Downregulation of FGF Signaling by Spry4 Overexpression Leads to Shape Impairment, Enamel Irregularities, and Delayed Signaling Center Formation in the Mouse Molar.

FGF signaling plays a critical role in tooth development, and mutations in modulators of this pathway produce a number of striking phenotypes. However, many aspects of the role of the FGF pathway in regulating the morphological features and the mineral quality of the dentition remain unknown. Here, we used transgenic mice overexpressing the FGF negative feedback regulator Sprouty4 under the epithelial keratin 14 promoter (K14-Spry4) to achieve downregulation of signaling in the epithelium. This led to highly penetrant defects affecting both cusp morphology and the enamel layer. We characterized the phenotype of erupted molars, identified a developmental delay in K14-Spry4 transgenic embryos, and linked this with changes in the tooth developmental sequence. These data further delineate the role of FGF signaling in the development of the dentition and implicate the pathway in the regulation of tooth mineralization. © 2019 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

FGF Signaling Regulates the Number of Posterior Taste Papillae by Controlling Progenitor Field Size

The sense of taste is fundamental to our ability to ingest nutritious substances and to detect and avoid potentially toxic ones. Sensory taste buds are housed in papillae that develop from epithelial placodes. Three distinct types of gustatory papillae reside on the rodent tongue: small fungiform papillae are found in the anterior tongue, whereas the posterior tongue contains the larger foliate papillae and a single midline circumvallate papilla (CVP). Despite the great variation in the number of CVPs in mammals, its importance in taste function, and its status as the largest of the taste papillae, very little is known about the development of this structure. Here, we report that a balance between Sprouty (Spry) genes and Fgf10, which respectively antagonize and activate receptor tyrosine kinase (RTK) signaling, regulates the number of CVPs. Deletion of Spry2 alone resulted in duplication of the CVP as a result of an increase in the size of the placode progenitor field, and Spry1−/−;Spry2−/− embryos had multiple CVPs, demonstrating the redundancy of Sprouty genes in regulating the progenitor field size. By contrast, deletion of Fgf10 led to absence of the CVP, identifying FGF10 as the first inductive, mesenchyme-derived factor for taste papillae. Our results provide the first demonstration of the role of epithelial-mesenchymal FGF signaling in taste papilla development, indicate that regulation of the progenitor field size by FGF signaling is a critical determinant of papilla number, and suggest that the great variation in CVP number among mammalian species may be linked to levels of signaling by the FGF pathway

Risk of recurrence in surgically resected stage I adenocarcinoma of the lung: histopathologic and immunohistochemical analysis

STUDY OBJECTIVES: Stage I adenocarcinoma of the lung is the most common type of lung cancer. A better understanding of the histopathology and molecular biology of lung cancer might improve the capability to predict the outcome for any individual patient. The purpose of this study was to evaluate several histopathologic and molecular markers in order to assess their prognostic value in stage I adenocarcinoma. METHODS: Fifty-five patients at the Seoul National University Bundang Hospital were enrolled in the study. Histopathologic factors and molecular markers were selected. RESULTS: Multivariate analysis demonstrated that necrosis, lymphatic vessel invasion, E-cadherin, p53, and Ki-67 emerged as independent prognostic factors of recurrence. When patients were grouped according to low or high risk according to the number of factors involved, the difference in disease-free survival between these groups was statistically significant. CONCLUSIONS: In resected stage I adenocarcinoma, necrosis, lymphatic vessel invasion, E-cadherin, and p53 have been identified as independent predictors of disease-free survival

Epidermal Growth Factor Receptor Mutation and Pathologic-Radiologic Correlation Between Multiple Lung Nodules with Ground-Glass Opacity Differentiates Multicentric Origin from Intrapulmonary Spread

