integrity. However, since our analysis used cross-sectional CPZ measures, future studies should include measurements of lifetime dosage. The observed impact of WM abnormalities on function further highlights the importance of WM for SCZ pathology. The association of structure and function seems sex-specific. Men show a stronger effect of chronicity. For females, cognition mediates the effect of structure on function, suggesting the role of cognitive reserve. Our approach provides the first step towards evidence-based medicine, by demonstrating the apparent relationship between structural pathology and functional outcome and suggesting possible mediators of this relationship, including duration of illness, cognition, medication, and sex. [ABSTRACT FROM AUTHOR]

Background: A great number of studies using resting-state functional MRI (rsfMRI) have been conducted for revealing altered functional connectivity in schizophrenia. Although the default mode network has been predominantly investigated, other resting-state networks (RSNs) can be networks of interest for unveiling the neurobiological basis of schizophrenia. Our study investigated changes in functional connectivity in the nine RSNs in recent-onset schizophrenia. Methods: We performed a rsfMRI in 46 patients with recent-onset schizophrenia and 22 healthy controls. In the preprocessing steps, independent component analysis (ICA)-based automatic removal of motion artifacts was applied to eliminate motion-related components from an individual-level ICA. Group ICA and dual regression were performed for voxel-wise comparisons between the groups with the non-parametric permutation test using threshold-free cluster enhancement and a corrected-p < 0.05 for multiple comparisons. We used the Positive and Negative Syndrome Scale scores for the correlation analysis of symptom severity with functional connectivity in the patient group. Results: The control group had areas with a significant group difference in activity compared to that of the patient group in which it existed in the left supplementary motor cortex and supramarginal gyrus (the executive control network) and the right postcentral gyrus (the auditory network). There were no significant correlations of symptom severity with the functional connectivity of these regions. Discussion: The left supplementary motor cortex, supramarginal gyrus, and right postcentral gyrus having areas with a significant group difference may have a role in the pathophysiology of schizophrenia, given their language and auditory information processing functions. [ABSTRACT FROM AUTHOR]

Background: Several machine-learning (ML) algorithms have been deployed in the diagnostic classification of schizophrenia. Compared to other ML methods, the 3D convolutional neural network (CNN) has an advantage of learning complex and subtle patterns in data and preserving spatial information, which is a more suitable tool for brain imaging data. Although resting-state functional MRI (rsfMRI) data has been used in previous ML studies relating to the diagnostic classification of schizophrenia, a limited number of studies have been conducted using resting-state functional connectivity resulted from group independent component analysis (ICA) and dual regression. The objective of this study was to investigate whether a successful diagnostic classification of schizophrenia vs. healthy controls could be achieved by the 3D CNN using resting-state networks in which areas with a significant group difference in activity existed. Methods: T1 and rsfMRI data were collected in 46 patients with recentonset schizophrenia and 22 healthy controls. In the pre-processing steps of rsfMRI, the ICA-based automatic removal of motion artifacts was applied to subject-level ICA results and the resulting rsfMRI data were temporally concatenated for group ICA and dual regression. The executive control and auditory networks had areas with significantly higher activity in the control group compared with the patient group. The independent components (ICs) respective to the executive control and auditory networks were used as input for the 3D CNN model which was developed to discriminate the schizophrenia patients from the healthy controls. Results: The 3D CNN model using the executive control and auditory networks as inputs showed classification accuracies of 65~70%, and error rates of 30~35% approximately. Discussion: Our findings suggest that the 3D CNN model using rsfMRI data can be useful for learning patterns implicated in schizophrenia and identifying discriminative patterns of schizophrenia in brain imaging data. [ABSTRACT FROM AUTHOR]