Reelin and APP Cooperatively Modulate Dendritic Spine Formation In Vitro and In Vivo

Amyloid precursor protein (APP) plays an important role in the pathogenesis of Alzheimer’s disease (AD), but the normal function of APP at synapses is poorly understood. We and others have found that APP interacts with Reelin and that each protein is individually important for dendritic spine formation, which is associated with learning and memory, in vitro. However, whether Reelin acts through APP to modulate dendritic spine formation or synaptic function remains unknown. In the present study, we found that Reelin treatment significantly increased dendritic spine density and PSD-95 puncta number in primary hippocampal neurons. An examination of the molecular mechanisms by which Reelin regulates dendritic spinogenesis revealed that Reelin enhanced hippocampal dendritic spine formation in a Ras/ERK/CREB signaling-dependent manner. Interestingly, Reelin did not increase dendritic spine number in primary hippocampal neurons when APP expression was reduced or in vivo in APP knockout (KO) mice. Taken together, our data are the first to demonstrate that Reelin acts cooperatively with APP to modulate dendritic spine formation and suggest that normal APP function is critical for Reelin-mediated dendritic spinogenesis at synapses.

Classification of microvascular invasion of hepatocellular carcinoma: correlation with prognosis and magnetic resonance imaging

Background/Aims@#The microvascular invasion (MVI) of hepatocellular carcinoma (HCC) involves a wide histological spectrum, and it is unclear whether the degree of MVI correlates with patient prognosis or imaging findings. Here, we evaluate the prognostic value of MVI classification and analyze the radiologic features predictive of MVI. @*Methods@#Using a retrospective cohort of 506 patients with resected solitary HCCs, the histological and imaging features of MVI were reviewed and correlated with clinical data. @*Results@#MVI-positive HCCs invading ≥5 vessels or those with ≥50 invaded tumor cells were significantly associated with decreased overall survival (OS). The 5-year OS, recurrence-free survival (RFS), and beyond Milan criteria RFS rates were significantly poorer in patients with severe MVI compared with those with mild or no MVI. Severe MVI was a significant independent predictive factor for OS (odds ratio [OR], 2.962; p<0.001), RFS (OR, 1.638; p=0.002), and beyond Milan criteria RFS (OR, 2.797; p<0.001) on multivariable analysis. On MRI, non-smooth tumor margins (OR, 2.224; p=0.023) and satellite nodules (OR, 3.264; p<0.001) were independently associated with the severe-MVI group on multivariable analysis. Both non-smooth tumor margins and satellite nodules were associated with worse 5-year OS, RFS, and beyond Milan criteria RFS. @*Conclusions@#Histologic risk classification of MVI according to the number of invaded microvessels and invading carcinoma cells was a valuable predictor of prognosis in HCC patients. Non-smooth tumor margin and satellite nodules were significantly associated with severe MVI and poor prognosis.

Prognostic significance of viable tumor size measurement in hepatocellular carcinomas after preoperative locoregional treatment

Background@#Preoperative locoregional treatment (LRT) for hepatocellular carcinoma (HCC) often induces intratumoral necrosis without affecting the overall tumor size, and residual viable tumor size (VTS) on imaging is an important clinical parameter for assessing post-treatment response. However, for surgical specimens, it is unclear whether the VTS would be more relevant to prognosis compared to total tumor size (TTS). @*Methods@#A total of 142 surgically resected solitary HCC cases were retrospectively reviewed. The TTS and VTS were assessed by applying the modified Response Evaluation Criteria in Solid Tumors method to the resected specimens, and correlated with the clinicopathological features and survival. @*Results@#As applying VTS, 13/142 cases (9.2%) were down-staged to ypT1a. Although the survival analysis results for overall survival according to TTS or VTS were similar, VTS was superior to predict disease-free survival (DFS; p = .023) compared to TTS (p = .08). In addition, multivariate analysis demonstrated VTS > 2 cm to be an independent predictive factor for decreased DFS (p = .001). In the subpopulation of patients with LRT (n = 54), DFS in HCCs with TTS or VTS > 2 cm were significantly shorter than those with TTS or VTS ≤ 2 cm (p = .047 and p = .001, respectively). Interestingly, HCCs with TTS > 2 cm but down-staged to VTS ≤ 2 cm after preoperative LRT had similar survival to those with TTS ≤ 2 cm. @*Conclusions@#Although the prognostic impact of tumor size was similar regardless of whether TTS or VTS was applied, reporting VTS may help to increase the number of candidates for surgery in HCC patients with preoperative LRT.