IntroductionNo standard guidelines detailing recommendations for the selection and treatment for multiple lung nodules with ground-glass opacity (GGO) have been established. For treatment decision, we analyzed epidermal growth factor receptor (EGFR)/K-ras somatic aberrations and pathologic-radiologic correlation in multiple lung nodules presented as GGO to differentiate multifocal lesions from intrapulmonary spread.MethodsTwenty-four patients with multiple lung nodules presented as GGO were identified to investigate somatic mutations of EGFR (exon 18–21) and K-ras (codons 2, 13, and 61). This series included 18 atypical adenomatous hyperplasias (AAH), 15 bronchioloalveolar carcinomas (BAC), and 23 adenocarcinomas (ADC) obtained from 24 patients.ResultsHigh frequency of discordant EGFR mutations (17 of 24, 70.8%) could discriminate tumor clonality (18 of 24, 75%) of multiple lung neoplastic nodules presented as GGO. EGFR mutations were common in AAH (38.9%), BAC (46.7%), and ADC (39.1%). In case 4, AAH and BAC had different mutational changes, and in case 10, the BAC lesion contains EGFR mutation that is not in the invasive ADC. In case 17, the BAC had more mutational changes than the carcinoma. The pure GGO appearance in the radiologic examination corresponded preinvasive pathologic change.ConclusionsThis study showed that synchronous BAC and/or ADC can have different EGFR or K-ras mutational profiles suggesting these lesions arise as independent events rather than intrapulmonary spread or systemic metastasis. This has significant implication in staging and treatment. These findings might be a clue to establish guidelines of the multiple neoplastic lung nodules with GGO

Expression of MicroRNAs in the Stem Cell Niche of the Adult Mouse Incisor

Peer reviewe

Video-assisted thoracic surgery sleeve resection and bronchoplasty using 3D imaging system: its safety and efficacy

Background Video-assisted thoracic surgery sleeve resection with bronchial anastomosis or bronchoplasty is a technically demanding procedure. Three-dimensional endoscopic surgery has been reported to be helpful in decreasing operation time and improving spatial perception with less surgical errors, but there have been rare reports about relatively difficult thoracoscopic procedures utilizing 3D thoracoscope. We performed this study to evaluate early clinical outcomes of thoracoscopic sleeve resection and bronchoplasty utilizing 3D thoracoscope. Methods Data from a total of 36 patients who underwent thoracoscopic sleeve lobectomy or bronchoplasty at our institution from December 2015 to October 2017 were retrospectively reviewed. Three-port approach with one utility incision was used with a 10 mm, 30° three-dimensional thoracoscope. Twenty-three patients (81%) were male, and mean age was 65.9 ± 9.4 years. Fourteen patients (38.9%) underwent sleeve resection with bronchial anastomosis, 22 (61.1%) underwent wedge or simple bronchoplasty, and one patient received concomitant PA procedure. Bronchial anastomosis sites were not covered with viable tissue flaps. Results There was no (0%) suture needle injury from spatial misperception during bronchoplasty or sleeve anastomosis. There was no (0%) operative mortality. The pathologic report revealed squamous cell carcinoma (63.9%), adenocarcinoma (19.4%), carcinoid (6.9%), adenosquamous carcinoma (3.4%), and sarcomatoid carcinoma (2.8%). One (2.8%) late mortality was due to systemic recurrence of sarcomatoid carcinoma. There was no (0.0%) anastomotic failure. The mean number of dissected lymph nodes were 27.4 ± 13.2, and mean operation time was 216.8 ± 60.0 min. Median postoperative 24-h drain amount was 315 mL. Median chest tube days and hospital days were 4 and 6, respectively. Two patients (5.6%) had complications greater than Clavien-Dindo grade II—one case of ARDS, and the other case of a delayed bronchopleural fistula. Conclusions Thoracoscopic sleeve resection and bronchoplasty utilizing HD 3D thoracoscope is a safe and effective procedure with excellent early clinical outcomes. Further investigation for long-term outcomes will be needed

Additional mechanical pleurodesis after thoracoscopic wedge resection and covering procedure for primary spontaneous pneumothorax

BACKGROUND: Additional mechanical pleurodesis for the treatment of primary spontaneous pneumothorax (PSP) is believed to reduce the recurrence of PSP, and a covering procedure with absorbable mesh also shows comparable results. This study was conducted to determine whether additional mechanical pleurodesis would be effective in reducing recurrence after thoracoscopic wedge resection and covering procedure. MATERIALS AND METHODS: Between May 2003 and August 2005, 99 patients underwent thoracoscopic bullectomy with staple line covering with absorbable cellulose mesh and fibrin glue followed by an additional mechanical pleurodesis. These patients were compared with 98 patients who underwent thoracoscopic bullectomy with staple line coverage alone. RESULTS: The additional mechanical pleurodesis group had findings comparable to those of the coverage group for duration of postoperative chest drainage, length of hospital stay, and complication rate. After median follow-up of 29.2 months, postoperative recurrence occurred in four patients (4.0%). CONCLUSIONS: Additional mechanical pleurodesis after covering procedure is also effective in decreasing postoperative recurrence of PSP

Epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements in lung cancer with nodular ground-glass opacity

Vår uppsats handlar om formativ bedömning och vad det innebär att arbeta så i undervisningen. Vi tolkar att rådande läroplaner beskriver ett uppdrag som ligger i linje med ett formativt arbetssätt. Syftet var att ta reda på om lärare i samhällskunskap som arbetar på gymnasiet arbetar formativt och hur de gör det. Ett annat vanligt namn för formativ bedömning är bedömning för lärande (BFL). Genom kvalitativa intervjuer har vi frågat gymnasielärare i samhällskunskap hur de arbetar med bedömning, om de arbetar formativt och om det finns någon samsyn på deras respektive gymnasieskolor kring bedömning. Vi ville också veta vad formativt arbete innebär. Bedömning för lärande fokuserar på lärandet och hur eleven kan utvecklas och nå framgång i lärandet. Genom att konkretisera mål, syfte och kunskapskvaliteter så att eleven förstår dessa kan eleven få syn på sitt eget lärande. När eleven ges makt över sitt eget lärande leder det till ökad motivation. I formativ bedömning arbetar läraren bland annat med feedback och kamrat- och självvärdering. Vårt resultat visar att lärarna vi intervjuat i stor utsträckning arbetar summativt med formativa inslag i varierande grad, förutom en av lärarna som arbetar på en gymnasieskola i Borås som arbetar enligt bedömning för lärande. Studien visar att det råder brist på samsyn kring bedömning på gymnasie-skolorna, förutom på skolan i Borås där det finns tid avsatt för möten och samtal kring formativ bedömning. Litteraturen visar på de positiva effekterna av bedömning för lärande vilket också styrks av intervjun med läraren i Borås

Phase Contrast Microradiography of Mouse Lung Using Synchrotron X-ray: Correlation with Optical Microscopy

Purpose: The purpose of this study is to evaluate the feasibility of phase contrast X-ray microtomography and microradiography, using a polychromatic synchrotron X-ray, for analysis of the mouse lung microstructure. Materials and Methods: Normal mice were used for experiments. Some of the mouse lungs were prepared by the lung fixation-inflation method. The resulting sponge-like inflated lung samples were used for microtomography. The remaining mouse lungs were cut into 10 um sections and were used for microradiography and optical microscopic correlation. The experiments on mouse lung samples were per-formed at the 7B2 beamline of the Pohang Light Source in Korea. Results: Phase contrast X-ray microtomography of inflated lung samples showed individual alveolar structure on 3-D reconstruction. Phase contrast microradiographs of thin lung samples showed microstructure of lung, such as alveoli and bronchioles, and were well correlated with optical microscopic images. Conclusions: The results indicate that the phase contrast X-ray microtomography and microradiography using polychromatic synchrotron X-ray is feasible for evaluation of microstructure of the lung.X115sciescopuskc