Prognostic significance of viable tumor size measurement in hepatocellular carcinomas after preoperative locoregional treatment

Background@#Preoperative locoregional treatment (LRT) for hepatocellular carcinoma (HCC) often induces intratumoral necrosis without affecting the overall tumor size, and residual viable tumor size (VTS) on imaging is an important clinical parameter for assessing post-treatment response. However, for surgical specimens, it is unclear whether the VTS would be more relevant to prognosis compared to total tumor size (TTS). @*Methods@#A total of 142 surgically resected solitary HCC cases were retrospectively reviewed. The TTS and VTS were assessed by applying the modified Response Evaluation Criteria in Solid Tumors method to the resected specimens, and correlated with the clinicopathological features and survival. @*Results@#As applying VTS, 13/142 cases (9.2%) were down-staged to ypT1a. Although the survival analysis results for overall survival according to TTS or VTS were similar, VTS was superior to predict disease-free survival (DFS; p = .023) compared to TTS (p = .08). In addition, multivariate analysis demonstrated VTS > 2 cm to be an independent predictive factor for decreased DFS (p = .001). In the subpopulation of patients with LRT (n = 54), DFS in HCCs with TTS or VTS > 2 cm were significantly shorter than those with TTS or VTS ≤ 2 cm (p = .047 and p = .001, respectively). Interestingly, HCCs with TTS > 2 cm but down-staged to VTS ≤ 2 cm after preoperative LRT had similar survival to those with TTS ≤ 2 cm. @*Conclusions@#Although the prognostic impact of tumor size was similar regardless of whether TTS or VTS was applied, reporting VTS may help to increase the number of candidates for surgery in HCC patients with preoperative LRT.

Liquid-Based Cytology Features of Papillary Squamotransitional Cell Carcinoma of the Uterine Cervix

No abstract available.

Quantitative Evaluation of Hepatic Steatosis Using Normalized Local Variance in a Rat Model: Comparison with Histopathology as the Reference Standard

OBJECTIVE: To evaluate the diagnostic performance of the normalized local variance (NLV) ultrasound technique in the assessment of hepatic steatosis, and to identify the factors that influence the NLV value using histopathological examination as the reference standard. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were fed a methionine-choline-deficient diet for variable periods (0, 2, 4, 6, 8, 10, or 12 days or 2, 3, or 4 weeks; four rats per group). At the end of each diet duration, magnetic resonance spectroscopy (MRS) and NLV examination were performed. Thereafter, the rats were sacrificed and their livers were histopathologically evaluated. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic capability of the NLV value in the detection of varying degrees of hepatic steatosis. Univariate and multivariate linear regressions were used to determine the factors associated with the NLV value. RESULTS: The areas under the ROC curve for the detection of mild, moderate, and severe hepatic steatosis were 0.953, 0.896, and 0.735, respectively. The NLV value showed comparable diagnostic performance to that of MRS in the detection of ≥ mild or ≥ moderate hepatic steatosis. Multivariate linear regression analysis revealed that the degree of hepatic steatosis was the only significant factor affecting the NLV value (p < 0.001). CONCLUSION: The NLV value of ultrasound demonstrated satisfactory diagnostic performance in the assessment of varying degrees of hepatic steatosis. The degree of hepatic steatosis was the only significant factor that affected the NLV value.

Cytomorphological Features of Hyperchromatic Crowded Groups in Liquid-Based Cervicovaginal Cytology: A Single Institutional Experience

BACKGROUND: Hyperchromatic crowed groups (HCGs) are defined as three-dimensional aggregates of crowded cells with hyperchromatic nuclei, and are frequently encountered in cervicovaginal liquid-based cytology (LBC). Here, we aimed to examine the prevalence of HCGs in cervicovaginal LBC and the cytomorphological characteristics of various epithelial cell clusters presenting as HCGs.METHODS: We first examined the prevalence of HCGs in a “routine cohort” of LBC cytology (n=331), consisting of all cervicovaginal LBCs accessioned over 3 days from outpatient clinics (n=179) and the screening population (n=152). Then we examined a second “high-grade epithelial cell abnormalities (H-ECA) cohort” (n=69) of LBCs diagnosed as high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma (SCC), or adenocarcinoma during 1 year.RESULTS: HCGs was observed in 34.4% of the routine cohort and were significantly more frequent in the epithelial cell abnormality category compared to the non-neoplastic category (p=.003). The majority of HCGs represented atrophy (70%). Of the 69 histologically confirmed H-ECA cases, all contained HCGs. The majority of cases were HSIL (62%), followed by SCC (16%). Individually scattered neoplastic cells outside the HCGs were significantly more frequent in SCCs compared to glandular neoplasia (p=.002). Despite the obscuring thick nature of the HCGs, examining the edges and the different focal planes of the HCGs and the background were helpful in defining the nature of the HCGs.CONCLUSIONS: HCGs were frequently observed in cervicovaginal LBC and were mostly non-neoplastic; however, neoplastic HCGs were mostly high-grade lesions. Being aware of the cytomorphological features of different HCGs is important in order to avoid potential false-negative cytology interpretation.

A Mother's Experience of Hospitalization of Her Newborn in the Neonatal Intensive Care Unit

PURPOSE: The purpose of this study was to explore and describe the meaning and essence of a mother's experience of hospitalization of her newborn in the neonatal intensive care unit (NICU). METHODS: This study employed a qualitative research design. An interview was conducted with a mother whose newborn was hospitalized in the NICU, and the data were analyzed using Giorgi's phenomenological method. RESULTS: Five main themes and 19 formulated meanings were indentified. The 5 themes were ‘drowning in pain’, ‘just look outside the glass door’, ‘being a pillar’, ‘a deepening attachment’, and ‘prepare for nurturing with hope’. CONCLUSION: The results of this study provided an in-depth understanding of the experience of a mother with a newborn in the NICU. These results can be used in the development of a nursing intervention program that provides psychological and emotional support to the mother and family.